Response properties of neurons in the cat's putamen during auditory discrimination.

Science.gov (United States)

Zhao, Zhenling; Sato, Yu; Qin, Ling

2015-10-01

The striatum integrates diverse convergent input and plays a critical role in the goal-directed behaviors. To date, the auditory functions of striatum are less studied. Recently, it was demonstrated that auditory cortico-striatal projections influence behavioral performance during a frequency discrimination task. To reveal the functions of striatal neurons in auditory discrimination, we recorded the single-unit spike activities in the putamen (dorsal striatum) of free-moving cats while performing a Go/No-go task to discriminate the sounds with different modulation rates (12.5 Hz vs. 50 Hz) or envelopes (damped vs. ramped). We found that the putamen neurons can be broadly divided into four groups according to their contributions to sound discrimination. First, 40% of neurons showed vigorous responses synchronized to the sound envelope, and could precisely discriminate different sounds. Second, 18% of neurons showed a high preference of ramped to damped sounds, but no preference for modulation rate. They could only discriminate the change of sound envelope. Third, 27% of neurons rapidly adapted to the sound stimuli, had no ability of sound discrimination. Fourth, 15% of neurons discriminated the sounds dependent on the reward-prediction. Comparing to passively listening condition, the activities of putamen neurons were significantly enhanced by the engagement of the auditory tasks, but not modulated by the cat's behavioral choice. The coexistence of multiple types of neurons suggests that the putamen is involved in the transformation from auditory representation to stimulus-reward association. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical Exchange Saturation Transfer MR Imaging Is Superior to Diffusion Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: a Study on Substantia Nigra and Striatum

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Chunmei eLi

2015-10-01

Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date the diagnosis of PD is still based primarily on the clinical manifestations which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical-exchange-saturation-transfer (CEST imaging and diffusion-tensor imaging (DTI in PD at 3 Tesla by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3 Tesla MR system, using an 8-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym(3.5ppm, and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen and caudate. The MTRasym(3.5ppm value, the total CEST signal intensity and fractional anisotropy (FA value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004 and P < 0.001, respectively. The MTRasym(3.5ppm values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively. There were no significant differences for the mean diffusivity (MD in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD.

Pulvinar projections to the striatum and amygdala

Directory of Open Access Journals (Sweden)

Jonathan D Day-Brown

2010-11-01

Full Text Available Visually-guided movement is possible in the absence of conscious visual perception, a phenomenon referred to as blindsight. Similarly, fearful images can elicit emotional responses in the absence of their conscious perception. Both capabilities are thought to be mediated by pathways from the retina through the superior colliculus (SC and pulvinar nucleus. To define potential pathways that underlie behavioral responses to unperceived visual stimuli, we examined the projections from the pulvinar nucleus to the striatum and amygdala in the tree shrew (Tupaia belangeri, a species considered to be a protypical primate. The tree shrew brain has a large pulvinar nucleus that contains two SC-recipient subdivisions; the dorsal (Pd and central (Pc pulvinar both receive topographic (specific projections from SC, and Pd receives an additional nontopographic (diffuse projection from SC (Chomsung et al., 2008; JCN 510:24-46. Anterograde and retrograde tract tracing revealed that both Pd and Pc project to the caudate and putamen, and Pd, but not Pc, additionally projects to the lateral amygdala. Using immunocytochemical staining for substance P (SP and parvalbumin (PV to reveal the patch/matrix organization of tree shrew striatum, we found that SP-rich/PV-poor patches interlock with a PV-rich/SP-poor matrix. Confocal microscopy revealed that tracer-labeled pulvinostriatal terminals preferentially innervate the matrix. Electron microscopy revealed that the postsynaptic targets of tracer-labeled pulvino-striatal and pulvino-amygdala terminals are spines, demonstrating that the pulvinar nucleus projects to the spiny output cells of the striatum matrix and the lateral amygdala, potentially relaying: 1 topographic visual information from SC to striatum to aid in guiding precise movements, and 2 nontopographic visual information from SC to the amygdala alerting the animal to potentially dangerous visual images.

Caudate Microstimulation Increases Value of Specific Choices.

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Santacruz, Samantha R; Rich, Erin L; Wallis, Joni D; Carmena, Jose M

2017-11-06

Value-based decision-making involves an assessment of the value of items available and the actions required to obtain them. The basal ganglia are highly implicated in action selection and goal-directed behavior [1-4], and the striatum in particular plays a critical role in arbitrating between competing choices [5-9]. Previous work has demonstrated that neural activity in the caudate nucleus is modulated by task-relevant action values [6, 8]. Nonetheless, how value is represented and maintained in the striatum remains unclear since decision-making in these tasks relied on spatially lateralized responses, confounding the ability to generalize to a more abstract choice task [6, 8, 9]. Here, we investigate striatal value representations by applying caudate electrical stimulation in macaque monkeys (n = 3) to bias decision-making in a task that divorces the value of a stimulus from motor action. Electrical microstimulation is known to induce neural plasticity [10, 11], and caudate microstimulation in primates has been shown to accelerate associative learning [12, 13]. Our results indicate that stimulation paired with a particular stimulus increases selection of that stimulus, and this effect was stimulus dependent and action independent. The modulation of choice behavior using microstimulation was best modeled as resulting from changes in stimulus value. Caudate neural recordings (n = 1) show that changes in value-coding neuron activity are stimulus value dependent. We argue that caudate microstimulation can differentially increase stimulus values independent of action, and unilateral manipulations of value are sufficient to mediate choice behavior. These results support potential future applications of microstimulation to correct maladaptive plasticity underlying dysfunctional decision-making related to neuropsychiatric conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

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Mattfeld, Aaron T.; Stark, Craig E. L.

2015-01-01

The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. PMID:25560298

Correlation between the availability of dopamine transporter and olfactory function in healthy subjects

International Nuclear Information System (INIS)

Pak, Kyoungjune; Kim, Keunyoung; Kim, In Joo; Lee, Myung Jun; Lee, Jae Meen; Kim, Bum Soo; Kim, Seong-Jang

2018-01-01

Olfactory dysfunction in Parkinson's disease is usually prodromal to other symptoms. In this study, we aimed to explore the association of olfactory function with the availabilities of striatal dopamine transporter (DAT) in healthy subjects. Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database (www.ppmi-info.org/data). The study population consisted of healthy controls with screening 123 I-FP-CIT single photon emission tomography (SPECT). University of Pennsylvania Smell Identification Test (UPSIT) was assessed to evaluate the olfactory function. Totally, 181 healthy subjects (117 male, 64 female) with 123 I-FP-CIT SPECT data were included in this study. Specific binding ratios (SBRs) of the caudate nucleus (rho = -0.4217, p < 0.0001), putamen (rho = -0.2292, p = 0.0019), and striatum (rho=-0.3425, p < 0.0001) showed a reduction with ageing. SBRs of the caudate nucleus, putamen, and striatum were positively correlated with UPSIT (rho = 0.3716, p < 0.0001; rho = 0.3655, p < 0.0001; rho = 0.3880, p < 0.0001). After controlling for age by partial correlation, SBRs of the caudate nucleus, putamen, and striatum showed an influence on UPSIT (rho = 0.3288, p < 0.0001; rho = 0.3374, p < 0.0001; rho = 0.3511, p < 0.0001). Olfactory function is associated with the availability of striatal DAT independent of age in healthy subjects. (orig.)

Evaluation of striatal dopamine transporter density using ({sup 123}I)-{beta}-CIT SPECT in schizophrenic patients treated with olanzapine: pilot study

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Kim, Chul Eung; Moon, Hey Won; Choe, Won Sick; Kim, Chang Ho; Chi, Dae Yoon [Inha Univ., Incheon (Korea, Republic of)

2002-08-01

This pilot study was performed to understand the pharmacological effect of olanzapine, an atypical antipsychotic agent, on dopamine transporter in schizophrenic patients. Six patients (3 male, 3 female) with schizophrenia, who had not taken any psychotropic drugs for at least four weeks, were studied. Nuclear imaging using ({sup 123}I)-{beta}-CIT SPECT was obtained before and after 4-week treatment with olanzapine. Analysis of ROI on the striatum, caudate nucleus, and putamen was performed. Post-treatment uptake was significantly increased in all the ROIs compared with pre-treatment uptake. This preliminary study with the small number of schizophrenic patients suggested an increase in uptake of dopamine transporter in the striatum, caudate nucleus, and putamen after 4-week treatment with olanzapine, which warrants a large-scaled controlled study to confirm the current findings.

Shape Abnormalities of the Caudate Nucleus Correlate with Poorer Gait and Balance

DEFF Research Database (Denmark)

Macfarlane, Matthew D; Looi, Jeffrey C L; Walterfang, Mark

2015-01-01

published method and volumes calculated. The relationships between volume and physical performance on the SPPB were investigated with shape analysis using the spherical harmonic shape description toolkit. RESULTS: There was no correlation between the severity of WMHs and striatal volumes. Caudate nuclei...... volume correlated with performance on the SPPB at baseline but not at follow-up, with subsequent shape analysis showing left caudate changes occurred in areas corresponding to inputs of the dorsolateral prefrontal, premotor, and motor cortex. There was no correlation between putamen volumes...

Regional differences in gene expression and promoter usage in aged human brains

KAUST Repository

Pardo, Luba M.; Rizzu, Patrizia; Francescatto, Margherita; Vitezic, Morana; Leday, Gwenaë l G.R.; Sanchez, Javier Simon; Khamis, Abdullah M.; Takahashi, Hazuki; van de Berg, Wilma D.J.; Medvedeva, Yulia A.; van de Wiel, Mark A.; Daub, Carsten O.; Carninci, Piero; Heutink, Peter

2013-01-01

To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites

Basal ganglia disorders studied by positron emission tomography

International Nuclear Information System (INIS)

Shinotoh, Hitoshi

1994-01-01

Recent development of positron emitting radioligands has made it possible to investigate the alterations of neurotransmitter systems associated with basal ganglia disorders in vivo. The functional integrity of nigro-striatal dopaminergic terminals may be studied with [ 18 F]6-fluoro-L-dopa ([ 18 F]dopa), and striatal dopamine receptor density with suitable PET ligands. [ 18 F]dopa uptake in the striatum (putamen) is markedly reduced in patients with Parkinson's disease (PD). [ 18 F]dopa-PET is capable of detecting sub-clinical nigral dysfunction in asymptomatic patients with familial PD and those who become Parkinsonian on conventional doses of dopamine receptor antagonists. While putamen [ 18 F]dopa uptake is reduced to a similar level in patients with multiple system atrophy (MSA) and PD, caudate [ 18 F] dopa uptake is lower in MSA than PD. However, [ 18 F]dopa PET cannot consistently distinguish MSA from PD because individual ranges of caudate [ 18 F]dopa uptake overlap. D 1 and D 2 receptor binding is markedly reduced in the striatum (posterior putamen) of MSA patients. Therefore, dopamine receptor imaging is useful for the differential diagnosis of MSA and PD. Similar marked reductions in putamen and caudate [ 18 F]dopa uptake have been observed in patients with progressive supranuclear palsy (PSP). Moderate reductions in D 2 receptor binding have been reported in the striatum of PSP patients. The reduction in D 2 receptor binding is more prominent in the caudate than putamen. Striatal [ 18 F]dopa uptake is normal or only mildly reduced in patients with dopa responsive dystonia (DRD). D 2 receptor binding is markedly reduced in patients with Huntington's disease, while striatal [ 18 F]dopa uptake is normal or mildly reduced. In summary, PET can demonstrate characteristic patterns of disruption of dopaminergic systems associated with basal ganglia disorders. These PET findings are useful in the differential diagnosis of basal ganglia disorders. (J.P.N.) 55 refs

Basal ganglia disorders studied by positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

1994-04-01

Recent development of positron emitting radioligands has made it possible to investigate the alterations of neurotransmitter systems associated with basal ganglia disorders in vivo. The functional integrity of nigro-striatal dopaminergic terminals may be studied with [[sup 18]F]6-fluoro-L-dopa ([[sup 18]F]dopa), and striatal dopamine receptor density with suitable PET ligands. [[sup 18]F]dopa uptake in the striatum (putamen) is markedly reduced in patients with Parkinson's disease (PD). [[sup 18]F]dopa-PET is capable of detecting sub-clinical nigral dysfunction in asymptomatic patients with familial PD and those who become Parkinsonian on conventional doses of dopamine receptor antagonists. While putamen [[sup 18]F]dopa uptake is reduced to a similar level in patients with multiple system atrophy (MSA) and PD, caudate [[sup 18]F] dopa uptake is lower in MSA than PD. However, [[sup 18]F]dopa PET cannot consistently distinguish MSA from PD because individual ranges of caudate [[sup 18]F]dopa uptake overlap. D[sub 1] and D[sub 2] receptor binding is markedly reduced in the striatum (posterior putamen) of MSA patients. Therefore, dopamine receptor imaging is useful for the differential diagnosis of MSA and PD. Similar marked reductions in putamen and caudate [[sup 18]F]dopa uptake have been observed in patients with progressive supranuclear palsy (PSP). Moderate reductions in D[sub 2] receptor binding have been reported in the striatum of PSP patients. The reduction in D[sub 2] receptor binding is more prominent in the caudate than putamen. Striatal [[sup 18]F]dopa uptake is normal or only mildly reduced in patients with dopa responsive dystonia (DRD). D[sub 2] receptor binding is markedly reduced in patients with Huntington's disease, while striatal [[sup 18]F]dopa uptake is normal or mildly reduced. In summary, PET can demonstrate characteristic patterns of disruption of dopaminergic systems associated with basal ganglia disorders. (J.P.N.) 55 refs.

A common neural code for social and monetary rewards in the human striatum.

Science.gov (United States)

Wake, Stephanie J; Izuma, Keise

2017-10-01

Although managing social information and decision making on the basis of reward is critical for survival, it remains uncertain whether differing reward type is processed in a uniform manner. Previously, we demonstrated that monetary reward and the social reward of good reputation activated the same striatal regions including the caudate nucleus and putamen. However, it remains unclear whether overlapping activations reflect activities of identical neuronal populations or two overlapping but functionally independent neuronal populations. Here, we re-analyzed the original data and addressed this question using multivariate-pattern-analysis and found evidence that in the left caudate nucleus and bilateral nucleus accumbens, social vs monetary reward were represented similarly. The findings suggest that social and monetary rewards are processed by the same population of neurons within these regions of the striatum. Additional findings demonstrated similar neural patterns when participants experience high social reward compared to viewing others receiving low social reward (potentially inducing schadenfreude). This is possibly an early indication that the same population of neurons may be responsible for processing two different types of social reward (good reputation and schadenfreude). These findings provide a supplementary perspective to previous research, helping to further elucidate the mechanisms behind social vs non-social reward processing. © The Author (2017). Published by Oxford University Press.

CRFR1 in the ventromedial caudate putamen modulates acute stress-enhanced expression of cocaine locomotor sensitization.

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Liu, Shuli; Wang, Zhiyan; Li, Yijing; Sun, Xiaowei; Ge, Feifei; Yang, Mingda; Wang, Xinjuan; Wang, Na; Wang, Junkai; Cui, Cailian

2017-07-15

Repeated exposure to psychostimulants induces a long-lasting enhancement of locomotor activity called behavioral sensitization, which is often reinforced by stress after drug withdrawal. The mechanisms underlying these phenomena remain elusive. Here we explored the effects of acute stress 3 or 14 days after the cessation of chronic cocaine treatment on the expression of locomotor sensitization induced by a cocaine challenge in rats and the key brain region and molecular mechanism underlying the phenomenon. A single session of forced swimming, as an acute stress (administered 2 days after the cessation of cocaine), significantly enhanced the expression of cocaine locomotor sensitization 14 days after the final cocaine injection (challenge at 12 days after acute stress) but not 3 days after the cessation of cocaine (challenge at 1 day after acute stress). The result indicated that acute stress enhanced the expression of cocaine locomotor sensitization after incubation for 12 days rather than 1 day after the last cocaine injection. Moreover, the enhancement in locomotor sensitization was paralleled by a selective increase in the number of the c-Fos + cells, the level of CRFR1 mRNA in the ventromedial caudate putamen (vmCPu). Furthermore, the enhancement was significantly attenuated by CRFR1 antagonist NBI-27914 into the vmCPu, implying that the up-regulation of CRFR1 in the vmCPu seems to be critical in the acute stress-enhanced expression of cocaine locomotor sensitization. The findings demonstrate that the long-term effect of acute stress on the expression of cocaine locomotor sensitization is partially mediated by CRFR1 in the vmCPu. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Relationship of striatal 99Tcm-TRODAT-1 specific uptake and motor's severity in patients with Parkinson's disease

International Nuclear Information System (INIS)

Bian Yanzhu; Liu Huang; Feng Jue; Wei Qiang; Li Jinfu; Liu Guozhang

2004-01-01

Objective: To investigate the relationship of striatal 99 Tc m -2β-((N, N'-bis (2-mercap-toethyl) ethylene diamino) methyl), 3β-(4-chlorophenyl) tropane, ( 99 Tc m -TRODAT-1) specific uptake values (SUVs) and motor's severity in patients with Parkinson's disease (PD). Methods: 35 patients with PD were examined by 99 Tc m -TRODAT-1 SPECT dopamine transporter brain imaging. The SUVs of the striatum and its subregions, including the putamen and caudate nucleus, were calculated by semi-quantity region of interest (ROI) technique with the radiation ratios of target/cerebellum. Motor's severity of PD was measured by Unified Parkinson's Disease Rating Scale (UPDRS). Motor UPDRS scores were divided into four subscales, bradykinesia scores, rigidity scores, postural instability scores and tremor scores. Results: SUVs of putamen correlated best with the motor UPDRS scores(r=-0.846, P<0.001), followed by that of striatum and caudate nucleus. Among the four major clinical signs of PD, the bradykinesia scores (X1) correlated best with SUVs of putamen(r=-0.858, P<0.001), followed by rigidity scores (X2) and postural instability scores. There was no significant correlation between tremor scores and SUVs of putamen (Y). A regression equation (Y=2.345-0.0418 X1-0.0580 X2) was founded by stepwise multiple linear regression analysis. Conclusions: The SUVs of striatum (especially SUVs of putamen) was a useful marker to evaluate the motor's severity of PD and monitor the progression of PD. (authors)

Separate groups of dopamine neurons innervate caudate head and tail encoding flexible and stable value memories

Directory of Open Access Journals (Sweden)

Hyoung F Kim

2014-10-01

Full Text Available Dopamine neurons are thought to be critical for reward value-based learning by modifying synaptic transmissions in the striatum. Yet, different regions of the striatum seem to guide different kinds of learning. Do dopamine neurons contribute to the regional differences of the striatum in learning? As a first step to answer this question, we examined whether the head and tail of the caudate nucleus of the monkey (Macaca mulatta receive inputs from the same or different dopamine neurons. We chose these caudate regions because we previously showed that caudate head neurons learn values of visual objects quickly and flexibly, whereas caudate tail neurons learn object values slowly but retain them stably. Here we confirmed the functional difference by recording single neuronal activity while the monkey performed the flexible and stable value tasks, and then injected retrograde tracers in the functional domains of caudate head and tail. The projecting dopaminergic neurons were identified using tyrosine hydroxylase immunohistochemistry. We found that two groups of dopamine neurons in the substantia nigra pars compacta project largely separately to the caudate head and tail. These groups of dopamine neurons were mostly separated topographically: head-projecting neurons were located in the rostral-ventral-medial region, while tail-projecting neurons were located in the caudal-dorsal-lateral regions of the substantia nigra. Furthermore, they showed different morphological features: tail-projecting neurons were larger and less circular than head-projecting neurons. Our data raise the possibility that different groups of dopamine neurons selectively guide learning of flexible (short-term and stable (long-term memories of object values.

Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus in Parkinson's disease

NARCIS (Netherlands)

Luchetti, Sabina; Bossers, Koen; Frajese, Giovanni Vanni; Swaab, Dick F.

2010-01-01

There is emerging evidence from animal studies for a neuroprotective role of sex steroids in neurodegenerative diseases, but studies in human brain are lacking. We have carried out an extensive study of the neurosteroid biosynthetic pathways in substantia nigra (SN), caudate nucleus (CN) and putamen

The dorsal striatum and ventral striatum play different roles in the programming of social behaviour: a tribute to Lex Cools.

Science.gov (United States)

van den Bos, Ruud

2015-02-01

Early work by Lex Cools suggested that the caudate nucleus (dorsal striatum) plays a role in programming social behaviour: enhanced activity in the caudate nucleus increased the extent to which ongoing behaviour is controlled by the individual's own behaviour (internal control) rather than by that of its partners (external control). Interestingly, later studies by others have indicated that the ventral striatum plays a role in external rather than internal control. Here, I discuss the role of these different striatal areas - and the emotional (ventral striatum) and cognitive control (dorsal striatum) system in which they are embedded - in the organization of social behaviour in the context of locus of control. Following on from this discussion, I will pay particular attention to individual differences in social behaviour (individuals with more internal or external control), focusing on the role of dopamine, serotonin and the effects of stress-related challenges in relation to their different position in a dominance hierarchy. I will subsequently allude to potential psychological and behavioural problems in the social domain following on from these differences in locus of control ['social obliviousness' (dorsal stratum) and 'social impulsivity' (ventral striatum)]. In doing so, I provide as a tribute a historical account of the early research by Lex Cools.

Topography and chemoarchitecture of the striatum and pallidum in a monotreme, the short-beaked echidna (Tachyglossus aculeatus).

Science.gov (United States)

Ashwell, K W S

2008-09-01

The topography and chemoarchitecture of the striatum and pallidum in a monotreme, the short-beaked echidna (Tachyglossus aculeatus) have been studied using Nissl staining in conjunction with myelin staining, enzyme reactivity to acetylcholinesterase and NADPH diaphorase, and immunoreactivity to parvalbumin, calbindin, calretinin, tyrosine hydroxylase, neuropeptide Y, and neurofilament protein (SMI-32 antibody). All those components of the striatum and pallidum found in eutherian mammals could also be identified in the echidna's brain, with broad chemoarchitectural similarities to those regions in eutherian brains also apparent. There was a clear chemoarchitectural gradient visible with parvalbumin immunoreactivity of neurons and fibers, suggesting a subdivision of the echidna caudatoputamen into weakly reactive rostrodorsomedial and strongly reactive caudoventrolateral components. This may, in turn, relate to subdivision into associative versus sensorimotor CPu and reflect homology to the caudate and putamen of primates. Moreover, the chemoarchitecture of the echidna striatum suggested the presence of striosome-matrix architecture. The morphology of identified neuronal groups (i.e., parvalbumin, calbindin, and neuropeptide Y immunoreactive) in the echidna striatum and pallidum showed many similarities to those seen in eutherians, although the pattern of distribution of calbindin immunoreactive neurons was more uniform in the caudatoputamen of the echidna than in therians. These observations indicate that the same broad features of striatal and pallidal organization apply across all mammals and suggest that these common features may have arisen before the divergence of the monotreme and therian lineages.

The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

1992-12-01

The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1992-12-01

The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

A selective involvement of putamen functional connectivity in youth with internet gaming disorder.

Science.gov (United States)

Hong, Soon-Beom; Harrison, Ben J; Dandash, Orwa; Choi, Eun-Jung; Kim, Seong-Chan; Kim, Ho-Hyun; Shim, Do-Hyun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2015-03-30

Brain cortico-striatal circuits have consistently been implicated in the pathology of addiction related disorders. We applied a reliable seed-based analysis of the resting-state brain activity to comprehensively delineate the subdivisions of striatal functional connectivity implicated in internet gaming disorder. Among twelve right-handed male adolescents with internet gaming disorder and 11 right-handed and gender-matched healthy controls, we examined group differences in the functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen, as well as the association of these connectivity indices with behavioral measures of internet use. Adolescents with internet gaming disorder showed significantly reduced dorsal putamen functional connectivity with the posterior insula-parietal operculum. More time spent playing online games predicted significantly greater functional connectivity between the dorsal putamen and bilateral primary somatosensory cortices in adolescents with internet gaming disorder, and significantly lower functional connectivity between the dorsal putamen and bilateral sensorimotor cortices in healthy controls. The dorsal putamen functional connectivity was significantly and specifically different in adolescents with internet gaming disorder. The findings suggest a possible biomarker of internet gaming disorder. Copyright © 2015. Published by Elsevier B.V.

The role of the putamen in language: a meta-analytic connectivity modeling study.

Science.gov (United States)

Viñas-Guasch, Nestor; Wu, Yan Jing

2017-12-01

The putamen is a subcortical structure that forms part of the dorsal striatum of basal ganglia, and has traditionally been associated with reinforcement learning and motor control, including speech articulation. However, recent studies have shown involvement of the left putamen in other language functions such as bilingual language processing (Abutalebi et al. 2012) and production, with some authors arguing for functional segregation of anterior and posterior putamen (Oberhuber et al. 2013). A further step in exploring the role of putamen in language would involve identifying the network of coactivations of not only the left, but also the right putamen, given the involvement of right hemisphere in high order language functions (Vigneau et al. 2011). Here, a meta-analytic connectivity modeling technique was used to determine the patterns of coactivation of anterior and bilateral putamen in the language domain. Based on previous evidence, we hypothesized that left putamen coactivations would include brain regions directly associated with language processing, whereas right putamen coactivations would encompass regions involved in broader semantic processes, such as memory and visual imagery. The results showed that left anterior putamen coactivated with clusters predominantly in left hemisphere, encompassing regions directly associated with language processing, a left posterior putamen network spanning both hemispheres, and cerebellum. In right hemisphere, coactivations were in both hemispheres, in regions associated with visual and orthographic processing. These results confirm the differential involvement of right and left putamen in different language components, thus highlighting the need for further research into the role of putamen in language.

Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

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Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

2016-02-01

We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

(123I)β-CIT and SPECT in essential tremor and Parkinson's disease

International Nuclear Information System (INIS)

Asenbaum, S.; Bruecke, T.; Pirker, W.; Bencsits, G.; Pruckmayer, M.; Angelberger, P.

1997-01-01

Resting and postural tremor may occur in essential tremor (ET) and Parkinson's disease (PD). The aim of the present study was to investigate the cocaine derivative [ 123 I] β-CIT, which labels striatal dopamine transporters, and SPECT in differentiating these diseases. Methods: 30 healthy volunteers, 32 patients with ET and 29 patients with idiopathic PD of Hoehn/Yahr stage I were investigated. Specific over nondisplaceable binding ratios (target/cerebellum-1) were calculated for the striatum, the caudate nucleus and the putamen separately as well as a ratio putamen/caudate and the percent deviation of each patient's ratio from ageexpected control values. Results: striatal ( 123 I]β-CIT binding ratios in ET were within normal ranges and showed only a discrete elevation to age-expected control values (+ 14.6 %). In PD significantly reduced specific binding was evident not only contralaterally to the clinically affected side (putamen: - 62 %, caudate nucleus: - 35 %), but also ipsilaterally (putamen: - 45 %, caudate nucleus: - 22 %). All investigated parameters differed significantly between PD and controls and ET respectively. Conclusion: imaging striatal dopamine transporters with ( 123 I)β-CIT and SPECT could clearly distinguish between ET and PD in an early stage of the disease. Findings do not suggest a subclinical involvement of dopaminergic nigrostriatal neurons in ET. (author)

Differential reward coding in the subdivisions of the primate caudate during an oculomotor task.

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Nakamura, Kae; Santos, Gustavo S; Matsuzaki, Ryuichi; Nakahara, Hiroyuki

2012-11-07

The basal ganglia play a pivotal role in reward-oriented behavior. The striatum, an input channel of the basal ganglia, is composed of subdivisions that are topographically connected with different cortical and subcortical areas. To test whether reward information is differentially processed in the different parts of the striatum, we compared reward-related neuronal activity along the dorsolateral-ventromedial axis in the caudate nucleus of monkeys performing an asymmetrically rewarded oculomotor task. In a given block, a target in one position was associated with a large reward, whereas the other target was associated with a small reward. The target position-reward value contingency was switched between blocks. We found the following: (1) activity that reflected the block-wise reward contingency emerged before the appearance of a visual target, and it was more prevalent in the dorsal, rather than central and ventral, caudate; (2) activity that was positively related to the reward size of the current trial was evident, especially after reward delivery, and it was more prevalent in the ventral and central, rather than dorsal, caudate; and (3) activity that was modulated by the memory of the outcomes of the previous trials was evident in the dorsal and central caudate. This multiple reward information, together with the target-direction information, was represented primarily by individual caudate neurons, and the different reward information was represented in caudate subpopulations with distinct electrophysiological properties, e.g., baseline firing and spike width. These results suggest parallel processing of different reward information by the basal ganglia subdivisions defined by extrinsic connections and intrinsic properties.

Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

International Nuclear Information System (INIS)

Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

2004-01-01

Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2→3.9%, CA: 57.4→14.1%, ST: 17.7→0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction

Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

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Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

2004-07-01

Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [{sup 11}C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2{yields}3.9%, CA: 57.4{yields}14.1%, ST: 17.7{yields}0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction.

Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task.

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Wittmann, Marc; Leland, David S; Paulus, Martin P

2007-06-01

Delay discounting refers to the fact that an immediate reward is valued more than the same reward if it occurs some time in the future. To examine the neural substrates underlying this process, we studied 13 healthy volunteers who repeatedly had to decide between an immediate and parametrically varied delayed hypothetical reward using a delay discounting task during event-related functional magnetic resonance imaging. Subject's preference judgments resulted in different discounting slopes for shorter ( or =1 year) delays. Neural activation associated with the shorter delays relative to the longer delays was associated with increased activation in the head of the left caudate nucleus and putamen. When individuals selected the delayed relative to the immediate reward, a strong activation was found in bilateral posterior insular cortex. Several brain areas including the left caudate nucleus showed a correlation between the behaviorally determined discounting and brain activation for the contrast of intervals with delays or =1 year. These results suggest that (1) the posterior insula, which is a critical component of the decision-making neural network, is involved in delaying gratification and (2) the degree of neural activation in the striatum, which plays a fundamental role in reward prediction and in time estimation, may code for the time delay.

Effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine-somatostatin interactions in the striatum

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Martin-Iverson, M.T.; Radke, J.M.; Vincent, S.R.

1986-06-01

The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin.

Decreased Left Putamen and Thalamus Volume Correlates with Delusions in First-Episode Schizophrenia Patients

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Xiaojun Huang

2017-11-01

Full Text Available BackgroundDelusional thinking is one of the hallmark symptoms of schizophrenia. However, the underlying neural substrate for delusions in schizophrenia remains unknown. In an attempt to further our understanding of the neural basis of delusions, we explored gray matter deficits and their clinical associations in first-episode schizophrenia patients with and without delusions.MethodsTwenty-four first-episode schizophrenia patients with delusions and 18 without delusions as well as 26 healthy controls (HC underwent clinical assessment and whole-brain structural imaging which were acquired a 3.0 T scanner. Voxel-based morphometry was used to explore inter-group differences in gray matter volume using analysis of covariance, and Spearman correlation coefficients (rho between the Scale for the Assessment of Positive Symptoms (SAPS-delusion scores and mean regional brain volumes was obtained.ResultsPatients with delusions showed decreased brain gray matter volumes in the left putamen, thalamus, and caudate regions compared with HC. Patients with delusions also showed decreased regional volume in the left putamen and thalamus compared with patients without delusions. SAPS-delusion scores were negatively correlated with the gray matter volumes of the left putamen and thalamus.DiscussionLeft putamen and thalamus volume loss may be biological correlates of delusions in schizophrenia.

Different loss of dopamine transporter according to subtype of multiple system atrophy

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Kim, Hae Won [Keimyung University Dongsan Medical Center, Department of Nuclear Medicine, Daegu (Korea, Republic of); Keimyung University, Department of Nuclear Medicine, School of Medicine, Jung-gu, Daegu (Korea, Republic of); Kim, Jae Seung; Oh, Minyoung; Oh, Jungsu S.; Lee, Sang Joo; Oh, Seung Jun [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Chung, Sun Ju; Lee, Chong Sik [University of Ulsan College of Medicine, Department of Neurology, Asan Medical Center, Seoul (Korea, Republic of)

2016-03-15

The aim of this study was to evaluate whether striatal dopamine transporter (DAT) loss as measured by {sup 18}F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane ([{sup 18}F]FP-CIT) PET differs according to the metabolic subtype of multiple system atrophy (MSA) as assessed by [{sup 18}F]FDG PET. This retrospective study included 50 patients with clinically diagnosed MSA who underwent [{sup 18}F]FP-CIT and [{sup 18}F]FDG brain PET scans. The PET images were analysed using 12 striatal subregional volume-of-interest templates (bilateral ventral striatum, anterior caudate, posterior caudate, anterior putamen, posterior putamen, and ventral putamen). The patients were classified into three metabolic subtypes according to the [{sup 18}F]FDG PET findings: MSA-P{sub m} (striatal hypometabolism only), MSA-mixed{sub m} (both striatal and cerebellar hypometabolism), and MSA-C{sub m} (cerebellar hypometabolism only). The subregional glucose metabolic ratio (MR{sub gluc}), subregional DAT binding ratio (BR{sub DAT}), and intersubregional ratio (ISR{sub DAT}; defined as the BR{sub DAT} ratio of one striatal subregion to that of another striatal subregion) were compared according to metabolic subtype. Of the 50 patients, 13 presented with MSA-P{sub m}, 16 presented with MSA-mixed{sub m}, and 21 presented with MSA-C{sub m}. The BR{sub DAT} of all striatal subregions in the MSA-P{sub m} and MSA-mixed{sub m} groups were significantly lower than those in the MSA-C{sub m} group. The posterior putamen/anterior putamen ISR{sub DAT} and anterior putamen/ventral striatum ISR{sub DAT} in the MSA-P{sub m} and MSA-mixed{sub m} groups were significantly lower than those in the MSA-C{sub m} group. Patients with MSA-P{sub m} and MSA-mixed{sub m} showed more severe DAT loss in the striatum than patients with MSA-C{sub m}. Patients with MSA-C{sub m} had more diffuse DAT loss than patients with MSA-P{sub m} and MSA-mixed{sub m}. (orig.)

Dopamine receptor gene expression by enkephalin neurons in rat forebrain

International Nuclear Information System (INIS)

Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B.

1990-01-01

In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons

Dopamine receptor gene expression by enkephalin neurons in rat forebrain

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Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B. (Universite de Bordeaux II (France))

1990-01-01

In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons.

The influence of puberty on subcortical brain development.

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Goddings, Anne-Lise; Mills, Kathryn L; Clasen, Liv S; Giedd, Jay N; Viner, Russell M; Blakemore, Sarah-Jayne

2014-03-01

Puberty is characterized by hormonal, physical and psychological transformation. The human brain undergoes significant changes between childhood and adulthood, but little is known about how puberty influences its structural development. Using a longitudinal sample of 711 magnetic resonance imaging scans from 275 individuals aged 7-20years, we examined how subcortical brain regions change in relation to puberty. Our regions of interest included the amygdala, hippocampus and corpus striatum including the nucleus accumbens (NA), caudate, putamen and globus pallidus (GP). Pubertal development was significantly related to structural volume in all six regions in both sexes. Pubertal development and age had both independent and interactive influences on volume for the amygdala, hippocampus and putamen in both sexes, and the caudate in females. There was an interactive puberty-by-age effect on volume for the NA and GP in both sexes, and the caudate in males. These findings suggest a significant role for puberty in structural brain development. © 2013. Published by Elsevier Inc. All rights reserved.

Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

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Bergstrom, B P; Garris, P A

1999-03-01

The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

The discriminating nature of dopamine transporter image in parkinsonism: the competency of dopaminergic transporter imaging in differential diagnosis of parkinsonism {sup 123}I-FP-CIT SPECT study

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Kim, Bom Sahn; Jang, Sung June; Eo, Jae Seon; Park, Eun Kyung; Kim, Yu Kyeong; Kim, Jong Min; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2007-08-15

The aim of this study was to evaluate the discriminating nature of {sup 123}I-FP-CIT SPECT in patients with parkinsonism. {sup 123}I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4 {+-} 10.0 yr) and 237 patients with parkinsonism (65.9 {+-} 9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. BPs of NC (3.37 {+-} 0.57, 3.10{+-} 0.41, 3.23 {+-} 0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31 {+-} 0.64, 3.06 {+-} 0.61, 3.14 {+-} 0.63) and Alzheimer's disease; AD (3.33 {+-} 0.60, 3.29 {+-} 0.79, 3.31 {+-} 0.70), but were higher than those of Parkinson's disease; PD (1.92 {+-} 0.74, 1.39 {+-}0.68, 1.64 {+-} 0.68), multiple system atrophy; MSA (2.36 {+-} 1.07, 2.16 {+-} 0.91, 2.26 {+-} 0.96), and dementia with Lewy body; DLB (1.95{+-} 0.72, 1.64 {+-} 0.65, 1.79 {+-} 0.66)({rho} < 0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC ({rho} < 0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA ({rho} < 0.05). Dopamine transporter image of {sup 123}I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.

Value and probability coding in a feedback-based learning task utilizing food rewards.

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Tricomi, Elizabeth; Lempert, Karolina M

2015-01-01

For the consequences of our actions to guide behavior, the brain must represent different types of outcome-related information. For example, an outcome can be construed as negative because an expected reward was not delivered or because an outcome of low value was delivered. Thus behavioral consequences can differ in terms of the information they provide about outcome probability and value. We investigated the role of the striatum in processing probability-based and value-based negative feedback by training participants to associate cues with food rewards and then employing a selective satiety procedure to devalue one food outcome. Using functional magnetic resonance imaging, we examined brain activity related to receipt of expected rewards, receipt of devalued outcomes, omission of expected rewards, omission of devalued outcomes, and expected omissions of an outcome. Nucleus accumbens activation was greater for rewarding outcomes than devalued outcomes, but activity in this region did not correlate with the probability of reward receipt. Activation of the right caudate and putamen, however, was largest in response to rewarding outcomes relative to expected omissions of reward. The dorsal striatum (caudate and putamen) at the time of feedback also showed a parametric increase correlating with the trialwise probability of reward receipt. Our results suggest that the ventral striatum is sensitive to the motivational relevance, or subjective value, of the outcome, while the dorsal striatum codes for a more complex signal that incorporates reward probability. Value and probability information may be integrated in the dorsal striatum, to facilitate action planning and allocation of effort. Copyright © 2015 the American Physiological Society.

99mTc-TRODAT-1 SPECT Imaging in Early and Late Onset Parkinson’s Disease

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Payam Sasannezhad

2017-06-01

Full Text Available Objective(s: 99mTc-TRODAT-1, which binds to the dopamine transporter, could be used to image the dopaminergic system in diagnosis of Parkinson’s disease (PD. PD can be classified into two groups: late onset Parkinson’s disease (LOPD and early onset Parkinson’s disease (EOPD. In this study we tried to determine the TRODAT SPECT findings in EOPD as compared to LOPD.Methods: Fifteen patients were studied. The diagnosis of PD was defined by clinical criteria based on UK Parkinson’s Disease Society Brain Bank criteria. Six patients whose age at onset of PD were younger than 50 were defined as patients with EOPD and 9 patients with older than 50 years were defined as patients with LOPD. All patients underwent 99mTc-TRODAT Brain SPECT.Results: There was a significant decrease of striatal 99mTc-TRODAT-1 (TRODAT binding in PD patients in both EOPD and LOPD. No significant difference was noticed between EOPD and LOPD in disease stage and symptoms. In visual analysis, 20 (66.67% caudate nucleuses had decreased tracer uptake while all 30 (100% putamens had decreased or absent tracer uptake. No significant difference between EOPD and LOPD was noticed in visual analysis. Striatum, Caudate and Putamen uptake ratio to background were calculated. No significant difference was noticed between EOPD and LOPD in these ratios. However there was significant difference in visual analysis (tracer uptake as well as in uptake ratio between putamen and caudate nucleuses in both groups (P=0.001. On the other word, we found more diminished uptake in putamen as compared the caudate. Frequency and severity of putamen involvement were much more than caudate.Conclusion: 99mTc-TRODAT-1 SPECT imaging showed lower presynaptical dopami-nergical terminals density in both EOPD and LOPD. There was no difference between EOPD and LOPD in TRODAT uptake. Putamen showed more involvement and more diminished TRODAT uptake.

Double dissociation of the anterior and posterior dorsomedial caudate-putamen in the acquisition and expression of associative learning with the nicotine stimulus.

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Charntikov, Sergios; Pittenger, Steven T; Swalve, Natashia; Li, Ming; Bevins, Rick A

2017-07-15

Tobacco use is the leading cause of preventable deaths worldwide. This habit is not only debilitating to individual users but also to those around them (second-hand smoking). Nicotine is the main addictive component of tobacco products and is a moderate stimulant and a mild reinforcer. Importantly, besides its unconditional effects, nicotine also has conditioned stimulus effects that may contribute to the tenacity of the smoking habit. Because the neurobiological substrates underlying these processes are virtually unexplored, the present study investigated the functional involvement of the dorsomedial caudate putamen (dmCPu) in learning processes with nicotine as an interoceptive stimulus. Rats were trained using the discriminated goal-tracking task where nicotine injections (0.4 mg/kg; SC), on some days, were paired with intermittent (36 per session) sucrose deliveries; sucrose was not available on interspersed saline days. Pre-training excitotoxic or post-training transient lesions of anterior or posterior dmCPu were used to elucidate the role of these areas in acquisition or expression of associative learning with nicotine stimulus. Pre-training lesion of p-dmCPu inhibited acquisition while post-training lesions of p-dmCPu attenuated the expression of associative learning with the nicotine stimulus. On the other hand, post-training lesions of a-dmCPu evoked nicotine-like responding following saline treatment indicating the role of this area in disinhibition of learned motor behaviors. These results, for the first time, show functionally distinct involvement of a- and p-dmCPu in various stages of associative learning using nicotine stimulus and provide an initial account of neural plasticity underlying these learning processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention

International Nuclear Information System (INIS)

Tomasi, D.; Fowler, J.; Tomasi, D.; Volkow, N.D.; Wang, R.L.; Telang, F.; Wang, Chang L.; Ernst, T.; Fowler, J.S.

2009-01-01

Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [ 11 C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus. These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

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De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with

Regional specialization within the human striatum for diverse psychological functions.

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Pauli, Wolfgang M; O'Reilly, Randall C; Yarkoni, Tal; Wager, Tor D

2016-02-16

Decades of animal and human neuroimaging research have identified distinct, but overlapping, striatal zones, which are interconnected with separable corticostriatal circuits, and are crucial for the organization of functional systems. Despite continuous efforts to subdivide the human striatum based on anatomical and resting-state functional connectivity, characterizing the different psychological processes related to each zone remains a work in progress. Using an unbiased, data-driven approach, we analyzed large-scale coactivation data from 5,809 human imaging studies. We (i) identified five distinct striatal zones that exhibited discrete patterns of coactivation with cortical brain regions across distinct psychological processes and (ii) identified the different psychological processes associated with each zone. We found that the reported pattern of cortical activation reliably predicted which striatal zone was most strongly activated. Critically, activation in each functional zone could be associated with distinct psychological processes directly, rather than inferred indirectly from psychological functions attributed to associated cortices. Consistent with well-established findings, we found an association of the ventral striatum (VS) with reward processing. Confirming less well-established findings, the VS and adjacent anterior caudate were associated with evaluating the value of rewards and actions, respectively. Furthermore, our results confirmed a sometimes overlooked specialization of the posterior caudate nucleus for executive functions, often considered the exclusive domain of frontoparietal cortical circuits. Our findings provide a precise functional map of regional specialization within the human striatum, both in terms of the differential cortical regions and psychological functions associated with each striatal zone.

Test-retest reliability of {sup 11}C-ORM-13070 in PET imaging of α{sub 2C}-adrenoceptors in vivo in the human brain

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Lehto, Jussi; Peltonen, Juha M.; Volanen, Iina; Scheinin, Mika [University of Turku, Clinical Research Services Turku CRST, Turku (Finland); TYKSLAB, Unit of Clinical Pharmacology, Turku (Finland); Virta, Jere R. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); Oikonen, Vesa; Roivainen, Anne; Luoto, Pauliina; Arponen, Eveliina; Helin, Semi; Virtanen, Kirsi [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Hietamaeki, Johanna; Holopainen, Aila; Rouru, Juha; Sallinen, Jukka [Orion Pharma, Turku (Finland); Kailajaervi, Marita [Turku Imanet, GE Healthcare, Turku (Finland); Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); University of Turku, Clinical Research Services Turku CRST, Turku (Finland)

2015-01-15

α{sub 2C}-Adrenoceptors share inhibitory presynaptic functions with the more abundant α{sub 2A}-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α{sub 2}-adrenoceptor subtypes. PET imaging with the specific α{sub 2C}-adrenoceptor antagonist tracer [{sup 11}C]ORM-13070 was performed twice in six healthy male subjects to investigate the test-retest reliability of tracer binding. The bound/free ratio of tracer uptake relative to nonspecific uptake into the cerebellum during the time interval of 5 - 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test-retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [{sup 11}C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autoradiography. PET data analysis results obtained with a compartmental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method. The results of this study support the use of [{sup 11}C]ORM-13070 PET in the quantitative assessment of α{sub 2C}-adrenoceptors in the human brain in vivo. Reliable assessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios. (orig.)

Advanced Parkinson’s disease effect on goal-directed and habitual processes involved in visuomotor associative learning

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Fadila eHadj-Bouziane

2013-01-01

Full Text Available The present behavioral study readdresses the question of habit learning in Parkinson's disease. Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding versus following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under sixty years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by Parkinson's disease. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced Parkinson's disease stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal

Psychopathy Moderates the Relationship between Orbitofrontal and Striatal Alterations and Violence: The Investigation of Individuals Accused of Homicide

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Bess Y. H. Lam

2017-12-01

Full Text Available Brain structural abnormalities in the orbitofrontal cortex (OFC and striatum (caudate and putamen have been observed in violent individuals. However, a uni-modal neuroimaging perspective has been used and prior findings have been mixed. The present study takes the multimodal structural brain imaging approaches to investigate the differential gray matter volumes (GMV and cortical thickness (CTh in the OFC and striatum between violent (accused of homicide and non-violent (not accused of any violent crimes individuals with different levels of psychopathic traits (interpersonal and unemotional qualities, factor 1 psychopathy and the expressions of antisocial disposition and impulsivity, factor 2 psychopathy. Structural Magnetic Resonance Imaging data, psychopathy and demographic information were assessed in sixty seven non-violent or violent adults. The results showed that the relationship between violence and the GMV in the right lateral OFC varied across different levels of the factor 1 psychopathy. At the subcortical level, the psychopathy level (the factor 1 psychopathy moderated the positive relationship of violence with both left and right putamen GMV as well as left caudate GMV. Although the CTh findings were not significant, overall findings suggested that psychopathic traits moderated the relationship between violence and the brain structural morphology in the OFC and striatum. In conclusion, psychopathy takes upon a significant role in moderating violent behavior which gives insight to design and implement prevention measures targeting violent acts, thereby possibly mitigating their occurrence within the society.

Brain structure and functional connectivity associated with pornography consumption: the brain on porn.

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Kühn, Simone; Gallinat, Jürgen

2014-07-01

Since pornography appeared on the Internet, the accessibility, affordability, and anonymity of consuming visual sexual stimuli have increased and attracted millions of users. Based on the assumption that pornography consumption bears resemblance with reward-seeking behavior, novelty-seeking behavior, and addictive behavior, we hypothesized alterations of the frontostriatal network in frequent users. To determine whether frequent pornography consumption is associated with the frontostriatal network. In a study conducted at the Max Planck Institute for Human Development in Berlin, Germany, 64 healthy male adults covering a wide range of pornography consumption reported hours of pornography consumption per week. Pornography consumption was associated with neural structure, task-related activation, and functional resting-state connectivity. Gray matter volume of the brain was measured by voxel-based morphometry and resting state functional connectivity was measured on 3-T magnetic resonance imaging scans. We found a significant negative association between reported pornography hours per week and gray matter volume in the right caudate (P < .001, corrected for multiple comparisons) as well as with functional activity during a sexual cue-reactivity paradigm in the left putamen (P < .001). Functional connectivity of the right caudate to the left dorsolateral prefrontal cortex was negatively associated with hours of pornography consumption. The negative association of self-reported pornography consumption with the right striatum (caudate) volume, left striatum (putamen) activation during cue reactivity, and lower functional connectivity of the right caudate to the left dorsolateral prefrontal cortex could reflect change in neural plasticity as a consequence of an intense stimulation of the reward system, together with a lower top-down modulation of prefrontal cortical areas. Alternatively, it could be a precondition that makes pornography consumption more rewarding.

[Right extremities pain caused by a malacia lesion in the left putamen:a resting functional magnetic resonance imaging of the marginal division of the human brain].

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Chen, Zhi-Ye; Ma, Lin

2014-04-01

To explore the role of marginal division of the human brain in the pain modulation. Resting functional magnetic resonance imaging was applied in a patient with right extremities pain caused by a malacia lesion in the left putamen and in 8 healthy volunteers. Marginal division was defined using manual drawing on structure images, and was applied to the computation of fuctional connectivity maps. The functional connectivities in the left marginal division showed an evident decrease in the patient when compared with healthy controls. These connectivities were mainly located in the bilateral head of caudate nucleus, putamen, and left globus pallidus. The marginal division may be involved in the pain modulation.

The visual corticostriatal loop through the tail of the caudate: Circuitry and function

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Carol A Seger

2013-12-01

Full Text Available Although high level visual cortex projects to a specific region of the striatum, the tail of the caudate, and participates in corticostriatal loops, the function of this visual corticostriatal system is not well understood. This article first reviews what is known about the anatomy of the visual corticostriatal loop across mammals, including rodents, cats, monkeys, and humans. Like other corticostriatal systems, the visual corticostriatal system includes both closed loop components (recurrent projections that return to the originating cortical location and open loop components (projections that terminate in other neural regions. The article then reviews what previous empircal research has shown about the function of the tail of the caudate. The article finally addresses the possible functions of the closed and open loop connections of the visual loop in the context of theories and computational models of corticostriatal function.

Bilateral symmetrical low density areas in the striatum

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Okabe, Ichiro; Shimoizumi, Hideo; Miyao, Masutomo; Kamoshita, Shigehiko

1986-01-01

A 10-year-old boy, who showed low density areas at bilateral striatal portion on brain CT, was reported. Characteristic clinical features were summarized as follows: 1. Onset in childhood (3 years old), 2. gait disturbance, dysarthria, involuntaly movement such as choreoathetosis and dystonia, 3. mild mental retardation (IQ 70), and 4. slowly progressive course over several years. Family history was unremarkable. His parents were not consanguineous. He was well until 3 years old, when he developed gait disturbance. At the age of 4, CT showed hypodensity lesions in the bilateral putamens, and right caudate was involved at 7, followed by bilateral caudate involvements at 10. Laboratory findings including blood lactate, pyruvate, serum copper, ceruloplasmin, aminoacids, urine and CSF catecholamines were within normal limits. TRH and thiamine therapies were ineffective L-dopa was slightly effective in movements, but symptoms were slowly progressive. We reviewed fourteen reported cases which were similar to our case in their onset, symptoms, clinical course and CT findings. Although the etiology was unknown, this case is possibly a new disease entity. (author)

Effects of motion correction for dynamic [11C]Raclopride brain PET data on the evaluation of endogenous dopamine release in striatum

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Lee, Jae Sung; Kim, Yu Kyeong; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun; Choe, Yearn Seong; Kang, Eun Joo

2005-01-01

Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head motion correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a momentary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task:110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury.

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De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Hellyer, Peter J; Jolly, Amy E; Patel, Maneesh C; Cole, James H; Leech, Robert; Sharp, David J

2018-01-01

Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of

Effects of motion correction for dynamic [{sup 11}C]Raclopride brain PET data on the evaluation of endogenous dopamine release in striatum

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Lee, Jae Sung; Kim, Yu Kyeong; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Choe, Yearn Seong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kang, Eun Joo [Kangwon University, Chunchon (Korea, Republic of)

2005-10-15

Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head motion correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. [{sup 11}C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a momentary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task:110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion

The significance of 18F-FP-β-CIT dopamine transporter PET imaging in early diagnosis of Parkinson's disease

International Nuclear Information System (INIS)

Wang Jian; Jiang Yuping; Guo Liping; Yang Liqin; Wu Jianjun; Ding Zhengtong; Guan Yihui; Zhao Jun; Xiang Jingde; Chen Zhengping; Su Huilin

2003-01-01

Objective: To evaluate the 18 F-N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-β-CIT) dopamine transporter (DAT) PET imaging in diagnosing Parkinson's disease with early stage and assessing the severity of their disability. Methods: 4 healthy controls, 21 parkinsonian patients with early stage and 10 parkinsonian patients with advanced stage were studied, the ratio of [ region of interest (ROI)-cerebellum]/cerebellum was measured and compared. The correlation between DAT binding in striatum and unified Parkinson's disease rating scale (UPDRS) motor scores was also determined. Results: In patients with early stage (Hoehn and Yahr stage I-II) , the DAT binding uptake in the caudate, anterior putamen and posterior putamen was significantly reduced to 71.8%, 43.8% and 23.6% of the control value respectively, and more pronounced reduction of the uptake was found in the striatum contralateral to the predominant symptoms. Compared with age-matched controls, there was a significant reduction of DAT binding in the ipsilateral (preclinical) striatum of hemi-parkinsonian patients with Hoehn and Yahr stage 1 or 1.5. In the patients with advanced stage, the corresponding figure were further reduced to 51.9%, 31.8%, 15.8%. The DAT binding uptake in striatum of all parkinsonian patients showed significantly negative correlation with UPDRS motor scores, especially in the subregion of posterior putamen. Conclusion: 18 F-FP-β-CIT DAT PET imaging is helpful in diagnosing Parkinson's disease with early stage and assessing the severity of their disability

Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.

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Newman-Tancredi, A; Cussac, D; Brocco, M; Rivet, J M; Chaput, C; Touzard, M; Pasteau, V; Millan, M J

2001-11-30

Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [35S]GTPgammaS binding) at cloned hD2 (and hD3) receptors. At rat striatal membranes, dopamine stimulated [35S]GTPgammaS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D2/D3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D2 receptor antagonist, L741,626. Further, novel antagonists selective for D3 and D4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D3 and D4 receptor-selective doses of S33084 and S18126, respectively. In functional ([35S]GTPgammaS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (approximately 50% stimulation), but significantly greater on the lesioned side (approximately 80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion

The left dorsolateral prefrontal cortex and caudate pathway: New evidence for cue-induced craving of smokers.

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Yuan, Kai; Yu, Dahua; Bi, Yanzhi; Wang, Ruonan; Li, Min; Zhang, Yajuan; Dong, Minghao; Zhai, Jinquan; Li, Yangding; Lu, Xiaoqi; Tian, Jie

2017-09-01

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty-five young male smokers and 26 age- and gender-matched nonsmokers participated in the smoking cue-reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC-efferent pathways contributed to smoking cue-induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue-induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC-caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC-caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC-caudate pathway in smoking cue-induced craving in smokers, which may reflect top-down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644-4656, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The implication of frontostriatal circuits in young smokers: A resting-state study.

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Yuan, Kai; Yu, Dahua; Bi, Yanzhi; Li, Yangding; Guan, Yanyan; Liu, Jixin; Zhang, Yi; Qin, Wei; Lu, Xiaoqi; Tian, Jie

2016-06-01

The critical roles of frontostriatal circuits had been revealed in addiction. With regard to young smokers, the implication of frontostriatal circuits resting-state functional connectivity (RSFC) in smoking behaviors and cognitive control deficits remains unclear. In this study, the volume of striatum subsets, i.e., caudate, putamen, and nucleus accumbens, and corresponding RSFC differences were investigated between young smokers (n1  = 60) and nonsmokers (n2  = 60), which were then correlated with cigarette smoking measures, such as pack_years-cumulative effect of smoking, Fagerström Test for Nicotine Dependence (FTND)-severity of nicotine addiction, Questionnaire on Smoking Urges (QSU)-craving state, and Stroop task performances. Additionally, mediation analysis was carried out to test whether the frontostriatal RSFC mediates the relationship between striatum morphometry and cognitive control behaviors in young smokers when applicable. We revealed increased volume of right caudate and reduced RSFC between caudate and dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex in young smokers. Significant positive correlation between right caudate volume and QSU as well as negative correlation between anterior cingulate cortex-right caudate RSFC and FTND were detected in young smokers. More importantly, DLPFC-caudate RSFC strength mediated the relationship between caudate volume and incongruent errors during Stroop task in young smokers. Our results demonstrated that young smokers showed abnormal interactions within frontostriatal circuits, which were associated with smoking behaviors and cognitive control impairments. It is hoped that our study focusing on frontostriatal circuits could provide new insights into the neural correlates and potential novel therapeutic targets for treatment of young smokers. Hum Brain Mapp 37:2013-2026, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [18F]F-PEB

International Nuclear Information System (INIS)

Patel, Shil; Hamill, Terence G.; Connolly, Brett; Jagoda, Elaine; Li Wenping; Gibson, Raymond E.

2007-01-01

Binding of [ 18 F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([ 18 F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (K D =0.1-0.15 nM, n≥3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [ 18 F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (B max ) measured using [ 18 F]F-PEB followed the rank order cortex∼caudate-putamen/striatum>cerebellum for all three species, with the cerebellum B max being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [ 18 F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex∼caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum) from all three species confirmed previous in vivo

The discriminating nature of dopamine transporter image in parkinsonism: the competency of dopaminergic transporter imaging in differential diagnosis of parkinsonism 123I-FP-CIT SPECT study

International Nuclear Information System (INIS)

Kim, Bom Sahn; Jang, Sung June; Eo, Jae Seon; Park, Eun Kyung; Kim, Yu Kyeong; Kim, Jong Min; Lee, Won Woo; Kim, Sang Eun

2007-01-01

The aim of this study was to evaluate the discriminating nature of 123 I-FP-CIT SPECT in patients with parkinsonism. 123 I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4 ± 10.0 yr) and 237 patients with parkinsonism (65.9 ± 9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. BPs of NC (3.37 ± 0.57, 3.10± 0.41, 3.23 ± 0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31 ± 0.64, 3.06 ± 0.61, 3.14 ± 0.63) and Alzheimer's disease; AD (3.33 ± 0.60, 3.29 ± 0.79, 3.31 ± 0.70), but were higher than those of Parkinson's disease; PD (1.92 ± 0.74, 1.39 ±0.68, 1.64 ± 0.68), multiple system atrophy; MSA (2.36 ± 1.07, 2.16 ± 0.91, 2.26 ± 0.96), and dementia with Lewy body; DLB (1.95± 0.72, 1.64 ± 0.65, 1.79 ± 0.66)(ρ 123 I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism

Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats

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Schmidt, R H; Ingvar, M; Lindvall, O; Stenevi, U; Bjoerklund, A

1982-03-01

Dopaminergic innervation of the caudate nucleus in adult rats can be partially restored by the grafting of embryonic substantia nigra into the overlying parietal cortex with concomitant compensation of certain behavioral abnormalities. In this study the function of such grafts was investigated neurochemically by quantification of transmitter metabolism and glucose utilization in the reinnervated target. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle received a single graft to the dorsal caudate-putamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudate-putamen from initially less than 0.5% to an average of 13.6% of normal in rats with behavioral compensation. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine, which is a measure of the rate of transmitter turnover, were equivalent in transplanted and normal control rats. Moreover, measurements of DOPA accumulation for a 30-min period after DOPA decarboxylase inhibition indicated similar fractional dopamine turnover rates in normal and transplant-reinnervated tissues. Correlations between rotational behavior and dopamine concentrations showed that reinnervation to only 3% of normal was sufficient to counterbalance the motor asymmetry. Measurements of glucose utilization by (14C)deoxyglucose autoradiography indicated equivalent metabolic rates for the grafted tissue and the intact substantia nigra. Overall the results indicate that behaviorally functional neuronal grafts spontaneously metabolize dopamine and utilize glucose at rates characteristic of the intact nigrostriatal system. This provides further evidence that ectopic intracortical nigral transplants can reinstate dopaminergic neurotransmission in regions of the host brain initially denervated by the 6-hydroxydopamine lesion.

Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain.

Science.gov (United States)

Cumming, Paul; Rosa-Neto, Pedro; Watanabe, Hideaki; Smith, Donald; Bender, Dirk; Clarke, Paul B S; Gjedde, Albert

2003-07-01

Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [(11)C]raclopride to dopamine D(2,3) receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [(11)C]raclopride for dopamine D(2,3) receptors. However, the sensitivity of [(11)C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [(11)C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [(15)O]water. Neither a low dose of nicotine (50 mu kg(-1), iv) nor a high dose of nicotine (500 microg kg(-1), iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [(11)C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [(11)C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition

Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

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Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte; Rasmussen, Hans

2010-01-01

of a false discovery rate correction (p brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse. RESULTS: We found......BACKGROUND: Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular...... healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use...

The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood.

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Manza, Peter; Zhang, Sheng; Hu, Sien; Chao, Herta H; Leung, Hoi-Chung; Li, Chiang-Shan R

2015-02-15

The basal ganglia nuclei are critical for a variety of cognitive and motor functions. Much work has shown age-related structural changes of the basal ganglia. Yet less is known about how the functional interactions of these regions with the cerebral cortex and the cerebellum change throughout the lifespan. Here, we took advantage of a convenient sample and examined resting state functional magnetic resonance imaging data from 250 adults 18 to 49 years of age, focusing specifically on the caudate nucleus, pallidum, putamen, and ventral tegmental area/substantia nigra (VTA/SN). There are a few main findings to report. First, with age, caudate head connectivity increased with a large region of ventromedial prefrontal/medial orbitofrontal cortex. Second, across all subjects, pallidum and putamen showed negative connectivity with default mode network (DMN) regions such as the ventromedial prefrontal cortex and posterior cingulate cortex, in support of anti-correlation of the "task-positive" network (TPN) and DMN. This negative connectivity was reduced with age. Furthermore, pallidum, posterior putamen and VTA/SN connectivity to other TPN regions, such as somatomotor cortex, decreased with age. These results highlight a distinct effect of age on cerebral functional connectivity of the dorsal striatum and VTA/SN from young to middle adulthood and may help research investigating the etiologies or monitoring outcomes of neuropsychiatric conditions that implicate dopaminergic dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

Aberrant resting-state corticostriatal functional connectivity in cirrhotic patients with hyperintense globus pallidus on T1-weighted MR imaging.

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Xi-Qi Zhu

Full Text Available Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting

Striatal dopamine transporter, regional cerebral blood flow and glucose utilization in MPTP-induced parkinson disease mice model

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Gao Yunchao; Wu Chunying; Xiang Jingde; Lin Xiangtong; Zhu Huiqing

2005-01-01

Objective: To explore the variation of regional cerebral blood flow (rCBF), glucose utilization as well as the neurotoxic effect on dopaminergic neurons induced by neurotoxin 1-methy-4-phenyl-1,2,3,6-tetrahy-dropyridine (MPTP). Methods: Eight-week old male C57BL/6 mice were given a total dose of 0-80 mg/kg MPTP intraperitoneally. Ten days later the mice were sacrificed for tyrosine hydroxylase (TH)-immunopositive cell count- ing in substantia nigra using SP immunohistochemistry. Vivo autoradiography was employed to measure striatal do- pamine transporter (DAT) loss, rCBF and glucose utilization in striatum and thalamus. Results: The extents of DAT depletion and TH-immunopositive cell loss were positively correlated (r=0.998, P O.2), while glucose utilization was only slightly reduced in caudate/putamen and thalamus by 3.0% and 5.4% in 80 mg/kg MPTP-treated mice (P<0.05). Conclusion: Significant dose-dependent relationship was in presence of MPTP induced dopaminergic neurons loss, changes of rCBF in caudate/putamen and thalamus were not significant, while the glucose utilization was slightly decreased in higher dose group. (authors)

Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using {sup 18}F-FDG

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Kim, J.H. [Research Institute for Advanced Industrial Technology, Korea University, Sejong (Korea, Republic of); Son, Y.D.; Kim, H.K.; Oh, C.H., E-mail: ohch@korea.ac.kr [College of Health Science, Gachon University, Incheon, (Korea, Republic of); Kim, J.M. [College of Science and Technology, Korea University, Sejong (Korea, Republic of); Kim, Y.B. [Gachon University School of Medicine, Incheon (Korea, Republic of); Lee, C. [Bioimaging Research Team, Korea Basic Science Institute, Cheongju (Korea, Republic of)

2018-02-01

Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using {sup 18}F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using {sup 18}F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using 18F-FDG

International Nuclear Information System (INIS)

Kim, J.H.; Son, Y.D.; Kim, H.K.; Oh, C.H.; Kim, J.M.; Kim, Y.B.; Lee, C.

2018-01-01

Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using 18 F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using 18 F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction.

Science.gov (United States)

Qian, David C; Molfese, David L; Jin, Jennifer L; Titus, Alexander J; He, Yixuan; Li, Yafang; Vaissié, Maxime; Viswanath, Humsini; Baldwin, Philip R; Krahe, Ralf; Salas, Ramiro; Amos, Christopher I

2017-09-19

Nearly 6 million deaths and over a half trillion dollars in healthcare costs worldwide are attributed to tobacco smoking each year. Extensive research efforts have been pursued to elucidate the molecular underpinnings of smoking addiction and facilitate cessation. In this study, we genotyped and obtained both resting state and task-based functional magnetic resonance imaging from 64 non-smokers and 42 smokers. Smokers were imaged after having smoked normally ("sated") and after having not smoked for at least 12 h ("abstinent"). While abstinent smokers did not differ from non-smokers with respect to pairwise resting state functional connectivities (RSFCs) between 12 brain regions of interest, RSFCs involving the caudate and putamen of sated smokers significantly differed from those of non-smokers (P smoking status (P = 0.015). Moreover, abstinent smokers with lower CR experienced greater withdrawal symptoms (P = 0.024), which suggests CR may be related to smoking urges. Associations between genetic variants and CR, adjusted for smoking status, were identified by genome-wide association study (GWAS). Genes containing or exhibiting caudate-specific expression regulation by these variants were enriched within Gene Ontology terms that describe cytoskeleton functions, synaptic organization, and injury response (P < 0.001, FDR < 0.05). By integrating genomic and imaging data, novel insights into potential mechanisms of caudate activation and homeostasis are revealed that may guide new directions of research toward improving our understanding of addiction pathology.

PROJECTIONS OF DORSAL AND MEDIAN RAPHE NUCLEI TO DORSAL AND VENTRAL STRIATUM

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G. R. Hassanzadeh G. Behzadi

2007-08-01

Full Text Available The ascending serotonergic projections are derived mainly from mesencephalic raphe nuclei. Topographical projections from mesencephalic raphe nuclei to the striatum were examined in the rat by the retrograde transport technique of HRP (horseradish peroxidase. In 29 rats stereotaxically injection of HRP enzyme were performed in dorsal and ventral parts of striatum separately. The extent of the injection sites and distribution of retrogradely labeled neuronal cell bodies were drawed on representative sections using a projection microscope. Following ipsilateral injection of HRP into the dorsal striatum, numerous labeled neurons were seen in rostral portion of dorsal raphe (DR nucleus. In the same level the cluster of labeled neurons were hevier through caudal parts of DR. A few neurons were also located in lateral wing of DR. More caudally some labeled neurons were found in lateral, medial line of DR. In median raphe nucleus (MnR the labeled neurons were scattered only in median portion of this nucleus. The ipsilateral injection of HRP into the ventral region of striatum resulted on labeling of numerous neurons in rostral, caudal and lateral portions of DR. Through the caudal extension of DR on 4th ventricle level, a large number of labeled neurons were distributed along the ventrocaudal parts of DR. In MnR, labeled neurons were observed only in median part of this nucleus. These findings suggest the mesencephalic raphe nuclei projections to caudo-putamen are topographically organized. In addition dorsal and median raphe nuclei have a stronger projection to the ventral striatum.

Rostrocaudal gradients of dopamine D_2/3 receptor binding in striatal subregions measured with [¹¹C]raclopride and high-resolution positron emission tomography

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Alakurtti, Kati; Johansson, Jarkko J; Tuokkola, Terhi

2013-01-01

scanned with brain-dedicated high-resolution research tomography (HRRT, Siemens Medical Solutions, Knoxville, TN, USA) and [(11)C]raclopride. Coronally defined regions of interest (ROIs) of the caudate nucleus, putamen and ventral striatum (VST) were sampled plane-by-plane, 1.5mm apart, on spatially...... observed in the VST. The novelty of this study lies in the presentation, for the first time, of the D2/3 receptor binding gradients in each striatal subregion in the brains of living healthy humans. The high spatial resolution provided by HRRT enables frequent sampling of BPND along the longitudinal extent...

Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [{sup 18}F]F-PEB

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Patel, Shil [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)], E-mail: shailendra_patel@merck.com; Hamill, Terence G.; Connolly, Brett; Jagoda, Elaine; Li Wenping; Gibson, Raymond E. [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)

2007-11-15

Binding of [{sup 18}F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([{sup 18}F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (K{sub D}=0.1-0.15 nM, n{>=}3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [{sup 18}F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (B{sub max}) measured using [{sup 18}F]F-PEB followed the rank order cortex{approx}caudate-putamen/striatum>cerebellum for all three species, with the cerebellum B{sub max} being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [{sup 18}F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex{approx}caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum

Reduced binding potential of GABA-A/benzodiazepine receptors in individuals at ultra-high risk for psychosis: an [18F]-fluoroflumazenil positron emission tomography study.

Science.gov (United States)

Kang, Jee In; Park, Hae-Jeong; Kim, Se Joo; Kim, Kyung Ran; Lee, Su Young; Lee, Eun; An, Suk Kyoon; Kwon, Jun Soo; Lee, Jong Doo

2014-05-01

Altered transmission of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, may contribute to the development of schizophrenia. The purpose of the present study was to investigate the presence of GABA-A/benzodiazepine (BZ) receptor binding abnormalities in individuals at ultra-high risk (UHR) for psychosis in comparison with normal controls using [(18)F]-fluoroflumazenil (FFMZ) positron emission tomography (PET). In particular, we set regions of interest in the striatum (caudate, putamen, and nucleus accumbens) and medial temporal area (hippocampus and parahippocampal gyrus). Eleven BZ-naive people at UHR and 15 normal controls underwent PET scanning using [(18)F]-FFMZ to measure GABA-A/BZ receptor binding potential. The regional group differences between UHR individuals and normal controls were analyzed using Statistical Parametric Mapping 8 software. Participants were evaluated using the structured interview for prodromal syndromes and neurocognitive function tasks. People at UHR demonstrated significantly reduced binding potential of GABA-A/BZ receptors in the right caudate. Altered GABAergic transmission and/or the imbalance of inhibitory and excitatory systems in the striatum may be present at the putative prodromal stage and play a pivotal role in the pathophysiology of psychosis.

3D texture analysis reveals imperceptible MRI textural alterations in the thalamus and putamen in progressive myoclonic epilepsy type 1, EPM1.

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Sanna Suoranta

Full Text Available Progressive myoclonic epilepsy type 1 (EPM1 is an autosomal recessively inherited neurodegenerative disorder characterized by young onset age, myoclonus and tonic-clonic epileptic seizures. At the time of diagnosis, the visual assessment of the brain MRI is usually normal, with no major changes found later. Therefore, we utilized texture analysis (TA to characterize and classify the underlying properties of the affected brain tissue by means of 3D texture features. Sixteen genetically verified patients with EPM1 and 16 healthy controls were included in the study. TA was performed upon 3D volumes of interest that were placed bilaterally in the thalamus, amygdala, hippocampus, caudate nucleus and putamen. Compared to the healthy controls, EPM1 patients had significant textural differences especially in the thalamus and right putamen. The most significantly differing texture features included parameters that measure the complexity and heterogeneity of the tissue, such as the co-occurrence matrix-based entropy and angular second moment, and also the run-length matrix-based parameters of gray-level non-uniformity, short run emphasis and long run emphasis. This study demonstrates the usability of 3D TA for extracting additional information from MR images. Textural alterations which suggest complex, coarse and heterogeneous appearance were found bilaterally in the thalamus, supporting the previous literature on thalamic pathology in EPM1. The observed putamenal involvement is a novel finding. Our results encourage further studies on the clinical applications, feasibility, reproducibility and reliability of 3D TA.

Hemiballism due to the lesion in the striatum demonstrated by CT scan

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Kojima, S; Ito, N; Hirayama, K [Chiba Univ. (Japan). School of Medicine; Tochigi, S

1981-09-01

Two cases of hemiballism due to vascular lesions in the striatum demonstrated by CT scan were reported. Case 1 was a 58-year-old man with hypertension and diabetes mellitus, who had cerebral hemorrhage in the right striatum. Hemiballistic movements, which were confined to his face, neck and trunk as well as limbs of the left side, appeared soon after CVA and improved on treatment with haloperidol up to 4 mg per day. Case 2 was a 63-year-old woman with hypertension, who had probable cerebral infarct in the right striatum. The hemiballistic movements, confined to her right side, appeared soon after CVA and improved on treatment with chlorpromazine up to 50 mg per day, and perphenazine up to 6 mg per day. Whereas case 1 had contralateral hemiballism, case 2 had homolateral hemiballism, both due to vascular lesions in the striatum. Although it has been generally accepted, from postmortem and experimental studies, that the lesion responsible for hemiballism was localized in the contralateral subthalamic nucleus, a few cases of hemiballism have been reported, in which the subthalamic nucleus (Luys' body) and its connections appeared to be intact at necropsy. The present cases of hemiballism with involvement of the striatum without involvement of the subthalamic nucleus by CT scan, seem to be the first reported cases. It is not clear in the CT scan whether the subthalamic nucleus is also involved in addition to the striatal lesion, however, it is unlikely due to different vascular supplies to these areas. From a clinical and an experimental point of view, we would like to propose that hemiballism can occur due to the lesion in the striatum, especially the caudate nucleus even when the subthalamic nucleus and its connections are intact.

18F-FDG PET-CT pattern in idiopathic normal pressure hydrocephalus

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Ryan A. Townley

Full Text Available Background: Idiopathic normal pressure hydrocephalus (iNPH is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not well understood. We explored FDG-PET abnormalities in iNPH patients in order to determine if FDG-PET may serve as a biomarker to differentiate iNPH from common neurodegenerative disorders. Methods: We retrospectively compared 18F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years to age and sex matched controls, as well as patients diagnosed with clinical Alzheimer's disease dementia (AD, Dementia with Lewy Bodies (DLB and Parkinson's Disease Dementia (PDD, and behavioral variant frontotemporal dementia (bvFTD. Partial volume corrected and uncorrected images were reviewed separately. Results: Patients with iNPH, when compared to controls, AD, DLB/PDD, and bvFTD, had significant regional hypometabolism in the dorsal striatum, involving the caudate and putamen bilaterally. These results remained highly significant after partial volume correction. Conclusions: In this study, we report a FDG-PET pattern of hypometabolism in iNPH involving the caudate and putamen with preserved cortical metabolism. This pattern may differentiate iNPH from degenerative diseases and has the potential to serve as a biomarker for iNPH in future studies. These findings also further our understanding of the pathophysiology underlying the iNPH clinical presentation. Keywords: FDG-PET, Normal pressure hydrocephalus, Hypometabolism, Caudate, Biomarker

Dopamine transporter SPECT in patients with Parkinson's disease

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Hamano, Tadanori; Tsuchida, Tatsuro; Hirayama, Mikio; Fujiyama, Jiro; Mutoh, Tatsuro; Yonekura, Yoshiharu; Kuriyama, Masaru [Fukui Medical Univ., Matsuoka (Japan)

2000-03-01

The major neuropathological feature in Parkinson's disease (PD) is severe degeneration of the dopamine (DA) neurons in the substantia nigra. Dopamine transporter (DAT) is an important protein in the regulation of DA neurotransmission. It has been reported that PD patients show a loss of DAT in striatum. We report here the findings of single photon emission computed tomography (SPECT) of the DAT with 2{beta}-carboxymethoxy-3{beta}-(4[{sup 123}I]iodophenyl)tropane ([{sup 123}I]{beta}-CIT) to investigate striatal DAT in 10 patients with PD, one patient with vascular parkinsonism (VP), and one patient with dystonia syndrome. Patients were evaluated using the Webster rating scale. Specific/nondisplaceable striatal binding ratio (V3'') was obtained in each case. In PD patients, the uptake of [{sup 123}I]{beta}-CIT was reduced, especially in the tail of putamen compared with caudate nucleus. Even in the early stage of PD, the uptake of {beta}-CIT was reduced not only in the severely affected side, but also in the mildly disturbed side of the brain. Putamen caudate ratio was generally low in PD patients. In VP patient, the uptake was reduced, but putamen caudate ratio was not decreased. V3'' values showed significant correlation with the severity of clinical symptoms such as self-care, facies, posture, gait, speech, and Hoehn-Yahr's stage. On the other hand, V3'' values were not significantly correlated with the degree of tremor, seborrhea, and duration of the illness. In conclusion, we found that SPECT of the [{sup 123}I]{beta}-CIT is a useful method for the diagnosis in the patients presenting parkinsonism, and for the clinico-physiological estimation of parkinsonian symptoms such as self-care, facies, posture, gait, and speech. (author)

Dopamine transporter SPECT in patients with Parkinson's disease

International Nuclear Information System (INIS)

Hamano, Tadanori; Tsuchida, Tatsuro; Hirayama, Mikio; Fujiyama, Jiro; Mutoh, Tatsuro; Yonekura, Yoshiharu; Kuriyama, Masaru

2000-01-01

The major neuropathological feature in Parkinson's disease (PD) is severe degeneration of the dopamine (DA) neurons in the substantia nigra. Dopamine transporter (DAT) is an important protein in the regulation of DA neurotransmission. It has been reported that PD patients show a loss of DAT in striatum. We report here the findings of single photon emission computed tomography (SPECT) of the DAT with 2β-carboxymethoxy-3β-(4[ 123 I]iodophenyl)tropane ([ 123 I]β-CIT) to investigate striatal DAT in 10 patients with PD, one patient with vascular parkinsonism (VP), and one patient with dystonia syndrome. Patients were evaluated using the Webster rating scale. Specific/nondisplaceable striatal binding ratio (V3'') was obtained in each case. In PD patients, the uptake of [ 123 I]β-CIT was reduced, especially in the tail of putamen compared with caudate nucleus. Even in the early stage of PD, the uptake of β-CIT was reduced not only in the severely affected side, but also in the mildly disturbed side of the brain. Putamen caudate ratio was generally low in PD patients. In VP patient, the uptake was reduced, but putamen caudate ratio was not decreased. V3'' values showed significant correlation with the severity of clinical symptoms such as self-care, facies, posture, gait, speech, and Hoehn-Yahr's stage. On the other hand, V3'' values were not significantly correlated with the degree of tremor, seborrhea, and duration of the illness. In conclusion, we found that SPECT of the [ 123 I]β-CIT is a useful method for the diagnosis in the patients presenting parkinsonism, and for the clinico-physiological estimation of parkinsonian symptoms such as self-care, facies, posture, gait, and speech. (author)

Modulation of neurotransmitter release in the region of the caudate nucleus by diet and neurotoxins

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Kurstjens, N P

1987-01-01

In this thesis the effects of dietary manipulation, ethanol and neurotoxins on the basal and electrically evoked release of dopamine and acetylcholine from the caudate nucleus of mature animals are presented together with an evaluation of the presynaptic acetylcholine and dopamine receptors controlling acetylcholine and dopamine release. A standardised superfusion technique was used to monitor the effect of apomorphine, in the presence of (R-S)- sulpiride or haloperidol, on the electrically induced release of (/sup 3/ H)-acetylcholine in slices of rat corpus striatum. The effect of ethanol and dietary manipulation on the basal and electrically evoke release of (/sup 3/H)-acetylfholine from rat striatal slices, in the presence of specific agonists and antagonists was evaluated. From this study it is possible to deduce that diet and neurotoxins exerted a measurable effect on the mechanisms controlling release of neurotransmitters in the region of the caudate nucleus. These changes were determined in mature animals previously considered to have cerebral activity, which was not subject to dietary fluctuaations. No changes in the activity of the presynaptic dopamine receptor of the acetylcholine nerve terminals of the striatal slice could be measured.

Early and Degressive Putamen Atrophy in Multiple Sclerosis

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Julia Krämer

2015-09-01

Full Text Available Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS. Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS. 68 patients with RRMS and 26 healthy controls (HC were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV. Patient’s relative putamen volume (RPV, expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson’s Disease Stages?

Science.gov (United States)

Hopes, Lucie; Grolez, Guillaume; Moreau, Caroline; Lopes, Renaud; Ryckewaert, Gilles; Carrière, Nicolas; Auger, Florent; Laloux, Charlotte; Petrault, Maud; Devedjian, Jean-Christophe; Bordet, Regis; Defebvre, Luc; Jissendi, Patrice; Delmaire, Christine; Devos, David

2016-01-01

Introduction Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson’s disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. Methods Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. Results The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. Conclusion Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease. PMID:27035571

File list: ALL.Neu.10.AllAg.Putamen [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Neu.20.AllAg.Putamen [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Neu.20.AllAg.Putamen hg19 All antigens Neural Putamen SRX998291,SRX1096826,SRX9...98289 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.20.AllAg.Putamen.bed ...

File list: ALL.Neu.05.AllAg.Putamen [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Neu.05.AllAg.Putamen hg19 All antigens Neural Putamen SRX998291,SRX1096826,SRX9...98289 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.05.AllAg.Putamen.bed ...

Subcortical intelligence: caudate volume predicts IQ in healthy adults.

Science.gov (United States)

Grazioplene, Rachael G; G Ryman, Sephira; Gray, Jeremy R; Rustichini, Aldo; Jung, Rex E; DeYoung, Colin G

2015-04-01

This study examined the association between size of the caudate nuclei and intelligence. Based on the central role of the caudate in learning, as well as neuroimaging studies linking greater caudate volume to better attentional function, verbal ability, and dopamine receptor availability, we hypothesized the existence of a positive association between intelligence and caudate volume in three large independent samples of healthy adults (total N = 517). Regression of IQ onto bilateral caudate volume controlling for age, sex, and total brain volume indicated a significant positive correlation between caudate volume and intelligence, with a comparable magnitude of effect across each of the three samples. No other subcortical structures were independently associated with IQ, suggesting a specific biological link between caudate morphology and intelligence. © 2014 Wiley Periodicals, Inc.

Evaluation of Tourette's syndrome by 99mTc-TRODAT-1 SPECT/CT imaging

International Nuclear Information System (INIS)

Liu Hong; Dong Feng; Meng Zhaowei; Zhang Benshu; Tan Jian; Wang Yu

2010-01-01

Clinical evidence indicates that the Tourette's syndrome (TS) is associated with hyperactivity of the dopaminergic system; however, imaging studies of dopamine transporter (DAT) in TS patients remain controversial. In this study, we aimed to study DAT binding capacities in a relatively larger sample of drug-naive patients with TS in comparison with controlled subjects by 99m -Tc-TRODAT-1 single photon emission computed tomography (SPECT)/CT imaging. We also aimed to look for any possible correlations between DAT and age, disease duration or tic severity of TS, which have not been thoroughly investigated in previous studies. We tried to provide more evidence for the understanding of the physiopathological mechanism of TS from the molecular imaging perspective. Eighteen drug-naive patients with TS and 8 age- and gender-matched healthy subjects were recruited. Severity of TS was measured with Yale Global Tic Severity Scale. Brain SPECT/CT was performed 2.5 h after injection of 99m Tc-TRODAT-1. Regions of interest were drawn on the striatum including its sub-regions of caudate and putamen. The cerebellum was used as the reference region. DAT uptake ratio was calculated by subtracting the mean counts per pixel in the cerebellum from the mean counts per pixel in the striatum, caudate or putamen and by dividing the result by the mean counts per pixel in the cerebellum. Comparisons of DAT uptake ratios between TS patients and controls, and comparisons in bilateral striatum and sub-regions in TS patients were carried out. Correlation analysis between DAT uptake ratios and clinical data were also conducted. TS patients showed significantly higher uptake of 99m Tc-TRODAT-1 in bilateral striatum in comparison with the controls. There was no group-specific preferential lateralization in striatal uptake. DAT uptake ratios were not correlated with age and tic severity scores, but significant negative correlation with disease duration was found. High level of DAT was demonstrated

The role of the dorsoanterior striatum in implicit motivation: The case of the need for power

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Oliver C Schultheiss

2013-04-01

Full Text Available Implicit motives like the need for power (nPower scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (a enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions in behavioral studies and (b activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka, Nakamura, Sakai, and Nakahara's (2002; Current Opinion in Neurobiology, 12(2, 217-222 model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation.

A Study of volumetric variations of basal nuclei in the normal human brain by magnetic resonance imaging.

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Elkattan, Amal; Mahdy, Amal; Eltomey, Mohamed; Ismail, Radwa

2017-03-01

Knowledge of the effects of healthy aging on brain structures is necessary to identify abnormal changes due to diseases. Many studies have demonstrated age-related volume changes in the brain using MRI. 60 healthy individuals who had normal MRI aged from 20 years to 80 years were examined and classified into three groups: Group I: 21 persons; nine males and 12 females aging between 20-39 years old. Group II: 22 persons; 11 males and 11 females aging between 40-59 years old. Group III: 17 persons; eight males and nine females aging between 60-80 years old. Volumetric analysis was done to evaluate the effect of age, gender and hemispheric difference in the caudate and putamen by the slicer 4.3.3.1 software using 3D T1-weighted images. Data were analyzed by student's unpaired t test, ANOVA and regression analysis. The volumes of the measured and corrected caudate nuclei and putamen significantly decreased with aging in males. There was a statistically insignificant relation between the age and the volume of the measured caudate nuclei and putamen in females but there was a statistically significant relation between the age and the corrected caudate nuclei and putamen. There was no significant difference on the caudate and putamen volumes between males and females. There was no significant difference between the right and left caudate nuclei volumes. There was a leftward asymmetry in the putamen volumes. The results can be considered as a base to track individual changes with time (aging and CNS diseases). Clin. Anat. 30:175-182, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Habitual action video game playing is associated with caudate nucleus-dependent navigational strategies.

Science.gov (United States)

West, Greg L; Drisdelle, Brandi Lee; Konishi, Kyoko; Jackson, Jonathan; Jolicoeur, Pierre; Bohbot, Veronique D

2015-06-07

The habitual playing of video games is associated with increased grey matter and activity in the striatum. Studies in humans and rodents have shown an inverse relationship between grey matter in the striatum and hippocampus. We investigated whether action video game playing is also associated with increased use of response learning strategies during navigation, known to be dependent on the caudate nucleus of the striatum, when presented in a dual solution task. We tested 26 action video game players (actionVGPs) and 33 non-action video game players (nonVGPs) on the 4-on-8 virtual maze and a visual attention event-related potential (ERP) task, which elicits a robust N-2-posterior-controlateral (N2pc) component. We found that actionVGPs had a significantly higher likelihood of using a response learning strategy (80.76%) compared to nonVGPs (42.42%). Consistent with previous evidence, actionVGPs and nonVGPs differed in the way they deployed visual attention to central and peripheral targets as observed in the elicited N2pc component during an ERP visual attention task. Increased use of the response strategy in actionVGPs is consistent with previously observed increases in striatal volume in video game players (VGPs). Using response strategies is associated with decreased grey matter in the hippocampus. Previous studies have shown that decreased volume in the hippocampus precedes the onset of many neurological and psychiatric disorders. If actionVGPs have lower grey matter in the hippocampus, as response learners normally do, then these individuals could be at increased risk of developing neurological and psychiatric disorders during their lifetime. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Right putamen and age are the most discriminant features to diagnose Parkinson's disease by using 123I-FP-CIT brain SPET data by using an artificial neural network classifier, a classification tree (ClT).

Science.gov (United States)

Cascianelli, S; Tranfaglia, C; Fravolini, M L; Bianconi, F; Minestrini, M; Nuvoli, S; Tambasco, N; Dottorini, M E; Palumbo, B

2017-01-01

The differential diagnosis of Parkinson's disease (PD) and other conditions, such as essential tremor and drug-induced parkinsonian syndrome or normal aging brain, represents a diagnostic challenge. 123 I-FP-CIT brain SPET is able to contribute to the differential diagnosis. Semiquantitative analysis of radiopharmaceutical uptake in basal ganglia (caudate nuclei and putamina) is very useful to support the diagnostic process. An artificial neural network classifier using 123 I-FP-CIT brain SPET data, a classification tree (CIT), was applied. CIT is an automatic classifier composed of a set of logical rules, organized as a decision tree to produce an optimised threshold based classification of data to provide discriminative cut-off values. We applied a CIT to 123 I-FP-CIT brain SPET semiquantitave data, to obtain cut-off values of radiopharmaceutical uptake ratios in caudate nuclei and putamina with the aim to diagnose PD versus other conditions. We retrospectively investigated 187 patients undergoing 123 I-FP-CIT brain SPET (Millenium VG, G.E.M.S.) with semiquantitative analysis performed with Basal Ganglia (BasGan) V2 software according to EANM guidelines; among them 113 resulted affected by PD (PD group) and 74 (N group) by other non parkinsonian conditions, such as Essential Tremor and drug-induced PD. PD group included 113 subjects (60M and 53F of age: 60-81yrs) having Hoehn and Yahr score (HY): 0.5-1.5; Unified Parkinson Disease Rating Scale (UPDRS) score: 6-38; N group included 74 subjects (36M and 38 F range of age 60-80 yrs). All subjects were clinically followed for at least 6-18 months to confirm the diagnosis. To examinate data obtained by using CIT, for each of the 1,000 experiments carried out, 10% of patients were randomly selected as the CIT training set, while the remaining 90% validated the trained CIT, and the percentage of the validation data correctly classified in the two groups of patients was computed. The expected performance of an "average

L-DOPA reverses the elevated density of D/sub 2/ dopamine receptors in Parkinson's diseased striatum

Energy Technology Data Exchange (ETDEWEB)

Guttman, M; Seeman, P

1985-01-01

Striatal dopamine receptors werde studied using (/sup 3/H)-spiperone in postmortem tissues of thirty-six patients with Parkinson's Disease. Each tissue was analyzed by the receptor saturation method. In non-treated patients, the D/sub 2/ dopamine receptor density was elevated in the caudate nucleus and putamen compared to controls. In L-DOPA-treated patients, the receptor density was the same as controls. The dissociation constant for (/sup 3/H)-spiperone was similar in all groups. The elevated density of D/sub 2/ receptors in non-treated patients may indicate dopaminergic supersensitivity in this disease. The elevated density was reversed with dopamine agonist therapy, but the density was not lower than control tissues.

Distinct changes in CREB phosphorylation in frontal cortex and striatum during contingent and non-contingent performance of a visual attention task

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Mirjana eCarli

2011-10-01

Full Text Available The cyclic-AMP response element binding protein (CREB family of transcription factors has been implicated in numerous forms of behavioural plasticity. We investigated CREB phosphorylation along some nodes of corticostriatal circuitry such as frontal cortex (FC and dorsal (caudate putamen, CPu and ventral (nucleus accumbens, NAC striatum in response to the contingent or non-contingent performance of the five-choice serial reaction time task (5-CSRTT used to assess visuospatial attention. Three experimental manipulations were used; an attentional performance group (contingent, master, a group trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished (non-contingent, yoked and a control group matched for food deprivation and exposure to the test apparatus (untrained. Rats trained on the 5-CSRTT (both master and yoked had higher levels of CREB protein in the FC, CPu and NAC compared to untrained controls. Despite the divergent behaviour of master and yoked rats CREB activity in the FC was not substantially different. In rats performing the 5-CSRTT (master, CREB activity was completely abolished in the CPu whereas in the NAC it remained unchanged. In contrast, CREB phosphorylation in CPu and NAC increased only when the contingency changed from goal-dependent to goal-independent reinforcement (yoked. The present results indicate that up-regulation of CREB protein expression across cortical and striatal regions possibly reflects the extensive instrumental learning and performance whereas increased CREB activity in striatal regions may signal the unexpected change in the relationship between instrumental action and reinforcement.

Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

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Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2005-07-01

Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25{+-}2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% {+-} 1.3% and 10.6% {+-} 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% {+-} 4.5% vs. 6.6% {+-} 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release.

Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

International Nuclear Information System (INIS)

Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

2005-01-01

Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25±2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% ± 1.3% and 10.6% ± 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% ± 4.5% vs. 6.6% ± 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release

Brain microstructural correlates of visuospatial choice reaction time in children

DEFF Research Database (Denmark)

Madsen, Kathrine Skak; Baaré, William F C; Skimminge, Arnold

2011-01-01

The corticospinal tracts and the basal ganglia continue to develop during childhood and adolescence, and indices of their maturation can be obtained using diffusion-weighted imaging. Here we show that a simple measure of visuomotor function is correlated with diffusion parameters...... anisotropy (FA) in the corticospinal tracts, after controlling for age, gender, and handedness. Mean MD and/or FA were extracted from the right and left corticospinal tracts, putamen, and caudate nuclei. As predicted, faster 5-choice RTs were associated with lower MD in the corticospinal tracts, putamen......, and caudate. MD effects on RT were bilateral in the corticospinal tracts and putamen, whilst right caudate MD was more strongly related to performance than was left caudate MD. Our results suggest a link between motor performance variability in children and diffusivity in the motor system, which may...

Dopamine transporter imaging in rapid eye movement sleep behavior disorder

International Nuclear Information System (INIS)

Kim, Yu Kyeong; Yoon, In Young; Kim, Jong Min; Jeong, Seok Hoon; Kim, Ji Sun; Lee, Byung Chul; Lee, Won Woo; Kim, Sang Eun

2007-01-01

The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is still unknown. However, involvement of dopaminergic system in RBD has been hypothesized because of frequent association with degenerative movement disorders such as Parkinson's disease. The purpose of this study was to examine the extent and pattern of loss of dopamine transporter in RBD using FP-CIT SPECT. Fourteen patient with idiopathic RBD (mean age:665 yrs, M:F=10:3) participated in this study. Polysonmography confirmed loss of REM atonia and determined RBD severities by amount of tonic/phasic muscle activity during REM sleep in all cases. To compare with RBD, 14 early idiopathic Parkinson's disease rated as Hoehn and Yahr stage 1 (IPD) and 12 healthy controls were also selected. All participants performed single-photon emission computed tomography (SPECT) imaging 3 hours after injection of [123I]FP-CIT. Regions of interest were drawn on bilateral caudate and putamen, whole striatum and occipital cortex. Specific binding for dopamine transporters (DAT) were calculated using region to occipital uptake ratio based on the transient equilibrium method. Overall mean of DAT density in the striatum was lower in RBD group than controls, and higher than IPD group, However, DAT density in most individual RBD was still within normal range, and total striatal DAT density was not correlated with severity of RBD. Meanwhile, the caudate to putamen uptake ratio (C/P ratio) in RBD group was insignificantly higher than those in healthy controls. Nevertheless, C/P ratio within RBD group was reversely correlated with the RBD severity. Our study suggested that nigrostriatal dopaminergic degeneration could be a part of the pathogenesis of RBD, but not essential for the development of RBD. Further longitudinal evaluation of presynaptic dopaminergic system in idiopathic RBD may guarantee the more understanding for RBD and associated neurodegenerative disease

Dopamine transporter imaging in rapid eye movement sleep behavior disorder

Energy Technology Data Exchange (ETDEWEB)

Kim, Yu Kyeong; Yoon, In Young; Kim, Jong Min; Jeong, Seok Hoon; Kim, Ji Sun; Lee, Byung Chul; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2007-07-01

The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is still unknown. However, involvement of dopaminergic system in RBD has been hypothesized because of frequent association with degenerative movement disorders such as Parkinson's disease. The purpose of this study was to examine the extent and pattern of loss of dopamine transporter in RBD using FP-CIT SPECT. Fourteen patient with idiopathic RBD (mean age:665 yrs, M:F=10:3) participated in this study. Polysonmography confirmed loss of REM atonia and determined RBD severities by amount of tonic/phasic muscle activity during REM sleep in all cases. To compare with RBD, 14 early idiopathic Parkinson's disease rated as Hoehn and Yahr stage 1 (IPD) and 12 healthy controls were also selected. All participants performed single-photon emission computed tomography (SPECT) imaging 3 hours after injection of [123I]FP-CIT. Regions of interest were drawn on bilateral caudate and putamen, whole striatum and occipital cortex. Specific binding for dopamine transporters (DAT) were calculated using region to occipital uptake ratio based on the transient equilibrium method. Overall mean of DAT density in the striatum was lower in RBD group than controls, and higher than IPD group, However, DAT density in most individual RBD was still within normal range, and total striatal DAT density was not correlated with severity of RBD. Meanwhile, the caudate to putamen uptake ratio (C/P ratio) in RBD group was insignificantly higher than those in healthy controls. Nevertheless, C/P ratio within RBD group was reversely correlated with the RBD severity. Our study suggested that nigrostriatal dopaminergic degeneration could be a part of the pathogenesis of RBD, but not essential for the development of RBD. Further longitudinal evaluation of presynaptic dopaminergic system in idiopathic RBD may guarantee the more understanding for RBD and associated neurodegenerative disease.

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

Science.gov (United States)

Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna; Vilchez, Crystal; Veith, Jennifer; Brodie, Jonathan D; Dewey, Stephen L

2017-08-01

Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18 FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic

Symptomatic laterality and magnetic resonance imaging (MRI) of the putamen in striatonigral degeneration (SND)

Energy Technology Data Exchange (ETDEWEB)

Yanagihara, Chie; Ichikawa, Keiji; Kageyama, Yasufumi; Satou, Mutsumi; Hoshino, Masataka (Hyogo Prefectural Amagasaki Hospital (Japan))

1994-04-01

The relationship between sympatomatic laterality and lesions of the putamen was investigated by magnetic resonance (MR) imaging in 6 patients with striatonigral degeneration (SND). According to Yahr's classification, one patient had I, III, and V each, and 3 had IV. All patients had asymmetric onset of parkinsonism. They developed variable cerebellar ataxia and/or autonomic failure. T1-weighted imaging was most superior in delineating atrophy of the putamen and laterality. The atrophy and lateral difference of the putamen were associated with progression of symptoms. Both the area and the maximum transverse diameter of the putamen were significantly decreased. Atophied putamen extended from the dorsal to the abdominal sides with symptom progression. Attention should be paid to the dorsal side of the putamen in delineating the atrophy and bilateral difference. The measurement of the maximum transverse diameter of the dorsal atrophy of the putamen was a simple, useful means for assessing the atrophy of the putamen. The diameter 7.4 mm or less of the putamen suggested the presence of atrophy. (N.K.).

Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.

Science.gov (United States)

Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, Damiaan

2016-02-01

Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

18F-FDG PET-CT pattern in idiopathic normal pressure hydrocephalus.

Science.gov (United States)

Townley, Ryan A; Botha, Hugo; Graff-Radford, Jonathan; Boeve, Bradley F; Petersen, Ronald C; Senjem, Matthew L; Knopman, David S; Lowe, Val; Jack, Clifford R; Jones, David T

2018-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not well understood. We explored FDG-PET abnormalities in iNPH patients in order to determine if FDG-PET may serve as a biomarker to differentiate iNPH from common neurodegenerative disorders. We retrospectively compared 18 F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years) to age and sex matched controls, as well as patients diagnosed with clinical Alzheimer's disease dementia (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD), and behavioral variant frontotemporal dementia (bvFTD). Partial volume corrected and uncorrected images were reviewed separately. Patients with iNPH, when compared to controls, AD, DLB/PDD, and bvFTD, had significant regional hypometabolism in the dorsal striatum, involving the caudate and putamen bilaterally. These results remained highly significant after partial volume correction. In this study, we report a FDG-PET pattern of hypometabolism in iNPH involving the caudate and putamen with preserved cortical metabolism. This pattern may differentiate iNPH from degenerative diseases and has the potential to serve as a biomarker for iNPH in future studies. These findings also further our understanding of the pathophysiology underlying the iNPH clinical presentation.

fMRI of Simultaneous Interpretation Reveals the Neural Basis of Extreme Language Control.

Science.gov (United States)

Hervais-Adelman, Alexis; Moser-Mercer, Barbara; Michel, Christoph M; Golestani, Narly

2015-12-01

We used functional magnetic resonance imaging (fMRI) to examine the neural basis of extreme multilingual language control in a group of 50 multilingual participants. Comparing brain responses arising during simultaneous interpretation (SI) with those arising during simultaneous repetition revealed activation of regions known to be involved in speech perception and production, alongside a network incorporating the caudate nucleus that is known to be implicated in domain-general cognitive control. The similarity between the networks underlying bilingual language control and general executive control supports the notion that the frequently reported bilingual advantage on executive tasks stems from the day-to-day demands of language control in the multilingual brain. We examined neural correlates of the management of simultaneity by correlating brain activity during interpretation with the duration of simultaneous speaking and hearing. This analysis showed significant modulation of the putamen by the duration of simultaneity. Our findings suggest that, during SI, the caudate nucleus is implicated in the overarching selection and control of the lexico-semantic system, while the putamen is implicated in ongoing control of language output. These findings provide the first clear dissociation of specific dorsal striatum structures in polyglot language control, roles that are consistent with previously described involvement of these regions in nonlinguistic executive control. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mindfulness meditation modulates reward prediction errors in the striatum in a passive conditioning task

Directory of Open Access Journals (Sweden)

Ulrich eKirk

2015-02-01

Full Text Available Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of rewards and cues that predict reward. Evidence indicates that mindfulness-based approaches reduce reward anticipation signal in the striatum to negative and positive incentives suggesting the hypothesis that such training influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error signals. We found diminished positive and negative prediction error-related blood-oxygen level-dependent (BOLD responses in the putamen in meditators compared with controls. In the meditators, this decrease in striatal BOLD responses to reward prediction was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1 were elevated in both meditators and controls. These results provide evidence that experienced mindfulness meditators show attenuated reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study

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Jakobson, Mo Susanna; Riklund, Katrine [Umeaa University, Department of Radiation Sciences, Diagnostic Radiology, Umeaa (Sweden); Linder, Jan; Forsgren, Lars [Umeaa University, Department of Pharmacology and Clinical Neuroscience, Neurology, Umeaa (Sweden); Larsson, Anne; Johansson, Lennart [Umeaa University, Department of Radiation Sciences, Radiation Physics, Umeaa (Sweden)

2010-11-15

The aim of this study was to assess the diagnostic contribution of pre- and postsynaptic dopamine SPECT in drug-naive patients with early idiopathic parkinsonism and to investigate possible differences between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and possible differences in motor subtypes of parkinsonism. A group of 128 newly diagnosed idiopathic parkinsonian patients and 48 healthy controls was studied. Presynaptic baseline SPECT with {sup 123}I-FP-CIT was performed in all patients and in 120 patients also a baseline postsynaptic SPECT with {sup 123}I-IBZM. Clinical diagnoses were reassessed after 12 months. Presynaptic uptake in the putamen and caudate was significantly reduced in patients compared to controls. Presynaptic uptake ratios were not different between PD patients and patients with APS, and postsynaptic uptake in APS was not significantly reduced compared to PD or controls. In half of the APS patients both pre- and postsynaptic uptake ratios were reduced on the same side in the striatum. Impaired motor performance was associated with decreased presynaptic uptake in the putamen in PD. The postural instability and gait difficulty (PIGD) subtype of PD had lower presynaptic uptake ratios than patients with tremor-dominated (TD) symptoms. Not only presynaptic putamen uptake ratios, but also caudate ratios were reduced in a majority of the patients in our study. At baseline scan, i.e. in an early stage of the disease, the accuracy of excluding APS in the whole study population was 85% using a combination of pre- and postsynaptic SPECT. Already at baseline, lower presynaptic SPECT ratios were seen in PD with PIGD at onset compared to those with TD subtype. (orig.)

The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance

DEFF Research Database (Denmark)

Innocenti, Giorgio M.; Dyrby, Tim Bjørn; Andersen, Kasper Winther

2017-01-01

The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species......, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4–0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon...... diameters and conduction distance are monkey and, by extrapolation,

Different subcellular localization of neurotensin-receptor and neurotensin-acceptor sites in the rat brain dopaminergic system.

Science.gov (United States)

Schotte, A; Rostène, W; Laduron, P M

1988-04-01

The subcellular localization of neurotensin-receptor sites (NT2 sites) and neurotensin-acceptor sites (NT1 sites) was studied in rat caudate-putamen by isopycnic centrifugation in sucrose density gradients. [3H]Neurotensin binding to NT2 sites occurred as a major peak at higher sucrose densities, colocalized with [3H]dopamine uptake, and as a small peak at a lower density; whereas binding to NT1 sites occurred as a single large peak at an intermediate density. 6-Hydroxydopamine lesions of the median forebrain bundle resulted in a total loss of NT2 sites in the caudate-putamen but did not affect NT2 sites in the nucleus accumbens and the olfactory tubercle. NT1 sites were not affected. Kainic acid injections into the rat caudate-putamen led to a partial decrease of NT1 sites in this region 5 days later. After a few weeks they returned to normal. Therefore NT2 sites are probably associated with presynaptic nigrostriatal dopaminergic terminals in the caudate-putamen but not in the nucleus accumbens and the olfactory tubercle. A possible association of NT1 sites with glial cells is suggested.

A comparison between the conventional manual ROI method and an automatic algorithm for semiquantitative analysis of SPECT studies

International Nuclear Information System (INIS)

Pagan, L; Novi, B; Guidarelli, G; Tranfaglia, C; Galli, S; Lucchi, G; Fagioli, G

2011-01-01

In this study, the performance of a free software for automatic segmentation of striatal SPECT brain studies (BasGanV2 - www.aimn.it) and a standard manual Region Of Interest (ROI) method were compared. The anthropomorphic Alderson RSD phantom, filled with solutions at different concentration of 123 I-FP-CIT with Caudate-Putamen to Background ratios between 1 and 8.7 and Caudate to Putamen ratios between 1 and 2, was imaged on a Philips-Irix triple head gamma camera. Images were reconstructed using filtered back-projection and processed with both BasGanV2, that provides normalized striatal uptake values on volumetric anatomical ROIs, and a manual method, based on average counts per voxel in ROIs drawn in a three-slice section. Caudate-Putamen/Background and Caudate/Putamen ratios obtained with the two methods were compared with true experimental ratios. Good correlation was found for each method; BasGanV2, however, has higher R index (BasGan R mean = 0.95, p mean = 0.89, p 123 I-FP-CIT SPECT data with, moreover, the advantage of the availability of a control subject's database.

The Role of Corticostriatal Systems in Speech Category Learning.

Science.gov (United States)

Yi, Han-Gyol; Maddox, W Todd; Mumford, Jeanette A; Chandrasekaran, Bharath

2016-04-01

One of the most difficult category learning problems for humans is learning nonnative speech categories. While feedback-based category training can enhance speech learning, the mechanisms underlying these benefits are unclear. In this functional magnetic resonance imaging study, we investigated neural and computational mechanisms underlying feedback-dependent speech category learning in adults. Positive feedback activated a large corticostriatal network including the dorsolateral prefrontal cortex, inferior parietal lobule, middle temporal gyrus, caudate, putamen, and the ventral striatum. Successful learning was contingent upon the activity of domain-general category learning systems: the fast-learning reflective system, involving the dorsolateral prefrontal cortex that develops and tests explicit rules based on the feedback content, and the slow-learning reflexive system, involving the putamen in which the stimuli are implicitly associated with category responses based on the reward value in feedback. Computational modeling of response strategies revealed significant use of reflective strategies early in training and greater use of reflexive strategies later in training. Reflexive strategy use was associated with increased activation in the putamen. Our results demonstrate a critical role for the reflexive corticostriatal learning system as a function of response strategy and proficiency during speech category learning. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry.

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Tao, Guozhi; Datta, Sushmita; He, Renjie; Nelson, Flavia; Wolinsky, Jerry S; Narayana, Ponnada A

2009-07-15

Tensor based morphometry (TBM) was applied to determine the atrophy of deep gray matter (DGM) structures in 88 relapsing multiple sclerosis (MS) patients. For group analysis of atrophy, an unbiased atlas was constructed from 20 normal brains. The MS brain images were co-registered with the unbiased atlas using a symmetric inverse consistent nonlinear registration. These studies demonstrate significant atrophy of thalamus, caudate nucleus, and putamen even at a modest clinical disability, as assessed by the expanded disability status score (EDSS). A significant correlation between atrophy and EDSS was observed for different DGM structures: (thalamus: r=-0.51, p=3.85 x 10(-7); caudate nucleus: r=-0.43, p=2.35 x 10(-5); putamen: r=-0.36, p=6.12 x 10(-6)). Atrophy of these structures also correlated with 1) T2 hyperintense lesion volumes (thalamus: r=-0.56, p=9.96 x 10(-9); caudate nucleus: r=-0.31, p=3.10 x 10(-3); putamen: r=-0.50, p=6.06 x 10(-7)), 2) T1 hypointense lesion volumes (thalamus: r=-0.61, p=2.29 x 10(-10); caudate nucleus: r=-0.35, p=9.51 x 10(-4); putamen: r=-0.43, p=3.51 x 10(-5)), and 3) normalized CSF volume (thalamus: r=-0.66, p=3.55 x 10(-12); caudate nucleus: r=-0.52, p=2.31 x 10(-7), and putamen: r=-0.66, r=2.13 x 10(-12)). More severe atrophy was observed mainly in thalamus at higher EDSS. These studies appear to suggest a link between the white matter damage and DGM atrophy in MS.

Reduced striatal volumes in Parkinson’s disease: a magnetic resonance imaging study

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Pitcher Toni L

2012-08-01

Full Text Available Abstract Background The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease (PD is still poorly understood. Methods High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined. Putamen, caudate, and intracranial volumes were manually traced in the axial plane of 3D reconstructed images. Striatal nuclei volumes were normalized to intracranial volume for statistical comparison. Disease status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale. Cognitive status was assessed using global status tests and detailed neuropsychological testing. Results Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender. Caudate volumes were reduced by 11% (p = 0.001 and putamen volumes by 8.1% (p = 0.025. PD striatal volumes were not found to be significantly correlated with cognitive or motor decline. Conclusion Small, but significant reductions in the volume of both the caudate and putamen occur in PD brains. These reductions are independent of the effects of age and gender, however the relation of these reductions to the functional loss of dopamine, which is characteristic of PD, remains unclear.

Functionally distinct contributions of the anterior and posterior putamen during sublexical and lexical reading

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Marion eOberhuber

2013-11-01

Full Text Available Previous studies have investigated orthographic-to-phonological mapping during reading by comparing brain activation for (1 reading words to object naming, or (2 reading pseudowords (e.g. phume to words (e.g. plume. Here we combined both approaches to provide new insights into the underlying neural mechanisms. In fMRI data from 25 healthy adult readers, we first identified activation that was greater for reading words and pseudowords relative to picture and color naming. The most significant effect was observed in the left putamen, extending to both anterior and posterior borders. Second, consistent with previous studies, we show that both the anterior and posterior putamen are involved in articulating speech with greater activation during our overt speech production tasks (reading, repetition, object naming and color naming than silent one-back-matching on the same stimuli. Third, we compared putamen activation for words versus pseudowords during overt reading and auditory repetition. This revealed that the anterior putamen was most activated by reading pseudowords, whereas the posterior putamen was most activated by words irrespective of whether the task was reading words or auditory word repetition. The pseudoword effect in the anterior putamen is consistent with prior studies that associated this region with the initiation of novel sequences of movements. In contrast, the heightened word response in the posterior putamen is consistent with other studies that associated this region with memory guided movement. Our results illustrate how the functional dissociation between the anterior and posterior putamen supports sublexical and lexical processing during reading.

Frontostriatal Dysfunction During Decision Making in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder.

Science.gov (United States)

Norman, Luke J; Carlisi, Christina O; Christakou, Anastasia; Murphy, Clodagh M; Chantiluke, Kaylita; Giampietro, Vincent; Simmons, Andrew; Brammer, Michael; Mataix-Cols, David; Rubia, Katya

2018-03-24

The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity. Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12-18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups. Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects. The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity. Copyright © 2018 Society of Biological Psychiatry. Published by

Evaluation of Tourette's syndrome by 99Tcm-TRODAT-1 SPECT imaging

International Nuclear Information System (INIS)

Dong Feng; Liu Hong; Meng Zhaowei; Tan Jian; Zhang Benshu

2011-01-01

Objective: To observe dopamine transporter (DAT) binding capacity using 99 Tc m -TRODAT-1 in drug-naive patients with Tourette's syndrome (TS) on SPECT imaging, and explore possible correlations between 99 Tc m -TRODAT-1 uptake ratio and TS patient's age, disease duration, and tic severity. Methods: Eighteen drug-naive TS patients, male 14, female 4, as well as 8 age- and gender-matched healthy subjects were recruited. Brain SPECT imaging was performed 2. 5 h after intravenous injection of 11.1 - 14.8 MBq/kg 99 Tc m -TRODAT-1. ROI was drawn on the striatum including its sub-regions of caudate and putamen, with cerebellum as the background. Striatum/cerebellum ratio was calculated. Comparisons of the ratios between TS patients and controls were carried out by independent-sample t-test. Pearson correlation analysis was performed between DAT uptake ratios of striatum and patients' age, disease duration, tic severity. Results: Compared with the control, higher symmetrically striatum uptake of 99 Tc m -TRODAT-1 in TS patients was observed (2.17±0.23 vs 1.87±0.24, t=2.957, P 0.05)and tic severity(r=0.345, P>0.05) scores were not significantly correlated with specific uptake ratios measured in the striatum. But there was significant negative correlation between disease duration and the specific uptake ratios (r=-0.483, P 99 Tc m -TRODAT-1 SPECT imaging may play an adjuvant role for initial evaluation of untreated TS. (authors)

Regional differences in gene expression and promoter usage in aged human brains

KAUST Repository

Pardo, Luba M.

2013-02-19

To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

Brain microstructural correlates of visuospatial choice reaction time in children

DEFF Research Database (Denmark)

Madsen, Kathrine Skak; Baaré, William F C; Skimminge, Arnold

2011-01-01

, and caudate. MD effects on RT were bilateral in the corticospinal tracts and putamen, whilst right caudate MD was more strongly related to performance than was left caudate MD. Our results suggest a link between motor performance variability in children and diffusivity in the motor system, which may...

Virtual water maze learning in human increases functional connectivity between posterior hippocampus and dorsal caudate.

Science.gov (United States)

Woolley, Daniel G; Mantini, Dante; Coxon, James P; D'Hooge, Rudi; Swinnen, Stephan P; Wenderoth, Nicole

2015-04-01

Recent work has demonstrated that functional connectivity between remote brain regions can be modulated by task learning or the performance of an already well-learned task. Here, we investigated the extent to which initial learning and stable performance of a spatial navigation task modulates functional connectivity between subregions of hippocampus and striatum. Subjects actively navigated through a virtual water maze environment and used visual cues to learn the position of a fixed spatial location. Resting-state functional magnetic resonance imaging scans were collected before and after virtual water maze navigation in two scan sessions conducted 1 week apart, with a behavior-only training session in between. There was a large significant reduction in the time taken to intercept the target location during scan session 1 and a small significant reduction during the behavior-only training session. No further reduction was observed during scan session 2. This indicates that scan session 1 represented initial learning and scan session 2 represented stable performance. We observed an increase in functional connectivity between left posterior hippocampus and left dorsal caudate that was specific to scan session 1. Importantly, the magnitude of the increase in functional connectivity was correlated with offline gains in task performance. Our findings suggest cooperative interaction occurs between posterior hippocampus and dorsal caudate during awake rest following the initial phase of spatial navigation learning. Furthermore, we speculate that the increase in functional connectivity observed during awake rest after initial learning might reflect consolidation-related processing. © 2014 Wiley Periodicals, Inc.

Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I

International Nuclear Information System (INIS)

Shingai, Yoshitoshi; Tateno, Amane; Arakawa, Ryosuke; Sakayori, Takeshi; Kim, WooChan; Okubo, Yoshiro; Suzuki, Hidenori

2014-01-01

Dopamine transporter (DAT) density is considered as a marker of pre-synaptic function. Numerous neuroimaging studies have consistently demonstrated an age-related decrease in DAT density in normal human brain. However, the precise degree of the regional decline is not yet clear. The purpose of this study was to evaluate the effect of the normal aging process on DAT densities in human-specific brain regions including the substantia nigra and thalamus using positron emission tomography (PET) with [ 18 F]FE-PE2I, a new PET radioligand with high affinity and selectivity for DAT. Thirty-six healthy volunteers ranging in age from 22 to 80 years were scanned with PET employing [ 18 F]FE-PE2I for measuring DAT densities. Region of interest (ROI)-based analysis was used, and ROIs were manually defined for the caudate, putamen, substantia nigra, thalamus, and cerebellar cortex. DAT binding was quantified using a simplified reference tissue model, and the cerebellum was used as reference region. Estimations of binding potential in the caudate, putamen, substantia nigra, and thalamus were individually regressed according to age using simple regression analysis. Estimates of DAT loss per decade were obtained using the values from the regression slopes. There were 7.6, 7.7, and 3.4% per-decade declines in DAT in the caudate, putamen, and substantia nigra, respectively. By contrast, there was no age-related decline of DAT in the thalamus. [ 18 F]FE-PE2I allowed reliable quantification of DAT, not only in the caudate and putamen but also in the substantia nigra. From the results, we demonstrated the age-related decline in the caudate and putamen as reported in previous studies, and additionally for those in the substantia nigra for the first time. (author)

MR measurement of the basal ganglia volume in the tourette syndrome

International Nuclear Information System (INIS)

Liao Kaibing; Li Guiping; Yang Bo; Feng Gansheng

2014-01-01

Objective: To compare the volume of the basal ganglia in patients with Tourette syndrome (TS) and the normal volunteers and to explore the underlying anatomical basis of TS. Methods: Thirty-one cases of TS (TS subjects), 31 gender and age-matched subjects (the control subjects) were examined on a 3.0 T MRI system. The volume of the caudate nucleus, globus pallidus, putamen of the two sides and the brain volume were measured with volume analysis software, and the data were normalized according to the individual brain volume. Statistical analysis was performed using t test to compare between the TS subjects and the controls. Results: The volume of the both sides of the caudate nucleus, putamen and globus pallidus of TS subjects were (4.11 ±0.12) and (3.76 ±0.11), (2.28 ±0.12) and (2.35 ±0.28), (4.98 ±0.20) and (4.89 ±0.31) cm 3 , while they were (4.88 ±0.19) and (4.30 ±0.12), (2.28 ±0.12) and (2.35 ±0.28), (4.98 ±0.20) and (4.89 ±0.31) cm 3 in the controls, respectively. There were significant differences in the bilateral caudate nucleus and globus pallidus between the TS subjects and control subjects (t=2.97, 1.74, 3.72, 3.93, P<0.05), but there were no significant differences of the volume in the bilateral putamen between the TS and control subjects (t=0.47, 1.31, P>0.05). The volume was not significantly different between the left and right caudate nucleus in the TS subjects (t=1.81, P>0.05), but the left volume of the caudate nucleus was bigger in the control subjects compared with the right volume, however, there was significant difference between the bilateral caudate nucleus in the control subjects (t=2.34, P<0.05). There were no differences of volume between the bilateral globus pallidus and putamen in both the TS and control subjects (t=1.12, 1.44, 1.68, 0.38, P>0.05). Conclusion: The abnormal volume of caudate nucleus, putamen, and the globus pallidus may be involved in the pathogenesis of TS. (authors)

MRI volume measurement of basal ganglia volumes in patients with Tourette's syndrome

International Nuclear Information System (INIS)

Lu Jie; Li Kuncheng; Cao Yanxiang; Zhang Miao; Sui Xin; Zhang Xiaohua

2009-01-01

Objective: To evaluate MRI measurement of basal ganglia volumes in patients with Tourette's syndrome. Methods: Ten patients with Tourette's syndrome (TS) and 10 healthy volunteers were studied. Volumes of bilateral caudate, putamen and pallidum were measured, and the results were analyzed using paired t test. The basal ganglia volume was normalized according to individual brain volume. The basal ganglia volumes of TS patients were compared with normal control group using independent-sample t test. Results: In 10 healthy volunteers, volumes of the left caudate, putamen, pallidum were significantly larger compared with those of the right side (P 0.05) in TS patients. After normalized processing, the volumes of the left caudate (7.06 ± 0.48) cm 3 , putamen (8.81±1.01) cm 3 , pallidum (2.64± 0.38) cm 3 were smaller than those of control group [caudate (11.05±1.86) cm 3 , putamen (9.97± 1.11) cm 3 , pallidum (3.04±0.37) cm 3 ] (t=-6.577, -2.457, -2.376, P 3 in TS patients was significantly smaller compared with the control group (9.81±1.83) cm 3 (t=-4.258, P 0.05). Conclusion: The basal ganglia volumes were significantly decreased in patients with TS. MRI volumetric measurement was an important tool for evaluating pathologic changes of TS. (authors)

A Multi-tracer Dopaminergic PET Study of Young-Onset Parkinsonian Patients With and Without Parkin Gene Mutations

International Nuclear Information System (INIS)

Ribeiro, M.J.; Thobois, St.; Broussolle, E.; Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A.; Lohmann, E.; Agid, Y.; Brice, A.; Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A.; Tezenas du Montcel, S.; Tezenas du Montcel, S.; Pelissolo, A.; Dubois, B.; Mallet, L.; Pollak, P.; Agid, Y.; Brice, A.; Remy, Ph.; Remy, Ph.

2009-01-01

The impact of parkin gene mutations on nigrostriatal dopaminergic degeneration is not well established. The purpose of this study was to characterize by PET using 18 F-fluoro-L-3, 4- dihydroxyphenylalanine ( 18 F-fluoro-L-DOPA), 11 C-PE2I, and 11 C-raclopride the pattern of dopaminergic lesions in young-onset Parkinson disease (YOPD) patients with or without mutations of the parkin gene and to correlate the clinical and neuro-psychologic characteristics of these patients with PET results. Methods: A total of 35 YOPD patients were enrolled (16 with parkin mutation, 19 without). The uptake constant (K i ) of 18 F-fluoro- L-DOPA and the binding potential (BP) of 11 C-PE2I (BPDAT) and of 11 C-raclopride (BPD2) were calculated in the striatum. Comparisons were made between the 2 groups of YOPD and between controls and patients. For each radiotracer, parametric images were obtained, and statistical parametric mapping (SPM) analysis using a voxel-by-voxel statistical t test was performed. Correlations between the cognitive and motor status and PET results were analyzed. Results: In YOPD patients, 18 F-fluoro-L-DOPA K i values were reduced to 68% (caudate) and 40% (putamen) of normal values (P ≤ 0.0001). This decrease was symmetric and comparable for non-parkin and parkin patients. No correlation was found between the K i values and cognitive or motor status. 11 C-PE2I BPDAT values in YOPD patients were decreased to 56% (caudate) and 41% (putamen) of normal values (P ≤ 0.0001) and did not differ between the 2 YOPD populations. The mean 11 C-raclopride BPD2 values were reduced to 72% (caudate) and 84% (putamen) of the normal values (P ≤ 0.02) and did not differ between non-parkin and parkin patients. SPM analyses showed in patients an additional decrease of 11 C-raclopride in the frontal cortex and a decrease of 18 F-fluoro-L-DOPA and 11 C-PE2I uptake in the substantia nigra bilaterally (P ≤ 0.05, false-discovery rate-corrected). Conclusion: Carriers of parkin

Brain putamen volume changes in newly-diagnosed patients with obstructive sleep apnea

Directory of Open Access Journals (Sweden)

Rajesh Kumar

2014-01-01

Full Text Available Obstructive sleep apnea (OSA is accompanied by cognitive, motor, autonomic, learning, and affective abnormalities. The putamen serves several of these functions, especially motor and autonomic behaviors, but whether global and specific sub-regions of that structure are damaged is unclear. We assessed global and regional putamen volumes in 43 recently-diagnosed, treatment-naïve OSA (age, 46.4 ± 8.8 years; 31 male and 61 control subjects (47.6 ± 8.8 years; 39 male using high-resolution T1-weighted images collected with a 3.0-Tesla MRI scanner. Global putamen volumes were calculated, and group differences evaluated with independent samples t-tests, as well as with analysis of covariance (covariates; age, gender, and total intracranial volume. Regional differences between groups were visualized with 3D surface morphometry-based group ratio maps. OSA subjects showed significantly higher global putamen volumes, relative to controls. Regional analyses showed putamen areas with increased and decreased tissue volumes in OSA relative to control subjects, including increases in caudal, mid-dorsal, mid-ventral portions, and ventral regions, while areas with decreased volumes appeared in rostral, mid-dorsal, medial-caudal, and mid-ventral sites. Global putamen volumes were significantly higher in the OSA subjects, but local sites showed both higher and lower volumes. The appearance of localized volume alterations points to differential hypoxic or perfusion action on glia and other tissues within the structure, and may reflect a stage in progression of injury in these newly-diagnosed patients toward the overall volume loss found in patients with chronic OSA. The regional changes may underlie some of the specific deficits in motor, autonomic, and neuropsychologic functions in OSA.

Basketball training increases striatum volume.

Science.gov (United States)

Park, In Sung; Lee, Kea Joo; Han, Jong Woo; Lee, Nam Joon; Lee, Won Teak; Park, Kyung Ah; Rhyu, Im Joo

2011-02-01

The striatum is associated with the learning and retention of motor skills. Several studies have shown that motor learning induces neuronal changes in the striatum. We investigated whether macroscopic change in striatum volume occurs in a segment of the human population who learned basketball-related motor skills and practiced them throughout their entire athletic life. Three-dimensional magnetic resonance imaging volumetry was performed in basketball players and healthy controls, and striatum volumes were compared based on basketball proficiency, region and side. We identified morphological enlargement in the striatum of basketball players in comparison with controls. Our results suggest that continued practice and repetitive performance of basketball-related motor skills may induce plastic structural changes in the human striatum. Copyright © 2010 Elsevier B.V. All rights reserved.

Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder.

Science.gov (United States)

Wang, Gene-Jack; Volkow, Nora D; Wigal, Timothy; Kollins, Scott H; Newcorn, Jeffrey H; Telang, Frank; Logan, Jean; Jayne, Millard; Wong, Christopher T; Han, Hao; Fowler, Joanna S; Zhu, Wei; Swanson, James M

2013-01-01

Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated. We used positron emission tomography and [(11)C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands. Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005). Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.

[{sup 18}F]L.B.T.-999, a new radioligand to study the dopamine transporter with PET: characterization in baboons

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Saba, W.; Schollhorn, M.A.; Valette, H.; Dolle, F.; Bottlaender, M. [Service Hospitalier Frederic Joliot, DRM/DSV, 91 - Orsay (France); Chalon, S.; Garreau, L.; Emond, P.; Guilloteau, D. [Institut National de la Sante et de la Recherche Medicale (INSERM), U619, 37 - Tours (France); Deloye, J.B. [Cyclopharma, 63 - Clermont Ferrand (France)

2008-02-15

The dopamine transporter (D.A.T.) is the main regulator of the synaptic concentration of dopamine in the brain and plays a key role in many neurological and psychiatric diseases. The goal of the study was to characterize the properties of [{sup 18}F]L.B.T.-999 in baboons. Regional brain distribution was examined in vitro by autoradiographic studies on brain sections and in vivo by PET. Results of in vitro autoradiographic studies were in agreement with the localisation of the D.A.T. and revealed high level of [{sup 18}F]L.B.T.-999 binding in the putamen and caudate, moderate level in the midbrain, and low level in the cortex and cerebellum. In PET study, the time course of the concentration of [{sup 18}F]L.B.T.-999 in different regions of the brain showed that the highest accumulation of [{sup 18}F]L.B.T.-999 was observed in the striatum with a peak uptake at 50 min (maximum = 5.7 {+-} 1.7 and 4.7 {+-}1.0% I.D./100 ml in putamen and caudate nucleus respectively, n 5). The radioactivity uptake peaked at 8 min in the midbrain (2.3 {+-} 1.2% I.D./100 ml) and decreased rapidly as a function of time. The lowest uptake was observed in the cortex (0.62 {+-}0.1 % I.D./100 ml, at 50 min) and in the cerebellum (0.44 {+-} 0.08% I.D./100 ml, at 50 min). In the test retest studies (n = 3) the variability of the uptake was 5% in the putamen and 6% in the caudate. Following HPLC analysis of plasma samples, [{sup 18}F]L.B.T.-999 was rapidly metabolized. Unchanged [{sup 18}F]L.B.T.-999 accounted for around 21% and 7% of the radioactivity at 30 and 120 min post-injection respectively. The region to cerebellum radioactivity ratio was calculated. This ratio reached a maximum at 110 min post injection (22.1 {+-} 4.6 and 18.8 {+-} 2.1 in the putamen and the caudate respectively) and remained stable during the time of the PET scan (4 h). This ratio was 4.21 {+-} 0.92, 2.0 {+-} 0.3 and 1.6 {+-} 0.2 in the midbrain, thalamus, and cortical structure at 110 min post-injection. Binding

Enhanced striatal dopamine release during food stimulation in binge eating disorder

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Wang, g.j.; Wang, G.-J.; Geliebter, A.; Volkow, N.D.; Telang, F.W.; Logan, Jaynbe, M.C.; Galanti, K.; Selig, P.A.; Han, H.; Zhu, W.; Wong, C.T.; Fowler, J.S.

2011-01-13

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [{sup 11}C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.

Enhanced striatal dopamine release during food stimulation in binge eating disorder

International Nuclear Information System (INIS)

Wang, G.-J.; Geliebter, A.; Volkow, N.D.; Telang, F.W.; Logan, J.; Jaynbe, M.C.; Galanti, K.; Selig, P.A.; Han, H.; Zhu, W.; Wong, C.T.; Fowler, J.S.

2011-01-01

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [ 11 C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.

Relationship between striatal [123I]β-CIT binding and four major clinical signs in Parkinson's disease

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Shinotoh, Hitoshi; Uchida, Yoshitaka; Ito, Hisao; Hattori, Takamichi

2000-01-01

We investigated the correlation between clinical severity and striatal [ 123 I]β-CIT binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65±7 years, Hoehn-Yahr stage: 1 to 3). The clinical severity of PD patients was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after withdrawal of antiparkinsonian medication at least 12 hours before assessment. [ 123 I]β-CIT binding in the caudate and putamen was measured at 3 hours [V'' 3 (day 1)], and at 24 hours [V'' 3 (day 2)] after tracer injection with small square ROIs. The specific striatal uptake index (day 2) was calculated with large square ROIs that encompassed the whole striatum. The best correlation (r=-0.82, p 3 (day 2) and the motor UPDRS scores. When the motor UPDRS scores were divided into four subscales, bradykinesia was the only sign that correlated significantly with putamenal V'' 3 (day 2) (r=-0.81, p 123 I]β-CIT SPECT is a useful marker of disease severity in PD with potential utility in the serial monitoring of disease progression. (author)

The relation of putamen nucleus 6-[18F]fluoro-L-m-tyrosine uptake to total Unified Parkinson's Disease Rating Scale scores

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Buchy, R.

2002-01-01

The contribution of dopaminergic deficiency in the striatum to the severity of locomotor disability in Parkinson's disease has been consistently shown with 6-[ 18 F]fluoro-L-DOPA in positron emission tomography. Recently, 6-[ 18 F]fluoro-L-m-tyrosine, an alternative tracer with similar distribution kinetics has been used to facilitate data analysis. Locomotor disability in Parkinson's disease can be measured using the Unified Parkinson's Disease Rating Scale. The Unified Parkinson's Disease Rating Scale was used in conjunction with 6-[ 18 F]fluoro-L-m-tyrosine -PET to clinically examine a group of five Parkinson's disease patients. An inverse relation similar to that previously demonstrated with 6-[ 18 F]fluoro-L-DOPA was found between the putamen nucleus 6-[ 18 F]fluoro-L-m-tyrosine influx constant and Unified Parkinson's Disease Rating Scale score. This finding suggests that like 6-[ 18 F]fluoro-L-m-tyrosine can be used to accurately measure the degree of locomotor disability caused by Parkinson's disease. (author)

Evidence for a caudate role in aphasia from FDG positron emission tomography

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Metter, E.J.; Riege, W.H.; Hanson, W.R.; Phelps, M.; Kuhl, D.E.

1982-01-01

In a recent study correlations between language function and regional glucose metabolism from FDG positron computed tomography were examined. Caudate metabolism correlated with PICA speaking and comprehension factors, as well as BDAE mean writing and reading scores. To identify the language function implicated with caudate metabolism in these eleven patients, twenty subtests making up these two PICA factors and mean BDAE scores were correlated to caudate metabolism. Also a principle components analysis on the twenty subtests identified three factors, only one of which correlated with caudate metabolism. Evidence was found that the caudate has a functional relationship to recognition or motor planning of simple and overlearned materials. This involved simple syntax, low levels of abstraction, identification or sequencing of phonetic and semantic material. This role appeared related to but independent of Broca and frontal lobe function, and may involve the focusing of cortical functions, by allowing two or more regions to interact together

A simple algorithm for subregional striatal uptake analysis with partial volume correction in dopaminergic PET imaging

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Lue Kunhan; Lin Hsinhon; Chuang Kehshih; Kao Chihhao, K.; Hsieh Hungjen; Liu Shuhsin

2014-01-01

In positron emission tomography (PET) of the dopaminergic system, quantitative measurements of nigrostriatal dopamine function are useful for differential diagnosis. A subregional analysis of striatal uptake enables the diagnostic performance to be more powerful. However, the partial volume effect (PVE) induces an underestimation of the true radioactivity concentration in small structures. This work proposes a simple algorithm for subregional analysis of striatal uptake with partial volume correction (PVC) in dopaminergic PET imaging. The PVC algorithm analyzes the separate striatal subregions and takes into account the PVE based on the recovery coefficient (RC). The RC is defined as the ratio of the PVE-uncorrected to PVE-corrected radioactivity concentration, and is derived from a combination of the traditional volume of interest (VOI) analysis and the large VOI technique. The clinical studies, comprising 11 patients with Parkinson's disease (PD) and 6 healthy subjects, were used to assess the impact of PVC on the quantitative measurements. Simulations on a numerical phantom that mimicked realistic healthy and neurodegenerative situations were used to evaluate the performance of the proposed PVC algorithm. In both the clinical and the simulation studies, the striatal-to-occipital ratio (SOR) values for the entire striatum and its subregions were calculated with and without PVC. In the clinical studies, the SOR values in each structure (caudate, anterior putamen, posterior putamen, putamen, and striatum) were significantly higher by using PVC in contrast to those without. Among the PD patients, the SOR values in each structure and quantitative disease severity ratings were shown to be significantly related only when PVC was used. For the simulation studies, the average absolute percentage error of the SOR estimates before and after PVC were 22.74% and 1.54% in the healthy situation, respectively; those in the neurodegenerative situation were 20.69% and 2

Transplantation of ES cells to Parkinson model rat irradiated with carbon ion beam

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Inaji, Motoki; Okauchi, Takashi; Nagai, Yuji; Nojima, Kumie; Suhara, Tetsuya

2004-01-01

The present study was designed to make a new Parkinson disease model using carbon ion beam. In this year, we irradiated right middle forebrain bundle of adult rats with charged carbon particles (290 MeV/nucleon, Mono peak, 150 Gy) and damaged right dopaminergic neurons pathway. To irradiate precisely, rats were set in the stereotactic frame with ear bars which was developed in this year. In 4 weeks after the irradiation, we performed methamphetamine induced rotation test and the autoradiography measurement on dopamine transporter using [ 11 C]PE2I to assess degeneration of dopaminergic neurons in caudate putamen (Cpu). As a result, ipsilateral rotation was observed and the distributions of dopamine transporter in the striatum decreased significantly. These results are similar to those of 6-OHDA lesioned rats, and indicate validity of this model. (author)

Association of body mass index and the depletion of nigrostriatal dopamine in Parkinson's disease.

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Lee, Jae Jung; Oh, Jungsu S; Ham, Jee H; Lee, Dong H; Lee, Injoo; Sohn, Young H; Kim, Jae S; Lee, Phil Hyu

2016-02-01

Several antecedent studies had reported close relationship between low body weight and Parkinson's disease (PD). However, there have been few investigations about the role of body weight to nigrostriatal dopaminergic neurodegeneration. This study enrolled 398 de novo patients with PD whom underwent [18F] N-(3-Fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography scan and body mass index (BMI) measurement. The relationships between BMI and dopamine transporter (DAT) activity were analyzed using linear regression analysis. A multivariate analysis adjusted for age, gender, disease duration, smoking status, coffee and tea consumption, and residence area revealed that BMI remained independently and significantly associated with DAT activity in all striatal subregions. Moreover, multiple logistic regression analyses showed that BMI was a significant predictor for the lowest quartile of DAT activity in the anterior putamen, ventral striatum, caudate nucleus, and total striatum. The present findings suggest that a low BMI might be closely associated with low density of nigrostriatal dopaminergic neurons in PD, which could support the evidence for the role of low body weight to PD-related pathologies. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of levodopa therapy on dopamine transporter SPECT imaging with{sup 123}I-FP-CIT in patients with Parkinson's disease

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Schillaci, Orazio; Filippi, Luca; Manni, Carlo; Danieli, Roberta; Simonetti, Giovanni [University Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome (Italy); Pierantozzi, Mariangela; Brusa, Livia; Bernardi, Giorgio; Stanzione, Paolo [University Tor Vergata, Department of Neurological Sciences, Rome (Italy); Santa Lucia Foundation I.R.C.C.S., Rome (Italy)

2005-12-01

The aim of this study was to evaluate, by means of {sup 123}I-FP-CIT SPECT, the effect of chronic treatment with levodopa on striatal dopamine transporter (DAT) in patients with Parkinson's disease. Fifteen patients under stable levodopa/carbidopa monotherapy were imaged twice: at baseline on medication and after at least 20 days of treatment wash-out. DAT levels were assessed from SPECT imaging for the entire striatum, the right and left striatum, the right and left putamen and the right and left caudate, as a ratio of regional brain activities using the formula: (striatal region of interest-occipital)/occipital. During levodopa wash-out, despite a worsening in patients' clinical disability (H and Y mean stage 2.53{+-}0.58 versus 1.73{+-}0.45 on therapy, p<0.001), striatal{sup 123}I-FP-CIT levels were not significantly different from those at baseline in any of the brain regions examined. The results of this study suggest that levodopa does not affect{sup 123}I-FP-CIT brain imaging and confirm that it is not necessary to withdraw this medication to measure DAT levels with SPECT. (orig.)

CD73 is a major regulator of adenosinergic signalling in mouse brain.

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Natalia Kulesskaya

Full Text Available CD73 (ecto-5'-nucleotidase is a cell surface enzyme that regulates purinergic signalling by desphosphorylating extracellular AMP to adenosine. 5'-nucleotidases are known to be expressed in brain, but the expression of CD73 and its putative physiological functions at this location remain elusive. Here we found, using immunohistochemistry of wild-type and CD73 deficient mice, that CD73 is prominently expressed in the basal ganglia core comprised of striatum (caudate nucleus and putamen and globus pallidus. Furthermore, meninges and the olfactory tubercle were found to specifically express CD73. Analysis of wild type (wt and CD73 deficient mice revealed that CD73 confers the majority of 5'-nucleotidase activity in several areas of the brain. In a battery of behavioural tests and in IntelliCage studies, the CD73 deficient mice demonstrated significantly enhanced exploratory locomotor activity, which probably reflects the prominent expression of CD73 in striatum and globus pallidus that are known to control locomotion. Furthermore, the CD73 deficient mice displayed altered social behaviour. Overall, our data provide a novel mechanistic insight into adenosinergic signalling in brain, which is implicated in the regulation of normal and pathological behaviour.

Molecular Imaging on the Cerebral Pathological Damage Target of Ketamine Dependence

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YANG Hong-jie1,2;HU Shu1;JIA Shao-wei1;GAO Zhou1;WANG Tong3;ZHAO Zheng-qin1

2014-02-01

Full Text Available To study the cerebral pathological damage target which result from abusing ketamine through molecular imaging techniques， 20 cases of ketamine dependent patients looking for treatment at the Peking University Shenzhen Hospital and 31 healthy volunteers were included in this study, all of them got brain SPECT DAT imaging. The results were analyzed by SPSS 16.0. The bilateral caudate nucleus and putamen of healthy volunteers were roughly equally large, and the radioactive distribution of DAT in healthy volunteers were uniform and symmetrical. The bilateral corpora striatum showed typical “panda eyes” pattern. But the bilateral corpora striatum of ketamine dependent patients got smaller in shape, got disorders in pattern, and the radioactive distribution of DAT reduced or defected or even got disturbance and with much more non-specific radioactive. The V, m and Ra of bilateral corpora striatum in ketamine dependent patients were （21.03±3.15） cm3, （22.08±3.31） g and （5.37±1.08） %, respectively, which were significantly lower than the healthy volunteers (p<0.01. The cerebral pathological damage target which resulted from abusing ketamine was similar to those of compound codeine phosphate antitussive solution dependence, heroin dependence and MDMA dependence, all of these psychoactive substances damaged the function of DAT.

Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

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Lindefors, N; Brene, S; Herrera-Marschitz, M; Persson, H

1989-01-01

In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

Segmentation and volumetric analysis of the caudate nucleus in Alzheimer's disease

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Jiji, Sudevan; Smitha, Karavallil Achuthan; Gupta, Arun Kumar; Pillai, Vellara Pappukutty Mahadevan; Jayasree, Ramapurath S.

2013-01-01

Objectives: A quantitative volumetric analysis of caudate nucleus can provide valuable information in early diagnosis and prognosis of patients with Alzheimer's diseases (AD). Purpose of the study is to estimate the volume of segmented caudate nucleus from MR images and to correlate the variation in the segmented volume with respect to the total brain volume. We have also tried to evaluate the caudate nucleus atrophy with the age related atrophy of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) in a group of Alzheimer's disease patients. Methods: 3D fast low angle shot (3D FLASH) brain MR images of 15 AD patients, 15 normal volunteers and 15 patients who had normally diagnosed MR images were included in the study. Brain tissue and caudate nuclei were segmented using the statistical parametric mapping package and a semi-automatic tool, respectively and the volumes were estimated. Volume of segmented caudate nucleus is correlated with respect to the total brain volume. Further, the caudate nucleus atrophy is estimated with the age related atrophy of WM, GM and CSF in a group of AD patients. Results: Significant reduction in the caudate volume of AD patients was observed compared to that of the normal volunteers. Statistical analysis also showed significant variation in the volume of GM and CSF of AD patients. Among the patients who had normal appearing brain, 33% showed significant changes in the caudate volume. We hypothesize that these changes can be considered as an indication of early AD. Conclusion: The method of volumetric analysis of brain structures is simple and effective way of early diagnosis of neurological disorders like Alzheimer's disease. We have illustrated this with the observed changes in the volume of caudate nucleus in a group of patients. A detailed study with more subjects will be useful in correlating these results for early diagnosis of AD

Learning and motivation in the human striatum.

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Shohamy, Daphna

2011-06-01

The past decade has seen a dramatic change in our understanding of the role of the striatum in behavior. Early perspectives emphasized a role for the striatum in habitual learning of stimulus-response associations and sequences of actions. Recent advances from human neuroimaging research suggest a broader role for the striatum in motivated learning. New findings demonstrate that the striatum represents multiple learning signals and highlight the contribution of the striatum across many cognitive domains and contexts. Recent findings also emphasize interactions between the striatum and other specialized brain systems for learning. Together, these findings suggest that the striatum contributes to a distributed network that learns to select actions based on their predicted value in order to optimize behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis

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Varrone, Andrea; Dickson, John C.; Tossici-Bolt, Livia; Sera, Terez; Asenbaum, Susanne; Booij, Jan; Kapucu, Ozlem L.; Kluge, Andreas; Knudsen, Gitte M.; Koulibaly, Pierre Malick; Nobili, Flavio; Pagani, Marco; Sabri, Osama; Borght, Thierry vander; Laere, Koen van; Tatsch, Klaus

2013-01-01

Dopamine transporter (DAT) imaging with [ 123 I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [ 123 I]FP-CIT SPECT scans in healthy controls. SPECT data from 139 healthy controls (74 men, 65 women; age range 20 - 83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR). A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade. This study provides a large database of [ 123 I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for

Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome.

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Bloch, Michael H; Leckman, James F; Zhu, Hongtu; Peterson, Bradley S

2005-10-25

Most children with Tourette syndrome (TS) experience a marked decline in the severity of tic symptoms during adolescence. Currently no clinical measures can predict whose tic symptoms will persist into adulthood. Previous cross-sectional imaging studies have identified reduced caudate nucleus volumes in subjects with TS. To evaluate whether caudate nucleus volumes in childhood can predict the severity of tic or obsessive-compulsive symptoms at follow-up in early adulthood. In a prospective longitudinal study, clinical status and basal ganglia volumes of 43 children with TS were measured on high-resolution magnetic resonance images before age 14 years. Follow-up clinical assessments were conducted after age 16 years, an average of 7.5 years later. Linear regression and Tobit regression analyses were used to assess the association of basal ganglia volumes measured in childhood with the severity of tic and obsessive-compulsive disorder (OCD) symptoms at the time of childhood MRI and at follow-up in early adulthood. Volumes of the caudate nucleus correlated significantly and inversely with the severity of tic and OCD symptoms in early adulthood. Caudate volumes did not correlate with the severity of symptoms at the time of the MRI scan. Caudate volumes in children with Tourette syndrome predict the severity of tic and obsessive-compulsive symptoms in early adulthood. This study provides compelling evidence that morphologic disturbances of the caudate nucleus within cortico-striatal-thalamo-cortical circuits are central to the persistence of both tics and obsessive-compulsive symptoms into adulthood.

Resting state functional connectivity of the anterior striatum and prefrontal cortex predicts reading performance in school-age children.

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Alcauter, Sarael; García-Mondragón, Liliana; Gracia-Tabuenca, Zeus; Moreno, Martha B; Ortiz, Juan J; Barrios, Fernando A

2017-11-01

The current study investigated the neural basis of reading performance in 60 school-age Spanish-speaking children, aged 6 to 9years. By using a data-driven approach and an automated matching procedure, we identified a left-lateralized resting state network that included typical language regions (Wernicke's and Broca's regions), prefrontal cortex, pre- and post-central gyri, superior and middle temporal gyri, cerebellum, and subcortical regions, and explored its relevance for reading performance (accuracy, comprehension and speed). Functional connectivity of the left frontal and temporal cortices and subcortical regions predicted reading speed. These results extend previous findings on the relationship between functional connectivity and reading competence in children, providing new evidence about such relationships in previously unexplored regions in the resting brain, including the left caudate, putamen and thalamus. This work highlights the relevance of a broad network, functionally synchronized in the resting state, for the acquisition and perfecting of reading abilities in young children. Copyright © 2017 Elsevier Inc. All rights reserved.

A Multi-tracer Dopaminergic PET Study of Young-Onset Parkinsonian Patients With and Without Parkin Gene Mutations

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Ribeiro, M.J. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Thobois, St.; Broussolle, E. [University of Lyon, Hospices Civils de Lyon, Neurological Hospital, Lyon (France); Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A. [INSERM, Paris (France); Lohmann, E.; Agid, Y.; Brice, A. [Department of the Nervous System Disorders, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A. [UPMC University of Paris, Paris (France); Tezenas du Montcel, S. [Unit of de Biostatistics and Medical Information and Unit of Medical Research, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Tezenas du Montcel, S. [Modelisation in Clinical Research, UPMC University of Paris, Paris (France); Pelissolo, A. [Department of Psychiatry, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Dubois, B. [Centre de Reference sur la Maladie de Pick, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Mallet, L. [Behaviour, Emotion and Basal Ganglia, Center of Clinical Investigation, INSERM Avenir Group, Paris (France); Pollak, P. [Department of Clinical and Biological Neurosciences, University Hospital of Grenoble, Grenoble (France); Agid, Y. [Clinical Investigation Center, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Brice, A. [Department of Genetics and Cytogenetics, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Remy, Ph. [CEA, I2BM, MIRCEN, URA CEA-CNRS 2210, Orsay (France); Remy, Ph. [CHU Henri Mondor, AP-HP and Faculte de Medecine Paris 12, Creteil (France)

2009-07-01

The impact of parkin gene mutations on nigrostriatal dopaminergic degeneration is not well established. The purpose of this study was to characterize by PET using {sup 18}F-fluoro-L-3, 4- dihydroxyphenylalanine ({sup 18}F-fluoro-L-DOPA), {sup 11}C-PE2I, and {sup 11}C-raclopride the pattern of dopaminergic lesions in young-onset Parkinson disease (YOPD) patients with or without mutations of the parkin gene and to correlate the clinical and neuro-psychologic characteristics of these patients with PET results. Methods: A total of 35 YOPD patients were enrolled (16 with parkin mutation, 19 without). The uptake constant (K{sub i}) of {sup 18}F-fluoro- L-DOPA and the binding potential (BP) of {sup 11}C-PE2I (BPDAT) and of {sup 11}C-raclopride (BPD2) were calculated in the striatum. Comparisons were made between the 2 groups of YOPD and between controls and patients. For each radiotracer, parametric images were obtained, and statistical parametric mapping (SPM) analysis using a voxel-by-voxel statistical t test was performed. Correlations between the cognitive and motor status and PET results were analyzed. Results: In YOPD patients, {sup 18}F-fluoro-L-DOPA K{sub i} values were reduced to 68% (caudate) and 40% (putamen) of normal values (P {<=} 0.0001). This decrease was symmetric and comparable for non-parkin and parkin patients. No correlation was found between the K{sub i} values and cognitive or motor status. {sup 11}C-PE2I BPDAT values in YOPD patients were decreased to 56% (caudate) and 41% (putamen) of normal values (P {<=} 0.0001) and did not differ between the 2 YOPD populations. The mean {sup 11}C-raclopride BPD2 values were reduced to 72% (caudate) and 84% (putamen) of the normal values (P {<=} 0.02) and did not differ between non-parkin and parkin patients. SPM analyses showed in patients an additional decrease of {sup 11}C-raclopride in the frontal cortex and a decrease of {sup 18}F-fluoro-L-DOPA and {sup 11}C-PE2I uptake in the substantia nigra bilaterally

Reduced caudate volume and enhanced striatal-DMN integration in chess experts.

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Duan, Xujun; He, Sheng; Liao, Wei; Liang, Dongmei; Qiu, Lihua; Wei, Luqing; Li, Yuan; Liu, Chengyi; Gong, Qiyong; Chen, Huafu

2012-04-02

The superior capability of chess experts largely depends on quick automatic processing skills which are considered to be mediated by the caudate nucleus. We asked whether continued practice or rehearsal of the skill over a long period of time can lead to structural changes in this region. We found that, comparing to novice controls, grandmaster and master level Chinese chess players (GM/Ms), who had a mean period of over 10years of tournament and training practice, exhibited significant smaller gray-matter volume in the bilateral caudate nuclei. When these regions were used as seeds in functional connectivity analysis in resting-state fMRI, significantly enhanced integration was found in GM/Ms between the caudate and the default mode network (DMN), a constellation of brain areas important for goal-directed cognitive performance and theory of mind. These findings demonstrate the structural changes in the caudate nucleus in response to its extensive engagement in chess problem solving, and its enhanced functional integration with widely distributed circuitry to better support high-level cognitive control of behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

CT anatomy of para-caval portion of the caudate lobe of the liver

International Nuclear Information System (INIS)

Matsui, Osamu; Takashima, Tsutomu; Kadoya, Masumi; Hirose, Jinichiro; Kameyama, Tomiaki; Choto, Shuichi; Konishi, Hideo

1988-01-01

Computed tomographic (CT) anatomy of the right border of the caudate lobe had been unclear. Recently, Kumon studied in full detail the anatomy of the caudate branches of the portal vein by corrosion liver cast study and revealed the para-caval portion (PCP) of the caudate lobe extending just right to the Spiegel lobe from the caudate process to the area between the roots of the right and middle hepatic veins. According to Kumon's study, we analyzed the perfusion defects seen on CT during arterial portography performed in patients with intrahepatic portal vein obstruction and studied CT anatomy of PCP. As a result, we consider that the area between the roots of the right and middle hepatic veins belongs to PCP in more than 70 % of patients. Therefore, we think that the area between the roots of the right and middle hepatic veins which had been classified as being in the anterior suprior area (S 8 ) should be reclassified as being in the caudate lobe (S 1 ). (author)

CT anatomy of para-caval portion of the caudate lobe of the liver

Energy Technology Data Exchange (ETDEWEB)

Matsui, Osamu; Takashima, Tsutomu; Kadoya, Masumi; Hirose, Jinichiro; Kameyama, Tomiaki; Choto, Shuichi; Konishi, Hideo

1988-07-01

Computed tomographic (CT) anatomy of the right border of the caudate lobe had been unclear. Recently, Kumon studied in full detail the anatomy of the caudate branches of the portal vein by corrosion liver cast study and revealed the para-caval portion (PCP) of the caudate lobe extending just right to the Spiegel lobe from the caudate process to the area between the roots of the right and middle hepatic veins. According to Kumon's study, we analyzed the perfusion defects seen on CT during arterial portography performed in patients with intrahepatic portal vein obstruction and studied CT anatomy of PCP. As a result, we consider that the area between the roots of the right and middle hepatic veins belongs to PCP in more than 70 % of patients. Therefore, we think that the area between the roots of the right and middle hepatic veins which had been classified as being in the anterior suprior area (S/sub 8/) should be reclassified as being in the caudate lobe (S/sub 1/).

Lesser sac hematoma as a sign of rupture of hepatocellular carcinoma in the caudate lobe

International Nuclear Information System (INIS)

Iwasaki, Yoshie; Tani, Ichiro; Nakajima, Yasuo; Ishikawa, Tohru; Umeda, Satoshi; Kusano, Shoichi

2001-01-01

The purpose of this study was to evaluate the CT findings of rupture of hepatocellular carcinoma (HCC) in the caudate lobe of the liver. The CT scans of five cases of rupture of HCC in the caudate lobe of the liver were retrospectively reviewed and correlated with clinical records. All cases showed exophytic tumors in the caudate lobe of the liver and high-attenuation hematomas in the lesser sac on CT. A lesser sac hematoma may be a sentinel clot sign of rupture of HCC in the caudate lobe. (orig.)

Three-compartment modeling of C-11 N-Methyl spiperone kinetics in the human brain

International Nuclear Information System (INIS)

Brooks, R.A.; Wong, D.F.; Di Chiro, G.; Wayner, R.T.; Douglass, K.H.; Frost, J.J.; Larson, S.M.; Wagner, H.N. Jr.

1984-01-01

N-Methyl spiperone, as well as spiperone, has been used to study the dopamine receptor system in the brain. The authors have applied a 3-compartment model consisting of vascular, extravascular unbound, and receptor-bound activity to two normal volunteers and one patient with Parkinson's disease. The model differs from that proposed by another study, in that, as in the Sokoloff model for deoxyglucose, there is no explicit term for blood flow. Furthermore, the authors used a 3-compartment model for the cerebellum as well as the caudate/putamen. Serial scans were obtained by PET for up to 2 hrs after injection of the tracer. Time-activity curves were generated over the caudate, putamen and cerebellum. The results indicate a close fit of the observed data to the 3-compatment model. In the model, K1 represents the rate constant of delivery of the tracer in the tissue from the vascular compartment. K2 is the reverse rate constant. K1 was approximately equal to K2 for the cerebellum. In the basal ganglia, K2 was less than K1 due to nonspecific binding in compartment 2. K3 represents the rate constant of binding of the tracer to the receptor binding sites in the cerebral cortex and basal ganglia and to nonspecific binding sites in the cerebellum which contains essentially no dopamine receptors. K4 represents the rate constant for dissociation of the tracer from the receptors. For N-methyl spiperone K4 is very low in the caudate/putamen. The 3-compartment model seemed to fit the data better than the 2-compartment model for both the caudate/putamen and cerebellar activity

Automatic brain caudate nuclei segmentation and classification in diagnostic of Attention-Deficit/Hyperactivity Disorder.

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Igual, Laura; Soliva, Joan Carles; Escalera, Sergio; Gimeno, Roger; Vilarroya, Oscar; Radeva, Petia

2012-12-01

We present a fully automatic diagnostic imaging test for Attention-Deficit/Hyperactivity Disorder diagnosis assistance based on previously found evidences of caudate nucleus volumetric abnormalities. The proposed method consists of different steps: a new automatic method for external and internal segmentation of caudate based on Machine Learning methodologies; the definition of a set of new volume relation features, 3D Dissociated Dipoles, used for caudate representation and classification. We separately validate the contributions using real data from a pediatric population and show precise internal caudate segmentation and discrimination power of the diagnostic test, showing significant performance improvements in comparison to other state-of-the-art methods. Copyright © 2012 Elsevier Ltd. All rights reserved.

Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

DEFF Research Database (Denmark)

Glenthoj, Andreas; Glenthøj, Birte Yding; Mackeprang, Torben

2007-01-01

or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two...... of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain...

Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

DEFF Research Database (Denmark)

Glenthoj, Andreas; Glenthoj, Birte Y; Mackeprang, Torben

2007-01-01

of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain...... or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two...

Complex population response of dorsal putamen neurons predicts the ability to learn.

Science.gov (United States)

Laquitaine, Steeve; Piron, Camille; Abellanas, David; Loewenstein, Yonatan; Boraud, Thomas

2013-01-01

Day-to-day variability in performance is a common experience. We investigated its neural correlate by studying learning behavior of monkeys in a two-alternative forced choice task, the two-armed bandit task. We found substantial session-to-session variability in the monkeys' learning behavior. Recording the activity of single dorsal putamen neurons we uncovered a dual function of this structure. It has been previously shown that a population of neurons in the DLP exhibits firing activity sensitive to the reward value of chosen actions. Here, we identify putative medium spiny neurons in the dorsal putamen that are cue-selective and whose activity builds up with learning. Remarkably we show that session-to-session changes in the size of this population and in the intensity with which this population encodes cue-selectivity is correlated with session-to-session changes in the ability to learn the task. Moreover, at the population level, dorsal putamen activity in the very beginning of the session is correlated with the performance at the end of the session, thus predicting whether the monkey will have a "good" or "bad" learning day. These results provide important insights on the neural basis of inter-temporal performance variability.

CT cold areas in both putamens in cases with history of perinatal asphyxia

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Ishizaki, Asayo; Maruyama, Hiroshi (Tokyo Women' s Medical Coll. (Japan))

1982-12-01

CT bilaterally showed a cold area in the putamen of 5 infants with cerebral palsy who had had asphyxia at birth. The etiology was discussed, and 4 of the cases were clinically studied. All four patients had convulsive tetraplegia, or convulsive bilateral paralysis with the element of athetosis. Three of them had a history of infantile epilepsy, accompanied by abnormal ocular movement. Two patients with tetraplegia showed marked hypotonia of the trunk in ventral support (Landau). Impairment of the bilateral putamens in the abnormal muscle tone was inferred.

Influence of scanning time window on the binding potentials of dopamine transporter in the brain of healthy volunteers with 11C-CFT PET imaging

International Nuclear Information System (INIS)

Qiu Chun; Zuo Chuantao; Zhang Zhengwei; Wu Ping; Zhang Huiwei; Guan Yihui

2013-01-01

Objective: To find the optimal scanning time window and then set up the normal binding potentials (BPs) of 2β-carbomethoxy-3β-(4-fluorophenyl)-(N- 11 C-methyl) tropane ( 11 C-CFT) DAT PET/CT imaging. Methods: Thirty-one healthy volunteers (20 males, 11 females, average age: (55.7±2.3) years), who all gave written informed consent, were divided into three age and gender-matched groups according to block randomization. Each group underwent static PET/CT scan in different time windows from 40-60 min, 60-80 min to 80-100 min after 11 C-CFT injection. To determine the best scanning time window, the ratios of caudate and putamen of all volunteers were analyzed using automatic ROI method (caudate (putamen)/parieto-occipital cotex-1) and compared by one-way analysis of variance and the least significant difference (LSD) t test. The ratio of the same area between different age-groups and gender-groups was compared with independent two-sample t test. Results: Ratios of left caudate (2.08±0.06, 1.75±0.07 and 1.77±0.12 respectively), right anterior putamen (2.33±0.06, 1.95±0.09 and 2.08±0.12 respectively) and bilateral posterior putamen (left: 1.88±0.66, 1.55±0.88 and 1.72±0.09; right: 1.98±0.07, 1.61±0.09 and 1.69±0.12) were all different in three time windows (F=3.588, 3.345, 4.479, 3.557, all P<0.05). There were significant differences in ratios of left caudate, right anterior and bilateral posterior putamen between 40-60 min and the 60-80 min (all P<0.05), as well as the ratios of left caudate between 40-60 min and the 80-100 min group (P<0.05). While no valid differences in ratios of those areas were shown between the groups of 60-80 min and 80-100 min scanning time window (all P>0.05). DAT densities in right and left side of caudate, anterior and posterior putamen were significantly lower in the group over 60 years of age than those under 60 years (t=-3.260, -3.090, -3.270, -3.190, -2.270, -3.110, all P<0.05), but were not different between gender

Water dissection technique of Toth for the treatment of hypertensive intracerebral putamen hemorrhage

International Nuclear Information System (INIS)

Wu Jiandong; Qian Surong; Lin Liqing; Wang Chenqiu; Wang Jianren; Wang Chen; Ying Guangzhong; Hui Guozhen

2008-01-01

Objective: To investige the possibility of water dissection technique of Toth for craniotomy with small bone flap through lateral fissure approach for the treatment of hypertensive intracerebral putamen hemorrhage. Methods: Twenty consecutive patients with hypertensive intracerebral putamen hemorrhage were treated by making a incision on sclap long about 6 cm across sylvian fissure, making a small bone flap about 3 cm x 3 cm, After opening dual, we injected water under microscopic control by a handheld syringe with a blunt needle applying repeated injection of physiological saline into the sylvian fissure to open it, opening the insular cortex, evacuation of intracerebral hematoma. Results: There was no further mortality. Patients who returned to ADL 1 and 2 (good recovery) after surgical treatment were 10, ADL 3 were 5, ADL 4 were 4, ADL 5 were 1. Conclusion: A method of water dissection technique of Toth for craniotomy with small bone flap through lateral fissure approach for the treatment of hypertensive intracerebral putamen hemorrhage is a method of convenient, safe, and with effective result. (authors)

Interest in politics modulates neural activity in the amygdala and ventral striatum.

Science.gov (United States)

Gozzi, Marta; Zamboni, Giovanna; Krueger, Frank; Grafman, Jordan

2010-11-01

Studies on political participation have found that a person's interest in politics contributes to the likelihood that he or she will be involved in the political process. Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters. Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self-report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion- and reward-related brain areas even when simply agreeing with written political opinions. © 2010 Wiley-Liss, Inc.

Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

Science.gov (United States)

Oakes, Terrence Rayford

1995-01-01

Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

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Kei Mizuno, Ph.D.

2016-01-01

Full Text Available Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years and 13 healthy children and adolescents (HCA (mean age, 13.7 ± 1.3 years performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

Distinct spatiotemporal patterns for disease duration and stage in Parkinson's disease

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Badoud, Simon [Geneva University Hospitals, Neurology Unit, Department of Clinical Neurosciences, Geneva (Switzerland); University of Fribourg, Neurophysiology Unit, Department of Medicine, Fribourg (Switzerland); University of Geneva, Faculty of Medicine, Geneva (Switzerland); Nicastro, Nicolas; Burkhard, Pierre R. [Geneva University Hospitals, Neurology Unit, Department of Clinical Neurosciences, Geneva (Switzerland); University of Geneva, Faculty of Medicine, Geneva (Switzerland); Garibotto, Valentina [University of Geneva, Faculty of Medicine, Geneva (Switzerland); Geneva University Hospitals, Nuclear Medicine and Molecular Imaging Unit, Department of Medical Imaging, Geneva (Switzerland); Haller, Sven [University of Geneva, Faculty of Medicine, Geneva (Switzerland); Centre de Diagnostique Radiologique de Carouge, Geneva (Switzerland); Uppsala University, Department of Surgical Sciences, Radiology, Uppsala (Sweden); University Hospital Freiburg, Department of Neuroradiology, Freiburg (Germany)

2016-03-15

To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson's disease (PD). This retrospective study included 970 consecutive patients undergoing {sup 123}I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 ± 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 ± 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other. Increasing disease stage was associated with an exponential decrease in {sup 123}I-ioflupane uptake (R {sup 2} = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p < 0.0001), whereas increasing disease duration was associated with a linear decrease in {sup 123}I-ioflupane uptake (p < 0.0001; R {sup 2} = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001). We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 {sup 123}I-ioflupane SPECT scans can be used for clinical and research applications. (orig.)

Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [123I]FP-CIT SPECT

International Nuclear Information System (INIS)

Huertas-Fernandez, I.; Benitez-Rivero, S.; Jesus, S.; Caceres-Redondo, M.T.; Martin-Rodriguez, J.F.; Carrillo, F.; Garcia-Gomez, F.J.; Marin-Oyaga, V.A.; Lojo, J.A.; Garcia-Solis, D.; Mir, P.

2015-01-01

The study's objective was to develop diagnostic predictive models using data from two commonly used [ 123 I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis. We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [ 123 I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [ 123 I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [ 123 I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [ 123 I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. The predictive models built with ROI data and SPM data from [ 123 I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their applicability across centres. (orig.)

Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys

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Alex G. Lee

2016-06-01

Full Text Available Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3 in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition. Striatal DRD2/3 availability in adulthood was measured in vivo by [11C]raclopride binding using positron emission tomography (PET. DRD2/3 availability was greater in caudate and putamen compared to ventral striatum as reported in PET studies of humans and other non-human primates. DRD2/3 availability in ventral striatum was also consistently greater in stress inoculated squirrel monkeys compared to no-stress controls. Squirrel monkeys exposed to stress inoculation in the presence of their mother did not differ from squirrel monkeys exposed to stress inoculation without maternal companionship. Similar effects in different social contexts extend the generality of our findings and together suggest that stress inoculation increases striatal DRD2/3 availability as a correlate of cognitive control in squirrel monkeys.

The role of stress in the pathogenesis and maintenance of obsessive-compulsive disorder.

Science.gov (United States)

Adams, T G; Kelmendi, B; Brake, C A; Gruner, P; Badour, C L; Pittenger, C

2018-01-01

Individuals with OCD often identify psychosocial stress as a factor that exacerbates their symptoms, and many trace the onset of symptoms to a stressful period of life or a discrete traumatic incident. However, the pathophysiological relationship between stress and OCD remains poorly characterized: it is unclear whether trauma or stress is an independent cause of OCD symptoms, a triggering factor that interacts with a preexisting diathesis, or simply a nonspecific factor that can exacerbate OCD along with other aspects of psychiatric symptomatology. Nonetheless, preclinical research has demonstrated that stress has conspicuous effects on corticostriatal and limbic circuitry. Specifically, stress can lead to neuronal atrophy in frontal cortices (particularly the medial prefrontal cortex), the dorsomedial striatum (caudate), and the hippocampus. Stress can also result in neuronal hypertrophy in the dorsolateral striatum (putamen) and amygdala. These neurobiological effects mirror reported neural abnormalities in OCD and may contribute to an imbalance between goal-directed and habitual behavior, an imbalance that is implicated in the pathogenesis and expression of OCD symptomatology. The modulation of corticostriatal and limbic circuits by stress and the resultant imbalance between habit and goal-directed learning and behavior offers a framework for investigating how stress may exacerbate or trigger OCD symptomatology.

Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

International Nuclear Information System (INIS)

Creese, I.; Florijn, W.J.; Tarazi, F.I.

1997-01-01

Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [ 3 H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D 3 receptors was not changed in any brain region by any of the drug treatments. [ 3 H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [ 3 H]nemonapride and [ 3 H]spiperone binding to dopamine D 2 -like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [ 3 H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [ 3 H]nemonapride and [ 3 H]spiperone binding in caudate-putamen, whereas it did not affect [ 3 H]raclopride binding. Clozapine did not significantly change D 2 -like striatal binding of [ 3 H]nemonapride, [ 3 H]spiperone or [ 3 H]raclopride. The differences in radioligand binding suggest that [ 3 H]nemonapride and [ 3 H]spiperone may be binding to additional subsets of dopamine D 2 -like receptors (including D 4 -like receptors) that are not recognized by [ 3 H]raclopride, which has high affinity for D 2 and D 3 receptors only.Quantification of [ 3 H]nemonapride or [ 3 H]spiperone binding in the presence of 300 nM raclopride (to block D 2 and D 3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D 4 -like receptors in the caudate-putamen using either radioligand. These results suggest that D 4 -like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients

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Marios Politis

2017-01-01

Full Text Available We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R availability in Parkinson's disease (PD patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

[Hepatocellular carcinoma originated in the caudate lobe. Surgical strategy for resection. A propos of a case].

Science.gov (United States)

Martínez-Mier, Gustavo; Esquivel-Torres, Sergio; Calzada-Grijalva, José Francisco; Grube-Pagola, Peter

2015-01-01

Hepatocellular carcinoma originating from the caudate lobe has a worse prognosis than other hepatocellular carcinoma in another segment of the liver. An isolated caudate lobe resection of the liver represents a significant technical challenge. Caudate lobe resection can be performed along with a lobectomy or as an isolated liver resection. There are very few reports about isolated caudate lobe liver resection. We report a case of successful isolated resection of hepatocellular carcinoma in the caudate lobe with excellent long-term survival. A 74 years old female with 8cm mass lesion in the caudate lobe without clinical or biochemical evidence of liver cirrhosis, serum alpha-fetoprotein 3.7 U/l, and negative hepatitis serology was evaluated for surgery. Complete resection of the lesion in 270minutes with Pringle maneuver for 13minutes was satisfactorily performed. Patient was discharged ten days after surgery without complications. Patient is currently asymptomatic, without deterioration of liver function and 48 month tumor free survival after the procedure. Isolated caudate lobe resection is an uncommon but technically possible procedure. In order to achieve a successful resection, one must have a detailed knowledge of complete liver anatomy. Tumor free margins must be obtained to provide long survival for these patients who have a malignancy in this anatomic location. Copyright © 2015. Published by Masson Doyma México S.A.

Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease

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Piotr Hadaczek

2016-01-01

Full Text Available Huntington's disease (HD is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV, AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP, with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.

Radioautographic localization of somatostatin-14 and somatostatin-28 binding sites in the rat brain

International Nuclear Information System (INIS)

Leroux, P.; Pelletier, G.

1984-01-01

Somatostatin-14 (S14) and its precursor, somatostatin-28 (S28), are widely distributed throughout the rat brain, suggesting that they could act as neurotransmitter or neuromodulator in the central nervous system. The present study was undertaken to study the localization of S14 and S28 receptors in the rat brain determined by ''in vitro'' radioautography. The study performed on slide mounted frozen brain section with iodinated S14 and S28 analogs revealed an identical distribution of binding sites for the two forms of somatostatin. A good correlation could be observed between receptor distribution and immunohistologically localized neuropeptides except for striatum and hypothalamus. However, receptors were not detectable in the hypothalamus and were found in low concentration in the caudate-putamen nucleus, two regions containing high amounts of S28 and S14, suggesting a high occupancy of receptors in these areas by endogenous peptides or an inverse correlation between receptor and peptide concentrations

Association Between Peripheral Inflammation and DATSCAN Data of the Striatal Nuclei in Different Motor Subtypes of Parkinson Disease

Directory of Open Access Journals (Sweden)

Hossein Sanjari Moghaddam

2018-04-01

Full Text Available The interplay between peripheral and central inflammation has a significant role in dopaminergic neural death in nigrostriatal pathway, although no direct assessment of inflammation has been performed in relation to dopaminergic neuronal loss in striatal nuclei. In this study, the correlation of neutrophil to lymphocyte ratio (NLR as a marker of peripheral inflammation to striatal binding ratios (SBRs of DAT SPECT images in bilateral caudate and putamen nuclei was calculated in 388 drug-naïve early PD patients [288 tremor dominant (TD, 73 postural instability and gait difficulty (PIGD, and 27 indeterminate] and 148 controls. NLR was significantly higher in PD patients than in age- and sex-matched healthy controls, and showed a negative correlation to SBR in bilateral putamen and ipsilateral caudate in all PD subjects. Among our three subgroups, only TD patients showed remarkable results. A positive association between NLR and motor severity was observed in TD subgroup. Besides, NLR could negatively predict the SBR in ipsilateral and contralateral putamen and caudate nuclei in tremulous phenotype. Nonetheless, we found no significant association between NLR and other clinical and imaging findings in PIGD and indeterminate subgroups, supporting the presence of distinct underlying pathologic mechanisms between tremor and non-tremor predominant PD at early stages of the disease.

Contribution to speech development of the right anterior putamen revealed with multivariate tensor-based morphometry.

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Vlasova, Roza; Yalin Wang; Dirks, Holly; Dean, Douglas; O'Muircheartaigh, Jonathan; Gonzalez, Sara; Binh Kien Nguyen; Nelson, Marvin D; Deoni, Sean; Lepore, Natasha

2017-07-01

In our previous study1, we suggested that the difference between tensor-based metrics in the anterior part of the right putamen between 21 and 18 months age groups associated with speech development during this ages. Here we used a correlational analysis between verbal scores and determinant of the Jacobian matrix to confirm our hypothesis. Significant correlations in anterior part of the right putamen between verbal scores and surface metric were revealed in the 18 and 21 age groups.

Morphology and morphometry of the caudate lobe of the liver in two populations.

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Sagoo, Mandeep Gill; Aland, R Claire; Gosden, Edward

2018-01-01

The caudate lobe of the liver has portal blood supply and hepatic vein drainage independent of the remainder of the liver and may be differentially affected in liver pathologies. Ultrasonographic measurement of the caudate lobe can be used to generate hepatic indices that may indicate cirrhosis. This study investigated the relationship of metrics of the caudate lobe and other morphological features of human livers from a northwest Indian Punjabi population (n = 50) and a UK Caucasian population (n = 25), which may affect the calculation of hepatic indices. The width of the right lobe of the liver was significantly smaller, while the anteroposterior diameter of the caudate lobe and both Harbin's Index and the Hess Index scores were significantly larger in NWI livers than in UKC livers. The Hess Index score, in particular, is much larger in the NWI population (265 %, p liver. These differences may affect the calculation of hepatic indices, resulting in a greater percentage of false positives of cirrhosis in the NWI population. Population-specific data are required to correctly determine normal ranges.

Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

International Nuclear Information System (INIS)

Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

1988-01-01

Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of 18 F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation

Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity.

Science.gov (United States)

Dunn, Julia P; Kessler, Robert M; Feurer, Irene D; Volkow, Nora D; Patterson, Bruce W; Ansari, Mohammad S; Li, Rui; Marks-Shulman, Pamela; Abumrad, Naji N

2012-05-01

Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S(I)) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [(18)F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S(I) was determined by modified oral glucose tolerance test. Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S(I) was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

European multicentre database of healthy controls for [{sup 123}I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis

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Varrone, Andrea [Karolinska University Hospital, R5:02, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, Ozlem L. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Knudsen, Gitte M. [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Koulibaly, Pierre Malick [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurophysiology Unit, Department of Neuroscience, Ophthalmology and Genetics, Genoa (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Borght, Thierry vander [Universite Catholique de Louvain, Nuclear Medicine Division, Mont-Godinne Medical Center, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Municipal Hospital of Karlsruhe Inc, Department of Nuclear Medicine, Karlsruhe (Germany)

2013-02-15

Dopamine transporter (DAT) imaging with [{sup 123}I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [{sup 123}I]FP-CIT SPECT scans in healthy controls. SPECT data from 139 healthy controls (74 men, 65 women; age range 20 - 83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR). A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade. This study provides a large database of [{sup 123}I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference

Executive dysfunction correlates with caudate nucleus atrophy in patients with white matter changes on MRI: A subset of LADIS

DEFF Research Database (Denmark)

Macfarlane, Matthew Duncan; Looi, Jeffrey Chee Leong; Walterfang, Mark

2013-01-01

and falls in cross-sectional and follow-up studies. Frontostriatal (or frontosubcortical) brain circuits may serve many of these functions, with the caudate nuclei playing a role in convergence of cognitive functions. This study aimed to determine whether reduced caudate volume relates to cognitive...... functions (executive functions, memory functions and speed of processing) and WMC. We determined caudate nuclei volumes, through manual tracing, on a subgroup of the LADIS study (n=66) from four centres with baseline and 3-year follow-up MRI scans. Regression analysis was used to assess relationships...... between caudate volume, cognitive function and WMC. Severity of WMC did not relate to caudate volume. Smaller caudate volumes were significantly associated with poorer executive functioning at baseline and at 3 years, but were not associated with scores of memory or speed of processing. Thus, in patients...

Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

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Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

2008-02-01

To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I = battery. We compared the FDG PET findings of each group of patients with controls. Group I patients frequently had memory and frontal executive dysfunction. They showed hypometabolism in the frontal cortex, anterior cerebellar hemisphere and vermis. They had parkinsonian motor deficits, but no basal ganglia hypometabolism. Group II and III patients frequently had multiple domain cognitive impairments, and showed hypometabolism in the frontal and parieto-temporal cortices. Hypometabolism of the bilateral caudate and the left posterolateral putamen was observed in Group II, and whole striatum in Group III. In summary, the cortical hypometabolism begins in the frontal cortex and spreads to the parieto-temporal cortex in MSA. This spreading pattern coincides with the progressive cognitive decline. Early caudate hypometabolism may also contribute to the cognitive impairment. Parkinsonian motor deficits precede putaminal hypometabolism that begins in its posterolateral part. Cerebellar hypometabolism occurs early in the clinical courses and seems to be a relevant metabolic descriptor of cerebellar deficits.

Mis-segmentation in voxel-based morphometry due to a signal intensity change in the putamen.

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Goto, Masami; Abe, Osamu; Miyati, Tosiaki; Aoki, Shigeki; Gomi, Tsutomu; Takeda, Tohoru

2017-12-01

The aims of this study were to demonstrate an association between changes in the signal intensity of the putamen on three-dimensional T1-weighted magnetic resonance images (3D-T1WI) and mis-segmentation, using the voxel-based morphometry (VBM) 8 toolbox. The sagittal 3D-T1WIs of 22 healthy volunteers were obtained for VBM analysis using the 1.5-T MR scanner. We prepared five levels of 3D-T1WI signal intensity (baseline, same level, background level, low level, and high level) in regions of interest containing the putamen. Groups of smoothed, spatially normalized tissue images were compared to the baseline group using a paired t test. The baseline was compared to the other four levels. In all comparisons, significant volume changes were observed around and outside the area that included the signal intensity change. The present study demonstrated an association between a change in the signal intensity of the putamen on 3D-T1WI and changed volume in segmented tissue images.

SPECT quantification of 123I - and - CIT in Parkinsonism

International Nuclear Information System (INIS)

Larcos, G.; Shaffi, M.; Hutton, B.F.; Hatton, R.; Kyme, A.; Fung, V.S.C.; Morris, J.G.L.

2002-01-01

Full text: Evaluation of presynaptic dopaminergic function using 2B-carboxymethoxy-3B-(4-[ 123 I] iodophenyl) tropane ( 123 I-and-CIT) SPECT has employed subjective or semi-quantitative methods. Our hypothesis is that disease classification in Parkinsonism may be improved by partial volume correction and co-registration with MRI. We studied seven patients (pts) with IPD (four men, three women, mean age=54.5+/-10.9 yrs; Hoehn and Yahr stage range 1-3; Schwab and England scale range: 30-100 [mean=67.1+/-26.9]) and two controls with 123 I- - CIT using 110-150 MBq and a dual-head camera equipped with fan-beam collimation. SPECT was registered to MRI and then aligned to a reference template. Specific to non-specific dopaminergic binding (UR) was calculated for the putamen and caudate nucleus, as well as the fractional volume (FV; fraction of the Structure affected) and residual uptake ratio (RUR; count density in area/remnant apparently unaffected by disease). Parameters that were statistically significant were the putamen (p; but not caudate) UR, FV and RUR. We conclude that: (a) it is possible to distinguish dopaminergic activity within the putamen from caudate using MRI image co-registration and (b) parameters other than UR may discriminate IPD from normal subjects and other entities. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

Science.gov (United States)

Aravamuthan, Bhooma R; Waugh, Jeff L

2016-01-01

Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain

Optimal scanning time window for 18F-FP-(+)-DTBZ (18F-AV-133) summed uptake measurements

International Nuclear Information System (INIS)

Lin, Kun-Ju; Lin, Wey-Yil; Hsieh, Chia-Ju; Weng, Yi-Hsin; Wey, Shiaw-Pyng; Lu, Chin-Song; Skovronsky, Daniel; Yen, Tzu-Chen; Chang, Chee-Jen; Kung, Mei-Ping

2011-01-01

18 F-9-fluoropropyl-(+)-dihydrotetrabenazine ( 18 F-AV-133) is a novel positron emission tomography tracer for imaging the vesicular monoamine transporter II in dopaminergic neuron degeneration, which might be indicative for Parkinson's disease (PD) and other parkinsonism. Studies were performed to optimize the imaging time window for calculating standardized uptake value ratio (SUVR) with correlation to distribution volume ratio (DVR) and in differentiating PD from normal controls (NCs). Methods: Thirteen 18 F-AV-133 positron emission tomography studies were conducted on four NCs (age, 62.3±4.9 years) and nine PD patients (age, 60.8±6.0 years) with Hoehn and Yahr stages 2 to 3. Dynamic images were acquired within 180 min (0–30, 50–140 and 160–180 min) and were rearranged into 14 of 10-min scans. The contralateral striatum was defined as the opposite striatum to the predominantly affected limbs. Volumes of interest (VOIs) of bilateral putamen, caudate nuclei and occipital cortex (OC; as the reference region) were delineated from individual magnetic resonance imaging. SUVRs of striatum to OC were computed from 14 dynamic image sets. The DVRs were computed from Logan graphic analysis by using OC as the input. The performance of SUVR was evaluated based on the correlation of SUVR at each time window to DVR, as well as the Cohen effect size (group mean SUVR difference between PD and NC/standard deviation). Results: 18 F-AV-133 uptake decreased in PD subjects at bilateral striatum especially at contralateral side with posterior putamen predominant as compared with NC. Consistent higher correlations of SUVRs to DVR for all VOIs were observed at later time window and reached to its maximal value of 0.9917 at 90–100 min. The group mean SUVR differences between NC and PD subjects increased and reached relatively stable values after 90 min. The effect sizes for all VOIs were stable across different time window and with the largest value around 90∼120 min

Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

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Creese, I; Florijn, W J; Tarazi, F I [Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ (United States)

1997-04-14

Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [{sup 3}H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D{sub 3} receptors was not changed in any brain region by any of the drug treatments. [{sup 3}H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding to dopamine D{sub 2}-like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [{sup 3}H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding in caudate-putamen, whereas it did not affect [{sup 3}H]raclopride binding. Clozapine did not significantly change D{sub 2}-like striatal binding of [{sup 3}H]nemonapride, [{sup 3}H]spiperone or [{sup 3}H]raclopride. The differences in radioligand binding suggest that [{sup 3}H]nemonapride and [{sup 3}H]spiperone may be binding to additional subsets of dopamine D{sub 2}-like receptors (including D{sub 4}-like receptors) that are not recognized by [{sup 3}H]raclopride, which has high affinity for D{sub 2} and D{sub 3} receptors only.Quantification of [{sup 3}H]nemonapride or [{sup 3}H]spiperone binding in the presence of 300 nM raclopride (to block D{sub 2} and D{sub 3} receptors) revealed that haloperidol, raclopride and clozapine up-regulated D{sub 4}-like receptors in the caudate-putamen using either radioligand. These results suggest that D{sub 4}-like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Like mother like daughter: putamen activation as a mechanism underlying intergenerational risk for depression.

Science.gov (United States)

Colich, Natalie L; Ho, Tiffany C; Ellwood-Lowe, Monica E; Foland-Ross, Lara C; Sacchet, Matthew D; LeMoult, Joelle L; Gotlib, Ian H

2017-09-01

Having a depressed mother is one of the strongest predictors for developing depression in adolescence. Given the role of aberrant reward processing in the onset and maintenance of depression, we examined the association between mothers' and their daughters' neural response to the anticipation of reward and loss. Fifteen non-depressed mothers with a history of recurrent depression and their never-disordered daughters, and 23 mothers without past or current depression and their never-disordered daughters, underwent functional magnetic resonance imaging while performing the monetary incentive delay task. To assess mother-daughter concordance, we first identified ROIs involved in the anticipation of reward and loss across all mother-daughter pairs. Within each of these ROIs, we examined the association between mothers' and daughters' neural response, and the interaction between group status and mothers' neural response in predicting daughters' neural response. We found a significant association between mothers' and daughters' putamen response to the anticipation of loss, regardless of mother's depression history. Furthermore, pubertal stage moderated the association between mother-daughter putamen concordance. Our findings suggest a unique role of the putamen in the maternal transmission of reward learning and have important implications for understanding disorders characterized by disturbances in reward learning and processing, such as major depression. © The Author (2017). Published by Oxford University Press.

CT and MRI findings of chorea associated with nonketotic hyperglycemia

International Nuclear Information System (INIS)

Hu Dongjin; Zhang Weidong; Wu Dingquan; Meng Lishi; Chen Jian

2008-01-01

Objective: To explore the imaging diagnosis of chorea associated with nonketotic hyperglycemia by describing its CT and MR findings and correlating those findings with the clinical manifestations. Methods: The imaging findings and clinical data from 6 patients with chorea associated with nonketotic hyperglycemia were retrospectively analyzed. All 6 patients had unenhanced CT scans, 1 also had MR imaging examination. Three of 6 patients had follow-up CT scans and 1 of 3 patients had follow-up MR imaging studies. Results: CT studies of all 6 patients showed unilateral or bilateral hyperdense striatum. The putamen was involved in all 6 patients, the caudate nucleus or lateral portion of the globus pallidus were involved in 5 of all 6 patients. All 3 follow-up CT studies depicted a decreased or resolved hyperdensity of the abnormal striatum. T 1 -weighted MR images in 1 patient showed the hyperintense lesions of bilateral lentiform nuclei, T 2 -weighted MR images of the patient showed the hypointense lesions of the corresponding lentiform nuclei, and its follow-up MR images depicted invariable signal intensity of T 1 -weighted and T 2 -weighted images. In all patients, the chorea resolved within 2 to 6 days after treatment of the hyperglycemia. Conclusion: The characteristic imaging findings of chorea associated with nonketotic hyperglycemia can suggest an accurate diagnosis. (authors)

Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease

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Jae Jung Lee

2015-09-01

Full Text Available Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD. In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age. Methods This study included 307 de novo PD patients (152 men and 155 women who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis. Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions. Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.

The effects of age on dopamine receptors measured by positron tomography in the living human brain

International Nuclear Information System (INIS)

Wong, D.F.; Wagner, E.N. Jr.; Dannals, R.F.

1984-01-01

C-11 n-methylspiperone has been used to measure dopamine (D2) receptors in the caudate and putamen of 30 normal persons. In vitro studies in rodent brain revealed a high affinity for dopamine (D2) receptors and five fold less for serotonin (S2) receptors. In vivo drug competition studies in rodents demonstrated that 90% of striatal binding is to dopamine receptors. In the frontal cortex, the majority of receptor binding is to serotonin receptors. Thirty normal volunteers aged 19 to 73 years were screened for normality by medical, neurological and neuropsychological examinations. Positron tomography was performed serially for 2 hours after injection. In 10 subjects there was good agreement between activity in arterial samples and that in venous samples from a heated hand. Binding in the dopamine rich caudate and putamen progressively increased while binding in the dopamine poor cerebellum decreased. The dopamine receptor density was estimated by the ratio of the caudate-to-cerebellar mean counts/pixel (Ca/Cb) and putamen-to-cerebellar mean counts/pixel (Pu/Cb). The ratios (Ca/Cb, Pu/Cb) increased linearly with time (r>0.95) for each subject. There was a decrease (Ca/Cb) with age (0.8%/yr) that could be approximated with a linear fit: (Ca/Cb = -.02 age + 3.92, r=.6). For the 21 males alone, the decrease was (1.1%/yr, r=.7 , p <.01), while for the 9 females there was no significant decrease with age. Similar findings were noted in the putamen. This decline in dopamine receptor density with age has been reported in rodent and human autopsy studies, but never before in the living human brain

Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease

International Nuclear Information System (INIS)

Spiegel, J.; Fassbender, K.; Dillmann, U.; Hellwig, D.; Samnick, S.; Moellers, M.-O.; Kirsch, C.-M.; Jost, W.

2007-01-01

In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I- 123 ]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p 0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor. (author)

Do manual and voxel-based morphometry measure the same? – A proof of concept study

Directory of Open Access Journals (Sweden)

Niels K. Focke

2014-04-01

Full Text Available Voxel-based morphometry (VBM is a commonly used method to study volumetric variations on a whole brain basis. However it is often criticised for potential confounds, mainly based on imperfect spatial registration. We therefore aimed to evaluate if VBM and gold-standard manual volumetry are measuring the same effects with respect to subcortical grey matter volumes. Manual regions-of-interest (ROIs were drawn in the hippocampus, amygdala, nucleus accumbens, thalamus, putamen, pallidum and caudate nucleus bilaterally. Resulting volumes were used for a whole brain VBM correlation analysis with SPM8. The hippocampus, amygdala, putamen and caudate nucleus were correctly identified by SPM using the contemporary high-dimensional normalization (DARTEL toolbox. This strongly suggests that VBM and manual volumetry both are indeed measuring the same effects with regard to subcortical brain structures.

CT-Guided Percutaneous Step-by-Step Radiofrequency Ablation for the Treatment of Carcinoma in the Caudate Lobe

Science.gov (United States)

Dong, Jun; Li, Wang; Zeng, Qi; Li, Sheng; Gong, Xiao; Shen, Lujun; Mao, Siyue; Dong, Annan; Wu, Peihong

2015-01-01

Abstract The location of the caudate lobe and its complex anatomy make caudate lobectomy and radiofrequency ablation (RFA) under ultrasound guidance technically challenging. The objective of the exploratory study was to introduce a novel modality of treatment of lesions in caudate lobe and discuss all details with our experiences to make this novel treatment modality repeatable and educational. The study enrolled 39 patients with liver caudate lobe tumor first diagnosed by computerized tomography (CT) or magnetic resonance imaging (MRI). After consultation of multi-disciplinary team, 7 patients with hepatic caudate lobe lesions were enrolled and accepted CT-guided percutaneous step-by-step RFA treatment. A total of 8 caudate lobe lesions of the 7 patients were treated by RFA in 6 cases and RFA combined with percutaneous ethanol injection (PEI) in 1 case. Median tumor diameter was 29 mm (range, 18–69 mm). A right approach was selected for 6 patients and a dorsal approach for 1 patient. Median operative time was 64 min (range, 59–102 min). Median blood loss was 10 mL (range, 8-16 mL) and mainly due to puncture injury. Median hospitalization time was 4 days (range, 2–5 days). All lesions were completely ablated (8/8; 100%) and no recurrence at the site of previous RFA was observed during median 8 months follow-up (range 3–11 months). No major or life-threatening complications or deaths occurred. In conclusion, percutaneous step-by-step RFA under CT guidance is a novel and effective minimally invasive therapy for hepatic caudate lobe lesions with well repeatability. PMID:26426638

Chronic motor cortex stimulation in patients with advanced Parkinson's disease and effects on striatal dopaminergic transmission as assessed by 123I-FP-CIT SPECT: a preliminary report.

Science.gov (United States)

Di Giuda, Daniela; Calcagni, Maria L; Totaro, Manuela; Cocciolillo, Fabrizio; Piano, Carla; Soleti, Francesco; Fasano, Alfonso; Cioni, Beatrice; Bentivoglio, Anna R; Giordano, Alessandro

2012-09-01

The objective of this study was to assess striatal dopamine transporter availability in patients with advanced Parkinson's disease (PD) before and after 13 months of unilateral extradural motor cortex stimulation (EMCS) with [123I]N-ω-fluoropropyl-2-β-carbo-methoxy-3-β-(4-iodophenyl)nortropane single photon emission computed tomography (123I-FP-CIT SPECT). Six PD patients (five women and one man, aged 63.2 ± 5.6 years) underwent 123I-FP-CIT SPECT and clinical evaluation [Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Quality of Life Scale (PDQL)] preoperatively, 8 and 13 months after EMCS. Striatum-to-occipital cortex, caudate-to-occipital cortex and putamen-to-occipital cortex 123I-FP-CIT uptake ratios were calculated using the region of interest method. Total and part III UPDRS scores significantly decreased at 8 and 13 months after stimulation (P=0.02 and 0.04, respectively); UPDRS part II and PDQL scores improved after 13 months (P=0.02 and 0.04, respectively). No significant differences in 123I-FP-CIT uptake ratios between baseline and follow-up were found in the examined regions. However, a progressive reduction in 123I-FP-CIT uptake ratios in the striatum contralateral to the implant was found. In contrast, no further decrease in 123I-FP-CIT uptake ratios was detected in the striatum ipsilateral to the implant. There were no correlations between changes in 123I-FP-CIT uptake ratios with disease duration, changes in medication dosage and motor UPDRS scores. Despite a small but highly selected sample of advanced PD patients, our results showed that no further dopamine transporter reduction occurred in the striatum ipsilateral to the implant side. This finding could lead to the hypothesis that EMCS might elicit a 'neuroprotective' effect, as suggested by significant clinical benefits.

[O-methyl-{sup 11}C]{beta}-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: Preparation, autoradiography, metabolite studies, and positron emission tomography examinations

Energy Technology Data Exchange (ETDEWEB)

Lundkvist, Camilla; Halldin, Christer; Swahn, Carl-Gunnar; Hall, Haakan; Karlsson, Per; Nakashima, Yoshifumi; Wang, Shaoyin; Milius, Richard A.; Neumeyer, John L.; Farde, Lars

1995-10-01

{beta}-CIT-FP [N-(3-fluoropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane] is a cocaine analogue with a high affinity for the dopamine transporter. [O-methyl-{sup 11}C]{beta}-CIT-FP ([{sup 11}C]{beta}-CIT-FP) was prepared byO -alkylation of the free acid with [{sup 11}C]methyl iodide. The total radiochemical yield of [{sup 11}C]{beta}-CIT-FP was 50 to 60% with an overall synthesis time of 30 min. The radiochemical purity was >99%, and the specific radioactivity at time of injection was about 37 GBq/{mu}mol (1000 Ci/mmol). Autoradiographic examination of [{sup 11}C]{beta}-CIT-FP binding in human brain postmortem demonstrated specific binding in the caudate nucleus and putamen. Positron emission tomography (PET) examination of [{sup 11}C]{beta}-CIT-FP in a Cynomolgus monkey demonstrated accumulation in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min. Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5, respectively. In a displacement experiment, radioactivity in the striatum but not in the cerebellum was reduced after injection of {beta}-CIT, indicating that striatal radioactivity following injection of [{sup 11}C]{beta}-CIT-FP is associated with dopamine transporter sites and that the binding is reversible. The fraction of the total radioactivity in plasma representing [{sup 11}C]{beta}-CIT-FP determined by high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95 min. [{sup 11}C]{beta}-CIT-FP should be a useful PET radioligand for the quantitation of dopamine transporters in the human brain in vivo.

Aberrant topology of striatum's connectivity is associated with the number of episodes in depression.

Science.gov (United States)

Meng, Chun; Brandl, Felix; Tahmasian, Masoud; Shao, Junming; Manoliu, Andrei; Scherr, Martin; Schwerthöffer, Dirk; Bäuml, Josef; Förstl, Hans; Zimmer, Claus; Wohlschläger, Afra M; Riedl, Valentin; Sorg, Christian

2014-02-01

In major depressive disorder, depressive episodes reoccur in ∼60% of cases; however, neural mechanisms of depressive relapse are poorly understood. Depressive episodes are characterized by aberrant topology of the brain's intrinsic functional connectivity network, and the number of episodes is one of the most important predictors for depressive relapse. In this study we hypothesized that specific changes of the topology of intrinsic connectivity interact with the course of episodes in recurrent depressive disorder. To address this hypothesis, we investigated which changes of connectivity topology are associated with the number of episodes in patients, independently of current symptoms and disease duration. Fifty subjects were recruited including 25 depressive patients (two to 10 episodes) and 25 gender- and age-matched control subjects. Resting-state functional magnetic resonance imaging, Harvard-Oxford brain atlas, wavelet-transformation of atlas-shaped regional time-series, and their pairwise Pearson's correlation were used to define individual connectivity matrices. Matrices were analysed by graph-based methods, resulting in outcome measures that were used as surrogates of intrinsic network topology. Topological scores were subsequently compared across groups, and, for patients only, related with the number of depressive episodes and current symptoms by partial correlation analysis. Concerning the whole brain connectivity network of patients, small-world topology was preserved but global efficiency was reduced and global betweenness-centrality increased. Aberrant nodal efficiency and centrality of regional connectivity was found in the dorsal striatum, inferior frontal and orbitofrontal cortex as well as in the occipital and somatosensory cortex. Inferior frontal changes were associated with current symptoms, whereas aberrant right putamen network topology was associated with the number of episodes. Results were controlled for effects of total grey matter

A clinico-MRI study of extrapyramidal symptoms in multiple system atrophy; Linear hyperintensity in the outer margin of the putamen

Energy Technology Data Exchange (ETDEWEB)

Konagaya, Masaaki; Iida, Mitsuo [Suzuka National Hospital, Mie (Japan); Konagaya, Yoko; Honda, Hitoshi

1993-06-01

We studied extrapyramidal symptoms and T2-weighted MRI findings of the putamen in 20 patients with multiple system atrophy (MSA) and 25 with idiopathic Parkinson's disease. Nine of the 20 MSA patients showed extrapyramidal symptoms. We could not observe cerebellar ataxia in two of the 9 patients because of severe rigidity and skinesia. Eight of the 9 MSA patients with extrapyramidal symptoms showed linear hyperintensity in the outer margin of the putamen. This abnormal intensity was bilateral and symmetric in most patients. However, in MSA patients without extrapyramidal symptoms, only one patient showed the linear hyperintensity. We could not find such abnormal intensity in any of the patients with Parkinson's disease. On proton density MRI, the signal intensity in the lesion was higher than that in the gray matter, which leads the speculation that the hyperintensity is gliosis of the putamen or increased extracellular fluid space caused by severe shrinkage of the putamen. These characteristic MRI findings may distinguish MSA with extrapyramidal symptoms from Parkinson's disease. (J.P.N.).

Preparation of a potential positron emission tomographic radioligand for the dopamine transporter

International Nuclear Information System (INIS)

Mueller, L.; Halldin, C.; Foged, C.; Karlsson, P.; Hall, H.; Swahn, C.G.; Suzdak, P.D.; Hohlweg, R.; Nielsen, E.B.; Frade, L.

1994-01-01

NNC 12-0722 (1-[2-(bis(4-fluorophenyl)-methoxy)ethyl]-4-methyl piperazine) is a new selective inhibitor of the dopamine transporter. [ 11 C]NNC 12-0722 was prepared by N-methylation of the desmethyl compound with [ 11 C]methyl iodide. The total radiochemical yield of [ 11 C]NNC 12-0722 was 40%-50% with an overall synthesis time of 30-35 min. The radiochemical purity was higher than 99% and the specific radioactivity about 1500 Ci/mmol (55 GBq/μmol). Autoradiographic examination of [ 11 C]NNC 12-0722 binding on whole hemisphere cryosections from human brain post mortem demonstrated specific binding in the caudate nucleus and putamen. In a positron emission tomographic examination of [ 11 C]NNC 12-0722 in a cynomolgus monkey there was a rapid uptake of radioactivity in the brain. In the striatum, a region with a high density of dopamine transporters, the radioactivity was two times higher than in the cerebellum. These results indicate that [ 11 C]NNC 12-0722 may be a useful radioligand for labelling of the dopamine transporter in man. (orig.)

Neuroanatomical correlates of Klinefelter syndrome studied in relation to the neuropsychological profile

DEFF Research Database (Denmark)

Skakkebæk, Anne; Gravholt, Claus Højbjerg; Rasmussen, Peter Mondrup

2014-01-01

, putamen, caudate, hippocampus, amygdala, temporal pole and frontal inferior orbita. Additionally, the right parahippocampal region and cerebellar volumes were reduced in KS patients. KS patients had significantly larger volumes in right postcentral gyrus, precuneus and parietal regions. Multivariate...

Short-term hypoxia/reoxygenation activates the angiogenic pathway ...

Indian Academy of Sciences (India)

2013-04-20

Apr 20, 2013 ... angiogenic pathway in the rat caudate putamen as a neuroprotective mechanism to hypoxia .... (1:3 w/v) with a homogenator (Pellet Pestle Motor Cordless, ..... showing that the capillary density in the rat cerebral cortex was.

Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [{sup 123}I]FP-CIT SPECT

Energy Technology Data Exchange (ETDEWEB)

Huertas-Fernandez, I.; Benitez-Rivero, S.; Jesus, S.; Caceres-Redondo, M.T.; Martin-Rodriguez, J.F.; Carrillo, F. [Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Seville (Spain); Garcia-Gomez, F.J.; Marin-Oyaga, V.A.; Lojo, J.A. [Hospital Universitario Virgen del Rocio, Servicio de Medicina Nuclear, UDIM, Seville (Spain); Garcia-Solis, D. [Hospital Universitario Virgen del Rocio, Servicio de Medicina Nuclear, UDIM, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, P. [Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain)

2015-01-15

The study's objective was to develop diagnostic predictive models using data from two commonly used [{sup 123}I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis. We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [{sup 123}I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [{sup 123}I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [{sup 123}I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [{sup 123}I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. The predictive models built with ROI data and SPM data from [{sup 123}I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their

Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice

DEFF Research Database (Denmark)

Licht, Cecilie L; Kirkegaard, Lisbeth; Zueger, Maha

2010-01-01

. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen......]citalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control....... Among post hoc analyzed regions, there was a 14% decrease in 5-HT(4) receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus...

Unusual magnetic resonance imaging features in Menkes disease

International Nuclear Information System (INIS)

Barnerias, C.; Desguerre, I.; Dulac, O.; Bahi-Buisson, N.; Boddaert, N.; Hertz-Pannier, L.; Boddaert, N.; Guiraud, P.; Hertz-Pannier, L.; Dulac, O.; Bahi-Buisson, N.; Hertz-Pannier, L.; Dulac, O.; Bahi-Buisson, N.; De Lonlay, P.

2008-01-01

We present a case of an inherited disorder of copper metabolism, Menkes disease in which MRI studies revealed the coexistence of T2 hyper-signal in the temporal white matter with an increase of apparent diffusion coefficient indicative of vasogenic oedema combined with T2 hyper-signal of the putamen and head of the caudate and decreased apparent diffusion coefficient indicative of cytotoxic oedema. These unusual MRI features emphasize the interest of newly developed techniques in early diagnosis in Menkes disease. The acute cerebral damage might result from the combined effects of acute metabolic stress due to infectious disease and prolonged status epilepticus, acting on a highly susceptible developing brain. Vasogenic oedema in the temporal white matter could be related to prolonged status epilepticus and vascular abnormalities. Cytotoxic oedema of the putamen and head caudate could result from energetic failure. (authors)

Unusual magnetic resonance imaging features in Menkes disease

Energy Technology Data Exchange (ETDEWEB)

Barnerias, C; Desguerre, I; Dulac, O; Bahi-Buisson, N [Hop Necker Enfants Malades, AP-HP, Dept Paediat Neurol and Metab Dis, F-75743 Paris 15 (France); Boddaert, N; Hertz-Pannier, L [Hop Necker Enfants Malad, AP-HP, Dept Pediat Radiol, F-75743 Paris (France); Boddaert, N [CEA, Serv Hosp Frederic Joliot, INSERM, U797, F-91406 Orsay (France); Guiraud, P [Univ Grenoble, Serv Biochim, Genet Hop, Grenoble (France); Hertz-Pannier, L; Dulac, O; Bahi-Buisson, N [INSERM, U663, F-75015 Paris (France); Hertz-Pannier, L; Dulac, O; Bahi-Buisson, N [Univ Paris 05, F-75005 Paris (France); De Lonlay, P [Hop Necker Enfants Malades, AP-HP, Dept Paediat Neurol and Metab Dis, F-75743 Paris 15 (France); Hop Necker Enfants Malades, AP HP, Ctr Reference Malad Metab, F-75743 Paris 15 (France)

2008-07-01

We present a case of an inherited disorder of copper metabolism, Menkes disease in which MRI studies revealed the coexistence of T2 hyper-signal in the temporal white matter with an increase of apparent diffusion coefficient indicative of vasogenic oedema combined with T2 hyper-signal of the putamen and head of the caudate and decreased apparent diffusion coefficient indicative of cytotoxic oedema. These unusual MRI features emphasize the interest of newly developed techniques in early diagnosis in Menkes disease. The acute cerebral damage might result from the combined effects of acute metabolic stress due to infectious disease and prolonged status epilepticus, acting on a highly susceptible developing brain. Vasogenic oedema in the temporal white matter could be related to prolonged status epilepticus and vascular abnormalities. Cytotoxic oedema of the putamen and head caudate could result from energetic failure. (authors)

Measuring the volume of caudate nucleus in healthy Chinese adults of the Han nationality on the high-resolution MRI

International Nuclear Information System (INIS)

Ni Mingfei; Chen Nan; Wang Xing; Wu Jianlin; Li Kuncheng; Zhou Xin; Zhou Yan; Chen Lin

2010-01-01

Objective: To explore the normal range of the caudate nucleus' volume in Chinese adults of the Han nationality and provide morphological data for the construction of database for Chinese Standard Brain. Methods: This was a clinical multi-center study. One thousand Chinese healthy volunteers (age range =18 to 70) recruited from 16 hospitals were divided into 5 groups, i.e, Group A (age range = 18 to 30), B (age range =31 to 40), C (age range =41 to 50), D (age range =51 to 60), and E (age range =61 to 70). Each group contained 100 males and 100 females. All of the volunteers were scanned by MR using T 1 weighted three-dimensional magnetization prepared rapid acquisition gradient echo sequence. The volume of caudate was measured manually using 3D volume analysis software. The difference of volumes of the caudate between male and female were analyzed by independent sample t-test, and among age groups by ANOVA. Pearson's correlation coefficient was used to characterize the relationship between volumes and age. The differences of measurements between left and right caudate nucleus were analyzed by paired t test. Results: (1) The mean volume of bilateral caudate nucleus in healthy Chinese adults was (10.973± 1.647) cm 3 . The mean volume of the the male's left and right caudate nucleus were (5.656±0.860) and (5.671±0.855) cm 3 respectively,no significant differences were found between the volume of left and right caudate nucleus (t=1.230, P>0.05). The mean volume of the the female's left and right caudate nucleus were (5.287±0.774) and (5.331±0.766) cm 3 respectively, and the right's was larger than the left's with significant differences (t=3.999, P<0.01); (2) Pearson correlation analysis showed a significant negative correlation between the nucleus volume and age (male and female's, left and right) (r=-0.561, -0.568, -0.548, -0.552, P<0.05). Conclusion: With high-resolution MRI and 3D volumetric analytic software (Midob), the volume of the caudate nucleus can be

Differential distribution of striatal [123I]β-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

International Nuclear Information System (INIS)

Messa, C.; Volonte, M.A.; Fazio, F.; Zito, F.; Carpinelli, A.; D'Amico, A.; Rizzo, G.; Moresco, R.M.; Paulesu, E.; Franceschi, M.; Lucignani, G.

1998-01-01

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([ 123 I]β-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [ 123 I]β-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24±2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3''). ANOVA revealed a global reduction of V3'' in all ROIs of PD and PSP patients compared with normal controls (P 123 I]β-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP. (orig.)

Coenzyme Q-responsive Leigh's encephalopathy in two sisters.

NARCIS (Netherlands)

Maldergem, L. van; Trijbels, J.M.F.; Mauro, S. Di; Sindelar, P.J.; Musumeci, O.; Janssen, A.J.M.; Delberghe, X.; Martin, J.J.; Gillerot, Y.

2002-01-01

A 31-year-old woman had encephalopathy, growth retardation, infantilism, ataxia, deafness, lactic acidosis, and increased signals of caudate and putamen on brain magnetic resonance imaging. Muscle biochemistry showed succinate:cytochrome c oxidoreductase (complex II-III) deficiency. Both clinical

Interaction between hippocampal and striatal systems predicts subsequent consolidation of motor sequence memory.

Directory of Open Access Journals (Sweden)

Geneviève Albouy

Full Text Available The development of fast and reproducible motor behavior is a crucial human capacity. The aim of the present study was to address the relationship between the implementation of consistent behavior during initial training on a sequential motor task (the Finger Tapping Task and subsequent sleep-dependent motor sequence memory consolidation, using functional magnetic resonance imaging (fMRI and total sleep deprivation protocol. Our behavioral results indicated significant offline gains in performance speed after sleep whereas performance was only stabilized, but not enhanced, after sleep deprivation. At the cerebral level, we previously showed that responses in the caudate nucleus increase, in parallel to a decrease in its functional connectivity with frontal areas, as performance became more consistent. Here, the strength of the competitive interaction, assessed through functional connectivity analyses, between the caudate nucleus and hippocampo-frontal areas during initial training, predicted delayed gains in performance at retest in sleepers but not in sleep-deprived subjects. Moreover, during retest, responses increased in the hippocampus and medial prefrontal cortex in sleepers whereas in sleep-deprived subjects, responses increased in the putamen and cingulate cortex. Our results suggest that the strength of the competitive interplay between the striatum and the hippocampus, participating in the implementation of consistent motor behavior during initial training, conditions subsequent motor sequence memory consolidation. The latter process appears to be supported by a reorganisation of cerebral activity in hippocampo-neocortical networks after sleep.

Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes.

Science.gov (United States)

Possin, Katherine L; Kim, Hosung; Geschwind, Michael D; Moskowitz, Tacie; Johnson, Erica T; Sha, Sharon J; Apple, Alexandra; Xu, Duan; Miller, Bruce L; Finkbeiner, Steven; Hess, Christopher P; Kramer, Joel H

2017-07-01

Our brains represent spatial information in egocentric (self-based) or allocentric (landmark-based) coordinates. Rodent studies have demonstrated a critical role for the caudate in egocentric navigation and the hippocampus in allocentric navigation. We administered tests of egocentric and allocentric working memory to individuals with premotor Huntington's disease (pmHD), which is associated with early caudate nucleus atrophy, and controls. Each test had 80 trials during which subjects were asked to remember 2 locations over 1-sec delays. The only difference between these otherwise identical tests was that locations could only be coded in self-based or landmark-based coordinates. We applied a multiatlas-based segmentation algorithm and computed point-wise Jacobian determinants to measure regional variations in caudate and hippocampal volumes from 3T MRI. As predicted, the pmHD patients were significantly more impaired on egocentric working memory. Only egocentric accuracy correlated with caudate volumes, specifically the dorsolateral caudate head, right more than left, a region that receives dense efferents from dorsolateral prefrontal cortex. In contrast, only allocentric accuracy correlated with hippocampal volumes, specifically intermediate and posterior regions that connect strongly with parahippocampal and posterior parietal cortices. These results indicate that the distinction between egocentric and allocentric navigation applies to working memory. The dorsolateral caudate is important for egocentric working memory, which can explain the disproportionate impairment in pmHD. Allocentric working memory, in contrast, relies on the hippocampus and is relatively spared in pmHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treating and Downstaging Hepatocellular Carcinoma in the Caudate Lobe with Yttrium-90 Radioembolization

Energy Technology Data Exchange (ETDEWEB)

Ibrahim, Saad M. [Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology (United States); Kulik, Laura [Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Hepatology (United States); Baker, Talia [Northwestern University Feinberg School of Medicine, Division of Transplant Surgery (United States); Ryu, Robert K. [Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology (United States); Mulcahy, Mary F. [Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center (United States); Abecassis, Michael [Northwestern University Feinberg School of Medicine, Division of Transplant Surgery (United States); Salem, Riad; Lewandowski, Robert J., E-mail: r-lewandowski@northwestern.edu [Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology (United States)

2012-10-15

Purpose: This study was designed to determine the technical feasibility, safety, efficacy, and potential to downstage patients to within transplantation criteria when treating patients with hepatocellular carcinoma (HCC) of the caudate lobe using Y90 radioembolization. Methods: During a 4-year period, 8 of 291 patients treated with radioembolization for unresectable HCC had disease involving the caudate lobe. All patients were followed for treatment-related clinical/biochemical toxicities, serum tumor marker response, and treatment response. Imaging response was assessed with the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) classification schemes. Pathologic response was reported as percent necrosis at explantation. Results: Caudate lobe radioembolization was successfully performed in all eight patients. All patients presented with both cirrhosis and portal hypertension. Half were United Network for Organ Sharing (UNOS) stage T3 (n = 4, 50%). Fatigue was reported in half of the patients (n = 4, 50%). One (13%) grade 3/4 bilirubin toxicity was reported. One patient (13%) showed complete tumor response by WHO criteria, and three patients (38%) showed complete response using EASL guidelines. Serum AFP decreased by more than 50% in most patients (n = 6, 75%). Four patients (50%) were UNOS downstaged from T3 to T2, three of who underwent transplantation. One specimen showed histopathologic evidence of 100% complete necrosis, and two specimens demonstrated greater than 50% necrosis. Conclusions: Radioembolization with yttrium-90 appears to be a feasible, safe, and effective treatment option for patients with unresectable caudate lobe HCC. It has the potential to downstage patients to transplantation.

Striatal dopamine D2/3 receptor-mediated neurotransmission in major depression: Implications for anhedonia, anxiety and treatment response.

Science.gov (United States)

Peciña, Marta; Sikora, Magdalena; Avery, Erich T; Heffernan, Joseph; Peciña, Susana; Mickey, Brian J; Zubieta, Jon-Kar

2017-10-01

Dopamine (DA) neurotransmission within the brain's reward circuit has been implicated in the pathophysiology of depression and in both, cognitive and pharmacological mechanisms of treatment response. Still, a direct relationship between measures of DA neurotransmission and reward-related deficits in patients with depression has not been demonstrated. To gain insight into the symptom-specific alterations in the DA system in patients with depression, we used positron emission tomography (PET) and the D 2/3 receptor-selective radiotracer [ 11 C]raclopride in twenty-three non-smoking un-medicated Major Depressive Disorder (MDD) patients and sixteen healthy controls (HC). We investigated the relationship between D 2/3 receptor availability and baseline measures of depression severity, anxiety, anhedonia, and cognitive and pharmacological mechanisms of treatment response. We found that, compared to controls, patients with depression showed greater D 2/3 receptor availability in several striatal regions, including the bilateral ventral pallidum/nucleus accumbens (vPAL/NAc), and the right ventral caudate and putamen. In the depressed sample, D 2/3 receptor availability in the caudal portion of the ventral striatum (NAc/vPAL) correlated with higher anxiety symptoms, whereas D 2/3 receptor availability in the rostral area of the ventral striatum correlated negatively with the severity of motivational anhedonia. Finally, MDD non-remitters showed greater baseline anxiety, greater D 2/3 availability in the NAc/vPAL, and greater placebo-induced DA release in the bilateral NAc. Our results demonstrate abnormally high D 2/3 receptor availability in the ventral striatum of patients with MDD, which seem to be associated with comorbid anxiety symptoms and lack of response to antidepressants. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Long-term polarization of microglia upon alpha-synuclein overexpression in nonhuman primates

DEFF Research Database (Denmark)

Barkholt, Pernille; Sanchez-Guajardo, Vanesa Maria; Kirik, Denis

2012-01-01

We have previously shown that persistent ﰇ-sy- nuclein overexpression in ventral midbrain of marmoset leads to a distinctive neurodegenerative process and motor defects. The neurodegeneration was confined to caudate putamen dopaminergic fibers in animals overexpressing wild-type (wt) ﰇ-synuclein....

Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson's disease with and without dementia assessed using 123I-FP-CIT SPECT

International Nuclear Information System (INIS)

Colloby, Sean J.; McKeith, Ian G.; O'Brien, John T.; Williams, E. David; Burn, David J.; Lloyd, Jim J.

2005-01-01

The objective of this study was to investigate the rate of progression of nigrostriatal dopaminergic loss in subjects with dementia with Lewy bodies (DLB), Parkinson's disease (PD) and PD with dementia (PDD) using serial 123 I-FP-CIT SPECT imaging. We hypothesised that striatal rates of decline in patients would be greater than in controls, and that DLB and PDD would show similar rates, reflecting the similarity in neurobiological mechanisms of dopaminergic loss between the two disorders. We studied 20 patients with DLB, 20 with PD, 15 with PDD and 22 healthy age-matched controls. Semi-automated region of interest (ROI) analysis was performed on both baseline and repeat scans for each subject and mean striatal uptake ratios (caudate, anterior and posterior putamen) were calculated. Rates of decline in striatal binding between groups were assessed using ANCOVA. Significant differences between patients and controls were observed in caudate (DLB, PD, PDD, p≤0.01), anterior putamen (DLB, PDD, p≤0.05; PD, p=0.07) and posterior putamen (DLB, PD, PDD, p<0.006). Rates of decline were similar between DLB, PD and PDD. (orig.)

Test-retest reproducibility of dopamine D{sub 2/3} receptor binding in human brain measured by PET with [{sup 11}C]MNPA and [{sup 11}C]raclopride

Energy Technology Data Exchange (ETDEWEB)

Kodaka, Fumitoshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Ito, Hiroshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); National Institute of Radiological Sciences, Biophysics Program, Molecular Imaging Center, Chiba (Japan); Kimura, Yasuyuki; Fujie, Saori; Takano, Harumasa; Fujiwara, Hironobu; Sasaki, Takeshi; Suhara, Tetsuya [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Nakayama, Kazuhiko [Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Halldin, Christer; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden)

2013-04-15

Dopamine D{sub 2/3} receptors (D{sub 2/3}Rs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D{sub 2/3} {sup HIGH}), which has a high affinity for endogenous dopamine, and low-affinity state (D{sub 2/3} {sup LOW}). The density of D{sub 2/3} {sup HIGH} can be measured with (R)-2-{sup 11}CH{sub 3}O-N-n-propylnorapomorphine ([{sup 11}C]MNPA), while total density of D{sub 2/3} {sup HIGH} and D{sub 2/3} {sup LOW} (D{sub 2/3}Rs) can be measured with [{sup 11}C]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential (BP) of [{sup 11}C]MNPA to that of [{sup 11}C]raclopride ([{sup 11}C]MNPA/[{sup 11}C]raclopride) may reflect the proportion of the density of D{sub 2/3} {sup HIGH} to that of D{sub 2/3}Rs. In the caudate and putamen, [{sup 11}C]MNPA/[{sup 11}C]raclopride reflects the proportion of the density of D{sub 2} {sup HIGH} to that of D{sub 2}Rs. To evaluate the reliability of the PET paradigm with [{sup 11}C]MNPA and [{sup 11}C]raclopride, we investigated the test-retest reproducibility of non-displaceable BP (BP{sub ND}) measured with [{sup 11}C]MNPA and of [{sup 11}C]MNPA/[{sup 11}C]raclopride in healthy humans. Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [{sup 11}C]MNPA and [{sup 11}C]raclopride scans. BP{sub ND} values in the caudate and putamen were calculated. Test-retest reproducibility of BP{sub ND} of [{sup 11}C]MNPA and [{sup 11}C]MNPA/[{sup 11}C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). The absolute variability of [{sup 11}C]MNPA BP{sub ND} was 5.30 {+-} 3.96 % and 12.3 {+-} 7.95 % and the ICC values of [{sup 11}C]MNPA BP{sub ND} were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [{sup 11}C]MNPA/[{sup 11}C]raclopride was 6.11 {+-} 3.68 % and 11.60 {+-} 5.70 % and the ICC values of [{sup

Grey matter morphological anomalies in the caudate head in first-episode psychosis patients with delusions of reference.

Science.gov (United States)

Tao, Haojuan; Wong, Gloria H Y; Zhang, Huiran; Zhou, Yuan; Xue, Zhimin; Shan, Baoci; Chen, Eric Y H; Liu, Zhening

2015-07-30

Delusions of reference (DOR) are theoretically linked with aberrant salience and associative learning. Previous studies have shown that the caudate nucleus plays a critical role in the cognitive circuits of coding prediction errors and associative learning. The current study aimed at testing the hypothesis that abnormalities in the caudate nucleus may be involved in the neuroanatomical substrate of DOR. Structural magnetic resonance imaging of the brain was performed in 44 first-episode psychosis patients (with diagnoses of schizophrenia or schizophreniform disorder) and 25 healthy controls. Patients were divided into three groups according to symptoms: patients with DOR as prominent positive symptom; patients with prominent positive symptoms other than DOR; and patients with minimal positive symptoms. All groups were age-, gender-, and education-matched, and patient groups were matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to identify group differences in grey matter density. Relationships were explored between grey matter density and DOR. Patients with DOR were found to have reduced grey matter density in the caudate compared with patients without DOR and healthy controls. Grey matter density values of the left and right caudate head were negatively correlated with DOR severity. Decreased grey matter density in the caudate nucleus may underlie DOR in early psychosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neural mechanisms underlying motivation of mental versus physical effort.

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Liane Schmidt

2012-02-01

Full Text Available Mental and physical efforts, such as paying attention and lifting weights, have been shown to involve different brain systems. These cognitive and motor systems, respectively, include cortical networks (prefronto-parietal and precentral regions as well as subregions of the dorsal basal ganglia (caudate and putamen. Both systems appeared sensitive to incentive motivation: their activity increases when we work for higher rewards. Another brain system, including the ventral prefrontal cortex and the ventral basal ganglia, has been implicated in encoding expected rewards. How this motivational system drives the cognitive and motor systems remains poorly understood. More specifically, it is unclear whether cognitive and motor systems can be driven by a common motivational center or if they are driven by distinct, dedicated motivational modules. To address this issue, we used functional MRI to scan healthy participants while performing a task in which incentive motivation, cognitive, and motor demands were varied independently. We reasoned that a common motivational node should (1 represent the reward expected from effort exertion, (2 correlate with the performance attained, and (3 switch effective connectivity between cognitive and motor regions depending on task demand. The ventral striatum fulfilled all three criteria and therefore qualified as a common motivational node capable of driving both cognitive and motor regions of the dorsal striatum. Thus, we suggest that the interaction between a common motivational system and the different task-specific systems underpinning behavioral performance might occur within the basal ganglia.

Frontal-striatum dysfunction during reward processing: Relationships to amotivation in schizophrenia.

Science.gov (United States)

Chung, Yu Sun; Barch, Deanna M

2016-04-01

Schizophrenia is characterized by deficits of context processing, thought to be related to dorsolateral prefrontal cortex (DLPFC) impairment. Despite emerging evidence suggesting a crucial role of the DLPFC in integrating reward and goal information, we do not know whether individuals with schizophrenia can represent and integrate reward-related context information to modulate cognitive control. To address this question, 36 individuals with schizophrenia (n = 29) or schizoaffective disorder (n = 7) and 27 healthy controls performed a variant of a response conflict task (Padmala & Pessoa, 2011) during fMRI scanning, in both baseline and reward conditions, with monetary incentives on some reward trials. We used a mixed state-item design that allowed us to examine both sustained and transient reward effects on cognitive control. Different from predictions about impaired DLPFC function in schizophrenia, we found an intact pattern of increased sustained DLPFC activity during reward versus baseline blocks in individuals with schizophrenia at a group level but blunted sustained activations in the putamen. Contrary to our predictions, individuals with schizophrenia showed blunted cue-related activations in several regions of the basal ganglia responding to reward-predicting cues. Importantly, as predicted, individual differences in anhedonia/amotivation symptoms severity were significantly associated with reduced sustained DLPFC activation in the same region that showed overall increased activity as a function of reward. These results suggest that individual differences in motivational impairments in schizophrenia may be related to dysfunction of the DLPFC and striatum in motivationally salient situations. (c) 2016 APA, all rights reserved).

Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice

DEFF Research Database (Denmark)

Licht, Cecilie Löe; Kirkegaard, Lisbeth; Zueger, Maha

2010-01-01

. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen...

Urethritis due to corynebacterium striatum: An emerging germ.

Science.gov (United States)

Frikh, Mohammed; El Yaagoubi, Imad; Lemnouer, Abdelhay; Elouennass, Mostafa

2015-01-01

Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is part of mucous and skin flora. It has been considered as a causative agent of many infections in intensive care, neurology, traumatology and urology, but was never implicated in non-gonococcal urethritis. We report the case of a nosocomial urethritis due to Corynebacterium striatum following resection of an intrameatus condyloma.

Clinical Significance of F 18 FP CIT Dual Time Point PET Imaging in Idiopathic Parkinson's Disease

International Nuclear Information System (INIS)

Oh, Jin Kyoung; Yoo, Ik Dong; Seo, Ye Young; Chung, Youg An; Yoo, Ie Ryung; Kim, Sung Hoon; Song, In Uk

2011-01-01

The purpose of this study was to investigate the diagnostic value of dual time point F 18 FP CIT PET imaging in idiopathic Parkinson's disease (PD). Twenty four patients with PD (mean age 69.6) and 18 healthy people (mean age 70.26) underwent two sequential PET/CT scans (dual time point imaging) at 90 and 210 min after F 18 FP CIT injection. Tracer activity of region of interest was measured in the caudate, putamen and a reference region in the brain from both time points. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were obtained in the control group. The percent change in tracer activity between 90 and 210 min images was calculated. The SOR values and the percent change in tracer activity were compared between the patients and healthy control group. The SOR values for the caudate, anterior and posterior putamen at both 90 and 210 min images were significantly reduced in the patients with PD. The lowest P value was obtained for the anterior and posterior putamen (p<0.001) at both time points. There were significant differences of the percent change in tracer activity for the anterior and posterior putamen in the two groups (p=0.01) F 18 FP CIT PET scans at 90 and 210 min after injection are both able to diagnose PD. Therefore, the 90 min image by itself in sufficient for diagnosing PD.

Comparison of the performance of {sup 18}F-FP-CIT brain PET/MR and simultaneous PET/CT: A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Kwon, Sang Don; Chun, Kyung Ah [Dept. of Nuclear Medicine, Yeungnam University Hospital, Daegu (Korea, Republic of)

2016-09-15

{sup 18}F-FP-CIT [{sup 1'}8F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane] has been well established and used for the differential diagnosis of atypical parkinsonian disorders. Recently, combined positron emission tomography (PET)/magnetic resonance (MR) was proposed as a viable alternative to PET/computed tomography (CT). The aim of this study was to compare the performances of conventional {sup 18}F-FP-CIT brain PET/CT and simultaneous PET/MR by visual inspection and quantitative analysis. Fifteen consecutive patients clinically suspected of having Parkinson's disease were recruited for the study.{sup 18}F-FP-CIT PET was performed during PET/CT and PET/MR. PET/CT image acquisition was started 90 min after intravenous injection of {sup 18}F-FP-CIT and then PET/MR images were acquired. Dopamine transporter (DAT) density in bilateral striatal subregions was assessed visually. Quantitative analyses were performed on bilateral striatal volumes of interest (VOIs) using average standardized uptake values (SUVmeans). Intraclass correlation coefficients (ICCs) and their 95 % confidence intervals (CIs) were assessed to compare PET/CT and PET/MR data. Bland-Altman plots were drawn to perform method-comparisons. All subjects showed a preferential decrease in DAT binding in the posterior putamen (PP), with relative sparing of the ventral putamen (VP). Bilateral striatal subregional binding ratio (BR) determined PET/CT and PET/MR demonstrated close interequipment correspondence (BRright caudate - ICC, 0.944; 95 % CI, 0.835-0.981, BRleft caudate - ICC, 0.917; 95 % CI, 0.753-0.972, BRright putamen - ICC, 0.976; 95 % CI, 0.929-0.992 and BRleft putamen - ICC, 0.970; 95 % CI, 0.911-0.990, respectively), and Bland-Altman plots showed interequipment agreement between the two modalities. It is known that MR provides more information about anatomical changes associated with brain diseases and to enable the anatomical allocations of

Spectrum of MRI findings in 58 patients with methanol intoxication: Long-term visual and neurological correlation

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Sahar M. Elkhamary

2016-09-01

Conclusion: Spectrum of residual MRI Findings in patients who survived methanol poisoning included bilateral optic nerve atrophy and enhancement, bilateral putamen and caudate necrosis as well as subcortical white matter high SI at T2WI. Diffusion WI did not have additional value in chronic stage.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

In response to hypoxia, tissues have to implement numerous mechanisms to enhance oxygen delivery, including the activation of angiogenesis. This work investigates the angiogenic response of the hypoxic caudate putamen after several recovery times. Adult Wistar rats were submitted to acute hypoxia and analysed after ...

75 FR 24428 - Spirodiclofen; Pesticide Tolerances

Science.gov (United States)

2010-05-05

... observed at terminal sacrifice in the chronic toxicity study. Cytoplasmic vacuolation in the adrenal cortex... mg/ kg/day; caudate putamen, parietal cortex, hippocampal gyrus, and dentate gyrus); there was no.... 601 et seq.) do not apply. This final rule directly regulates growers, food processors, food handlers...

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

On direct comparison of the two groups, Fl subjects showed additional activation in parts of primary visual cortex, thalamus, cerebellum, inferior and middle frontal gyrus. Conversely, FDs showed greater activation in inferior frontal gyms, precentral gyms, putamen, caudate nucleus and superior parietal lobule as compared ...

Multi-modal neuroimaging in premanifest and early Huntington's disease: 18 month longitudinal data from the IMAGE-HD study.

Science.gov (United States)

Domínguez D, Juan F; Egan, Gary F; Gray, Marcus A; Poudel, Govinda R; Churchyard, Andrew; Chua, Phyllis; Stout, Julie C; Georgiou-Karistianis, Nellie

2013-01-01

IMAGE-HD is an Australian based multi-modal longitudinal magnetic resonance imaging (MRI) study in premanifest and early symptomatic Huntington's disease (pre-HD and symp-HD, respectively). In this investigation we sought to determine the sensitivity of imaging methods to detect macrostructural (volume) and microstructural (diffusivity) longitudinal change in HD. We used a 3T MRI scanner to acquire T1 and diffusion weighted images at baseline and 18 months in 31 pre-HD, 31 symp-HD and 29 controls. Volume was measured across the whole brain, and volume and diffusion measures were ascertained for caudate and putamen. We observed a range of significant volumetric and, for the first time, diffusion changes over 18 months in both pre-HD and symp-HD, relative to controls, detectable at the brain-wide level (volume change in grey and white matter) and in caudate and putamen (volume and diffusivity change). Importantly, longitudinal volume change in the caudate was the only measure that discriminated between groups across all stages of disease: far from diagnosis (>15 years), close to diagnosis (fractional anisotropy, FA), only longitudinal FA change was sensitive to group differences, but only after diagnosis. These findings further confirm caudate atrophy as one of the most sensitive and early biomarkers of neurodegeneration in HD. They also highlight that different tissue properties have varying schedules in their ability to discriminate between groups along disease progression and may therefore inform biomarker selection for future therapeutic interventions.

Gender differences in brain activity toward unpleasant linguistic stimuli concerning interpersonal relationships: an fMRI study.

Science.gov (United States)

Shirao, Naoko; Okamoto, Yasumasa; Okada, Go; Ueda, Kazutaka; Yamawaki, Shigeto

2005-10-01

Women are more vulnerable to psychosocial stressors such as interpersonal conflicts than men, and are more susceptible to some psychiatric disorders. We hypothesized that there are differences in the brain activity of men and women while perceiving unpleasant linguistic stimuli concerning interpersonal relationships, and that they underlie the different sensitivity toward these stressful stimuli. We carried out a functional magnetic resonance imaging (fMRI) study on 13 young female adults and 13 young male adults who performed an emotional decision task including sets of unpleasant words concerning interpersonal relationships and sets of neutral words. In the women, the unpleasant words more significantly activated the bilateral caudate nuclei and left putamen than the neutral words. However, among the men, there was no difference in the level of activation of any brain area induced by the unpleasant or neutral word stimuli. Upon performing the task, there was a significant gender difference in brain activation. Moreover, among the female subjects, the activation in the bilateral caudate nuclei and left thalamus was negatively correlated with the average rating of pleasantness of the words concerning interpersonal conflicts by the subject. These results demonstrate gender differences in brain activity in processing unpleasant linguistic stimuli related to interpersonal conflicts. Our data suggest that the bilateral caudate nuclei and left putamen play an important role in the perception of words concerning interpersonal conflicts in women. The bilateral caudate nuclei and left thalamus may regulate a woman's sensitivity to unpleasant information about interpersonal difficulties.

Cocaine exposure shifts the balance of associative encoding from ventral to dorsolateral striatum

Directory of Open Access Journals (Sweden)

Yuji Takahashi

2007-12-01

Full Text Available Both dorsal and ventral striatum are implicated in the "habitization" of behavior that occurs in addiction. Here we examined the effect of cocaine exposure on associative encoding in these two regions. Neural activity was recorded during go/no-go discrimination learning and reversal. Activity in ventral striatum developed and reversed rapidly, tracking the valence of the predicted outcome, whereas activity in dorsolateral striatum developed and reversed more slowly, tracking discriminative responding. This difference is consistent with the putative roles of these two areas in promoting habit-like behavior. Dorsolateral striatum has been directly implicated in habit or stimulus response learning, whereas ventral striatum appears to be involved indirectly by allowing cues associated with reward to exert a general motivational influence on responding. Interestingly cocaine exposure did not uniformly enhance processing across both regions. Instead cocaine reduced the degree and flexibility of cue-evoked firing in ventral striatum while marginally enhanced cue-selective firing in dorsolateral striatum. Thus cocaine exposure causes regionally specific effects on neural processing in striatum; these effects may promote the habitization of behavior by shifting control from ventral to dorsolateral regions.

D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride

International Nuclear Information System (INIS)

Farde, L.; Wiesel, F.A.; Stone-Elander, S.; Halldin, C.; Nordstroem, A.L.H.; Hall, H.; Sedvall, G.

1990-01-01

Several groups have reported increased densities of D2 dopamine receptors in the basal ganglia of schizophrenic brains postmortem. The significance of this finding has been questioned, since an upregulation of receptor number may be a neuronal response to neuroleptic drug treatment. We have used positron emission tomography and [ 11 C]raclopride to examine central D2 dopamine receptor binding in 20 healthy subjects and 18 newly admitted, young, neuroleptic-naive patients with schizophrenia. An in vivo saturation procedure was applied for quantitative determination of D2 dopamine receptor density (Bmax) and affinity (Kd). When the two groups were compared, no significant difference in Bmax or Kd values was found in the putamen or the caudate nucleus. The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was thus not supported by the present findings. In the patients but not in the healthy controls, significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus

Sex linked recessive dystonia parkinsonism of Panay, Philippines (XDP).

Science.gov (United States)

Lee, L V; Munoz, E L; Tan, K T; Reyes, M T

2001-12-01

Sex linked dystonia parkinsonism (XDP), also referred to as "lubag" in American literature, was described in 1975 occurring endemically in Panay, Philippines. It is an adult onset, sex linked, predominantly male, severe, progressive movement disorder with high penetrance and a high frequency of generalisation. The movement disorder is characterised by dystonic movements, usually starting in the 3rd or 4th decade, spreading to generalisation within two to five years. The dystonia coexists or is replaced by parkinsonism usually beyond the 10th year of illness. No treatment has been found to be effective. Neuroimaging shows caudate and putamenal atrophy in patients reaching the parkinsonian stage. Neuropathology reveals pronounced atrophy of the caudate and putamen, mostly in the cases with long standing illness. The sex linked pattern of inheritance has been established. Genetic studies have located the affected gene (DYT3) to Xq13.1, with one group mapping the XDP gene to a < 350 kb locus in the DXS 7117-DXS 559 region.

125I-iomazenil - benzodiazepine receptor binding and serum corticosterone level during psychological stress in a rat model

International Nuclear Information System (INIS)

Fukumitsu, Nobuyoshi; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

2004-01-01

To test the hypothesis that benzodiazepine receptor density decreases in response to stress, we correlated 125 I-iomazenil ( 125 I-IMZ) binding with serum corticosterone levels in a rat model. Wistar male rats were divided into four groups; control group (CON, 10 rats), no physical or psychological stress; and one-, three-, and five-day stress groups of 12 rats each (1-DAY, 3-DAY, and 5-DAY, respectively), receiving psychological stress for the given number of days. Psychological stress were given to rats with a communication box. The standardized uptake value (SUV) of 125 I-iomazenil of the 3-DAY and 5-DAY showed that 125 I-iomazenil - benzodiazepine receptor binding was significantly reduced in the cortices, accumbens nuclei, amygdala and caudate putamen (p 125 I-IMZ is a useful radioligand to reflect received stress and its binding in the cortices, accumbens nuclei, amygdala and caudate putamen is strongly affected by psychological stress

Haloperidol-induced striatal Nur77 expression in a non-human primate model of tardive dyskinesia

Science.gov (United States)

Mahmoudi, Souha; Blanchet, Pierre J.; Lévesque, Daniel

2015-01-01

Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication arising in patients chronically exposed to antipsychotic drugs. As several modern (so-called atypical) antipsychotic drugs are common offenders, the widening clinical indications for prescription as well as exposure of vulnerable individuals, TD will remain a significant drug-induced unwanted side effect. In addition, the pathophysiology of TD remains elusive and therapeutics difficult. Based on rodent experiments, we have previously shown that the transcriptional factor Nur77 (also known as NGFI-B or Nr4a1) is induced in the striatum following antipsychotic drug exposure as part of a long-term neuroadaptive process. To confirm this, we exposed adult capuchin (Cebus apella) monkeys to prolonged treatments with haloperidol (median 18.5 months, N=11) or clozapine (median 6 months, N=6). Six untreated animals were used as controls. Six haloperidol-treated animals developed mild TD movements similar to those found in humans. No TD was observed in the clozapine group. Postmortem analysis of Nur77 expression measured by in situ hybridization revealed a stark contrast between the two drugs, as Nur77 mRNA levels in the caudate-putamen were strongly upregulated in animals exposed to haloperidol while spared following clozapine treatment. Interestingly, within the haloperidol-treated group, TD-free animals showed higher Nur77 expression in putamen subterritories compared to dyskinetic animals. This suggests that Nur77 expression might be associated with a reduced risk to TD in this experimental model and could provide a novel target for drug intervention. PMID:23551242

Striatal abnormalities in trichotillomania: A multi-site MRI analysis

Directory of Open Access Journals (Sweden)

Masanori Isobe

2018-01-01

Full Text Available Trichotillomania (hair-pulling disorder is characterized by the repetitive pulling out of one's own hair, and is classified as an Obsessive-Compulsive Related Disorder. Abnormalities of the ventral and dorsal striatum have been implicated in disease models of trichotillomania, based on translational research, but direct evidence is lacking. The aim of this study was to elucidate subcortical morphometric abnormalities, including localized curvature changes, in trichotillomania. De-identified MRI scans were pooled by contacting authors of previous peer-reviewed studies that examined brain structure in adult patients with trichotillomania, following an extensive literature search. Group differences on subcortical volumes of interest were explored (t-tests and localized differences in subcortical structure morphology were quantified using permutation testing. The pooled sample comprised N = 68 individuals with trichotillomania and N = 41 healthy controls. Groups were well-matched in terms of age, gender, and educational levels. Significant volumetric reductions were found in trichotillomania patients versus controls in right amygdala and left putamen. Localized shape deformities were found in bilateral nucleus accumbens, bilateral amygdala, right caudate and right putamen. Structural abnormalities of subcortical regions involved in affect regulation, inhibitory control, and habit generation, play a key role in the pathophysiology of trichotillomania. Trichotillomania may constitute a useful model through which to better understand other compulsive symptoms. These findings may account for why certain medications appear effective for trichotillomania, namely those modulating subcortical dopamine and glutamatergic function. Future work should study the state versus trait nature of these changes, and the impact of treatment.

Smoking-induced dopamine release studied with [11C]raclopride PET

International Nuclear Information System (INIS)

Kim, Yu Kyeong; Cho, Sang Soo; Lee, Do Hoon

2005-01-01

It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with and regulates the activation of the dopaminergic neuron. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [ 11 C]raclopride. Four male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.3±2.6 years) were enrolled in this study. Dopamine D2 receptor radioligand, [ 11 C]raclopride was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurements of plasma nicotine levels were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as striatal-cerebellar/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean change in binding potential between the baseline and smoking in caudate, Putamen and ventral striatum was 3.7 % , 4.0 % and 8.6 %, respectively. This indicated the striatal dopamine release by smoking. The reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (r 2 =0.91, p=0.04). These data demonstrate that in vivo imaging with [ 11 C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking

Carbon-11 labeled papaverine as a PET tracer for imaging PDE10A: radiosynthesis, in vitro and in vivo evaluation

Energy Technology Data Exchange (ETDEWEB)

Tu Zhude [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)], E-mail: tuz@mir.wustl.edu; Xu Jinbin; Jones, Lynne A.; Li Shihong; Mach, Robert H. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)

2010-05-15

Papaverine, 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, a specific inhibitor of phosphodiesterase (PDE) 10A with IC{sub 50} values of 36 nM for PDE10A, 1,300 nM for PDE3A and 320 nM for PDE4D, has served as a useful pharmaceutical tool to study the physiological role of PDE10A. Here, we report the radiosynthesis of [{sup 11}C]papaverine and the in vitro and in vivo evaluation of [{sup 11}C]papaverine as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of papaverine with {sup 11}C was achieved by O-methylation of the corresponding des-methyl precursor with [{sup 11}C]methyl iodide. [{sup 11}C]papaverine was obtained with {approx}70% radiochemical yield and a specific activity >10 Ci/{mu}mol. In vitro autoradiography studies of rat and monkey brain sections revealed selective binding of [{sup 11}C]papaverine to PDE10A enriched regions: the striatum of rat brain and the caudate and putamen of rhesus monkey brain. The biodistribution of [{sup 11}C]papaverine in rats at 5 min demonstrated an initially higher accumulation in striatum than in other brain regions, however the washout was rapid. MicroPET imaging studies in rhesus macaques similarly displayed initial specific uptake in the striatum with very rapid clearance of [{sup 11}C]papaverine from brain. Our initial evaluation suggests that despite papaverine's utility for in vitro studies and as a pharmaceutical tool, [{sup 11}C]papaverine is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Analogs of papaverine having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

Smoking-induced dopamine release studied with [{sup 11}C]raclopride PET

Energy Technology Data Exchange (ETDEWEB)

Kim, Yu Kyeong; Cho, Sang Soo; Lee, Do Hoon [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

2005-07-01

It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with and regulates the activation of the dopaminergic neuron. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [{sup 11}C]raclopride. Four male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.3{+-}2.6 years) were enrolled in this study. Dopamine D2 receptor radioligand, [{sup 11}C]raclopride was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurements of plasma nicotine levels were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as striatal-cerebellar/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean change in binding potential between the baseline and smoking in caudate, Putamen and ventral striatum was 3.7 % , 4.0 % and 8.6 %, respectively. This indicated the striatal dopamine release by smoking. The reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (r{sup 2}=0.91, p=0.04). These data demonstrate that in vivo imaging with [{sup 11}C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.

Dopamine release in ventral striatum of pathological gamblers losing money

DEFF Research Database (Denmark)

Linnet, J; Peterson, E; Doudet, D J

2010-01-01

Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money. Objective: To investigate dopaminergic neurotransmission in relation to monetary reward and punishment in pathological gambling. Pathological gamblers (PG) often continue...... gambling despite losses, known as 'chasing one's losses'. We therefore hypothesized that losing money would be associated with increased dopamine release in the ventral striatum of PG compared with healthy controls (HC). Method: We used Positron Emission Tomography (PET) with [(11)C]raclopride to measure...... dopamine release in the ventral striatum of 16 PG and 15 HC playing the Iowa Gambling Task (IGT). Results: PG who lost money had significantly increased dopamine release in the left ventral striatum compared with HC. PG and HC who won money did not differ in dopamine release. Conclusion: Our findings...

Noradrenergic modulation of neural erotic stimulus perception.

Science.gov (United States)

Graf, Heiko; Wiegers, Maike; Metzger, Coraline Danielle; Walter, Martin; Grön, Georg; Abler, Birgit

2017-09-01

We recently investigated neuromodulatory effects of the noradrenergic agent reboxetine and the dopamine receptor affine amisulpride in healthy subjects on dynamic erotic stimulus processing. Whereas amisulpride left sexual functions and neural activations unimpaired, we observed detrimental activations under reboxetine within the caudate nucleus corresponding to motivational components of sexual behavior. However, broadly impaired subjective sexual functioning under reboxetine suggested effects on further neural components. We now investigated the same sample under these two agents with static erotic picture stimulation as alternative stimulus presentation mode to potentially observe further neural treatment effects of reboxetine. 19 healthy males were investigated under reboxetine, amisulpride and placebo for 7 days each within a double-blind cross-over design. During fMRI static erotic picture were presented with preceding anticipation periods. Subjective sexual functions were assessed by a self-reported questionnaire. Neural activations were attenuated within the caudate nucleus, putamen, ventral striatum, the pregenual and anterior midcingulate cortex and in the orbitofrontal cortex under reboxetine. Subjective diminished sexual arousal under reboxetine was correlated with attenuated neural reactivity within the posterior insula. Again, amisulpride left neural activations along with subjective sexual functioning unimpaired. Neither reboxetine nor amisulpride altered differential neural activations during anticipation of erotic stimuli. Our results verified detrimental effects of noradrenergic agents on neural motivational but also emotional and autonomic components of sexual behavior. Considering the overlap of neural network alterations with those evoked by serotonergic agents, our results suggest similar neuromodulatory effects of serotonergic and noradrenergic agents on common neural pathways relevant for sexual behavior. Copyright © 2017 Elsevier B.V. and

Drug-related cue induced craving and the correlation between the activation in nucleus accumbens and drug craving: a fMRI study on heroin addicts

International Nuclear Information System (INIS)

Wang Yarong; Yang Lanying; Li Qiang; Yang Weichuan; Du Pang; Wang Wei

2010-01-01

Objective: To explore the neural mechanism underlying the craving of heroin addicts induced by picture-cue and the correlation between the brain activation degree in nucleus accumbens (NAc)/ the ventral striatum and the scores of patients self-report craving. Methods: Twelve active heroin addicts and 12 matched healthy controls underwent fMRI scan while viewing drug-related pictures and neutral pictures presented in a block design paradigm after anatomical scanning in GE 3.0 T scanner. The fMRI data were analyzed with SPM 5. The change of craving scores was tested by Wilcoxon signed rank test. The Pearson correlation between the activation of NAc/the ventral striatum and the heroin craving score was tested by SPSS 13.0. Results: The craving scores of heroin addicts ranged from 0 to 3.70 (median 0.15) before exposed to drug cue and 0 to 5.10 (median 3.25) after viewing drug-related pictures and showed statistical significance (Z=-2.666, P<0.05). There were 16 activated brain areas when heroin dependent patients exposed to visual drug-related cue vs. neutral visual stimuli. The activation brain regions belonged to two parts, one was limbic system (amygdale, hippocampus, putamen, anterior cingulate cortex and caudate), another was brain cortex (middle frontal cortex, inferior frontal cortex, precentral gyrus, middle temporal cortex, inferior temporal cortex, fusiform gyrus, precuneus and middle occipital gyrus). The MR signal activation magnitude of heroin addicts ranged from 0.19 to 3.50. The result displayed a significant positive correlation between the cue-induced fMRI activation in NAc/the ventral striatum and heroin craving severity (r=0.829, P<0.05). Conclusion: Heroin shared the same neural circuitry in part with other drugs of abuse for cue-induced craving, including brain reward circuitry, visualspatial attention circuit and working memory region. In addition, the dysfunction of NAc/the ventral striatum may attribute to heroin-related cue induced craving

Models for in vivo kinetic interactions of dopamine D2-neuroreceptors and 3-(2'-[18F]fluoroethyl)spiperone examined with positron emission tomography

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Bahn, M.M.; Huang, S.C.; Hawkins, R.A.; Satyamurthy, N.; Hoffman, J.M.; Barrio, J.R.; Mazziotta, J.C.; Phelps, M.E.

1989-01-01

The in vivo tracer kinetics of 3-(2'-[18F]fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics (n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant kd was found to be 0.0015 +/- 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well: this model is equivalent to model 2 with kd set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma-tissue fractional transport rate constant K1 and the net uptake constant K3 comparable to estimates using model 3 for both human and monkey studies

Ebselen (PZ-51) protects the Caudate putamen against hypoxia/ischemia induced neuronal damage.

NARCIS (Netherlands)

Knollema, S; Elting, JW; Dijkhuizen, RM; Nicolay, K; Korf, J; TerHorst, GJ

1996-01-01

Ebselen, a synthetic selenium-containing compound which exhibits glutathione peroxidase-like activity in vivo, is known for its beneficial effects on inflammation and tissue injury. Experiments were conducted to test whether ebselen dissolved in DiMethylSulfOxide (DMSO) could prevent damage in a rat

Ebselen (PZ-51) protects the caudate putamen against hypoxia/ischemia induced neuronal damage

NARCIS (Netherlands)

Knollema, S.; Elting, J.W.; Dijkhuizen, R.M.; Nicolaij, K.; Korf, J.; Horst, ter G.J.

1996-01-01

Ebselen, a synthetic selenium-containing compound which exhibits glutathione peroxidase-like activity in vivo, is known for its beneficial effects on inflammation and tissue injury. Experiments were conducted to test whether ebselen dissolved in DiMethylSulfOxide (DMSO) could prevent damage in a rat

Differentiation of dementia with lewy bodies from Alzheimer's disease using FDG PET and I-123-fluoropropyl-β-CIT SPECT

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Park, Eun Kyung; Cho, Sang Soo; Lee, Jae Sung; Kim, Jung Eun; Kim, Sang Yun; Lee, Won Woo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

2004-01-01

Dementia with Lewy bodies (DLB) shares clinical and pathological features with Alzheimer's disease (AD) and Parkinson's disease. The differentiation of DLB from these disorders poses difficulties. We compared regional cerebral metabolic impairment and dopaminergic neuronal integrity between patients with DLB and AD using FDG PET and I-123-fluoropropyl-β-CIT (FP-CIT) SPECT, respectively, as measures for differential diagnosis. Fourteen clinically diagnosed DLB patients, 15 probable AD patients, and 12 age- and gender-matched healthy controls were studied with FDG PET and FP-CIT SPECT. A voxel-wise comparison of PET images was performed using SPM99. A dopamine transporter (DAT) parameter V3 was calculated in striatal regions as (striatal VOIcerebellar VOI)/cerebellar VOI activity on SPECT images obtained 3 h after injection of 185 MBq FP-CIT. SPM analysis of PET images of DLB revealed hypometabolism bilaterally in the occipital cortices, lateral occipitotemporal gyri, cunei, caudate, and Thalami compared with controls, most pronounced in the occipital cortex compared with AD. In DLB, V3 in the caudate (1.07±0.55) and putamen (1.01±0.34) was significantly (P < 0.001) lower than in AD (2.73±0.75 and 3.17±0.88, respectively) and controls (3.00±0.45 and 3.11±0.31, respectively). There was no significant difference in striatal V3 between AD and controls. The ratio of putamen-to-caudate V3 was not significantly different between DLB (1.04±0.32) and controls (1.05±0.12), indicating that DATs in the caudate and putamen are evenly affected in DLB. In DLB, there was a significant correlation between striatal V3 and MMSE score (rho=0.97, P<0.01). These data demonstrate different biochemical features between DLB and AD, in terms of regional brain metabolism and dopaminergic neuronal integrity. Measures of the glucose metabolism in the occipital cortex and the striatal DAT density may be informative diagnostic aids to distinguish DLB from AD

Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder--a single photon emission computed tomography with [Tc(99m)]TRODAT-1 study.

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Szobot, Claudia M; Shih, Ming Chi; Schaefer, Thais; Júnior, Neivo; Hoexter, Marcelo Q; Fu, Ying Kai; Pechansky, Flávio; Bressan, Rodrigo A; Rohde, Luis A P

2008-04-15

Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc(99m)]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (pADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.

Cerebral blood flow and metabolism analysis in parkinsonian disorders; Pathologie extrapyramidale. Apport de l'imagerie de perfusion et du metabolisme (TEP, TEM)

Energy Technology Data Exchange (ETDEWEB)

Defebvre, L. [Hopital Roger Salengro, Service de Neurologie, 59 - Lille (France)

1999-12-01

Main metabolic and hemodynamic abnormalities detected by single photon emission computerized tomography and positron emission tomography in extra-pyramidal disorders are reported. In the first stage of Parkinson's disease, cortical metabolism and perfusion can be in normal range or moderately and uniformly reduced. A significant decrease may appear with the disease evolution. Marked abnormalities are observed in parkinsonian patients with dementia (subcortical dementia), involving especially the frontal cortex. A marked diffuse cortical hypo-metabolism (temporal, parietal, occipital and frontal cortex) may suggest the diagnosis of dementia with Lewy bodies, especially in case of fluctuating cognitive decline with recurrent visual hallucinations. In progressive supra-nuclear palsy, a frontal cortex hypo-metabolism is reported precociously, preceding sometimes the cognitive impairment. Metabolic pattern find in multiple system atrophy reflects dysfunction of both nigrostriatal pathways and striatum, with a decrease glucose uptake in putamen and caudate nucleus which also involves cerebellum for the patients with cerebellar syndrome. In cortico-basal degeneration, asymmetric fronto-parietal and striatal hypo-metabolism observed in the controlateral hemisphere to the clinically most affected side, constitute the main characteristic well correlated with apraxia. (author)

Computation of an MRI brain atlas from a population of Parkinson’s disease patients

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Angelidakis, L.; Papageorgiou, I. E.; Damianou, C.; Psychogios, M. N.; Lingor, P.; von Eckardstein, K.; Hadjidemetriou, S.

2017-11-01

Parkinson’s Disease (PD) is a degenerative disorder of the brain. This study presents an MRI-based brain atlas of PD to characterize associated alterations for diagnostic and interventional purposes. The atlas standardizes primarily the implicated subcortical regions such as the globus pallidus (GP), substantia nigra (SN), subthalamic nucleus (STN), caudate nucleus (CN), thalamus (TH), putamen (PUT), and red nucleus (RN). The data were 3.0 T MRI brain images from 16 PD patients and 10 matched controls. The images used were T1-weighted (T 1 w), T2-weighted (T 2 w) images, and Susceptibility Weighted Images (SWI). The T1w images were the reference for the inter-subject non-rigid registration available from 3DSlicer. Anatomic labeling was achieved with BrainSuite and regions were refined with the level sets segmentation of ITK-Snap. The subcortical centers were analyzed for their volume and signal intensity. Comparison with an age-matched control group unravels a significant PD-related T1w signal loss in the striatum (CN and PUT) centers, but approximately a constant volume. The results in this study improve MRI based PD localization and can lead to the development of novel biomarkers.

Spike-timing dependent plasticity in the striatum

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Elodie Fino

2010-06-01

Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.

Registration and Analysis of Bioelectric Activity of Sensory-Motor Cortex During the Electrical Stimulation of Nucleus Caudate in Rats

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Snežana Medenica-Milanović

2007-05-01

Full Text Available Background and purposeThe caudate circuit takes part in cognitive control of motor activity The purpose of the present work was registration and analysis of basic bioelectrical activity of ventral and dorsal sensory-motor cortex and nucleus caudate, study of the changes in EEG after nucleus caudate electrical stimulation and to identify of threshold level of electrical stimuli responsible for changes of electrical activity in registered brain area.Materials and methodsWe used 28 albino Wistar rat of both genders. After the animal fixation on stereotaxic apparatus to dry bone, the places for electrode fixation were marked. Two days after the electrodes had been implanted an EEG was registered so that the animals would adjust to the conditions and so they would repair the tissue reactions. EEG was registered with bipolar electrodes with ten-channeled apparatus. For first half an hour spontaneous activity of the brain was registered, and after that the head of nucleus caudate was stimulated with altered impulses of various voltages, frequency and duration.Results and conclusionsThreshold values of electric stimulus intensity from 3 to 5 V, frequency from 3 to 5 Hz, duration from 3 to 5 ms, by stimulation the head of nucleus caudate of rat, lead to the change of basal bioelectric activity of cerebrum. The change of bioelectric activity is firstly recorded in equilateral cortex, and with the higher intensity of the stimulus the changes overtake the contra lateral cortex.

Diagnosis of essential tremor vs. Parkinson's disease: NeuroSPECT by means of Trodat-1 Tc99m, a marker of Dopamine Transporter

International Nuclear Information System (INIS)

Mena, I.; Diaz, F.

2002-01-01

Background Information. We have recently reported that NeuroSPECT (NSP) of the Dopamine Transporter (DAT) is a highly sensitive method for early diagnosis of Parkinson's disease. Objectives. To evaluate the sensitivity of NSP of DAT in patients with essential tremor (E.T.) and compare them with parkinsonian patients (pts.) and normal controls, in order to assess the sensitivity to detect symptomatic impairment of concentration of DAT in Parkinson's Disease (PD) and normality in essential tremor, thus becoming an important diagnostic tool for this differential clinical diagnosis. Materials and Methods. The present study concerns 13 patients with essential tremor (E.T.), 20 pts. with Parkinson's Disease (P.D.). The ET pts, 5/13 were female and there mean age was 62 y. The PD pts age 62±11 years. The UPDRS V was 1, mean evolution, of 3.0 years, 5/20 were females. The average UPDRS III was 14,. They were compared with 25 healthy controls, 20/25 females, mean age was 54±14 years. The mean age of 13 E.T. pts was 60 y. (range 24-81 y). At onset of E.T. the mean age was 40 y. ( range 5-67 y.) 7 pts. were classified as sporadic tremor and 6 pts. as familial tremor. The frequency of tremor was 6.4 cycles/sec and the amplitude fluctuated between moderate and very intense. 8/13 pts suffered prolongation of postural tremor into resting tremor, while 3 of them had been diagnosed as P.D. at other Institutions. 3/13 pts had postural and brachial tremor, head tremor(5/13 pts.) voice or chin tremor in 1/13 pts. 3/13 pts suffered impairment of mild postural tremor during writing, eating or drinking. Three-dimensional images of the distribution of DAT in brain were gathered 4 hours after iv. injection of 30 mCi of Trodat-1 Tc 99m. Results. In normal controls there is maximal concentration of DAT in caudate and putamen. We establish a comparison with the occipital cortex where there is mild non specific concentration of DAT. In 13 pts. with Essential Tremor there was no significant

Demyelination of subcortical nuclei in multiple sclerosis

Science.gov (United States)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

Increased binding of [3H]apomorphine in caudate membranes after dopamine pretreatment in vitro

International Nuclear Information System (INIS)

McManus, C.; Hartley, E.J.; Seeman, P.

1978-01-01

Most patients with Parkinson's disease treated with L-dopa show a progressively deteriorating response which may possibly be attributed to an L-dopa-induced process of unknown origin. Long-term administration of dopamine-mimetic drugs to animals sometimes produces behavioural facilitation. To investigate one possible molecular mechanism of this facilitation or sensitization the effects of prolonged exposure, in vitro, of dopamine on the dopamine/neuroleptic receptors in the caudate nucleus of the calf were tested. Calf caudate homogenates pretreated with dopamine or other drugs were tested for the binding of [ 3 H]apomorphine, [ 3 H]haloperidol, 3H-WB-4101, or [ 3 H]naloxine. Pre-exposure with dopamine or noradrenaline lead to an increased binding of [ 3 H]apomorphine. The significance of the results is discussed. (author)

Loss of metabolites from monkey striatum during PET with FDOPA

DEFF Research Database (Denmark)

Cumming, P; Munk, O L; Doudet, D

2001-01-01

constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass

Science.gov (United States)

Menegas, William; Bergan, Joseph F; Ogawa, Sachie K; Isogai, Yoh; Umadevi Venkataraju, Kannan; Osten, Pavel; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2015-01-01

Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense ‘clusters’ of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs. DOI: http://dx.doi.org/10.7554/eLife.10032.001 PMID:26322384

Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations: A Resting-state Functional Magnetic Resonance Imaging Study.

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Chen, Cheng; Wang, Hui-Ling; Wu, Shi-Hao; Huang, Huan; Zou, Ji-Lin; Chen, Jun; Jiang, Tian-Zi; Zhou, Yuan; Wang, Gao-Hua

2015-12-05

Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination (AH). However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Auditory hallucinated patients group (n = 42 APG), no hallucinated patients group (n = 42 NPG) and normal controls (n = 84 NCs) were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index (degree centrality [DC]) across the entire brain networks was calculated and evaluated among three groups. DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG, the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.

The neural coding of expected and unexpected monetary performance outcomes: dissociations between active and observational learning.

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Bellebaum, C; Jokisch, D; Gizewski, E R; Forsting, M; Daum, I

2012-02-01

Successful adaptation to the environment requires the learning of stimulus-response-outcome associations. Such associations can be learned actively by trial and error or by observing the behaviour and accompanying outcomes in other persons. The present study investigated similarities and differences in the neural mechanisms of active and observational learning from monetary feedback using functional magnetic resonance imaging. Two groups of 15 subjects each - active and observational learners - participated in the experiment. On every trial, active learners chose between two stimuli and received monetary feedback. Each observational learner observed the choices and outcomes of one active learner. Learning performance as assessed via active test trials without feedback was comparable between groups. Different activation patterns were observed for the processing of unexpected vs. expected monetary feedback in active and observational learners, particularly for positive outcomes. Activity for unexpected vs. expected reward was stronger in the right striatum in active learning, while activity in the hippocampus was bilaterally enhanced in observational and reduced in active learning. Modulation of activity by prediction error (PE) magnitude was observed in the right putamen in both types of learning, whereas PE related activations in the right anterior caudate nucleus and in the medial orbitofrontal cortex were stronger for active learning. The striatum and orbitofrontal cortex thus appear to link reward stimuli to own behavioural reactions and are less strongly involved when the behavioural outcome refers to another person's action. Alternative explanations such as differences in reward value between active and observational learning are also discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Multi-modal neuroimaging in premanifest and early Huntington's disease: 18 month longitudinal data from the IMAGE-HD study.

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Juan F Domínguez D

Full Text Available IMAGE-HD is an Australian based multi-modal longitudinal magnetic resonance imaging (MRI study in premanifest and early symptomatic Huntington's disease (pre-HD and symp-HD, respectively. In this investigation we sought to determine the sensitivity of imaging methods to detect macrostructural (volume and microstructural (diffusivity longitudinal change in HD. We used a 3T MRI scanner to acquire T1 and diffusion weighted images at baseline and 18 months in 31 pre-HD, 31 symp-HD and 29 controls. Volume was measured across the whole brain, and volume and diffusion measures were ascertained for caudate and putamen. We observed a range of significant volumetric and, for the first time, diffusion changes over 18 months in both pre-HD and symp-HD, relative to controls, detectable at the brain-wide level (volume change in grey and white matter and in caudate and putamen (volume and diffusivity change. Importantly, longitudinal volume change in the caudate was the only measure that discriminated between groups across all stages of disease: far from diagnosis (>15 years, close to diagnosis (<15 years and after diagnosis. Of the two diffusion metrics (mean diffusivity, MD; fractional anisotropy, FA, only longitudinal FA change was sensitive to group differences, but only after diagnosis. These findings further confirm caudate atrophy as one of the most sensitive and early biomarkers of neurodegeneration in HD. They also highlight that different tissue properties have varying schedules in their ability to discriminate between groups along disease progression and may therefore inform biomarker selection for future therapeutic interventions.

Demyelination of subcortical nuclei in multiple sclerosis

International Nuclear Information System (INIS)

Krutenkova, E; Aitmagambetova, G; Khodanovich, M; Yarnykh, V; Bowen, J; Gangadharan, B; Henson, L; Mayadev, A; Repovic, P; Qian, P

2016-01-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus. (paper)

Ventral and Dorsal Striatum Networks in Obesity: Link to Food Craving and Weight Gain.

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Contreras-Rodríguez, Oren; Martín-Pérez, Cristina; Vilar-López, Raquel; Verdejo-Garcia, Antonio

2017-05-01

The food addiction model proposes that obesity overlaps with addiction in terms of neurobiological alterations in the striatum and related clinical manifestations (i.e., craving and persistence of unhealthy habits). Therefore, we aimed to examine the functional connectivity of the striatum in excess-weight versus normal-weight subjects and to determine the extent of the association between striatum connectivity and individual differences in food craving and changes in body mass index (BMI). Forty-two excess-weight participants (BMI > 25) and 39 normal-weight participants enrolled in the study. Functional connectivity in the ventral and dorsal striatum was indicated by seed-based analyses on resting-state data. Food craving was indicated with subjective ratings of visual cues of high-calorie food. Changes in BMI between baseline and 12 weeks follow-up were assessed in 28 excess-weight participants. Measures of connectivity in the ventral striatum and dorsal striatum were compared between groups and correlated with craving and BMI change. Participants with excess weight displayed increased functional connectivity between the ventral striatum and the medial prefrontal and parietal cortices and between the dorsal striatum and the somatosensory cortex. Dorsal striatum connectivity correlated with food craving and predicted BMI gains. Obesity is linked to alterations in the functional connectivity of dorsal striatal networks relevant to food craving and weight gain. These neural alterations are associated with habit learning and thus compatible with the food addiction model of obesity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Evaluating metabolites in patients with major depressive disorder who received mindfulness-based cognitive therapy and healthy controls using short echo MRSI at 7 Tesla.

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Li, Yan; Jakary, Angela; Gillung, Erin; Eisendrath, Stuart; Nelson, Sarah J; Mukherjee, Pratik; Luks, Tracy

2016-06-01

Our aim was to evaluate differences in metabolite levels between unmedicated patients with major depressive disorder (MDD) and healthy controls, to assess changes in metabolites in patients after they completed an 8-week course of mindfulness-based cognitive therapy (MBCT), and to exam the correlation between metabolites and depression severity. Sixteen patients with MDD and ten age- and gender-matched healthy controls were studied using 3D short echo-time (20 ms) magnetic resonance spectroscopic imaging (MRSI) at 7 Tesla. Relative metabolite ratios were estimated in five regions of interest corresponding to insula, anterior cingulate cortex (ACC), caudate, putamen, and thalamus. In all cases, MBCT reduced severity of depression. The ratio of total choline-containing compounds/total creatine (tCr) in the right caudate was significantly increased compared to that in healthy controls, while ratios of N-acetyl aspartate (NAA)/tCr in the left ACC, myo-inositol/tCr in the right insula, and glutathione/tCr in the left putamen were significantly decreased. At baseline, the severity of depression was negatively correlated with my-inositol/tCr in the left insula and putamen. The improvement in depression severity was significantly associated with changes in NAA/tCr in the left ACC. This study has successfully evaluated regional differences in metabolites for patients with MDD who received MBCT treatment and in controls using 7 Tesla MRSI.

Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort.

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Wade, Benjamin S C; Valcour, Victor G; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H; Gutman, Boris A; Thompson, Paul M

2015-01-01

Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%.

Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort

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Benjamin S.C. Wade

2015-01-01

Full Text Available Over 50% of HIV+ individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD and radial distances (RD defined on each region's surfaces. We also investigated effects of nadir CD4+ T-cell counts, viral load, time since diagnosis (TSD and cognition on subcortical morphology. Lastly, we explored whether HIV+ participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF model. The model was validated with 2-fold cross-validation. Volumes of HIV+ participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV+ people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV+ participants vs. controls, our RF model attained an area under the curve of 72%.

The impact of caudate lobe resection on margin status and outcomes in patients with hilar cholangiocarcinoma: a multi-institutional analysis from the US Extrahepatic Biliary Malignancy Consortium.

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Bhutiani, Neal; Scoggins, Charles R; McMasters, Kelly M; Ethun, Cecilia G; Poultsides, George A; Pawlik, Timothy M; Weber, Sharon M; Schmidt, Carl R; Fields, Ryan C; Idrees, Kamran; Hatzaras, Ioannis; Shen, Perry; Maithel, Shishir K; Martin, Robert C G

2018-04-01

The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma. A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes. A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival. Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation. Copyright © 2017 Elsevier Inc. All rights reserved.

Dopamine receptor and Gα(olf expression in DYT1 dystonia mouse models during postnatal development.

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Lin Zhang

Full Text Available DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated.We used Dyt1 knock out (Dyt1 KO, Dyt1 ΔGAG knock-in (Dyt1 KI, and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT or human ΔGAG mutant allele (DYT1 hMT. D1R, D2R, and Gα(olf protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60 male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14 male mice from the Dyt1 KI and KO lines. Dopamine receptor and Gα(olf protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1 KO mice.We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology.

Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate.

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Normandin, Louise; Carrier, Gaétan; Gardiner, Phillip F; Kennedy, Greg; Hazell, Alan S; Mergler, Donna; Butterworth, Roger F; Philippe, Suzanne; Zayed, Joseph

2002-09-01

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.

The meninges contribute to the conditioned taste avoidance induced by neural cooling in male rats.

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Wang, Yuan; Chambers, Kathleen C

2002-08-21

After consumption of a novel sucrose solution, temporary cooling of neural areas that mediate conditioned taste avoidance can itself induce conditioned avoidance to the sucrose. It has been suggested that this effect is either a result of inactivation of neurons in these areas or of cooling the meninges. In a series of studies, we demonstrated that cooling the outer layer of the meninges, the dura mater, does not contribute to the conditioned taste avoidance induced by cooling any of these areas. The present experiments were designed to determine whether the inner layers of the meninges are involved. If they are involved, then one would expect that cooling locations in the brain that do not mediate conditioned taste avoidance, such as the caudate putamen (CP), would induce conditioned taste avoidance as long as the meninges were cooled as well. One also would expect that cooling neural tissue without cooling the meninges would reduce the strength of the conditioned taste avoidance. Experiment 1 established that the temperature of the neural tissue and meninges around the cold probes implanted in the CP were cooled to temperatures that have been shown to block synaptic transmission. Experiment 2 demonstrated that cooling the caudate putamen and overlying cortex and meninges induced conditioned taste avoidance. In experiment 3, a circle of meninges was cut away so that the caudate putamen and overlying cortex could be cooled without cooling the meninges. The strength of the conditioned taste avoidance was substantially reduced, but it was not entirely eliminated. These data support the hypothesis that cooling the meninges contributes to the conditioned taste avoidance induced by neural cooling. They also allow the possibility that neural inactivation produces physiological changes that can induce conditioned taste avoidance. Copyright 2002 Elsevier Science B.V.

Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography

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Yanai, Kazuhiko; Tohoku Univ., Sendai; Iinuma, Kazuie; Miyabayashi, Shigeaki; Narisawa, Kuniaki; Tada, Keiya; Matsuzawa, Taiju; Tohoku Univ., Sendai; Ito, Masatoshi; Yamada, Kenji

1987-01-01

We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P<0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two sibling with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE. (orig.)

Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography

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Yanai, Kazuhiko; Iinuma, Kazuie; Miyabayashi, Shigeaki; Narisawa, Kuniaki; Tada, Keiya; Matsuzawa, Taiju; Ito, Masatoshi; Yamada, Kenji

1987-09-01

We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P<0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two sibling with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE.

Striatal kinetics of [11C]-(+)-nomifensine and 6-[18F]fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

International Nuclear Information System (INIS)

Tedroff, J.; Aquilonius, S.-M.; Laihinen, A.; Rinne, U.; Hartvig, P.; Anderson, J.; Lundqvist, H.; Haaparanta, M.; Solin, O.; Antoni, G.; Gee, A.D.; Ulin, J.; Laangstroem, B.

1990-01-01

The kinetics in brain of the dopamine reuptake blocking agent [ 11 C]-(+)-nomifensine and the L-dopa analogue 6-[ 18 F]fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-[ 18 F]fluoro-L-dopa utilization and [ 11 C]-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author)

The study of automatic brain extraction of basal ganglia based on atlas of Talairach in 18F-FDG PET images

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Zuo Chantao; Guan Yihui; Zhao Jun; Lin Xiangtong; Wang Jian; Zhang Jiange; Zhang Lu

2005-01-01

Objective: To establish a method which can extract functional areas of the brain basal ganglia automatically. Methods: 18 F-fluorodeoxyglucose (FDG) PET images were spatial normalized to Talairach atlas space through two steps, image registration and image deformation. The functional areas were extracted from three dimension PET images based on the coordinate obtained from atlas; caudate and putamen were extracted and rendered, the grey value of the area was normalized by whole brain. Results: The normal ratio of left caudate head, body and tail were 1.02 ± 0.04, 0.92 ± 0.07 and 0.71 ± 0.03, the right were 0.98 ± 0.03, 0.87 ± 0.04 and 0.71 ± 0.01 respectively. The normal ratio of left and right putamen were 1.20 ± 0.06 and 1.20 ± 0.04. The mean grey value between left and right basal ganglia had no significant difference (P>0.05). Conclusion: The automatic functional area extracting method based on atlas of Talairach is feasible. (authors)

Ketogenic diet alters dopaminergic activity in the mouse cortex.

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Church, William H; Adams, Ryan E; Wyss, Livia S

2014-06-13

The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Human brain activity associated with painful mechanical stimulation to muscle and bone.

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Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

2011-08-01

The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

Striatal kinetics of ( sup 11 C)-(+)-nomifensine and 6-( sup 18 F)fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

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Tedroff, J; Aquilonius, S -M [Department of Neurology, University Hospital (Sweden); Laihinen, A; Rinne, U [Department of Neurology, University of Turku (Finland); Hartvig, P [Department of Hospital Pharmacy, University Hospital (Sweden); Anderson, J [Department of Radiation Sciences, University Hospital (Sweden); Lundqvist, H [Svenberg Laboratory, Uppsala University (Sweden); Haaparanta, M; Solin, O [Medical Cyclotron Laboratory, University of Turku (Finland); Antoni, G; Gee, A D; Ulin, J; Laangstroem, B [Department of Organic Chemistry, University Hospital (Sweden)

1990-01-01

The kinetics in brain of the dopamine reuptake blocking agent ({sup 11}C)-(+)-nomifensine and the L-dopa analogue 6-({sup 18}F)fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-({sup 18}F)fluoro-L-dopa utilization and ({sup 11}C)-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author).

Beyond cytoarchitectonics: the internal and external connectivity structure of the caudate nucleus.

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Sonja A Kotz

Full Text Available While there is ample evidence on the functional and connectional differentiation of the caudate nucleus (CN, less is known about its potential microstructural subdivisions. However, this latter aspect is critical to the local information processing capabilities of the tissue. We applied diffusion MRI, a non-invasive in vivo method that has great potential for the exploration of the brain structure-behavior relationship, in order to characterize the local fiber structure in gray matter of the CN. We report novel evidence of a functionally meaningful structural tri-partition along the anterior-posterior axis of this region. The connectivity of the CN subregions is in line with connectivity evidence from earlier invasive studies in animal models. In addition, histological validation using polarized light imaging (PLI confirms these results, corroborating the notion that cortico-subcortico-cortical loops involve microstructurally differentiated regions in the caudate nucleus. Methodologically speaking, the comparison with advanced analysis of diffusion MRI shows that diffusion tensor imaging (DTI yields a simplified view of the CN fiber architecture which is refined by advanced high angular resolution imaging methods.

Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.

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Andersen, Anders H; Hardy, Peter A; Forman, Eric; Gerhardt, Greg A; Gash, Don M; Grondin, Richard C; Zhang, Zhiming

2015-02-01

The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemoembolization of Extrahepatic Collateral Arteries for Treatment of Hepatocellular Carcinoma in the Caudate Lobe of the Liver

International Nuclear Information System (INIS)

Woo, Sungmin; Kim, Hyo-Cheol; Chung, Jin Wook; Jung, Hyun-Seok; Hur, Saebeom; Lee, Myungsu; Jae, Hwan Jun

2015-01-01

PurposeThis study was designed to evaluate the efficacy and safety in performing chemoembolization of extrahepatic collateral arteries (EHC) for hepatocellular carcinoma (HCC) located in the caudate lobe.MethodsBetween January 2006 and November 2013, chemoembolization via EHC was performed in 35 patients with 35 caudate HCCs. Preprocedural and follow-up CT or MR scans, angiographic images, and medical records were reviewed retrospectively in consensus. Chi-square analysis was used to evaluate the relationship between tumor characteristics and type of EHC and that between tumor response and the characteristics of the tumor and chemoembolization.ResultsIn 31 (88.6 %) patients, EHCs supplying the caudate HCC originated from the right inferior phrenic artery (RIPA). The remaining four HCCs were supplied by the gastroduodenal artery, dorsal pancreatic artery, and right and left gastric arteries. Superselective catheterization of tumor-feeding vessels from the EHC was achieved in 27 patients (77.1 %). There were no major complications. Individual tumor response supplied by the EHC at follow-up contrast-enhanced CT were as follows: complete response (n = 18), partial response (n = 9), stable disease (n = 3), and progressive disease (n = 3). Non-RIPA EHCs were significantly more common in patients who had previously received chemoembolization via the RIPA (50 %) than those who had not (6.5 %; P = 0.01). There was no significant predictive factor associated with tumor response.ConclusionsHCC in the caudate lobe can be supplied by several EHCs. Chemoembolization via these arteries can be performed safely and effectively

Chemoembolization of Extrahepatic Collateral Arteries for Treatment of Hepatocellular Carcinoma in the Caudate Lobe of the Liver

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Woo, Sungmin; Kim, Hyo-Cheol, E-mail: angiointervention@gmail.com; Chung, Jin Wook; Jung, Hyun-Seok; Hur, Saebeom; Lee, Myungsu; Jae, Hwan Jun [Seoul National University Hospital, Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, and Clinical Research Institute (Korea, Republic of)

2015-04-15

PurposeThis study was designed to evaluate the efficacy and safety in performing chemoembolization of extrahepatic collateral arteries (EHC) for hepatocellular carcinoma (HCC) located in the caudate lobe.MethodsBetween January 2006 and November 2013, chemoembolization via EHC was performed in 35 patients with 35 caudate HCCs. Preprocedural and follow-up CT or MR scans, angiographic images, and medical records were reviewed retrospectively in consensus. Chi-square analysis was used to evaluate the relationship between tumor characteristics and type of EHC and that between tumor response and the characteristics of the tumor and chemoembolization.ResultsIn 31 (88.6 %) patients, EHCs supplying the caudate HCC originated from the right inferior phrenic artery (RIPA). The remaining four HCCs were supplied by the gastroduodenal artery, dorsal pancreatic artery, and right and left gastric arteries. Superselective catheterization of tumor-feeding vessels from the EHC was achieved in 27 patients (77.1 %). There were no major complications. Individual tumor response supplied by the EHC at follow-up contrast-enhanced CT were as follows: complete response (n = 18), partial response (n = 9), stable disease (n = 3), and progressive disease (n = 3). Non-RIPA EHCs were significantly more common in patients who had previously received chemoembolization via the RIPA (50 %) than those who had not (6.5 %; P = 0.01). There was no significant predictive factor associated with tumor response.ConclusionsHCC in the caudate lobe can be supplied by several EHCs. Chemoembolization via these arteries can be performed safely and effectively.

Nigrostriatal and Mesolimbic D2/3 Receptor Expression in Parkinson's Disease Patients with Compulsive Reward-Driven Behaviors.

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Stark, Adam J; Smith, Christopher T; Lin, Ya-Chen; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Kang, Hakmook; Donahue, Manus J; Kessler, Robert M; Zald, David H; Claassen, Daniel O

2018-03-28

The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D 2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D 2 -like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D 2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with ( n = 17) and without ( n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [ 18 F]fallypride, a high affinity D 2 -like receptor ligand that can measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). Striatal differences between ICB+/ICB- patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BP ND In this group, self-reported severity of ICB symptoms positively correlated with midbrain D 2/3 receptor BP ND Group differences in regional D 2/3 BP ND relationships were also notable: ICB+ (but not ICB-) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BP ND s. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D 2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response. SIGNIFICANCE STATEMENT The biologic determinants of

Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders.

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Monica Juuhl-Langseth

Full Text Available Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB in early onset schizophrenia spectrum disorders (EOS. To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS.Twenty-four patients with EOS and 33 healthy controls (HC were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables.The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034. There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship.Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups.

Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum.

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Goldfarb, Elizabeth V; Chun, Marvin M; Phelps, Elizabeth A

2016-01-20

Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory.

The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance.

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Innocenti, Giorgio M; Dyrby, Tim B; Andersen, Kasper Winther; Rouiller, Eric M; Caminiti, Roberto

2017-06-01

The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4-0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon diameters and conduction distance are <2 ms in the monkey and, by extrapolation, <4 ms in humans. This delay corresponds to the performance in Poffenberger's paradigm, a classical attempt to estimate central conduction delays, with a neuropsychological task. In both species, callosal cortico-striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported to dissociate syntax and prosody. The projection might originate from an overproduction of callosal projections in development, differentially pruned depending on species. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Disruption of caudate working memory activation in chronic blast-related traumatic brain injury

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Mary R. Newsome

2015-01-01

Full Text Available Mild to moderate traumatic brain injury (TBI due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes. Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate. Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results

CSF Biomarkers and Its Associations with 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report.

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Rui Gao

Full Text Available Cerebrospinal fluid (CSF biomarkers, such as α-synuclein (α-syn, amyloid beta peptide 1-42 (Aβ1-42, phosphorylated tau (181P (p-tau, and total tau (t-tau, have long been associated with the development of Parkinson disease (PD and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2 bindings measured with 18F-9-fluoropropyl-(+-dihydrotetrabenazine (18F-AV133 that is being developed as a biomarker for PD. We test the hypothesis that monoaminergic degeneration was correlated with CSF biomarker levels in untreated PD patients.The available online data from the Parkinson's Progression Markers Initiative study (PPMI project were collected and analyzed, which include demographic information, clinical evaluations, CSF biomarkers (α-syn, Aβ1-42, p-tau, and t-tau, 18F-AV133 brain PET, and T1 weighted MRIs. Region of interest (ROI and voxel-wise Pearson correlation between standardized uptake value ratio (SUVR and CSF biomarkers were calculated.Our major findings are: 1 Compared with controls, CSF α-syn and tau levels decreased significantly in PD; 2 α-syn was closely correlated with Aβ1-42 and tau in PD, especially in early-onset patients; and 3 hypothesis-driven ROI analysis found a significant negative correlation between CSF Aβ1-42 levels and VMAT2 densities in post cingulate, left caudate, left anterior putamen, and left ventral striatum in PDs. CSF t-tau and p-tau levels were significantly negatively related to VMAT2 SUVRs in substantia nigra and left ventral striatum, respectively. Voxel-wise analysis showed that left caudate, parahippocampal gyrus, insula and temporal lobe were negatively correlated with Aβ1-42. In addition, superior frontal gyrus and transverse temporal gyrus were negatively correlated with CSF p-tau levels.These results suggest that monoaminergic degeneration in PD is correlated with CSF biomarkers

Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

NARCIS (Netherlands)

Willuhn, Ingo; Burgeno, Lauren M; Groblewski, Peter A; Phillips, Paul E M

Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

The importance of complete excision of the caudate lobe in resection of hilar cholangiocarcinoma

NARCIS (Netherlands)

Dinant, Sander; Gerhards, Michael F.; Busch, Olivier R. C.; Obertop, Hugo; Gouma, Dirk J.; van Gulik, Thomas M.

2005-01-01

Background: The numbers of margin-negative resections and survival times have greatly improved because of a more aggressive surgical approach to resectable hilar cholanciocarcinoma (Klatskin tumour). It was shown initially by Japanese authors that complete resection of the caudate lobe together with

Increased binding of (/sup 3/H)apomorphine in caudate membranes after dopamine pretreatment in vitro

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McManus, C; Hartley, E J; Seeman, P [Toronto Univ., Ontario (Canada)

1978-07-01

Most patients with Parkinson's disease treated with L-dopa show a progressively deteriorating response which may possibly be attributed to an L-dopa-induced process of unknown origin. Long-term administration of dopamine-mimetic drugs to animals sometimes produces behavioural facilitation. To investigate one possible molecular mechanism of this facilitation or sensitization the effects of prolonged exposure, in vitro, of dopamine on the dopamine/neuroleptic receptors in the caudate nucleus of the calf were tested. Calf caudate homogenates pretreated with dopamine or other drugs were tested for the binding of (/sup 3/H)apomorphine, (/sup 3/H)haloperidol, 3H-WB-4101, or (/sup 3/H)naloxine. Pre-exposure with dopamine or noradrenaline lead to an increased binding of (/sup 3/H)apomorphine. The significance of the results is discussed.

Habit formation coincides with shifts in reinforcement representations in the sensorimotor striatum.

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Smith, Kyle S; Graybiel, Ann M

2016-03-01

Evaluating outcomes of behavior is a central function of the striatum. In circuits engaging the dorsomedial striatum, sensitivity to goal value is accentuated during learning, whereas outcome sensitivity is thought to be minimal in the dorsolateral striatum and its habit-related corticostriatal circuits. However, a distinct population of projection neurons in the dorsolateral striatum exhibits selective sensitivity to rewards. Here, we evaluated the outcome-related signaling in such neurons as rats performed an instructional T-maze task for two rewards. As the rats formed maze-running habits and then changed behavior after reward devaluation, we detected outcome-related spike activity in 116 units out of 1,479 recorded units. During initial training, nearly equal numbers of these units fired preferentially either after rewarded runs or after unrewarded runs, and the majority were responsive at only one of two reward locations. With overtraining, as habits formed, firing in nonrewarded trials almost disappeared, and reward-specific firing declined. Thus error-related signaling was lost, and reward signaling became generalized. Following reward devaluation, in an extinction test, postgoal activity was nearly undetectable, despite accurate running. Strikingly, when rewards were then returned, postgoal activity reappeared and recapitulated the original early response pattern, with nearly equal numbers responding to rewarded and unrewarded runs and to single rewards. These findings demonstrate that outcome evaluation in the dorsolateral striatum is highly plastic and tracks stages of behavioral exploration and exploitation. These signals could be a new target for understanding compulsive behaviors that involve changes to dorsal striatum function. Copyright © 2016 the American Physiological Society.

BAS-drive trait modulates dorsomedial striatum activity during reward response-outcome associations.

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Costumero, Víctor; Barrós-Loscertales, Alfonso; Fuentes, Paola; Rosell-Negre, Patricia; Bustamante, Juan Carlos; Ávila, César

2016-09-01

According to the Reinforcement Sensitivity Theory, behavioral studies have found that individuals with stronger reward sensitivity easily detect cues of reward and establish faster associations between instrumental responses and reward. Neuroimaging studies have shown that processing anticipatory cues of reward is accompanied by stronger ventral striatum activity in individuals with stronger reward sensitivity. Even though establishing response-outcome contingencies has been consistently associated with dorsal striatum, individual differences in this process are poorly understood. Here, we aimed to study the relation between reward sensitivity and brain activity while processing response-reward contingencies. Forty-five participants completed the BIS/BAS questionnaire and performed a gambling task paradigm in which they received monetary rewards or punishments. Overall, our task replicated previous results that have related processing high reward outcomes with activation of striatum and medial frontal areas, whereas processing high punishment outcomes was associated with stronger activity in insula and middle cingulate. As expected, the individual differences in the activity of dorsomedial striatum correlated positively with BAS-Drive. Our results agree with previous studies that have related the dorsomedial striatum with instrumental performance, and suggest that the individual differences in this area may form part of the neural substrate responsible for modulating instrumental conditioning by reward sensitivity.

Human dorsal striatum encodes prediction errors during observational learning of instrumental actions.

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Cooper, Jeffrey C; Dunne, Simon; Furey, Teresa; O'Doherty, John P

2012-01-01

The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of others. In this study, we investigated the extent to which human dorsal striatum is involved in observational as well as experiential instrumental reward learning. Human participants were scanned with fMRI while they observed a confederate over a live video performing an instrumental conditioning task to obtain liquid juice rewards. Participants also performed a similar instrumental task for their own rewards. Using a computational model-based analysis, we found reward prediction errors in the dorsal striatum not only during the experiential learning condition but also during observational learning. These results suggest a key role for the dorsal striatum in learning instrumental associations, even when those associations are acquired purely by observing others.

Anhedonia correlates with abnormal functional connectivity of the superior temporal gyrus and the caudate nucleus in patients with first-episode drug-naive major depressive disorder.

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Yang, Xin-Hua; Tian, Kai; Wang, Dong-Fang; Wang, Yi; Cheung, Eric F C; Xie, Guang-Rong; Chan, Raymond C K

2017-08-15

Recent empirical findings have suggested that imbalanced neural networks may underlie the pathophysiology of major depressive disorder (MDD). However, the contribution of the superior temporal gyrus (STG) and the caudate nucleus to its pathophysiology remains unclear. Functional magnetic resonance imaging (MRI) date were acquired from 40 patients with first-episode drug-naive MDD and 36 matched healthy controls during wakeful rest. We used whole-brain voxel-wise statistical maps to quantify within-group resting state functional connectivity (RSFC) and between-group differences of bilateral caudate and STG seeds. Compared with healthy controls, first-episode MDD patients were found to have reduced connectivity between the ventral caudate and several brain regions including the superior frontal gyrus (SFG), the superior parietal lobule (SPL) and the middle temporal gyrus (MTG), as well as increased connectivity with the cuneus. We also found increased connectivity between the left STG and the precuneus, the angular gyrus and the cuneus. Moreover, we found that increased anhedonia severity was correlated with the magnitude of ventral caudate functional connectivity with the cuneus and the MTG in MDD patients. Due to our small sample size, we did not correct the statistical threshold in the correlation analyses between clinical variables and connectivity abnormalities. The present study suggests that anhedonia is mainly associated with altered ventral caudate-cortical connectivity and highlights the importance of the ventral caudate in the neurobiology of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Loss of metabolites from monkey striatum during PET with FDOPA

DEFF Research Database (Denmark)

Cumming, P; Munk, O L; Doudet, D

2001-01-01

diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

Interaction between the 5-HT system and the basal ganglia: Functional implication and therapeutic perspective in Parkinson’s disease

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Cristina eMiguelez

2014-03-01

Full Text Available The neurotransmitter serotonin (5-HT has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7 and ligand-gated ion channels (5-HT3. The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN share common projecting areas, in the basal ganglia (BG nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen, subthalamic nucleus (STN, internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe and substantia nigra (pars compacta, SNc, and pars reticulata, SNr. The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson’s disease. This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating Parkinson’s disease and the motor complications induced by chronic treatment with L-DOPA.

Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease.

Science.gov (United States)

Miguelez, Cristina; Morera-Herreras, Teresa; Torrecilla, Maria; Ruiz-Ortega, Jose A; Ugedo, Luisa

2014-01-01

The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.

Characterisation of [11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

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Riss P. J.; Fowler J.; Riss, P.J.; Hooker, J.M.; Shea, C.; Xu, Y.; Carter, P.; Warner, D.; Ferrari V.; Kim, S.W.; Aigbirhio, F.I.; Fowler, J.S.; Roesch, F.

2011-10-25

N-(4-fluorobut-2-yn-1-yl)-2{beta}-carbomethoxy-3{beta}-(4{prime}-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [{sup 11}C]PR04.MZ ([{sup 11}C]-1) has been developed using GMP compliant equipment. An adult female Papioanubis baboon was studied using a test-retest protocol with [{sup 11}C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (fP), plasma input functions and metabolic degradation of the radiotracer [{sup 11}C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (VT) and non-displaceable binding potentials (BPND) for various brain regions and the blood were obtained from kinetic modelling. [{sup 11}C]-1 shows promising results as aselective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder.

Science.gov (United States)

Yang, Xin-hua; Huang, Jia; Lan, Yong; Zhu, Cui-ying; Liu, Xiao-qun; Wang, Ye-fei; Cheung, Eric F C; Xie, Guang-rong; Chan, Raymond C K

2016-01-04

Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD. We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making. Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls. These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD. Copyright © 2015 Elsevier Inc. All rights reserved.

Adenosine A(2A receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

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Masahiro Mishina

Full Text Available Adenosine A(2A receptors (A2ARs are thought to interact negatively with the dopamine D(2 receptor (D2R, so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD. However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET with [7-methyl-(11C]-(E-8-(3,4,5-trimethoxystyryl-1,3,7-trimethylxanthine ([(11C]TMSX in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test. In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test. In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an

Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

Directory of Open Access Journals (Sweden)

Silvana Vargas Superti

2009-04-01

Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

Lateralization of brain activity pattern during unilateral movement in Parkinson's disease.

Science.gov (United States)

Wu, Tao; Hou, Yanan; Hallett, Mark; Zhang, Jiarong; Chan, Piu

2015-05-01

We investigated the lateralization of brain activity pattern during performance of unilateral movement in drug-naïve Parkinson's disease (PD) patients with only right hemiparkinsonian symptoms. Functional MRI was obtained when the subjects performed strictly unilateral right hand movement. A laterality index was calculated to examine the lateralization. Patients had decreased activity in the left putamen and left supplementary motor area, but had increased activity in the right primary motor cortex, right premotor cortex, left postcentral gyrus, and bilateral cerebellum. The laterality index was significantly decreased in PD patients compared with controls (0.41 ± 0.14 vs. 0.84 ± 0.09). The connectivity from the left putamen to cortical motor regions and cerebellum was decreased, while the interactions between the cortical motor regions, cerebellum, and right putamen were increased. Our study demonstrates that in early PD, the lateralization of brain activity during unilateral movement is significantly reduced. The dysfunction of the striatum-cortical circuit, decreased transcallosal inhibition, and compensatory efforts from cortical motor regions, cerebellum, and the less affected striatum are likely reasons contributing to the reduced motor lateralization. The disruption of the lateralized brain activity pattern might be a reason underlying some motor deficits in PD, like mirror movements or impaired bilateral motor coordination. © 2015 Wiley Periodicals, Inc.

Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response

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Hilary M. Dorton

2018-01-01

Full Text Available Sugar consumption in the United States exceeds recommendations from the American Heart Association. Overconsumption of sugar is linked to risk for obesity and metabolic disease. Animal studies suggest that high-sugar diets alter functions in brain regions associated with reward processing, including the dorsal and ventral striatum. Human neuroimaging studies have shown that these regions are responsive to food cues, and that the gut-derived satiety hormones, glucagon-like peptide-1 (GLP-1, and peptide YY (PYY, suppress striatal food-cue responsivity. We aimed to determine the associations between dietary added sugar intake, striatal responsivity to food cues, and postprandial GLP-1 and PYY levels. Twenty-two lean volunteers underwent a functional magnetic resonance imaging (fMRI scan during which they viewed pictures of food and non-food items after a 12-h fast. Before scanning, participants consumed a glucose drink. A subset of 19 participants underwent an additional fMRI session in which they consumed water as a control condition. Blood was sampled for GLP-1, and PYY levels and hunger ratings were assessed before and ~75 min after drink consumption. In-person 24-h dietary recalls were collected from each participant on three to six separate occasions over a 2-month period. Average percent calories from added sugar were calculated using information from 24-h dietary recalls. A region-of-interest analysis was performed to compare the blood oxygen level-dependent (BOLD response to food vs. non-food cues in the bilateral dorsal striatum (caudate/putamen and ventral striatum (nucleus accumbens. The relationships between added sugar, striatal responses, and hormone changes after drink consumption were assessed using Spearman’s correlations. We observed a positive correlation between added sugar intake and BOLD response to food cues in the dorsal striatum and a similar trend in the nucleus accumbens after glucose, but not water, consumption

Smoking-induced dopamine release studied with [{sup 11}C]Raclopride PET

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Kim, Yu Kyeong; Cho, Sang Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Do Hoon [Center for Clinical Services, National Cancer Certer, Goyang (Korea, Republic of)] (and others)

2005-10-15

It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [{sup 11}C]raclopride. Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.4 {+-} 1.7 years) were enrolled in this study. [{sup 1C}]raclopride, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3 x 20s, 2 x 60s, 2 x 120s, 1 x 180s and 22 x 300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean decrease in binding potential of [{sup 1C}]raclopride between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, {rho} =0.4). These data demonstrate that in vivo imaging with [{sup 11}C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.

{sup 125}I-iomazenil - benzodiazepine receptor binding and serum corticosterone level during psychological stress in a rat model

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Fukumitsu, Nobuyoshi E-mail: GZL13162@nifty.ne.jp; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

2004-02-01

To test the hypothesis that benzodiazepine receptor density decreases in response to stress, we correlated {sup 125}I-iomazenil ({sup 125}I-IMZ) binding with serum corticosterone levels in a rat model. Wistar male rats were divided into four groups; control group (CON, 10 rats), no physical or psychological stress; and one-, three-, and five-day stress groups of 12 rats each (1-DAY, 3-DAY, and 5-DAY, respectively), receiving psychological stress for the given number of days. Psychological stress were given to rats with a communication box. The standardized uptake value (SUV) of {sup 125}I-iomazenil of the 3-DAY and 5-DAY showed that {sup 125}I-iomazenil - benzodiazepine receptor binding was significantly reduced in the cortices, accumbens nuclei, amygdala and caudate putamen (p<0.05). Serum corticosterone level ratio appeared to be slightly elevated in 3-DAY and 5-DAY, although this elevation was not significant. These data suggest that {sup 125}I-IMZ is a useful radioligand to reflect received stress and its binding in the cortices, accumbens nuclei, amygdala and caudate putamen is strongly affected by psychological stress.

The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)

Science.gov (United States)

Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

2010-01-01

The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia. PMID:20227397

Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

Science.gov (United States)

Alloway, Kevin D.; Smith, Jared B.; Mowery, Todd M.; Watson, Glenn D. R.

2017-01-01

The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS) region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS) region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R) associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf) nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm) nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD) and related neurological disorders. PMID:28790899

Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis--Preliminary fMRI findings.

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Raij, Tuukka T; Mäntylä, Teemu; Kieseppä, Tuula; Suvisaari, Jaana

2015-08-30

The dopamine theory proposes the relationship of delusions to aberrant signaling in striatal circuitries that can be normalized with dopamine D2 receptor-blocking drugs. Localization of such circuitries, as well as their upstream and downstream signaling, remains poorly known. We collected functional magnetic resonance images from first-episode psychosis patients and controls during an audiovisual movie. Final analyses included 20 patients and 20 controls; another sample of 10 patients and 10 controls was used to calculate a comparison signal-time course. We identified putamen circuitry in which the signal aberrance (poor correlation with the comparison signal time course) was predicted by the dopamine theory, being greater in patients than controls; correlating positively with delusion scores; and correlating negatively with antipsychotic-equivalent dosage. In Granger causality analysis, patients showed a compromised contribution of the cortical salience network to the putamen and compromised contribution of the putamen to the default mode network. Results were corrected for multiple comparisons at the cluster level with primary voxel-wise threshold p < 0.005 for the salience network contribution, but liberal primary threshold p < 0.05 was used in other group comparisons. If replicated in larger studies, these findings may help unify and extend current hypotheses on dopaminergic dysfunction, salience processing and pathogenesis of delusions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction.

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Brand, Matthias; Snagowski, Jan; Laier, Christian; Maderwald, Stefan

2016-04-01

One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Bilateral Electrolytic Lesions of the Dorsomedial Striatum on Motor Behavior and Instrumental Learning in Rats

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Pamphyle Abedi Mukutenga

2012-08-01

Full Text Available Introduction: The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum Methods: The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. Results: In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Discussion: Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control.

An adaption of the push-pull cannula method to study the in vivo release of [3H]dopamine synthesised from [3H]tyrosine in the cat caudate nucleus: effects of various physical and pharmacological treatments

International Nuclear Information System (INIS)

Nieoullon, A.; Cheramy, A.; Glowinski, J.

1977-01-01

The release of [ 3 H]dopamine ([ 3 H]DA) continuously synthesized from L-[3,5- 3 H]tyrosine from the caudate nucleus of the cat was estimated in halothane anaesthetized or 'encephale isole' animals. For this purpose, an improved superfusion cannula, avoiding tissue damage, was used. The best localization for the tip of the superfusion cannula was found first by determining the topographical distribution of endogenous DA within the caudate nucleus. A rostro-caudal heterogenous distribution of the transmitter was detected. In perfusion experiments, L-[3, 5 3 H]tyrosine was introduced continuously at a rate of 33 μl/min. [ 3 H]DA was the only catecholamine found in serial 15 min fractions as revealed by cochromatography. The spontaneous release of [ 3 H]DA was greater in anaesthetized than in 'encephale isole'cats; it represented 150 and 100 times the blank value, respectively. Depolarization by K + (30 mM) applied locally in the striatum or by electrical or mechanical stimulation of the substantia nigra caused a transitory increase in [ 3 H]DA release. Conversely, a decrease in nerve activity induced by tetrodotoxin (5 x 10 -7 M) or by electrocoagulation of the substantia nigra was associated with a decline in the amounts of [ 3 H]DA in superfusates. A temporary reduction in [ 3 H]DA release could also be obtained by a short-lasting cooling block of the substantia nigra. As expected, d-amphetamine (10 -5 M) and benzotropine (10 -6 M) added to the superfusing medium increased [ 3 H]DA release. These pharmacological results, as well as the changes in [ 3 H]DA release observed after various manipulations of the activity of dopaminergic neurones, confirms the validity and the high sensitivity of this approach. (author)

Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia.

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Jourdain, Vincent A; Schindlbeck, Katharina A; Tang, Chris C; Niethammer, Martin; Choi, Yoon Young; Markowitz, Daniel; Nazem, Amir; Nardi, Dominic; Carras, Nicholas; Feigin, Andrew; Ma, Yilong; Peng, Shichun; Dhawan, Vijay; Eidelberg, David

2017-10-19

In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hypercapnia. We therefore explored the possibility that, in the absence of levodopa, local hypercapnic CBF responses are abnormally increased in PD patients with levodopa-induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts. We used H215O PET to scan 24 unmedicated PD subjects (12 LID and 12 NLID) and 12 matched healthy subjects in the rest state under normocapnic and hypercapnic conditions. Hypercapnic CBF responses were compared to corresponding levodopa responses from the same subjects. Group differences in hypercapnic vasoreactivity were significant only in the posterior putamen, with greater CBF responses in LID subjects compared with the other subjects. Hypercapnic and levodopa-mediated CBF responses measured in this region exhibited distinct associations with disease severity: the former correlated with off-state motor disability ratings but not symptom duration, whereas the latter correlated with symptom duration but not motor disability. These are the first in vivo human findings linking LID to microvascular changes in the basal ganglia.

Hyperechoic caudate nuclei: a potential mimic of germinal matrix hemorrhage

International Nuclear Information System (INIS)

Schlesinger, A.E.; Shackelford, G.D.; Adcock, L.M.

1998-01-01

Background. We have encountered bilateral hyperechoic foci in the region of the germinal matrix on cranial sonograms in neonates that have an appearance similar to germinal matrix hemorrhage (GMH), but are unusual either due to the age of the patient at presentation or to the evolution of the foci on follow-up. We believe that these findings represent hyperechoic caudate nuclei (HCN) rather than GMH. Objective. To demonstrate that bilateral HCN can be seen on cranial sonography in neonates and can mimic bilateral GMH. Materials and methods. The cranial sonograms were reviewed in nine neonates (three term and six premature) who had HCN identified on at least one sonographic examination. CT (two patients) and MR (one patient) studies were also reviewed, as well as the neuropathological examination in one patient who died and had an autopsy. The patients' medical records were reviewed to identify any clinical markers for significant risk of perinatal ischemia. Results. There was clinical evidence for risk of ischemia in five of the nine neonates. All nine patients had bilateral HCN on the initial or follow-up studies. Small cysts were seen sonographically in two patients. CT was normal in one patient and revealed a small unilateral focus of increased attenuation in one infant (very small compared to the bilateral HCN). MR was normal in one patient. Histopathological examination of the brain was normal in the one patient who died and had an autopsy. Conclusion. Hyperechoic caudate nuclei can occur in neonates either as a normal finding, or possibly related to ischemia, and should not always be attributed to GMH. (orig.)

Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

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Kevin D. Alloway

2017-07-01

Full Text Available The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD and related neurological disorders.

Surprised at all the entropy: hippocampal, caudate and midbrain contributions to learning from prediction errors.

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Anne-Marike Schiffer

Full Text Available Influential concepts in neuroscientific research cast the brain a predictive machine that revises its predictions when they are violated by sensory input. This relates to the predictive coding account of perception, but also to learning. Learning from prediction errors has been suggested for take place in the hippocampal memory system as well as in the basal ganglia. The present fMRI study used an action-observation paradigm to investigate the contributions of the hippocampus, caudate nucleus and midbrain dopaminergic system to different types of learning: learning in the absence of prediction errors, learning from prediction errors, and responding to the accumulation of prediction errors in unpredictable stimulus configurations. We conducted analyses of the regions of interests' BOLD response towards these different types of learning, implementing a bootstrapping procedure to correct for false positives. We found both, caudate nucleus and the hippocampus to be activated by perceptual prediction errors. The hippocampal responses seemed to relate to the associative mismatch between a stored representation and current sensory input. Moreover, its response was significantly influenced by the average information, or Shannon entropy of the stimulus material. In accordance with earlier results, the habenula was activated by perceptual prediction errors. Lastly, we found that the substantia nigra was activated by the novelty of sensory input. In sum, we established that the midbrain dopaminergic system, the hippocampus, and the caudate nucleus were to different degrees significantly involved in the three different types of learning: acquisition of new information, learning from prediction errors and responding to unpredictable stimulus developments. We relate learning from perceptual prediction errors to the concept of predictive coding and related information theoretic accounts.

Surprised at all the entropy: hippocampal, caudate and midbrain contributions to learning from prediction errors.

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Schiffer, Anne-Marike; Ahlheim, Christiane; Wurm, Moritz F; Schubotz, Ricarda I

2012-01-01

Influential concepts in neuroscientific research cast the brain a predictive machine that revises its predictions when they are violated by sensory input. This relates to the predictive coding account of perception, but also to learning. Learning from prediction errors has been suggested for take place in the hippocampal memory system as well as in the basal ganglia. The present fMRI study used an action-observation paradigm to investigate the contributions of the hippocampus, caudate nucleus and midbrain dopaminergic system to different types of learning: learning in the absence of prediction errors, learning from prediction errors, and responding to the accumulation of prediction errors in unpredictable stimulus configurations. We conducted analyses of the regions of interests' BOLD response towards these different types of learning, implementing a bootstrapping procedure to correct for false positives. We found both, caudate nucleus and the hippocampus to be activated by perceptual prediction errors. The hippocampal responses seemed to relate to the associative mismatch between a stored representation and current sensory input. Moreover, its response was significantly influenced by the average information, or Shannon entropy of the stimulus material. In accordance with earlier results, the habenula was activated by perceptual prediction errors. Lastly, we found that the substantia nigra was activated by the novelty of sensory input. In sum, we established that the midbrain dopaminergic system, the hippocampus, and the caudate nucleus were to different degrees significantly involved in the three different types of learning: acquisition of new information, learning from prediction errors and responding to unpredictable stimulus developments. We relate learning from perceptual prediction errors to the concept of predictive coding and related information theoretic accounts.

Aversive counterconditioning attenuates reward signalling in the ventral striatum

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Anne Marije Kaag

2016-08-01

Full Text Available Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient rewards such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional Magnetic Resonance Imaging (fMRI. In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signalling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signalling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula.

The involvement of the striatum in decision making

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Goulet-Kennedy, Julie; Labbe, Sara; Fecteau, Shirley

2016-01-01

Decision making has been extensively studied in the context of economics and from a group perspective, but still little is known on individual decision making. Here we discuss the different cognitive processes involved in decision making and its associated neural substrates. The putative conductors in decision making appear to be the prefrontal cortex and the striatum. Impaired decision-making skills in various clinical populations have been associated with activity in the prefrontal cortex and in the striatum. We highlight the importance of strengthening the degree of integration of both cognitive and neural substrates in order to further our understanding of decision-making skills. In terms of cognitive paradigms, there is a need to improve the ecological value of experimental tasks that assess decision making in various contexts and with rewards; this would help translate laboratory learnings into real-life benefits. In terms of neural substrates, the use of neuroimaging techniques helps characterize the neural networks associated with decision making; more recently, ways to modulate brain activity, such as in the prefrontal cortex and connected regions (eg, striatum), with noninvasive brain stimulation have also shed light on the neural and cognitive substrates of decision making. Together, these cognitive and neural approaches might be useful for patients with impaired decision-making skills. The drive behind this line of work is that decision-making abilities underlie important aspects of wellness, health, security, and financial and social choices in our daily lives. PMID:27069380

Radiological imaging features of the basal ganglia that may predict progression to hemicraniectomy in large territory middle cerebral artery infarct

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Mian, Asim Z.; Edasery, David; Sakai, Osamu; Mustafa Qureshi, M. [Boston University School of Medicine, Department of Radiology, Boston Medical Center, Boston, MA 02118 (United States); Holsapple, James [Boston University School of Medicine, Department of Neurosurgery, Boston Medical Center, Boston, MA (United States); Nguyen, Thanh [Boston University School of Medicine, Department of Neurology, Boston Medical Center, Boston, MA (United States)

2017-05-15

Predicting which patients are at risk for hemicraniectomy can be helpful for triage and can help preserve neurologic function if detected early. We evaluated basal ganglia imaging predictors for early hemicraniectomy in patients with large territory anterior circulation infarct. This retrospective study evaluated patients with ischemic infarct admitted from January 2005 to July 2011. Patients with malignant cerebral edema refractory to medical therapy or with herniating signs such as depressed level of consciousness, anisocoria, and contralateral leg weakness were triaged to hemicraniectomy. Admission images were reviewed for presence of caudate, lentiform nucleus (putamen and globus pallidus), or basal ganglia (caudate + lentiform nucleus) infarction. Thirty-one patients with large territory MCA infarct, 10 (32%), underwent hemicraniectomy. Infarction of the caudate nucleus (9/10 vs 6/21, p = 0.002) or basal ganglia (5/10 vs 2/21, p = 0.02) predicted progression to hemicraniectomy. Infarction of the lentiform nucleus only did not predict progression to hemicraniectomy. Sensitivity for patients who did and did not have hemicraniectomy were 50% (5/10) and 90.5% (19/21). For caudate nucleus and caudate plus lentiform nucleus infarcts, the crude- and age-adjusted odds of progression to hemicraniectomy were 9.5 (1.4-64.3) and 6.6 (0.78-55.4), respectively. Infarction of the caudate nucleus or basal ganglia correlated with patients progressing to hemicraniectomy. Infarction of the lentiform nucleus alone did not. (orig.)

Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes.

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Jennifer S Richards

Full Text Available Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD. Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE in interindividual variability of total gray matter (GM, caudate, and putamen volumes. Brain volumes were derived from structural magnetic resonance imaging scans in participants with (N = 312 and without ADHD (N = 437 from N = 402 families (age M = 17.00, SD = 3.60. GxE effects between DAT1, 5-HTT, and DRD4 and social environments (maternal expressed warmth and criticism; positive and deviant peer affiliation as well as the possible moderating effect of age were examined using linear mixed modeling. We also tested whether findings depended on ADHD severity. Deviant peer affiliation was associated with lower caudate volume. Participants with low deviant peer affiliations had larger total GM volumes with increasing age. Likewise, developmentally sensitive GxE effects were found on total GM and putamen volume. For total GM, differential age effects were found for DAT1 9-repeat and HTTLPR L/L genotypes, depending on the amount of positive peer affiliation. For putamen volume, DRD4 7-repeat carriers and DAT1 10/10 homozygotes showed opposite age relations depending on positive peer affiliation and maternal criticism, respectively. All results were independent of ADHD severity. The presence of differential age-dependent GxE effects might explain the diverse and sometimes opposing results of environmental and genetic effects on brain volumes observed so far.

Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes.

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Richards, Jennifer S; Arias Vásquez, Alejandro; Franke, Barbara; Hoekstra, Pieter J; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Buitelaar, Jan K; Hartman, Catharina A

2016-01-01

Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD). Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE) in interindividual variability of total gray matter (GM), caudate, and putamen volumes. Brain volumes were derived from structural magnetic resonance imaging scans in participants with (N = 312) and without ADHD (N = 437) from N = 402 families (age M = 17.00, SD = 3.60). GxE effects between DAT1, 5-HTT, and DRD4 and social environments (maternal expressed warmth and criticism; positive and deviant peer affiliation) as well as the possible moderating effect of age were examined using linear mixed modeling. We also tested whether findings depended on ADHD severity. Deviant peer affiliation was associated with lower caudate volume. Participants with low deviant peer affiliations had larger total GM volumes with increasing age. Likewise, developmentally sensitive GxE effects were found on total GM and putamen volume. For total GM, differential age effects were found for DAT1 9-repeat and HTTLPR L/L genotypes, depending on the amount of positive peer affiliation. For putamen volume, DRD4 7-repeat carriers and DAT1 10/10 homozygotes showed opposite age relations depending on positive peer affiliation and maternal criticism, respectively. All results were independent of ADHD severity. The presence of differential age-dependent GxE effects might explain the diverse and sometimes opposing results of environmental and genetic effects on brain volumes observed so far.

Post-stroke dementia: the contribution of thalamus and basal ganglia changes.

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Lopes, Marcos Antonio; Firbank, Michael J; Widdrington, Michelle; Blamire, Andrew M; Kalaria, Raj N; O'Brien, John T

2012-04-01

The neurobiological basis of increased risk of dementia in stroke patients is unclear, though there are several related pathological changes, including white matter hyperintensities (WMH), and medial temporal atrophy. Subcortical gray matter structures have also been implicated in dementia resulting from vascular pathology, particularly vascular dementia. This study aimed to investigate the contribution of changes in subcortical gray matter structures to post-stroke dementia (PSD). T1- and T2-weighted images and T2-weighted fluid-attenuated inversion recovery (FLAIR) images were obtained on a 3-Tesla magnetic resonance (MR) system, in four groups aged over 75 years: post-stroke with dementia (PSD; 8), post-stroke no dementia (PSnoD; 33), Alzheimer's disease (AD; 26) and controls (30). Automated software was used to measure the volume of thalamus, putamen, caudate nucleus, and hippocampus as well as total WMH volume. The number of subcortical lacunes was also counted. The number of caudate lacunes was higher in the PSnoD group, compared with AD (p = 0.029) and controls (p = 0.019). The putamen volume was smaller in the stroke and AD groups, when compared with controls. In the whole stroke group, putamen lacunes were correlated with impairment in memory (Rey test; ρ = -0.365; p = 0.031), while WMH and hippocampal volume both correlated with global dysfunction. Our findings implicate a variety of neurobiological substrates of dementia, such as small vessel disease and Alzheimer pathology, which develop after stroke in an old older population, with a contribution from subcortical brain structures.

Dispositional mindfulness co-varies with smaller amygdala and caudate volumes in community adults.

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Adrienne A Taren

Full Text Available Mindfulness, a psychological process reflecting attention and awareness to what is happening in the present moment, has been associated with increased well-being and decreased depression and anxiety in both healthy and patient populations. However, little research has explored underlying neural pathways. Recent work suggests that mindfulness (and mindfulness training interventions may foster neuroplastic changes in cortico-limbic circuits responsible for stress and emotion regulation. Building on this work, we hypothesized that higher levels of dispositional mindfulness would be associated with decreased grey matter volume in the amgydala. In the present study, a self-report measure of dispositional mindfulness and structural MRI images were obtained from 155 healthy community adults. Volumetric analyses showed that higher dispositional mindfulness is associated with decreased grey matter volume in the right amygdala, and exploratory analyses revealed that higher dispositional mindfulness is also associated with decreased grey matter volume in the left caudate. Moreover, secondary analyses indicate that these amygdala and caudate volume associations persist after controlling for relevant demographic and individual difference factors (i.e., age, total grey matter volume, neuroticism, depression. Such volumetric differences may help explain why mindful individuals have reduced stress reactivity, and suggest new candidate structural neurobiological pathways linking mindfulness with mental and physical health outcomes.

Dispositional Mindfulness Co-Varies with Smaller Amygdala and Caudate Volumes in Community Adults

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Taren, Adrienne A.; Creswell, J. David; Gianaros, Peter J.

2013-01-01

Mindfulness, a psychological process reflecting attention and awareness to what is happening in the present moment, has been associated with increased well-being and decreased depression and anxiety in both healthy and patient populations. However, little research has explored underlying neural pathways. Recent work suggests that mindfulness (and mindfulness training interventions) may foster neuroplastic changes in cortico-limbic circuits responsible for stress and emotion regulation. Building on this work, we hypothesized that higher levels of dispositional mindfulness would be associated with decreased grey matter volume in the amgydala. In the present study, a self-report measure of dispositional mindfulness and structural MRI images were obtained from 155 healthy community adults. Volumetric analyses showed that higher dispositional mindfulness is associated with decreased grey matter volume in the right amygdala, and exploratory analyses revealed that higher dispositional mindfulness is also associated with decreased grey matter volume in the left caudate. Moreover, secondary analyses indicate that these amygdala and caudate volume associations persist after controlling for relevant demographic and individual difference factors (i.e., age, total grey matter volume, neuroticism, depression). Such volumetric differences may help explain why mindful individuals have reduced stress reactivity, and suggest new candidate structural neurobiological pathways linking mindfulness with mental and physical health outcomes. PMID:23717632

Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

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Mann, T; Zilles, K; Dikow, H; Hellfritsch, A; Cremer, M; Piel, M; Rösch, F; Hawlitschka, A; Schmitt, O; Wree, A

2018-03-15

Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D 1 , D 2 /D 3 , α 1 , α 2 , and 5HT 2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D 1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D 2 /D 3 receptor density, and 50% reduction in 5HT 2A receptor density. α 1 receptor density remained unaltered in hemi-PD and α 2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D 2 /D 3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D 2 /D 3 receptor density. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulus.

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Schur, E A; Kleinhans, N M; Goldberg, J; Buchwald, D; Schwartz, M W; Maravilla, K

2009-06-01

To develop a non-invasive method of studying brain mechanisms involved in energy homeostasis and appetite regulation in humans by using visual food cues that are relevant to individuals attempting weight loss. Functional magnetic resonance imaging (fMRI) was used to compare brain activation in regions of interest between groups of food photographs. Ten healthy, non-obese women who were not dieting for weight loss. Independent raters viewed food photographs and evaluated whether the foods depicted should be eaten by individuals attempting a calorically-restricted diet. Based on their responses, we categorized photographs into 'non-fattening' and 'fattening' food groups, the latter characterized by high-caloric content and usually also high-fat or high-sugar content. Blood oxygen level-dependent (BOLD) response was measured by fMRI while participants viewed photographs of 'fattening' food, 'non-fattening' food, and non-food objects. Viewing photographs of fattening food compared with non-food objects resulted in significantly greater activation in the brainstem; hypothalamus; left amygdala; left dorsolateral prefrontal cortex; left orbitofrontal cortex; right insular cortex; bilateral striatum, including the nucleus accumbens, caudate nucleus, and putamen; bilateral thalamus; and occipital lobe. By comparison, only the occipital region had greater activation by non-fattening food than by object photographs. Combining responses to all food types resulted in attenuation of activation in the brainstem, hypothalamus, and striatum. These findings suggest that, in non-obese women, neural circuits engaged in energy homeostasis and reward processing are selectively attuned to representations of high-calorie foods that are perceived as fattening. Studies to investigate hormonal action or manipulation of energy balance may benefit from fMRI protocols that contrast energy-rich food stimuli with non-food or low-calorie food stimuli.

Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D{sub 2} receptors

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Langer, Oliver; Halldin, Christer E-mail: christer.halldin@neuro.ks.se; Dolle, Frederic; Swahn, Carl-Gunnar; Olsson, Hans; Lundkvist, Per Karlsson; Hall, Haakan; Sandell, Johan; Vaufrey, Camilla; Loc' h, Christian; Franzoise; Crouzel, Christian; Maziere, Bernard; Farde, Lars

1999-07-01

Epidepride {l_brace}(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide= {r_brace} binds with a picomolar affinity (K{sub i}=24 pM) to the dopamine D{sub 2} receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D{sub 2} receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [{sup 11}C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/{mu}mol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [{sup 11}C]epidepride binding. The fraction of unchanged [{sup 11}C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [{sup 11}C]epidepride. The availability of [{sup 11}C]epidepride allows the PET-verification of the data obtained from quantitation studies with

Striatal adenosine A2A receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [18F]-MRS5425

International Nuclear Information System (INIS)

Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit; Shinkre, Bidhan; Ma Ying; Niu Gang; Trenkle, William C.; Jacobson, Kenneth A.; Chen Xiaoyuan; Kiesewetter, Dale O.

2011-01-01

Introduction: A 2A receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an 18 F-labeled A 2A analog radiotracer ([ 18 F]-MRS5425) for A 2A receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A 2A receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [ 18 F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D 2 agonist quinpirole (1.0 mg/kg) or D 2 antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A 2A receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

Striatal adenosine A{sub 2A} receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [{sup 18}F]-MRS5425

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Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Shinkre, Bidhan [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Ma Ying [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Niu Gang [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Trenkle, William C. [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jacobson, Kenneth A. [Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Chen Xiaoyuan [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Kiesewetter, Dale O., E-mail: dk7k@nih.gov [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States)

2011-08-15

Introduction: A{sub 2A} receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an {sup 18}F-labeled A{sub 2A} analog radiotracer ([{sup 18}F]-MRS5425) for A{sub 2A} receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A{sub 2A} receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [{sup 18}F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D{sub 2} agonist quinpirole (1.0 mg/kg) or D{sub 2} antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A{sub 2A} receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

Robotic resection of the liver caudate lobe: technical description and initial consideration.

Science.gov (United States)

Marino, Marco Vito; Glagolieva, Anastasiia; Guarrasi, Domenico

2018-03-01

Firstly described in 2002, the robotic liver surgery has not spread widely due to its high cost and the lack of a standardized training program. Still being considered as a 'development in progress' technique, it has however a potential to overcome the traditional limitations of the laparoscopic approach in liver interventions. We analyzed the postoperative outcomes of 10 patients who had undergone robotic partial resection of the caudate lobe (Spiegel lobe) from March 2014 to May 2016 in order to evaluate the advantages of robotic technique in hands of a young surgeon. The mean operative time was 258min (150-522) and the estimated blood loss 137ml (50-359), in none of the cases a blood transfusion was required. No patient underwent a conversion to open surgery; the overall morbidity was 2/10 (20%) and all the complications occurred (biliary fistula and pleural effusion) did not require a surgical revision. At histological examination, the mean tumour size was 2.63cm and we achieved R0-resection rate of 100%. The 90-day mortality rate was null. The 1-year overall and disease free-survival rates were 100% and 80%, respectively. Despite several concerns regarding the cost-effectiveness, a fully robotic partial resection of caudate lobe is an advantageous, implementable technique providing promising short-term postoperative outcomes with acceptable benefit-risk profile. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Quantitative Imaging of Cholinergic Interneurons Reveals a Distinctive Spatial Organization and a Functional Gradient across the Mouse Striatum.

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Miriam Matamales

Full Text Available Information processing in the striatum requires the postsynaptic integration of glutamatergic and dopaminergic signals, which are then relayed to the output nuclei of the basal ganglia to influence behavior. Although cellularly homogeneous in appearance, the striatum contains several rare interneuron populations which tightly modulate striatal function. Of these, cholinergic interneurons (CINs have been recently shown to play a critical role in the control of reward-related learning; however how the striatal cholinergic network is functionally organized at the mesoscopic level and the way this organization influences striatal function remains poorly understood. Here, we systematically mapped and digitally reconstructed the entire ensemble of CINs in the mouse striatum and quantitatively assessed differences in densities, spatial arrangement and neuropil content across striatal functional territories. This approach demonstrated that the rostral portion of the striatum contained a higher concentration of CINs than the caudal striatum and that the cholinergic content in the core of the ventral striatum was significantly lower than in the rest of the regions. Additionally, statistical comparison of spatial point patterns in the striatal cholinergic ensemble revealed that only a minor portion of CINs (17% aggregated into cluster and that they were predominantly organized in a random fashion. Furthermore, we used a fluorescence reporter to estimate the activity of over two thousand CINs in naïve mice and found that there was a decreasing gradient of CIN overall function along the dorsomedial-to-ventrolateral axis, which appeared to be independent of their propensity to aggregate within the striatum. Altogether this work suggests that the regulation of striatal function by acetylcholine across the striatum is highly heterogeneous, and that signals originating in external afferent systems may be principally determining the function of CINs in the

Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain

DEFF Research Database (Denmark)

Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

2016-01-01

anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d...... microstructure in the hippocampus, prefrontal cortex, caudate putamen and amygdala regions of CMS rat brains by comparison to brains from normal controls. To validate findings of CMS induced microstructural alteration, histology was performed to determine neurite, nuclear and astrocyte density. d-MRI based...... neurite density and tensor-based mean kurtosis (MKT) were significantly higher, while mean diffusivity (MD), extracellular diffusivity (Deff) and intra-neurite diffusivity(DL) were significantly lower in the amygdala of CMS rat brains. Deff was also significantly lower in the hippocampus and caudate...

Caudate Asymmetry: A Neurobiological Marker of Moderate Prenatal Alcohol Exposure in Young Adults

OpenAIRE

Willford, Jennifer; Day, Richard; Aizenstein, Howard; Day, Nancy

2010-01-01

This study identified structural changes in the caudate nucleus in offspring of mothers who drank moderate levels of alcohol during pregnancy. In addition, the effect of duration of alcohol use during pregnancy was assessed. Young adults were recruited from the Maternal Health Practices and Child Development Project. Three groups were evaluated: prenatal alcohol exposure (PAE) during all three trimesters (3T), PAE during the first trimester only (1T), and controls with no PAE (0T). Magnetic r...

Neuronal basis for evaluating selected action in the primate striatum.

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Yamada, Hiroshi; Inokawa, Hitoshi; Matsumoto, Naoyuki; Ueda, Yasumasa; Kimura, Minoru

2011-08-01

Humans and animals optimize their behavior by evaluating outcomes of individual actions and predicting how much reward the actions will yield. While the estimated values of actions guide choice behavior, the choices are also governed by other behavioral norms, such as rules and strategies. Values, rules and strategies are represented in neuronal activity, and the striatum is one of the best qualified brain loci where these signals meet. To understand the role of the striatum in value- and strategy-based decision-making, we recorded striatal neurons in macaque monkeys performing a behavioral task in which they searched for a reward target by trial-and-error among three alternatives, earned a reward for a target choice, and then earned additional rewards for choosing the same target. This task allowed us to examine whether and how values of targets and strategy, which were defined as negative-then-search and positive-then-repeat (or win-stay-lose-switch), are represented in the striatum. Large subsets of striatal neurons encoded positive and negative outcome feedbacks of individual decisions and actions. Once monkeys made a choice, signals related to chosen actions, their values and search- or repeat-type actions increased and persisted until the outcome feedback appeared. Subsets of neurons exhibited a tonic increase in activity after the search- and repeat-choices following negative and positive feedback in the last trials as the task strategy monkeys adapted. These activity profiles as a heterogeneous representation of decision variables may underlie a part of the process for reinforcement- and strategy-based evaluation of selected actions in the striatum. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats.

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Ippolita Cantuti-Castelvetri

2010-11-01

Full Text Available Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition.Quantitative real-time polymerase chain reaction (PCR was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes.TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.

Long-term occupational stress is associated with regional reductions in brain tissue volumes.

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Eva Blix

Full Text Available There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM and white matter (WM volumes, and the volumes of hippocampus, caudate, and putamen - structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment.

Long-Term Occupational Stress Is Associated with Regional Reductions in Brain Tissue Volumes

Science.gov (United States)

Blix, Eva; Perski, Aleksander; Berglund, Hans; Savic, Ivanka

2013-01-01

There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM) and white matter (WM) volumes, and the volumes of hippocampus, caudate, and putamen – structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment. PMID:23776438

Distribution of vesicular glutamate transporters in the human brain

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Erika eVigneault

2015-03-01

Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

Psychopathic traits are associated with cortical and subcortical volume alterations in healthy individuals.

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Vieira, Joana B; Ferreira-Santos, Fernando; Almeida, Pedro R; Barbosa, Fernando; Marques-Teixeira, João; Marsh, Abigail A

2015-12-01

Research suggests psychopathy is associated with structural brain alterations that may contribute to the affective and interpersonal deficits frequently observed in individuals with high psychopathic traits. However, the regional alterations related to different components of psychopathy are still unclear. We used voxel-based morphometry to characterize the structural correlates of psychopathy in a sample of 35 healthy adults assessed with the Triarchic Psychopathy Measure. Furthermore, we examined the regional grey matter alterations associated with the components described by the triarchic model. Our results showed that, after accounting for variation in total intracranial volume, age and IQ, overall psychopathy was negatively associated with grey matter volume in the left putamen and amygdala. Additional regression analysis with anatomical regions of interests revealed total triPM score was also associated with increased lateral orbitofrontal cortex (OFC) and caudate volume. Boldness was positively associated with volume in the right insula. Meanness was positively associated with lateral OFC and striatum volume, and negatively associated with amygdala volume. Finally, disinhibition was negatively associated with amygdala volume. Results highlight the contribution of both subcortical and cortical brain alterations for subclinical psychopathy and are discussed in light of prior research and theoretical accounts about the neurobiological bases of psychopathic traits. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Dopamine and μ-opioid receptor dysregulation in the brains of binge-eating female rats - possible relevance in the psychopathology and treatment of binge-eating disorder.

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Heal, David J; Hallam, Michelle; Prow, Michael; Gosden, Jane; Cheetham, Sharon; Choi, Yong K; Tarazi, Frank; Hutson, Peter

2017-06-01

Adult, female rats given irregular, limited access to chocolate develop binge-eating behaviour with normal bodyweight and compulsive/perseverative and impulsive behaviours similar to those in binge-eating disorder. We investigated whether (a) dysregulated central nervous system dopaminergic and opioidergic systems are part of the psychopathology of binge-eating and (b) these neurotransmitter systems may mediate the actions of drugs ameliorating binge-eating disorder psychopathology. Binge-eating produced a 39% reduction of striatal D 1 receptors with 22% and 23% reductions in medial and lateral caudate putamen and a 22% increase of striatal μ-opioid receptors. There was no change in D 1 receptor density in nucleus accumbens, medial prefrontal cortex or dorsolateral frontal cortex, striatal D 2 receptors and dopamine reuptake transporter sites, or μ-opioid receptors in frontal cortex. There were no changes in ligand affinities. The concentrations of monoamines, metabolites and estimates of dopamine (dopamine/dihydroxyphenylacetic acid ratio) and serotonin/5-hydroxyindolacetic acid ratio turnover rates were unchanged in striatum and frontal cortex. However, turnover of dopamine and serotonin in the hypothalamus was increased ~20% and ~15%, respectively. Striatal transmission via D 1 receptors is decreased in binge-eating rats while μ-opioid receptor signalling may be increased. These changes are consistent with the attenuation of binge-eating by lisdexamfetamine, which increases catecholaminergic neurotransmission, and nalmefene, a μ-opioid antagonist.

Inhibiting PKM[zeta] Reveals Dorsal Lateral and Dorsal Medial Striatum Store the Different Memories Needed to Support Adaptive Behavior

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Pauli, Wolfgang M.; Clark, Alexandra D.; Guenther, Heidi J.; O'Reilly, Randall C.; Rudy, Jerry W.

2012-01-01

Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or…

Dynorphin/KOP and nociceptin/NOP gene expression and epigenetic changes by cocaine in rat striatum and nucleus accumbens.

Science.gov (United States)

Caputi, Francesca Felicia; Di Benedetto, Manuela; Carretta, Donatella; Bastias del Carmen Candia, Sussy; D'Addario, Claudio; Cavina, Chiara; Candeletti, Sanzio; Romualdi, Patrizia

2014-03-03

Cocaine induces neurochemical changes of endogenous prodynorphin-kappa opioid receptor (pDYN-KOP) and pronociceptin/orphaninFQ-nociceptin receptor (pN/OFQ-NOP) systems. Both systems play an important role in rewarding mechanisms and addictive stimulus processing by modulating drug-induced dopaminergic activation in the mesocortico-limbic brain areas. They are also involved in regulating stress mechanisms related to addiction. The aim of this study was to investigate possible changes of gene expression of the dynorphinergic and nociceptinergic system components in the nucleus accumbens (NA) and in medial and lateral caudate putamen (mCPu and lCPu, respectively) of rats, following chronic subcutaneous infusion of cocaine. In addition, the epigenetic histone modifications H3K4me3 and H3K27me3 (an activating and a repressive marker, respectively) at the promoter level of the pDYN, KOP, pN/OFQ and NOP genes were investigated. Results showed that cocaine induced pDYN gene expression up-regulation in the NA and lCPu, and its down-regulation in the mCPu, whereas KOP mRNA levels were unchanged. Moreover, cocaine exposure decreased pN/OFQ gene expression in the NA and lCPu, while NOP mRNA levels appeared significantly increased in the NA and decreased in the lCPu. Specific changes of the H3K4me3 and H3K27me3 levels were found at pDYN, pN/OFQ, and NOP gene promoter, consistent with the observed gene expression alterations. The present findings contribute to better define the role of endogenous pDYN-KOP and pN/OFQ-NOP systems in neuroplasticity mechanisms following chronic cocaine treatment. The epigenetic histone modifications underlying the gene expression changes likely mediate the effects of cocaine on transcriptional regulation of specific gene promoters that result in long-lasting drug-induced plasticity. © 2013.

Proceedings of the Second Workshop on Numerical Analysis of Human and Surrogate Response to Accelerative Loading

Science.gov (United States)

2018-02-01

Thalamus Gray matter within cerebellum Caudate Putamen Ventricle s Voxelated data MRI Segmented data MPM model Discretization : 2 voxel = 1 MP 3D brain...model and the solution to the model • Math issue: “Solving the equations right”  Validation: Process of determining the degree to which a model is an...Microstructure and Mechanical Response Anisotropic within a layer: BV/TV is depth-dependent. Used discrete values for each of the 10 layers Orientation

Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease

OpenAIRE

Keene, C. Dirk; Rodrigues, Cecilia M. P.; Eich, Tacjana; Chhabra, Manik S.; Steer, Clifford J.; Low, Walter C.

2002-01-01

Huntington's disease (HD) is an untreatable neurological disorder caused by selective and progressive degeneration of the caudate nucleus and putamen of the basal ganglia. Although the etiology of HD pathology is not fully understood, the observed loss of neuronal cells is thought to occur primarily through apoptosis. Furthermore, there is evidence in HD that cell death is mediated through mitochondrial pathways, and mitochondrial deficits are commonly associated with HD. We have previously r...

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

International Nuclear Information System (INIS)

Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

2002-01-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

Energy Technology Data Exchange (ETDEWEB)

Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

2002-04-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms.

Science.gov (United States)

Müller-Vahl, Kirsten R; Grosskreutz, Julian; Prell, Tino; Kaufmann, Jörn; Bodammer, Nils; Peschel, Thomas

2014-01-07

Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS "only" (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.

Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements

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Jeffery G. Bednark

2015-07-01

Full Text Available Voluntary actions require the concurrent engagement and coordinated control of complex temporal (e.g. rhythm and ordinal motor processes. Using high-resolution functional magnetic resonance imaging (fMRI and multi-voxel pattern analysis (MVPA, we sought to determine the degree to which these complex motor processes are dissociable in basal ganglia and cortical networks. We employed three different finger-tapping tasks that differed in the demand on the sequential temporal rhythm or sequential ordering of submovements. Our results demonstrate that sequential rhythm and sequential order tasks were partially dissociable based on activation differences. The sequential rhythm task activated a widespread network centered around the SMA and basal-ganglia regions including the dorsomedial putamen and caudate nucleus, while the sequential order task preferentially activated a fronto-parietal network. There was also extensive overlap between sequential rhythm and sequential order tasks, with both tasks commonly activating bilateral premotor, supplementary motor, and superior/inferior parietal cortical regions, as well as regions of the caudate/putamen of the basal ganglia and the ventro-lateral thalamus. Importantly, within the cortical regions that were active for both complex movements, MVPA could accurately classify different patterns of activation for the sequential rhythm and sequential order tasks. In the basal ganglia, however, overlapping activation for the sequential rhythm and sequential order tasks, which was found in classic motor circuits of the putamen and ventro-lateral thalamus, could not be accurately differentiated by MVPA. Overall, our results highlight the convergent architecture of the motor system, where complex motor information that is spatially distributed in the cortex converges into a more compact representation in the basal ganglia.

Differences between Dorsal and Ventral Striatum in the Sensitivity of Tonically Active Neurons to Rewarding Events

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Kevin Marche

2017-07-01

Full Text Available Within the striatum, cholinergic interneurons, electrophysiologically identified as tonically active neurons (TANs, represent a relatively homogeneous group in terms of their functional properties. They display typical pause in tonic firing in response to rewarding events which are of crucial importance for reinforcement learning. These responses are uniformly distributed throughout the dorsal striatum (i.e., motor and associative striatum, but it is unknown, at least in monkeys, whether differences in the modulation of TAN activity exist in the ventral striatum (i.e., limbic striatum, a region specialized for processing of motivational information. To address this issue, we examined the activity of dorsal and ventral TANs in two monkeys trained on a Pavlovian conditioning task in which a visual stimulus preceded the delivery of liquid reward by a fixed time interval. We found that the proportion of TANs responding to the stimulus predictive of reward did not vary significantly across regions (58%–80%, whereas the fraction of TANs responding to reward was higher in the limbic striatum (100% compared to the motor (65% and associative striatum (52%. By examining TAN modulation at the level of both the population and the individual neurons, we showed that the duration of pause responses to the stimulus and reward was longer in the ventral than in the dorsal striatal regions. Also, the magnitude of the pause was greater in ventral than dorsal striatum for the stimulus predictive of reward but not for the reward itself. We found similar region-specific differences in pause response duration to the stimulus when the timing of reward was less predictable (fixed replaced by variable time interval. Regional variations in the duration and magnitude of the pause response were transferred from the stimulus to reward when reward was delivered in the absence of any predictive stimulus. It therefore appears that ventral TANs exhibit stronger responses to

Therapeutic window of dopamine D2/3 receptor occupancy to treat psychosis in Alzheimer's disease.

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Reeves, Suzanne; McLachlan, Emma; Bertrand, Julie; Antonio, Fabrizia D; Brownings, Stuart; Nair, Akshay; Greaves, Suki; Smith, Alan; Taylor, David; Dunn, Joel; Marsden, Paul; Kessler, Robert; Howard, Robert

2017-04-01

See Caravaggio and Graff-Guerrero (doi:10.1093/awx023) for a scientific commentary on this article.Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data. Non-linear mixed effects modelling was used to describe pharmacokinetic-occupancy curves in caudate, putamen and thalamus. Model outputs were used to estimate threshold steady state blood concentration and occupancy required to elicit a clinically relevant response (>25% reduction in scores on delusions, hallucinations and agitation domains of the Neuropsychiatric Inventory) and extrapyramidal side effects (Simpson Angus Scale scores > 3). Average steady state blood levels were low (71 ± 30 ng/ml), and associated with high D2/3 occupancies (65 ± 8%, caudate; 67 ± 11%, thalamus; 52 ± 11%, putamen). Antipsychotic clinical response occurred at a threshold concentration of 20 ng/ml and D2/3 occupancies of 43% (caudate), 25% (putamen), 43

Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease.

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Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf; Huang, Neng C; Poston, Kathleen L; Bronte-Stewart, Helen M; Schulte, Tilman

2015-09-01

Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance.

Schizophrenia alters intra-network functional connectivity in the caudate for detecting speech under informational speech masking conditions.

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Zheng, Yingjun; Wu, Chao; Li, Juanhua; Li, Ruikeng; Peng, Hongjun; She, Shenglin; Ning, Yuping; Li, Liang

2018-04-04

Speech recognition under noisy "cocktail-party" environments involves multiple perceptual/cognitive processes, including target detection, selective attention, irrelevant signal inhibition, sensory/working memory, and speech production. Compared to health listeners, people with schizophrenia are more vulnerable to masking stimuli and perform worse in speech recognition under speech-on-speech masking conditions. Although the schizophrenia-related speech-recognition impairment under "cocktail-party" conditions is associated with deficits of various perceptual/cognitive processes, it is crucial to know whether the brain substrates critically underlying speech detection against informational speech masking are impaired in people with schizophrenia. Using functional magnetic resonance imaging (fMRI), this study investigated differences between people with schizophrenia (n = 19, mean age = 33 ± 10 years) and their matched healthy controls (n = 15, mean age = 30 ± 9 years) in intra-network functional connectivity (FC) specifically associated with target-speech detection under speech-on-speech-masking conditions. The target-speech detection performance under the speech-on-speech-masking condition in participants with schizophrenia was significantly worse than that in matched healthy participants (healthy controls). Moreover, in healthy controls, but not participants with schizophrenia, the strength of intra-network FC within the bilateral caudate was positively correlated with the speech-detection performance under the speech-masking conditions. Compared to controls, patients showed altered spatial activity pattern and decreased intra-network FC in the caudate. In people with schizophrenia, the declined speech-detection performance under speech-on-speech masking conditions is associated with reduced intra-caudate functional connectivity, which normally contributes to detecting target speech against speech masking via its functions of suppressing masking-speech signals.

METHAMPHETAMINE-INDUCED CELL DEATH: SELECTIVE VULNERABILITY IN NEURONAL SUBPOPULATIONS OF THE STRIATUM IN MICE

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ZHU, J. P. Q.; XU, W.; ANGULO, J. A.

2010-01-01

Methamphetamine (METH) is an illicit and potent psychostimulant, which acts as an indirect dopamine agonist. In the striatum, METH has been shown to cause long lasting neurotoxic damage to dopaminergic nerve terminals and recently, the degeneration and death of striatal cells. The present study was undertaken to identify the type of striatal neurons that undergo apoptosis after METH. Male mice received a single high dose of METH (30 mg/kg, i.p.) and were killed 24 h later. To demonstrate that METH induces apoptosis in neurons, we combined terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining with immunohistofluorescence for the neuronal marker neuron-specific nuclear protein (NeuN). Staining for TUNEL and NeuN was colocalized throughout the striatum. METH induces apoptosis in approximately 25% of striatal neurons. Cell counts of TUNEL-positive neurons in the dorsomedial, ventromedial, dorsolateral and ventrolateral quadrants of the striatum did not reveal anatomical preference. The type of striatal neuron undergoing cell death was determined by combining TUNEL with immunohistofluorescence for selective markers of striatal neurons: dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH induces apoptosis in approximately 21% of dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000-positive neurons (projection neurons), 45% of GABA-parvalbumin-positive neurons in the dorsal striatum, and 29% of cholinergic neurons in the dorsal–medial striatum. In contrast, the SST-positive interneurons were refractory to METH-induced apoptosis. Finally, the amount of cell loss determined with Nissl staining correlated with the amount of TUNEL staining in the striatum of METH-treated animals. In conclusion, some of the striatal projection neurons and the GABA-parvalbumin and cholinergic interneurons were removed by apoptosis in the aftermath of METH. This

Higher landing accuracy in expert pilots is associated with lower activity in the caudate nucleus.

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Maheen M Adamson

Full Text Available The most common lethal accidents in General Aviation are caused by improperly executed landing approaches in which a pilot descends below the minimum safe altitude without proper visual references. To understand how expertise might reduce such erroneous decision-making, we examined relevant neural processes in pilots performing a simulated landing approach inside a functional MRI scanner. Pilots (aged 20-66 were asked to "fly" a series of simulated "cockpit view" instrument landing scenarios in an MRI scanner. The scenarios were either high risk (heavy fog-legally unsafe to land or low risk (medium fog-legally safe to land. Pilots with one of two levels of expertise participated: Moderate Expertise (Instrument Flight Rules pilots, n = 8 or High Expertise (Certified Instrument Flight Instructors or Air-Transport Pilots, n = 12. High Expertise pilots were more accurate than Moderate Expertise pilots in making a "land" versus "do not land" decision (CFII: d' = 3.62 ± 2.52; IFR: d' = 0.98 ± 1.04; p<.01. Brain activity in bilateral caudate nucleus was examined for main effects of expertise during a "land" versus "do not land" decision with the no-decision control condition modeled as baseline. In making landing decisions, High Expertise pilots showed lower activation in the bilateral caudate nucleus (0.97 ± 0.80 compared to Moderate Expertise pilots (1.91 ± 1.16 (p<.05. These findings provide evidence for increased "neural efficiency" in High Expertise pilots relative to Moderate Expertise pilots. During an instrument approach the pilot is engaged in detailed examination of flight instruments while monitoring certain visual references for making landing decisions. The caudate nucleus regulates saccade eye control of gaze, the brain area where the "expertise" effect was observed. These data provide evidence that performing "real world" aviation tasks in an fMRI provide objective data regarding the relative expertise of pilots and brain regions

Fluorine-18-fluorodeoxyglucose positron emission tomography (PET) brain imaging patterns in patients with suspected X-linked dystonia parkinsonism (study in progress)

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Santiago, J.F.Y.; Fugoso, L.; Evidente, V.G.H.

2004-01-01

Objective: X-linked dystonia-parkinsonism (XDP or Lubag) is an adult-onset dystonia syndrome that afflicts mostly Filipino men from the island of Panay, Philippines.It starts focally and becomes generalized or multifocal after the first five years. Parkinsonism is commonly encountered as the initial symptom before the onset of dystonia. Patients may manifest a wide spectrum of movement disorders, including myoclonus, chorea, akathisia, ballism and myorhythmia. Diagnosis is based on the clinical presentation, and the establishment of an x-linked recessive pattern of inheritance and maternal roots from the Panay Islands. Neuroimaging in advanced cases have demonstrated caudate and putaminal atrophy. Previous studies using PET have shown selective reduction in normalized striatal glucose metabolism. The purpose of this study is to describe the FDG distribution using PET imaging in Filipino patients with suspected or confirmed Lubag in various stages of their disease in order to determine if FDG-PET can be used in the initial diagnosis and staging of the disease. Methods and results: All patients presenting to the Movement Disorders Center of St. Lukes Medical Center with dystonia and Parkinsonism symptoms with X-linked recessive inheritance pattern and maternal roots traceable to the Panay Islands were sent for a Brain FDG PET Scan. Seven male patients with various movement disorders (dysarthria, face dystonia, Parkinsonism, hemibalismus, involuntary movements and rest tremors) with duration of symptoms from 1 to 5 years underwent a PET scan. All patients had non visualized bilateral putamen, four had hypometabolic caudate nuclei, one had intense (hypermetabolic) caudate nuclei. CT scan and MRI did not show any findings which may explain the movement disorder symptoms. More patients are being collected and gene typing is planned for some patients. Conclusions: This small series of patients demonstrate that patients with the phenotypic characteristics of X

Age-related decrease of 11C-N-methylspiperone in vivo binding to human striatum detected by PET

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Iyo, Masaomi; Yamasaki, Toshiro; Fukuda, Hiroshi

1989-01-01

The effect of aging on 11 C-N-methylspiperone binding to living human striatum was demonstrated using positron emission tomography. The ll normal volunteers (22 to 72 years old) participated in this study. The uptake of 11 C-N-methylspiperone in the brain following intravenous injection was highest in the striatum in individual subject. And the uptake in the striatum only gradually increased until the end of the study. The uptake of 11 C-N-methylspiperone in cerebellum peaked within 10 minutes following injection and then rapidly dropped. The association rate constant 'k 3 ' was calculated from the slope of the radioactivity-ratio of striatum to cerebellum versus the equivalent time. The equivalent time was calculated from the radioactivity of cerebellum as an input function. The exponential decrease of the k 3 value with aging was observed. The k 3 value of the youngest subject (22 years old, male) was 0.035/min, while that of the oldest one (72 years old, male) was found to be 0.020/min. These data suggested that the dopaminergic activity through D2 dopamine receptors reduces with aging in human striatum. (author)

Variable activation in striatal subregions across components of a social influence task in young adult cannabis users.

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Gilman, Jodi M; Lee, Sang; Kuster, John K; Lee, Myung Joo; Kim, Byoung Woo; van der Kouwe, Andre; Blood, Anne J; Breiter, Hans C

2016-05-01

Decades of research have demonstrated the importance of social influence in initiation and maintenance of drug use, but little is known about neural mechanisms underlying social influence in young adults who use recreational drugs. To better understand whether the neural and/or behavioral response to social influence differs in young adults using illicit drugs, 20 marijuana-using young adults (MJ) aged 18-25, and 20 controls (CON) performed a decision-making task in the context of social influence, while they underwent functional magnetic resonance imaging scans. A priori analyses focused on the nucleus accumbens (NAc), with post hoc analyses in the rest of the striatum. In this task, participants could choose to either follow or go against group influence. When subjects applied social information to response choice selection (independent of following or going against group influence), we observed activation in the middle striatum (caudate), in the MJ group only, that extended ventrally into the NAc. MJ users but not CON showed greater activation in the NAc but not the caudate while making choices congruent with group influence as opposed to choices going against group influence. Activation in the NAc when following social influence was associated with amount of drug use reported. In contrast, during the feedback phase of the task we observed significant NAc activation in both MJ and CON, along with dorsal caudate activation only in MJ participants. This NAc activation did not correlate with drug use. This study shows that MJ users, but not CON, show differential brain activation across striatal subregions when applying social information to make a decision, following versus going against a group of peers, or receiving positive feedback. The current work suggests that differential neural sensitivity to social influence in regions such as the striatum may contribute to the development and/or maintenance of marijuana use.

Overeating Behavior and Striatal Dopamine with 6-[18F]-Fluoro-L--Tyrosine PET

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Claire E. Wilcox

2010-01-01

Full Text Available Eating behavior may be affected by dopamine synthesis capacity. In this study, 6-[18F]-fluoro-L--tyrosine (FMT positron emission tomography (PET uptake in striatal subregions was correlated with BMI (kg/m2 and an estimate of the frequency of prior weight loss attempts in 15 healthy subjects. BMI was negatively correlated with FMT uptake in the dorsal caudate. Although the association between BMI and FMT uptake in the dorsal caudate was not significant upon correction for age and sex, the association fell within the range of a statistical trend. Weight loss attempts divided by years trying was also negatively correlated with FMT uptake in the dorsal putamen (=.05. These results suggest an association between low dorsal striatal presynaptic dopamine synthesis capacity and overeating behavior.

Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors.

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Lee, Yunjin; Kim, Hannah; Kim, Ji-Eun; Park, Jin-Young; Choi, Juli; Lee, Jung-Eun; Lee, Eun-Hwa; Han, Pyung-Lim

2018-07-01

The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.

Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms

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2014-01-01

Background Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS “only” (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Results Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Conclusions Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded. PMID:24397347

One pair of hands is not like another: caudate BOLD response in dogs depends on signal source and canine temperament

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Peter F. Cook

2014-09-01

Full Text Available Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog’s respective handler, an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog’s general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer. A group-level psychophysiological interaction (PPI connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications

Effect of ginseng saponina on nicotine-induced dopamine release in the rat nucleus accumbens and striatum

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Kim, Sang Eun; Shim, In Sop; Chung, June Key; Lee, Myung Chul

2002-01-01

We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum and nucleus accumbens of freely moving rats using in vivo microdialysis technique. Systemic pretreatment with GTS decreased striatal DA release induced by local infusion of nicotine into the striatum. However, GTS had no effect on the resting levels of extracellular DA in the striatum. GTS also blocked nicotine-induced DA release in the nucleus accumbens. The results of the present study suggest that GTS acts on the DA terminals to prevent DA release induced by nicotine. This may reflect the blocking effect of GTS on behavioral hyperactivity induced by psychostimulants

Effect of ginseng saponina on nicotine-induced dopamine release in the rat nucleus accumbens and striatum

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Kim, Sang Eun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Shim, In Sop [Kyunghee University, Seoul (Korea, Republic of); Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2002-10-01

We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum and nucleus accumbens of freely moving rats using in vivo microdialysis technique. Systemic pretreatment with GTS decreased striatal DA release induced by local infusion of nicotine into the striatum. However, GTS had no effect on the resting levels of extracellular DA in the striatum. GTS also blocked nicotine-induced DA release in the nucleus accumbens. The results of the present study suggest that GTS acts on the DA terminals to prevent DA release induced by nicotine. This may reflect the blocking effect of GTS on behavioral hyperactivity induced by psychostimulants.

Perfusion abnormality of the caudate nucleus in patients with paroxysmal kinesigenic choreoathetosis

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Joo, Eun Yeon; Hong, Seung Bong; Tae, Woo Suk; Kim, Jee Hyun; Han, Sun Jung; Seo, Dae Won; Lee, Kyung-Han; Kim, Byung Tae; Kim, Myoung-Hee; Kim, Seunghwan; Lee, Mann Hyung

2005-01-01

Previous cerebral blood flow and glucose metabolism studies suggest that the basal ganglia or thalamus is involved in the pathogenesis of paroxysmal kinesigenic choreoathetosis (PKC). However, the underlying cerebral abnormalities in idiopathic PKC have not been elucidated. To localise cerebral perfusion abnormalities in PKC, we performed interictal brain perfusion 99m Tc-ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in PKC patients and in normal controls. Sixteen patients with idiopathic PKC and 18 age- and sex-matched normal controls were included. The patients were de novo diagnosed as having PKC, or had not taken medication for at least 3 months; none of them had structural abnormalities on MRI. Patients had a history of PKC attacks of a duration not exceeding 5 min and starting either on one side or on both sides of the body. These attacks were always induced by a sudden initiation of voluntary movement. PKC attacks were recorded in a hospital after being induced by neurology staff in 13 of the 16 patients. Interictal brain perfusion 99m Tc-ECD SPECT was performed in all 16 patients and 18 normal controls. Differences between the cerebral perfusion in the PKC group and the normal control group were tested by statistical parametric mapping. Student's t test was used for inter-group comparisons. Compared with normal controls, patients with idiopathic PKC showed interictal hypoperfusion in the posterior regions of the bilateral caudate nuclei (false discovery rate-corrected P<0.001 with a small volume correction). This study showed that cerebral perfusion abnormality of bilateral caudate nuclei is present in idiopathic PKC. (orig.)

Perfusion abnormality of the caudate nucleus in patients with paroxysmal kinesigenic choreoathetosis

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Joo, Eun Yeon; Hong, Seung Bong; Tae, Woo Suk; Kim, Jee Hyun; Han, Sun Jung; Seo, Dae Won [Sungkyunkwan University School of Medicine, Department of Neurology, Samsung Medical Center and Center for Clinical Medicine, SBRI, Seoul (Korea); Lee, Kyung-Han; Kim, Byung Tae [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center and Center for Clinical Medicine, SBRI, Seoul (Korea); Kim, Myoung-Hee [Ewha Women' s University, Department of Computer Science and Engineering, Seoul (Korea); Kim, Seunghwan [POSTECH, APCTP/NCSL, Department of Physics, Pohang (Korea); Lee, Mann Hyung [Catholic University of Daegue, College of Pharmacy, Gyongbook (Korea)

2005-10-01

Previous cerebral blood flow and glucose metabolism studies suggest that the basal ganglia or thalamus is involved in the pathogenesis of paroxysmal kinesigenic choreoathetosis (PKC). However, the underlying cerebral abnormalities in idiopathic PKC have not been elucidated. To localise cerebral perfusion abnormalities in PKC, we performed interictal brain perfusion {sup 99m}Tc-ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in PKC patients and in normal controls. Sixteen patients with idiopathic PKC and 18 age- and sex-matched normal controls were included. The patients were de novo diagnosed as having PKC, or had not taken medication for at least 3 months; none of them had structural abnormalities on MRI. Patients had a history of PKC attacks of a duration not exceeding 5 min and starting either on one side or on both sides of the body. These attacks were always induced by a sudden initiation of voluntary movement. PKC attacks were recorded in a hospital after being induced by neurology staff in 13 of the 16 patients. Interictal brain perfusion {sup 99m}Tc-ECD SPECT was performed in all 16 patients and 18 normal controls. Differences between the cerebral perfusion in the PKC group and the normal control group were tested by statistical parametric mapping. Student's t test was used for inter-group comparisons. Compared with normal controls, patients with idiopathic PKC showed interictal hypoperfusion in the posterior regions of the bilateral caudate nuclei (false discovery rate-corrected P<0.001 with a small volume correction). This study showed that cerebral perfusion abnormality of bilateral caudate nuclei is present in idiopathic PKC. (orig.)

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders.

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Damiano, Cara R; Cockrell, Dillon C; Dunlap, Kaitlyn; Hanna, Eleanor K; Miller, Stephanie; Bizzell, Joshua; Kovac, Megan; Turner-Brown, Lauren; Sideris, John; Kinard, Jessica; Dichter, Gabriel S

2015-01-01

Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.

Extensive training and hippocampus or striatum lesions: effect on place and response strategies.

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Jacobson, Tara K; Gruenbaum, Benjamin F; Markus, Etan J

2012-02-01

The hippocampus has been linked to spatial navigation and the striatum to response learning. The current study focuses on how these brain regions continue to interact when an animal is very familiar with the task and the environment and must continuously switch between navigation strategies. Rats were trained to solve a plus maze using a place or a response strategy on different trials within a testing session. A room cue (illumination) was used to indicate which strategy should be used on a given trial. After extensive training, animals underwent dorsal hippocampus, dorsal lateral striatum or sham lesions. As expected hippocampal lesions predominantly caused impairment on place but not response trials. Striatal lesions increased errors on both place and response trials. Competition between systems was assessed by determining error type. Pre-lesion and sham animals primarily made errors to arms associated with the wrong (alternative) strategy, this was not found after lesions. The data suggest a qualitative change in the relationship between hippocampal and striatal systems as a task is well learned. During acquisition the two systems work in parallel, competing with each other. After task acquisition, the two systems become more integrated and interdependent. The fact that with extensive training (as something becomes a "habit"), behaviors become dependent upon the dorsal lateral striatum has been previously shown. The current findings indicate that dorsal lateral striatum involvement occurs even when the behavior is spatial and continues to require hippocampal processing. Published by Elsevier Inc.

Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum.

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Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C

2011-05-01

Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

SPECT study with I-123-Ioflupane (DaTSCAN) in patients with essential tremor. Is there any correlation with Parkinson's disease?

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Gerasimou, G.; Papanastasiou, E.; Arnaoutoglou, M.; Moralidis, E.; Aggelopoulou, T.; Gotzamani-Psarrakou, A.; Costa, D.C.; Bostanjiopoulou, S.

2012-01-01

The differential diagnosis between essential tremor (ET) and Parkinson's disease (PD) may be, in some cases, very difficult on clinical grounds alone. In addition, it is accepted that a small percentage of ET patients presenting symptoms and signs of possible PD may progress finally to a typical pattern of parkinsonism. Ioflupane, N-u-fluoropropyl-2a-carbomethoxy-3a-(4-iodophenyl) nortropane, also called FP-CIT, labelled with 123 I (commercially known as DaTSCAN) has been proven to be useful in the differential diagnosis between PD and ET and to confirm dopaminergic degeneration in patients with parkinsonism. The aim of this study is to identify dopaminergic degeneration in patients with PD and distinguish them from others with ET using semi-quantitative single photon emission computed tomography (SPECT) 123 I-Ioflupane (DaTSCAN) data in comparison with normal volunteers (NV), in addition with the respective ones of patients referred as suffering from ET, as well as, of patients with a PD diagnosis at an initial stage with a unilateral presentation of motor signs. Twenty-eight patients suffering from ET (10 males plus 18 females) and 28 NV (12 males and 16 females) were enroled in this study. In addition, 33 patients (11 males and 22 females) with an established diagnosis of PD with unilateral limb involvement (12 left hemi-body and 21 right hemi-body) were included for comparison with ET. We used DaTSCAN to obtain SPECT images and measure the radiopharmaceutical uptake in the striatum (S), as well as the caudate nucleus (CN) and putamen (P) in all individuals. Qualitative (Visual) interpretation of the SPECT data did not find any difference in the uptake of the radiopharmaceutical at the level of the S, CN and P between NV and ET patients. Reduced accumulation of the radiopharmaceutical uptake was found in the P of all PD patients. Semiquantitative analysis revealed significant differences between NV and ET patients in the striatum, reduced in the latter. There

Texture analysis of ultrahigh field T2*-weighted MR images of the brain: application to Huntington's disease.

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Doan, Nhat Trung; van den Bogaard, Simon J A; Dumas, Eve M; Webb, Andrew G; van Buchem, Mark A; Roos, Raymund A C; van der Grond, Jeroen; Reiber, Johan H C; Milles, Julien

2014-03-01

To develop a framework for quantitative detection of between-group textural differences in ultrahigh field T2*-weighted MR images of the brain. MR images were acquired using a three-dimensional (3D) T2*-weighted gradient echo sequence on a 7 Tesla MRI system. The phase images were high-pass filtered to remove phase wraps. Thirteen textural features were computed for both the magnitude and phase images of a region of interest based on 3D Gray-Level Co-occurrence Matrix, and subsequently evaluated to detect between-group differences using a Mann-Whitney U-test. We applied the framework to study textural differences in subcortical structures between premanifest Huntington's disease (HD), manifest HD patients, and controls. In premanifest HD, four phase-based features showed a difference in the caudate nucleus. In manifest HD, 7 magnitude-based features showed a difference in the pallidum, 6 phase-based features in the caudate nucleus, and 10 phase-based features in the putamen. After multiple comparison correction, significant differences were shown in the putamen in manifest HD by two phase-based features (both adjusted P values=0.04). This study provides the first evidence of textural heterogeneity of subcortical structures in HD. Texture analysis of ultrahigh field T2*-weighted MR images can be useful for noninvasive monitoring of neurodegenerative diseases. Copyright © 2013 Wiley Periodicals, Inc.

Bilingualism at the core of the brain. Structural differences between bilinguals and monolinguals revealed by subcortical shape analysis.

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Burgaleta, Miguel; Sanjuán, Ana; Ventura-Campos, Noelia; Sebastian-Galles, Núria; Ávila, César

2016-01-15

Naturally acquiring a language shapes the human brain through a long-lasting learning and practice process. This is supported by previous studies showing that managing more than one language from early childhood has an impact on brain structure and function. However, to what extent bilingual individuals present neuroanatomical peculiarities at the subcortical level with respect to monolinguals is yet not well understood, despite the key role of subcortical gray matter for a number of language functions, including monitoring of speech production and language control - two processes especially solicited by bilinguals. Here we addressed this issue by performing a subcortical surface-based analysis in a sample of monolinguals and simultaneous bilinguals (N=88) that only differed in their language experience from birth. This analysis allowed us to study with great anatomical precision the potential differences in morphology of key subcortical structures, namely, the caudate, accumbens, putamen, globus pallidus and thalamus. Vertexwise analyses revealed significantly expanded subcortical structures for bilinguals compared to monolinguals, localized in bilateral putamen and thalamus, as well as in the left globus pallidus and right caudate nucleus. A topographical interpretation of our results suggests that a more complex phonological system in bilinguals may lead to a greater development of a subcortical brain network involved in monitoring articulatory processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification

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Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

2011-01-01

Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…

Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum.

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Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan

2016-12-14

Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior. Converging evidence in human neuroimaging studies has shown that the reward prediction errors are correlated with activity in the ventral striatum. Our results demonstrate that this region is simultaneously correlated with a stimulus prediction error. Furthermore, the learning system that is currently dominating behavioral choice dynamically engages the ventral striatum for computing its prediction errors. This demonstrates that the prediction error representations are highly dynamic and influenced by various experimental context. This finding points to a general role of the ventral striatum in detecting expectancy violations and encoding error signals regardless of the specific nature of the reinforcer itself. Copyright © 2016 the authors 0270-6474/16/3612650-11$15.00/0.

Creutzfeldt jakob disease

International Nuclear Information System (INIS)

Haider, E.; Raja, S.; Wali, W.; Tariq, M.

2013-01-01

A case of 50 years of age, male with sporadic Creutzfeldt Jakob Disease (sCJD) is reported. Patient had dementia, behavioural abnormalities, unsteady gait and myoclonic jerks. Magnetic resonance imaging (MRI) brain T2 weighted and Fluid Attenuated Inverse Recovery (FLAIR) images showed abnormally increased signal intensity in caudate nucleus and putamen. Scalp electroencephalogram (EEG) revealed periodic synchronous biphasic sharp wave complexes. On the basis of history, clinical findings, typical MRI brain and EEG changes, diagnosis of sporadic CJD was made. (author)

Regional distribution of enkephalinase in rat brain by autoradiography

International Nuclear Information System (INIS)

Waksman, G.; Hamel, E.; Besselievre, R.; Fournie-Zaluski, M.C.; Roques, B.P.; Bouboutou, R.

1984-01-01

The first visualization of enkephalinase (neutral metalloendopeptidase, E.C.3.4.24.11) in rat brain was obtained by autoradiography, using a new tritiated inhibitor: [ 3 H]N-[(R, S) 3-(N-hydroxy) carboxamido-2-benzyl propanoyl]-glycine ( 3 H-HCBP-Gly). The preliminary analysis of sections clearly showed a discrete localization of enkephalinase in enkephalin enriched regions, such as caudate nucleus, putamen, globus pallidus, and substantia nigra. Moreover 3 H-HCBP-Gly binding also occured in choroid plexus and spinal cord [fr

Control of Huntington’s Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2

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Lea J. Hachigian

2017-12-01

Full Text Available Summary: Alteration of corticostriatal glutamatergic function is an early pathophysiological change associated with Huntington’s disease (HD. The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors. We note that Foxp2 encodes the longest polyglutamine repeat protein in the human reference genome, and we show that it can be sequestered into aggregates with polyglutamine-expanded mutant Huntingtin protein (mHTT. Foxp2 overexpression in HD model mice leads to altered expression of several genes associated with synaptic function, genes that present additional targets for normalization of corticostriatal dysfunction in HD. : Hachigian et al. demonstrate that manipulating levels of the striatum-enriched transcription factor Foxp2 can either rescue or mimic HD-associated behaviors in vivo. They link Foxp2 to the post-developmental regulation of the structure and function of the corticostriatal synapse. Keywords: Huntington’s disease, Foxp2, striatum, corticostriatal synapse

A fundamental study on accumulation of [125I]IBZM in the rat striatum and on effect of non-labeled ligand

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Ishikawa, Nobuyoshi; Nakamura, Toshihiko; Satou, Motohiro; Takeda, Tohoru; Wu, Jin; Motoji, Naomi; Shigematsu, Akiyo.

1995-01-01

Iodo-125-labeled iodobenzamide ([ 125 I]IBZM) is used as a specific binding radioligand to dopamine D 2 receptors with high affinity and selectivity. The radioligand was homogeneously distributed in the whole brain initially after anministration, and rapidly washed out from the dopamine receptor-poor area followed by persistent retention in the striatum. Regression curve generated from striatum/cortex PSL ratio indicated the constant washout rate from striatum and cortex respectively. In the pretreated rat by cold benzamide (2 mg/kg), the accumulation of the radioligand was significantly suppressed in the striatum (48.8%). Iodine-125-labeled iodo-benzamide has the promise for investigation of dopamine D 2 receptors in the living brain. (author)

Avoiding boredom: Caudate and insula activity reflects boredom-elicited purchase bias.

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Dal Mas, Dennis E; Wittmann, Bianca C

2017-07-01

People show a strong tendency to avoid boring situations, but the neural systems mediating this behavioural bias are yet unknown. We used functional magnetic resonance imaging (fMRI) to investigate how the anticipation of a boring task influences decisions to purchase entertainment. Participants accepted higher prices to avoid boredom compared to control tasks, and individual differences in boredom experience predicted the increase in price. This behavioural bias was associated with higher activity in the caudate nucleus during music purchases driven by boredom avoidance. Insula activation was increased during performance of the boring task and subsequently associated with individual differences in boredom-related decision making. These results identify a mechanism that drives decisions to avoid boring situations and potentially underlies consumer decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

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Kienast, Thorsten; Rapp, Michael; Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias; Wrase, Jana; Heinz, Andreas; Braus, Dieter F.; Smolka, Michael N.; Mann, Karl; Roesch, Frank; Cumming, Paul; Gruender, Gerhard; Bartenstein, Peter

2008-01-01

Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [ 18 F]DOPA for measurements of dopamine synthesis capacity and [ 18 F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [ 18 F]DOPA net influx constant K in app /[ 18 F]DMFP-binding potential (BP N D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

The Neural Representation of Goal-Directed Actions and Outcomes in the Ventral Striatum's Olfactory Tubercle

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Gadziola, Marie A.

2016-01-01

The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities between the ventral striatum's nucleus accumbens and olfactory tubercle (OT) suggests the distributed involvement of neurons within the ventral striatopallidal complex in motivated behaviors. Although the nucleus accumbens has an established role in representing goal-directed actions and their outcomes, it is not known whether this function is localized within the nucleus accumbens or distributed also within the OT. Answering such a fundamental question will expand our understanding of the neural mechanisms underlying motivated behaviors. Here we address whether the OT encodes natural reinforcers and serves as a substrate for motivational information processing. In recordings from mice engaged in a novel water-motivated instrumental task, we report that OT neurons modulate their firing rate during initiation and progression of the instrumental licking behavior, with some activity being internally generated and preceding the first lick. We further found that as motivational drive decreases throughout a session, the activity of OT neurons is enhanced earlier relative to the behavioral action. Additionally, OT neurons discriminate the types and magnitudes of fluid reinforcers. Together, these data suggest that the processing of reward information and the orchestration of goal-directed behaviors is a global principle of the ventral striatum and have important implications for understanding the neural systems subserving addiction and mood disorders. SIGNIFICANCE STATEMENT Goal-directed behaviors are widespread among animals and underlie complex behaviors ranging from food intake, social behavior, and even pathological conditions, such as gambling and drug addiction. The ventral striatum is a neural system critical for evaluating reward information and the initiation of goal-directed behaviors. Here we

Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

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Dong Seok Yi

Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

Amygdala and ventral striatum make distinct contributions to reinforcement learning

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Costa, Vincent D.; Monte, Olga Dal; Lucas, Daniel R.; Murray, Elisabeth A.; Averbeck, Bruno B.

2016-01-01

Summary Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with a RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys’ choice reaction times, which emphasized a speed-accuracy tradeoff that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL. PMID:27720488

The influence of cannabinoids on learning and memory processes of the dorsal striatum.

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Goodman, Jarid; Packard, Mark G

2015-11-01

Extensive evidence indicates that the mammalian endocannabinoid system plays an integral role in learning and memory. Our understanding of how cannabinoids influence memory comes predominantly from studies examining cognitive and emotional memory systems mediated by the hippocampus and amygdala, respectively. However, recent evidence suggests that cannabinoids also affect habit or stimulus-response (S-R) memory mediated by the dorsal striatum. Studies implementing a variety of maze tasks in rats indicate that systemic or intra-dorsolateral striatum infusions of cannabinoid receptor agonists or antagonists impair habit memory. In mice, cannabinoid 1 (CB1) receptor knockdown can enhance or impair habit formation, whereas Δ(9)THC tolerance enhances habit formation. Studies in human cannabis users also suggest an enhancement of S-R/habit memory. A tentative conclusion based on the available data is that acute disruption of the endocannabinoid system with either agonists or antagonists impairs, whereas chronic cannabinoid exposure enhances, dorsal striatum-dependent S-R/habit memory. CB1 receptors are required for multiple forms of striatal synaptic plasticity implicated in memory, including short-term and long-term depression. Interactions with the hippocampus-dependent memory system may also have a role in some of the observed effects of cannabinoids on habit memory. The impairing effect often observed with acute cannabinoid administration argues for cannabinoid-based treatments for human psychopathologies associated with a dysfunctional habit memory system (e.g. post-traumatic stress disorder and drug addiction/relapse). In addition, the enhancing effect of repeated cannabinoid exposure on habit memory suggests a novel neurobehavioral mechanism for marijuana addiction involving the dorsal striatum-dependent memory system. Copyright © 2015 Elsevier Inc. All rights reserved.

Vomeronasal inputs to the rodent ventral striatum.

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Ubeda-Bañon, I; Novejarque, A; Mohedano-Moriano, A; Pro-Sistiaga, P; Insausti, R; Martinez-Garcia, F; Lanuza, E; Martinez-Marcos, A

2008-03-18

Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and mice. The resulting anterograde labeling includes the olfactory tubercle, the islands of Calleja and sparse terminal fields in the shell of the nucleus accumbens and ventral pallidum. This projection has been confirmed by injections of retrograde tracers into the ventral striato-pallidum that render retrograde labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P in the ventral striato-pallidum of rats, and the anterograde tracing of the vomeronasal amygdaloid input in the same material confirm that, similar to reptiles, the ventral striatum of mammals includes a specialized vomeronasal structure (olfactory tubercle and islands of Calleja) displaying dense neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations. The possibility that parts of the accumbens shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded.

Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

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Kienast, Thorsten; Rapp, Michael [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias [University of Mainz, Department of Nuclear Medicine, Mainz (Germany); Wrase, Jana; Heinz, Andreas [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Central Institute of Mental Health, Mannheim (Germany); Braus, Dieter F. [University of Hamburg, Neuroimage Nord, Department of Psychiatry, Hamburg (Germany); Smolka, Michael N.; Mann, Karl [Central Institute of Mental Health, Mannheim (Germany); Roesch, Frank [University of Mainz, Institute of Nuclear Chemistry, Mainz (Germany); Cumming, Paul [PET Center and Center for Functionally Integrative Neuroscience, Aarhus (Denmark); Gruender, Gerhard [Aachen University Medical Center, Department of Psychiatry of the RWTH, Mainz (Germany); Bartenstein, Peter [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

2008-06-15

Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [{sup 18}F]DOPA for measurements of dopamine synthesis capacity and [{sup 18}F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [{sup 18}F]DOPA net influx constant K{sub in}{sup app} /[{sup 18}F]DMFP-binding potential (BP{sub N}D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

Somatic mtDNA mutation spectra in the aging human putamen.

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Siôn L Williams

Full Text Available The accumulation of heteroplasmic mitochondrial DNA (mtDNA deletions and single nucleotide variants (SNVs is a well-accepted facet of the biology of aging, yet comprehensive mutation spectra have not been described. To address this, we have used next generation sequencing of mtDNA-enriched libraries (Mito-Seq to investigate mtDNA mutation spectra of putamen from young and aged donors. Frequencies of the "common" deletion and other "major arc" deletions were significantly increased in the aged cohort with the fold increase in the frequency of the common deletion exceeding that of major arc deletions. SNVs also increased with age with the highest rate of accumulation in the non-coding control region which contains elements necessary for translation and replication. Examination of predicted amino acid changes revealed a skew towards pathogenic SNVs in the coding region driven by mutation bias. Levels of the pathogenic m.3243A>G tRNA mutation were also found to increase with age. Novel multimeric tandem duplications that resemble murine control region multimers and yeast ρ(- mtDNAs, were identified in both young and aged specimens. Clonal ∼50 bp deletions in the control region were found at high frequencies in aged specimens. Our results reveal the complex manner in which the mitochondrial genome alters with age and provides a foundation for studies of other tissues and disease states.

Putaminal mosaic visualized by tyrosine hydroxylase immunohistochemistry in the human neostriatum.

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Ryoma eMorigaki

2016-04-01

Full Text Available Among the basal ganglia-thalamocortical circuits, the putamen plays a critical role in the ‘motor’ circuits that control voluntary movements and motor learning. The human neostriatum comprises two functional subdivisions known as the striosome (patch and matrix compartments. Accumulating evidence suggests that compartment-specific dysregulations of dopamine activity might be involved in the disease-specific pathology and symptoms of human striatal diseases including movement disorders. This study was undertaken to examine whether or how striatal dopaminergic innervations are organized into the compartmentalized architecture found in the putamen of adult human brains. For this purpose, we used a highly sensitive immunohistochemistry technique to identify tyrosine hydroxylase (TH, EC 1.14.16.2, a marker for striatal dopaminergic axons and terminals, in formalin-fixed paraffin-embedded tissues obtained from autopsied human brains. Herein, we report that discrete compartmentalization of TH-labeled innervations occurs in the putamen, as in the caudate nucleus, with a higher density of TH labeling in the matrix compared to the striosomes. Our results provide anatomical evidence to support the hypothesis that compartment-specific dysfunction of the striosome-matrix dopaminergic systems might contribute to the genesis of movement disorders.

Clinical-pathomorphological correlation in patients with symptomatic dystonias

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Ivanović Nataša

2002-01-01

Full Text Available Symptomatic dystonia can be the result of various metabolic, degenerative diseases, the consumption of certain medications or exposure to toxic agents. However, only symptomatic dystonia with focal structural lesion provides a significant "window" for, at least indirect, perception of aetiopa-thogenesis and pathomorphological substratum of idiopathic dystonia. Our study included 57 patients with symptomatic dystonia, which as a base had focal or multifocal lesions, of whom 7 patients had generalized dystonia, 18 hemidystonia, 6 segmental dystonia, 7 torticollis, 6 blepharospasm, 7 hand dystonia, 3 spasmodic dysphonia, and 3 had oromandibular dystonia. Stroke was highly statistically the most frequent cause of structural lesions (33/57 or 58%. Relevant pathomorphological changes were present in 50/57 (88% patients, of whom 25 (50% had lesion in the lenticular nucleus (including individual damage of the putamen and globus pallidus, 12/50 (24% had damage of the thalamus and 6/50 (12% had damage of the brainstem. Generalized dystonia was most frequently associated with bilateral lesion of the putamen, hemidystonia with lesion of contralateral putamen, torticollis with damage of the caudate nucleus, hand dystonia with lesion of the thalamus and blepharospasm with lesion of the upper brainstem.

Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model

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Yi Lu

2018-02-01

Full Text Available Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD, while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo1H nuclear magnetic resonance (NMR spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI and taurine (Tau were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

Neuroradiologiske forandringer ved undertrykkelse af tics

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Larsen, Sara Bohn; Sørensen, Camilla Birgitte; Skov, Liselotte

2017-01-01

Neuroradiological changes by suppression of tics Tourette’s syndrome is characterized by involuntary tics. First choice of treatment has been pharmacological, but recently, behavioural therapy teaching patients to suppress their tics has been introduced. Neuroimaging studies have shown an increased...... activity in the prefrontal cortex, temporal lobes and caudate nucleus, and a decreased activity in globus pallidus and putamen during inhibition of tics. The activity in the frontal lobes changes with age, probably caused by a lack of compensatory hypertrophy. In order to fully understand the mechanism...

Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

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Dunnett, S B; Iversen, S D

1982-02-01

6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

Re-thinking the role of the dorsal striatum in egocentric/response strategy.

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Botreau, Fanny; Gisquet-Verrier, Pascale

2010-01-01

Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

Nicotine-induced activation of caudate and anterior cingulate cortex in response to errors in schizophrenia.

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Moran, Lauren V; Stoeckel, Luke E; Wang, Kristina; Caine, Carolyn E; Villafuerte, Rosemond; Calderon, Vanessa; Baker, Justin T; Ongur, Dost; Janes, Amy C; Evins, A Eden; Pizzagalli, Diego A

2018-03-01

Nicotine improves attention and processing speed in individuals with schizophrenia. Few studies have investigated the effects of nicotine on cognitive control. Prior functional magnetic resonance imaging (fMRI) research demonstrates blunted activation of dorsal anterior cingulate cortex (dACC) and rostral anterior cingulate cortex (rACC) in response to error and decreased post-error slowing in schizophrenia. Participants with schizophrenia (n = 13) and healthy controls (n = 12) participated in a randomized, placebo-controlled, crossover study of the effects of transdermal nicotine on cognitive control. For each drug condition, participants underwent fMRI while performing the stop signal task where participants attempt to inhibit prepotent responses to "go (motor activation)" signals when an occasional "stop (motor inhibition)" signal appears. Error processing was evaluated by comparing "stop error" trials (failed response inhibition) to "go" trials. Resting-state fMRI data were collected prior to the task. Participants with schizophrenia had increased nicotine-induced activation of right caudate in response to errors compared to controls (DRUG × GROUP effect: p corrected  state functional connectivity analysis, relative to controls, participants with schizophrenia had significantly decreased connectivity between the right caudate and dACC/bilateral dorsolateral prefrontal cortices. In sum, we replicated prior findings of decreased post-error slowing in schizophrenia and found that nicotine was associated with more adaptive (i.e., increased) post-error reaction time (RT). This proof-of-concept pilot study suggests a role for nicotinic agents in targeting cognitive control deficits in schizophrenia.

Existence and control of Go/No-Go decision transition threshold in the striatum.

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Jyotika Bahuguna

2015-04-01

Full Text Available A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

Existence and control of Go/No-Go decision transition threshold in the striatum.

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Bahuguna, Jyotika; Aertsen, Ad; Kumar, Arvind

2015-04-01

A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs) in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

Connectivity-based parcellation reveals distinct cortico-striatal connectivity fingerprints in Autism Spectrum Disorder.

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Balsters, Joshua H; Mantini, Dante; Wenderoth, Nicole

2018-04-15

Autism Spectrum Disorder (ASD) has been associated with abnormal synaptic development causing a breakdown in functional connectivity. However, when measured at the macro scale using resting state fMRI, these alterations are subtle and often difficult to detect due to the large heterogeneity of the pathology. Recently, we outlined a novel approach for generating robust biomarkers of resting state functional magnetic resonance imaging (RS-fMRI) using connectivity based parcellation of gross morphological structures to improve single-subject reproducibility and generate more robust connectivity fingerprints. Here we apply this novel approach to investigating the organization and connectivity strength of the cortico-striatal system in a large sample of ASD individuals and typically developed (TD) controls (N=130 per group). Our results showed differences in the parcellation of the striatum in ASD. Specifically, the putamen was found to be one single structure in ASD, whereas this was split into anterior and posterior segments in an age, IQ, and head movement matched TD group. An analysis of the connectivity fingerprints revealed that the group differences in clustering were driven by differential connectivity between striatum and the supplementary motor area, posterior cingulate cortex, and posterior insula. Our approach for analysing RS-fMRI in clinical populations has provided clear evidence that cortico-striatal circuits are organized differently in ASD. Based on previous task-based segmentations of the striatum, we believe that the anterior putamen cluster present in TD, but not in ASD, likely contributes to social and language processes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.

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Tortorella, C; Romano, R; Direnzo, V; Taurisano, P; Zoccolella, S; Iaffaldano, P; Fazio, L; Viterbo, R; Popolizio, T; Blasi, G; Bertolino, A; Trojano, M

2013-08-01

Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.

Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

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Julie eBoulanger Bertolus

2014-05-01

Full Text Available Interval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days post-natal during odor-fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed.

Antioxidant responses and photosynthetic behaviors of Kappaphycus alvarezii and Kappaphycus striatum (Rhodophyta, Solieriaceae) during low temperature stress.

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Li, Hu; Liu, Jianguo; Zhang, Litao; Pang, Tong

2016-12-01

Kappaphycus are farmed in tropical countries as raw material for carrageenan, which is widely used in food industry. The sea area available for farming is one limiting factor in the production of seaweeds. Though cultivation is spreading into subtropical regions, the lower seawater temperature is an important problem encountered in subtropical regions for the farming of Kappaphycus. This research of physiological response to low temperature stress will be helpful for screening Kappaphycus strains for growth in a lower temperature environment. Responses of antioxidant systems and photosystem II (PSII) behaviors in Kappaphycus alvarezii and Kappaphycus striatum were evaluated during low temperature treatments (23, 20, 17 °C). Compared with the controls at 26 °C, the H 2 O 2 concentrations increased in both species when the thalli were exposed to low temperatures (23, 20, 17 °C), but these increases were much greater in K. striatum than in K. alvarezii thalli, suggesting that K. striatum suffered more oxidative stress. The activities of some important antioxidant enzymes (e.g. superoxide dismutase and ascorbate peroxidase) and the hydroxyl free radical scavenging capacity were substantially higher at 23, 20 and 17 °C than at the control 26 °C in K. alvarezii, indicating that the antioxidant system of K. alvarezii enhanced its resistance to low temperature. However, no significant increases of antioxidant enzymes activities were observed at 20 and 17 °C in K. striatum. In addition, both the maximal efficiency of PSII photochemistry (F V /F m ) and the performance index (PI ABS ) decreased significantly in K. striatum at 23 °C, indicating that the photosynthetic apparatus was damaged at 23 °C. In contrast, no significant decreases of either F V /F m or PI ABS were observed in K. alvarezii at 23 °C. It is concluded that K. alvarezii has greater tolerance to low temperature than K. striatum.

Goal- and retrieval-dependent activity in the striatum during memory recognition.

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Clos, Mareike; Schwarze, Ulrike; Gluth, Sebastian; Bunzeck, Nico; Sommer, Tobias

2015-06-01

The striatum has been associated with successful memory retrieval but the precise functional link still remains unclear. One hypothesis is that striatal activity reflects an active evaluation process of the retrieval outcome dependent on the current behavioral goals rather than being a consequence of memory reactivation. We have recently shown that the striatum also correlates with confidence in memory recognition, which could reflect high subjective value ascribed to high certainty decisions. To examine whether striatal activity during memory recognition reflects subjective value indeed, we conducted an fMRI study using a recognition memory paradigm in which the participants rated not only the recognition confidence but also indicated the pleasantness associated with the previous memory retrieval. The results demonstrated a high positive correlation between confidence and pleasantness both on the behavioral and brain activation level particularly in the striatum. As almost all of variance in the striatal confidence signal could be explained by experienced pleasantness, this part of the striatal memory recognition response probably corresponds to greater subjective value of high confidence responses. While perceived oldness was also strongly correlated with striatal activity, this activation pattern was clearly distinct from that associated with confidence and pleasantness and thus could not be explained by higher subjective value to detect "old" items. Together, these results show that at least two independent processes contribute to striatal activation in recognition memory: a more flexible evaluation response dependent on context and goals captured by memory confidence and a potentially retrieval-related response captured by perceived oldness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum

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Haiyan Jiang

2018-05-01

Full Text Available The caudal region of the rodent striatum, called the tail of the striatum (TS, is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

Endoplasmic reticulum stress responses differ in meninges and associated vasculature, striatum, and parietal cortex after a neurotoxic amphetamine exposure.

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Thomas, Monzy; George, Nysia I; Saini, Upasana T; Patterson, Tucker A; Hanig, Joseph P; Bowyer, John F

2010-08-01

Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum. Adult, male Sprague-Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia. Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatum, and parietal cortex at 3 h or 1 day postdosing were monitored. AMPH increased the expression of some ERSR-related genes in all tissues. Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1 (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not. Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum and parietal cortex. Conversely, Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH.

Disrupted Reinforcement Signaling in Orbital Frontal Cortex and Caudate in Youths with Conduct Disorder/Oppositional Defiant Disorder and High Psychopathic Traits

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Finger, Elizabeth C.; Marsh, Abigail A.; Blair, Karina S.; Reid, Marguerite. E.; Sims, Courtney; Ng, Pamela; Pine, Daniel S.; Blair, R. James. R.

2010-01-01

OBJECTIVE Dysfunction in amygdala and orbital frontal cortex functioning has been reported in youths and adults with psychopathic traits. However, the specific nature of the computational irregularities within these brain structures remains poorly understood. The current study used the passive avoidance task to examine responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. METHOD 30 youths (N=15 with conduct disorder or oppositional defiant disorder plus high psychopathic traits and N=15 comparison subjects) completed a 3.0 T fMRI scan while performing a passive avoidance learning task. RESULTS Relative to comparison youth, youths with conduct disorder or oppositional defiant disorder plus psychopathic traits showed reduced orbitofrontal cortex responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as reduced caudate response to early stimulus-reinforcement exposure. Contrary to other predictions, however, there were no group differences in amygdala responsiveness specifically to these two task parameters. However, amygdala responsiveness throughout the task was reduced in the youths with conduct disorder or oppositional defiant disorder plus psychopathic traits. CONCLUSIONS This study demonstrates that youths with conduct disorder or oppositional defiant disorder plus psychopathic traits are marked by a compromised sensitivity to early reinforcement information in both orbitofrontal cortex and caudate and to reward outcome information within orbitofrontal cortex. They further suggest that the integrated functioning of the amygdala, caudate and orbitofrontal cortex may be disrupted in individuals with this disorder. PMID:21078707

A common currency for the computation of motivational values in the human striatum

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Li, Yansong; Dreher, Jean-Claude

2015-01-01

Reward comparison in the brain is thought to be achieved through the use of a ‘common currency’, implying that reward value representations are computed on a unique scale in the same brain regions regardless of the reward type. Although such a mechanism has been identified in the ventro-medial prefrontal cortex and ventral striatum in the context of decision-making, it is less clear whether it similarly applies to non-choice situations. To answer this question, we scanned 38 participants with fMRI while they were presented with single cues predicting either monetary or erotic rewards, without the need to make a decision. The ventral striatum was the main brain structure to respond to both cues while showing increasing activity with increasing expected reward intensity. Most importantly, the relative response of the striatum to monetary vs erotic cues was correlated with the relative motivational value of these rewards as inferred from reaction times. Similar correlations were observed in a fronto-parietal network known to be involved in attentional focus and motor readiness. Together, our results suggest that striatal reward value signals not only obey to a common currency mechanism in the absence of choice but may also serve as an input to adjust motivated behaviour accordingly. PMID:24837478

Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

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Mathew Jobin

2009-04-01

Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

Pramipexole but not imipramine or fluoxetine reverses the "depressive-like" behaviour in a rat model of preclinical stages of Parkinson's disease.

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Berghauzen-Maciejewska, Klemencja; Kuter, Katarzyna; Kolasiewicz, Wacław; Głowacka, Urszula; Dziubina, Anna; Ossowska, Krystyna; Wardas, Jadwiga

2014-09-01

Depression is a frequent comorbid disorder in Parkinson's disease and may antedate its motor symptoms. However, mechanisms underlying Parkinson's disease-associated depression are unknown and its current medication is insufficient. The aim of the present study was to compare antidepressant-like effects of imipramine, fluoxetine and pramipexole in a model of preclinical stages of Parkinson's disease in rats. 6-Hydroxydopamine was bilaterally injected into the ventrolateral region of the caudate-putamen in rats. This treatment induced moderate decreases in the levels of dopamine and its metabolites in the caudate-putamen, nucleus accumbens and frontal cortex and reduced the density of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta and ventral tegmental area. The lesion increased immobility measured in the forced swimming test without influencing locomotor activity. Chronic (13 days) administration of pramipexole (1mg/kg sc/twice a day) reversed prolongation of the immobility time in lesioned animals but did not stimulate their locomotion. Chronic pramipexole activated dopaminergic transmission in the brain structures which might contribute to its effectiveness in the forced swimming test. In contrast, the 13-day administration of imipramine (10mg/kg ip/day) and fluoxetine (10mg/kg ip/day) did not shorten the immobility time in lesioned rats but reduced their locomotion. The present study indicates that already a moderate lesion of dopaminergic neurons induces "depressive-like" behaviour in animals which is reversed by chronic administration of the antiparkinsonian drug, pramipexole. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased histone H3 phosphorylation in neurons in specific brain structures after induction of status epilepticus in mice.

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Tetsuji Mori

Full Text Available Status epilepticus (SE induces pathological and morphological changes in the brain. Recently, it has become clear that excessive neuronal excitation, stress and drug abuse induce chromatin remodeling in neurons, thereby altering gene expression. Chromatin remodeling is a key mechanism of epigenetic gene regulation. Histone H3 phosphorylation is frequently used as a marker of chromatin remodeling and is closely related to the upregulation of mRNA transcription. In the present study, we analyzed H3 phosphorylation levels in vivo using immunohistochemistry in the brains of mice with pilocarpine-induced SE. A substantial increase in H3 phosphorylation was detected in neurons in specific brain structures. Increased H3 phosphorylation was dependent on neuronal excitation. In particular, a robust upregulation of H3 phosphorylation was detected in the caudate putamen, and there was a gradient of phosphorylated H3(+ (PH3(+ neurons along the medio-lateral axis. After unilateral ablation of dopaminergic neurons in the substantia nigra by injection of 6-hydroxydopamine, the distribution of PH3(+ neurons changed in the caudate putamen. Moreover, our histological analysis suggested that, in addition to the well-known MSK1 (mitogen and stress-activated kinase/H3 phosphorylation/c-fos pathway, other signaling pathways were also activated. Together, our findings suggest that a number of genes involved in the pathology of epileptogenesis are upregulated in PH3(+ brain regions, and that H3 phosphorylation is a suitable indicator of strong neuronal excitation.

Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

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Fang, Chun-Kai; Chen, Hong-Wen; Wang, Wei-Hsun; Liu, Ren-Shen; Hwang, Jeng-Jong

2013-01-01

In this work, we used quantitative autoradiography to study the acute effect of cocaine, methamphetamine, and ketamine on the uptake of [ 18 F]FDOPA in the striatum of rats. Drugs were treated 0.5 h before (pre-treated), and 1.5 h after (post-treated) [ 18 F]FDOPA injections, rats were then sacrificed at 2 h post [ 18 F]FDOPA injections to determine the striatum/frontal cortex binding ratios in the striatum. The ratios were lower in the post-treated groups than those of the pre-treated groups, suggesting a net effect of inhibition of trapping of the tracer. The order of uptake inhibition is: ketamine>methamphetamine>cocaine

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

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Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

2012-02-15

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

[Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

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Liu, Ping; He, Xinrong; Guo, Mei

2010-04-01

To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P Calculus Bovis group was higher than combination group (P Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

Morphometric brain characterization of refractory obsessive-compulsive disorder: diffeomorphic anatomic registration using exponentiated Lie algebra.

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Tang, Wanjie; Li, Bin; Huang, Xiaoqi; Jiang, Xiaoyu; Li, Fei; Wang, Lijuan; Chen, Taolin; Wang, Jinhui; Gong, Qiyong; Yang, Yanchun

2013-10-01

Few studies have used neuroimaging to characterize treatment-refractory obsessive-compulsive disorder (OCD). This study sought to explore gray matter structure in patients with treatment-refractory OCD and compare it with that of healthy controls. A total of 18 subjects with treatment-refractory OCD and 26 healthy volunteers were analyzed by MRI using a 3.0-T scanner and voxel-based morphometry (VBM). Diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) was used to identify structural changes in gray matter associated with treatment-refractory OCD. A partial correlation model was used to analyze whether morphometric changes were associated with Yale-Brown Obsessive-Compulsive Scale scores and illness duration. Gray matter volume did not differ significantly between the two groups. Treatment-refractory OCD patients showed significantly lower gray matter density than healthy subjects in the left posterior cingulate cortex (PCC) and mediodorsal thalamus (MD) and significantly higher gray matter density in the left dorsal striatum (putamen). These changes did not correlate with symptom severity or illness duration. Our findings provide new evidence of deficits in gray matter density in treatment-refractory OCD patients. These patients may show characteristic density abnormalities in the left PCC, MD and dorsal striatum (putamen), which should be verified in longitudinal studies. © 2013. Published by Elsevier Inc. All rights reserved.

Isolation and characterization of neural stem cells from human fetal striatum

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Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

2005-01-01

This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

Manganese-Disrupted Interaction of Dopamine D1 and NMDAR in the Striatum to Injury Learning and Memory Ability of Mice.

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Song, Qifan; Deng, Yu; Yang, Xinxin; Bai, Ying; Xu, Bin; Liu, Wei; Zheng, Wenxue; Wang, Can; Zhang, Meng; Xu, Zhaofa

2016-12-01

Manganese (Mn) is widely regarded as a neurotoxic heavy metal that causes learning and memory deficits. Recently, it has been proved that the striatum is related to memory and learning ability. However, no previous study focused on the effect of Mn-induced learning and memory deficits on the striatum. This study aims to investigate the probable interaction of dopamine D1 receptor (DR1) and N-methyl-D-aspartate receptor (NMDAR), two cognition-related receptors in the striatum during Mn exposure. Mice are randomly divided into four groups, including control group, 12.5 mg/kg MnCl 2 group, 25 mg/kg MnCl 2 group, and 50 mg/kg MnCl 2 group. The mice receive intraperitoneal injections of 0, 12.5, 25, and 50 mg/kg MnCl 2 once daily for 2 weeks. Then, learning and memory ability, pathological changes, expression, and interaction of DR1 and NMDAR are determined. It has been found that Mn disrupted spatial learning and memory ability of mice by Morris water maze test and the passive avoidance test. Pathological and ultrastructure were injured. Mn decreased the immunohistochemical activities, protein levels, and messenger RNA (mRNA) expression of DR1, NR1, and NR2A. Mn exposure inhibited interaction between DR1 and NMDAR in striatum by double immunofluorescent staining and co-immunoprecipitation. In conclusion, our study illustrated that Mn caused learning and memory dysfunction via injury of striatum and inhibition of interaction between DR1 and NMDAR in striatum.

Characteristic MR features of encephalitis caused by Epstein-Barr virus: a case report

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Ono, Jiro [Division of Paediatrics, Toyonaka Municipal Hospital, Osaka (Japan)]|[Department of Paediatrics, Faculty of Medicine, Osaka Univ. (Japan); Shimizu, Kazuo [Division of Paediatrics, Toyonaka Municipal Hospital, Osaka (Japan); Harada, Koushi [Division of Radiology, Kaizuka Municipal Hospital, Osaka (Japan); Mano, Toshiyuki; Okada, Shintaro [Department of Paediatrics, Faculty of Medicine, Osaka Univ. (Japan)

1998-08-01

An 8-year-old girl showed symptoms of encephalitis during acute Epstein-Barr virus (EBV) infection. The diagnosis of EB virus infection was made by changes in the titres of EB virus-specific antibody. Cranial MRI demonstrated abnormal low and high signal intensities in the striatal body (putamen and caudate nucleus) on T1-weighted and T2-weighted images, respectively, during the acute phase. These abnormal findings had almost completely resolved 1 month later. EBV infection should be considered when lesions are localised to the basal ganglia. (orig.) With 1 fig., 5 refs.

Characteristic MR features of encephalitis caused by Epstein-Barr virus: a case report

International Nuclear Information System (INIS)

Ono, Jiro; Shimizu, Kazuo; Harada, Koushi; Mano, Toshiyuki; Okada, Shintaro

1998-01-01

An 8-year-old girl showed symptoms of encephalitis during acute Epstein-Barr virus (EBV) infection. The diagnosis of EB virus infection was made by changes in the titres of EB virus-specific antibody. Cranial MRI demonstrated abnormal low and high signal intensities in the striatal body (putamen and caudate nucleus) on T1-weighted and T2-weighted images, respectively, during the acute phase. These abnormal findings had almost completely resolved 1 month later. EBV infection should be considered when lesions are localised to the basal ganglia. (orig.)

Mu opioid receptor binding sites in human brain

International Nuclear Information System (INIS)

Pilapil, C.; Welner, S.; Magnan, J.; Zamir, N.; Quirion, R.

1986-01-01

Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand [ 3 H]DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of [ 3 H]DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas

Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

International Nuclear Information System (INIS)

Otsuka, Makoto; Ichiya, Yuici; Kuwabara, Yasuo

1989-01-01

Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author)

Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

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Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

2009-02-11

Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

The role of the striatum in effort-based decision-making in the absence of reward.

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Schouppe, Nathalie; Demanet, Jelle; Boehler, Carsten N; Ridderinkhof, K Richard; Notebaert, Wim

2014-02-05

Decision-making involves weighing costs against benefits, for instance, in terms of the effort it takes to obtain a reward of a given magnitude. This evaluation process has been linked to the dorsal anterior cingulate cortex (dACC) and the striatum, with activation in these brain structures reflecting the discounting effect of effort on reward. Here, we investigate how cognitive effort influences neural choice processes in the absence of an extrinsic reward. Using functional magnetic resonance imaging in humans, we used an effort-based decision-making task in which participants were required to choose between two options for a subsequent flanker task that differed in the amount of cognitive effort. Cognitive effort was manipulated by varying the proportion of incongruent trials associated with each choice option. Choice-locked activation in the striatum was higher when participants chose voluntarily for the more effortful alternative but displayed the opposite trend on forced-choice trials. The dACC revealed a similar, yet only trend-level significant, activation pattern. Our results imply that activation levels in the striatum reflect a cost-benefit analysis, in which a balance is made between effort discounting and the intrinsic motivation to choose a cognitively challenging task. Moreover, our findings indicate that it matters whether this challenge is voluntarily chosen or externally imposed. As such, the present findings contrast with classical findings on effort discounting that found reductions in striatum activation for higher effort by finding enhancements of the same neural circuits when a cognitively challenging task is voluntarily selected and does not entail the danger of losing reward.

In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

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Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

2012-10-15

In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

Gene expression in rat striatum following carbon monoxide poisoning

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Shuichi Hara

2017-06-01

Full Text Available Carbon monoxide (CO poisoning causes brain damage, which is attenuated by treatment with hydrogen [1,2], a scavenger selective to hydroxyl radical (·≡OH [3]. This suggests a role of ·≡OH in brain damage due to CO poisoning. Studies have shown strong enhancement of ·≡OH production in rat striatum by severe CO poisoning with a blood carboxyhemoglobin (COHb level >70% due to 3000 ppm CO, but not less severe CO poisoning with a blood COHb level at approximately 50% due to 1000 ppm CO [4]. Interestingly, 5% O2 causes hypoxia comparable with that by 3000 ppm CO and produces much less •OH than 3000 ppm CO does [4]. In addition, cAMP production in parallel with ·≡OH production [5] might contribute to ·≡OH production [6]. It is likely that mechanisms other than hypoxia contribute to brain damage due to CO poisoning [7]. To search for the mechanisms, we examined the effects of 1000 ppm CO, 3000 ppm CO and 5% O2 on gene expression in rat striatum. All array data have been deposited in the Gene Expression Omnibus (GEO database under accession number GSE94780.

Differential recruitment of the sensorimotor putamen and frontoparietal cortex during motor chunking in humans.

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Wymbs, Nicholas F; Bassett, Danielle S; Mucha, Peter J; Porter, Mason A; Grafton, Scott T

2012-06-07

Motor chunking facilitates movement production by combining motor elements into integrated units of behavior. Previous research suggests that chunking involves two processes: concatenation, aimed at the formation of motor-motor associations between elements or sets of elements, and segmentation, aimed at the parsing of multiple contiguous elements into shorter action sets. We used fMRI to measure the trial-wise recruitment of brain regions associated with these chunking processes as healthy subjects performed a cued-sequence production task. A dynamic network analysis identified chunking structure for a set of motor sequences acquired during fMRI and collected over 3 days of training. Activity in the bilateral sensorimotor putamen positively correlated with chunk concatenation, whereas a left-hemisphere frontoparietal network was correlated with chunk segmentation. Across subjects, there was an aggregate increase in chunk strength (concatenation) with training, suggesting that subcortical circuits play a direct role in the creation of fluid transitions across chunks. Copyright © 2012 Elsevier Inc. All rights reserved.

Hippocampal projections to the ventral striatum: from spatial memory to motivated behavior

NARCIS (Netherlands)

van der Meer, M.M.A; Ito, R.; Lansink, C.S.; Pennartz, C.M.A.; Derdikman, D.; Knierim, J.J.

2014-01-01

Multiple regions of the hippocampal formation project to the ventral striatum, a central node in brain circuits that subserve aspects of motivation. These projections emphasize information flow from the ventral (temporal) pole of the hippocampus and interact with converging projections and

Semantic memory retrieval circuit: role of pre-SMA, caudate, and thalamus.

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Hart, John; Maguire, Mandy J; Motes, Michael; Mudar, Raksha Anand; Chiang, Hsueh-Sheng; Womack, Kyle B; Kraut, Michael A

2013-07-01

We propose that pre-supplementary motor area (pre-SMA)-thalamic interactions govern processes fundamental to semantic retrieval of an integrated object memory. At the onset of semantic retrieval, pre-SMA initiates electrical interactions between multiple cortical regions associated with semantic memory subsystems encodings as indexed by an increase in theta-band EEG power. This starts between 100-150 ms after stimulus presentation and is sustained throughout the task. We posit that this activity represents initiation of the object memory search, which continues in searching for an object memory. When the correct memory is retrieved, there is a high beta-band EEG power increase, which reflects communication between pre-SMA and thalamus, designates the end of the search process and resultant in object retrieval from multiple semantic memory subsystems. This high beta signal is also detected in cortical regions. This circuit is modulated by the caudate nuclei to facilitate correct and suppress incorrect target memories. Copyright © 2012 Elsevier Inc. All rights reserved.

A longitudinal analysis of regional brain volumes in macaques exposed to X-irradiation in early gestation.

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Kristina Aldridge

Full Text Available Early gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate.Five Rhesus macaques were exposed to x-irradiation in early gestation (E30-E41, and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15-24%, p = 0.01 and in cortical gray matter (6-15%, p = 0.01. Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08. No group-by-age effects were significant.Due to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

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Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

2012-01-01

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

International Nuclear Information System (INIS)

Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita; Pope, Carey

2006-01-01

This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted in any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some

Exercise Mode Moderates the Relationship Between Mobility and Basal Ganglia Volume in Healthy Older Adults.

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Nagamatsu, Lindsay S; Weinstein, Andrea M; Erickson, Kirk I; Fanning, Jason; Awick, Elizabeth A; Kramer, Arthur F; McAuley, Edward

2016-01-01

To examine whether 12 months of aerobic training (AT) moderated the relationship between change in mobility and change in basal ganglia volume than balance and toning (BAT) exercises in older adults. Secondary analysis of a randomized controlled trial. Champaign-Urbana, Illinois. Community-dwelling older adults (N=101; mean age 66.4). Twelve-month exercise trial with two groups: AT and BAT. Mobility was assessed using the Timed Up and Go test. Basal ganglia (putamen, caudate nucleus, pallidum) was segmented from T1-weighted magnetic resonance images using the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain Software Library Integrated Registration and Segmentation Tool. Measurements were obtained at baseline and trial completion. Hierarchical multiple regression was conducted to examine whether exercise mode moderates the relationship between change in mobility and change in basal ganglia volume over 12 months. Age, sex, and education were included as covariates. Exercise significantly moderated the relationship between change in mobility and change in left putamen volume. Specifically, for the AT group, volume of the left putamen did not change, regardless of change in mobility. Similarly, in the BAT group, those who improved their mobility most over 12 months had no change in left putamen volume, although left putamen volume of those who declined in mobility levels decreased significantly. The primary finding that older adults who engaged in 12 months of BAT training and improved mobility exhibited maintenance of brain volume in an important region responsible for motor control provides compelling evidence that such exercises can contribute to the promotion of functional independence and healthy aging. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat.

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Brodnik, Zachary D; Double, Manda; España, Rodrigo A; Jaskiw, George E

2017-09-01

We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250-1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125-250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and/or disordered L-TYR transport have been implicated. Published by Elsevier Ltd.

Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum

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Salinas, Armando G.; Davis, Margaret I.; Lovinger, David M.; Mateo, Yolanda

2016-01-01

The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson’s disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix. PMID:27036891

Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

Science.gov (United States)

Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

2009-01-01

Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

Amphetamine-enhanced accumulation of [3H]-spiperone in mouse corpus striatum in vivo: Modification by other drugs

International Nuclear Information System (INIS)

Dorris, R.L.

1989-01-01

Other investigators have reported that amphetamine administered to rodents results in an increase in the in vivo accumulation of either the tritiated dopamine receptor ligand, spiperone or pimozide in the dopaminergic corpus striatum, (specific binding) while not altering that in the sparsely dopaminergically innervated cerebellum (non-specific binding). Experiments were undertaken to determine if the results could be replicated and if some other drugs would modify the effect. Male mice were injected with [ 3 H]-spiperone (20 μCi/Kg, 0.0003 mg/kg) s.c. and killed 2 hrs later for determination of radioactivity in corpus striatum and cerebellum. Amphetamine (20 mg/kg, i.p.) given 15 min before [ 3 H]-spiperone, increased accumulation in striatum but not cerebellum. The increase was inhibited by α - methyltyrosine (α-MT), haloperidol, reserpine or amantadine. It is suggested that the amphetamine-induced increase in accumulation of [ 3 H]-spiperone in corpus striatum (specific binding) depends on release of large amounts of dopamine, which then must be able to interact with the dopamine receptor. The antagonism of the effect by α-MT or reserpine can be explained by dopamine depletion, that of haloperidol by antagonism for binding at the receptor site. It is suggested that amantadine acts by a dual mechanism: (1) as a low efficacy agonist, it competes for binding to the receptor and (2) it has some ability to block dopamine release

Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

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Hiroaki Kawamichi

2016-11-01

Full Text Available Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68. Furthermore, we also conducted a voxel-based morphometry (VBM study of the effects of being in a romantic relationship (N = 113. Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward.

Preferential responses in amygdala and insula during presentation of facial contempt and disgust.

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Sambataro, Fabio; Dimalta, Savino; Di Giorgio, Annabella; Taurisano, Paolo; Blasi, Giuseppe; Scarabino, Tommaso; Giannatempo, Giuseppe; Nardini, Marcello; Bertolino, Alessandro

2006-10-01

Some authors consider contempt to be a basic emotion while others consider it a variant of disgust. The neural correlates of contempt have not so far been specifically contrasted with disgust. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks involved in the processing of facial contempt and disgust in 24 healthy subjects. Facial recognition of contempt was lower than that of disgust and of neutral faces. The imaging data indicated significant activity in the amygdala and in globus pallidus and putamen during processing of contemptuous faces. Bilateral insula and caudate nuclei and left as well as right inferior frontal gyrus were engaged during processing of disgusted faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly different activations in the amygdala. On the other hand, disgusted faces elicited greater activation than contemptuous faces in the right insula and caudate. Our findings suggest preferential involvement of different neural substrates in the processing of facial emotional expressions of contempt and disgust.

Anatomical and diffusion MRI of deep gray matter in pediatric spina bifida

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Ashley L. Ware

2014-01-01

Full Text Available Individuals with spina bifida myelomeningocele (SBM exhibit brain abnormalities in cortical thickness, white matter integrity, and cerebellar structure. Little is known about deep gray matter macro- and microstructure in this population. The current study utilized volumetric and diffusion-weighted MRI techniques to examine gray matter volume and microstructure in several subcortical structures: basal ganglia nuclei, thalamus, hippocampus, and amygdala. Sixty-six children and adolescents (ages 8–18; M = 12.0, SD = 2.73 with SBM and typically developing (TD controls underwent T1- and diffusion-weighted neuroimaging. Microstructural results indicated that hippocampal volume was disproportionately reduced, whereas the putamen volume was enlarged in the group with SBM. Microstructural analyses indicated increased mean diffusivity (MD and fractional anisotropy (FA in the gray matter of most examined structures (i.e., thalamus, caudate, hippocampus, with the putamen exhibiting a unique pattern of decreased MD and increased FA. These results provide further support that SBM differentially disrupts brain regions whereby some structures are volumetrically normal whereas others are reduced or enlarged. In the hippocampus, volumetric reduction coupled with increased MD may imply reduced cellular density and aberrant organization. Alternatively, the enlarged volume and significantly reduced MD in the putamen suggest increased density.

Voxel-based analysis of cerebral glucose metabolism in AD and non-AD degenerative dementia using statistical parametric mapping

International Nuclear Information System (INIS)

Li Zugui; Gao Shuo; Zhang Benshu; Ma Aijun; Cai Li; Li Dacheng; Li Yansheng; Liu Lei

2008-01-01

Objective: It is know that Alzheimer's disease (AD) and non-AD degenerative dementia have some clinical features in common. The aim of this study was to investigate the specific patterns of regional, cerebral glucose metabolism of AD and non-AD degenerative dementia patients, using a voxel-based 18 F-fluorodeoxyglucose (FDG) PET study. Methods: Twenty-three AD patients and 24 non-AD degenerative dementia patients including 9 Parkinson's disease with dementia(PDD), 7 frontal-temporal dementia (FTD), 8 dementia of Lewy bodies (DLB) patients, and 40 normal controls (NC)were included in the study. To evaluate the relative cerebral metabolic rate of glucose (rCMRglc), 18 F-FDG PET imaging was performed in all subjects. Subsequently, statistical comparison of PET data with NC was performed using statistical parametric mapping (SPM). Results: The AD-associated FDG imaging pattern typically presented as focal cortical hypometabolism in bilateral parietotemporal association cortes and(or) frontal lobe and the posterior cingulate gyms. As compared with the comparative NC, FTD group demonstrated significant regional reductions in rCMRglc in bilateral frontal, parietal lobes, the cingulate gyri, insulae, left precuneus, and the subcortical structures (including right putamen, right medial dorsal nucleus and ventral anterior nucleus). The PDD group showed regional reductions in rCMRglc in bilateral frontal cortexes, parietotemporal association cortexes, and the subcortical structures (including left caudate, right putamen, the dorsomedial thalamus, lateral posterior nucleus, and pulvinar). By the voxel-by-voxel comparison between the DLB group and NC group, regional reductions in rCMRglc included bilateral occipital cortexes, precuneuses, frontal and parietal lobes, left anterior cingulate gyms, right superior temporal cortex, and the subcortical structures including putamen, caudate, lateral posterior nucleus, and pulvinar. Conclusions: The rCMRglc was found to be different

Treatment of Small Hepatocellular Carcinoma (≤2 cm) in the Caudate Lobe with Sequential Transcatheter Arterial Chemoembolization and Radiofrequency Ablation

International Nuclear Information System (INIS)

Hyun, Dongho; Cho, Sung Ki; Shin, Sung Wook; Rhim, Hyunchul; Koh, Kwang Cheol; Paik, Seung Woon

2016-01-01

PurposeTo evaluate technical feasibility and treatment results of sequential transcatheter arterial chemoembolization (TACE) and cone-beam computed tomography-guided percutaneous radiofrequency ablation (CBCT-RFA) for small hepatocellular carcinoma (HCC) in the caudate lobe.Materials and MethodsInstitutional review board approved this retrospective study. Radiologic database was searched for the patients referred to perform TACE and CBCT-RFA for small caudate HCCs (≤2 cm) between February 2009 and February 2014. A total of 14 patients (12 men and 2 women, mean age; 61.3 years) were included. Percutaneous ultrasonography-guided RFA (pUS-RFA) and surgery were infeasible due to poor conspicuity, inconspicuity or no safe electrode pathway, and poor hepatic reserve. Procedural success (completion of both TACE and CBCT-RFA), technique efficacy (absence of tumor enhancement at 1 month after treatment), and complication were evaluated. Treatment results including local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), and progression-free survival (PFS) were analyzed.ResultsProcedural success and technique efficacy rates were 78.6 % (11/14) and 90.9 % (10/11), respectively. Average follow-up period was 45.3 months (range, 13.4–64.6 months). The 1-, 3-, and 5-year LTP probabilities were 0, 12.5, and 12.5 %, respectively. IDR occurred in seven patients (63.6 %, 7/11). The 1-, 3-, and 5-year PFS probabilities were 81.8, 51.9, and 26 %, respectively. The 1-, 3-, and 5-year OS probabilities were 100, 80.8, and 80.8 %, respectively.ConclusionCombination of TACE and CBCT-RFA seems feasible for small HCC in the caudate lobe not amenable to pUS-RFA and effective in local tumor control.

Treatment of Small Hepatocellular Carcinoma (≤2 cm) in the Caudate Lobe with Sequential Transcatheter Arterial Chemoembolization and Radiofrequency Ablation

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Hyun, Dongho; Cho, Sung Ki, E-mail: sungkismc.cho@samsung.com; Shin, Sung Wook; Rhim, Hyunchul [Sungkyunkwan University School of Medicine, Department of Radiology, Samsung Medical Center (Korea, Republic of); Koh, Kwang Cheol; Paik, Seung Woon [Sungkyunkwan University School of Medicine, Department of Medicine, Samsung Medical Center (Korea, Republic of)

2016-07-15

PurposeTo evaluate technical feasibility and treatment results of sequential transcatheter arterial chemoembolization (TACE) and cone-beam computed tomography-guided percutaneous radiofrequency ablation (CBCT-RFA) for small hepatocellular carcinoma (HCC) in the caudate lobe.Materials and MethodsInstitutional review board approved this retrospective study. Radiologic database was searched for the patients referred to perform TACE and CBCT-RFA for small caudate HCCs (≤2 cm) between February 2009 and February 2014. A total of 14 patients (12 men and 2 women, mean age; 61.3 years) were included. Percutaneous ultrasonography-guided RFA (pUS-RFA) and surgery were infeasible due to poor conspicuity, inconspicuity or no safe electrode pathway, and poor hepatic reserve. Procedural success (completion of both TACE and CBCT-RFA), technique efficacy (absence of tumor enhancement at 1 month after treatment), and complication were evaluated. Treatment results including local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), and progression-free survival (PFS) were analyzed.ResultsProcedural success and technique efficacy rates were 78.6 % (11/14) and 90.9 % (10/11), respectively. Average follow-up period was 45.3 months (range, 13.4–64.6 months). The 1-, 3-, and 5-year LTP probabilities were 0, 12.5, and 12.5 %, respectively. IDR occurred in seven patients (63.6 %, 7/11). The 1-, 3-, and 5-year PFS probabilities were 81.8, 51.9, and 26 %, respectively. The 1-, 3-, and 5-year OS probabilities were 100, 80.8, and 80.8 %, respectively.ConclusionCombination of TACE and CBCT-RFA seems feasible for small HCC in the caudate lobe not amenable to pUS-RFA and effective in local tumor control.

Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

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Makoto Ito

2015-11-01

Full Text Available Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS, the dorsomedial striatum (DMS, and the ventral striatum (VS identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

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Ito, Makoto; Doya, Kenji

2015-11-01

Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS), the dorsomedial striatum (DMS), and the ventral striatum (VS) identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information.

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Barbera, Giovanni; Liang, Bo; Zhang, Lifeng; Gerfen, Charles R; Culurciello, Eugenio; Chen, Rong; Li, Yun; Lin, Da-Ting

2016-10-05

An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior. VIDEO ABSTRACT. Published by Elsevier Inc.

Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings

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O’Dwyer, Laurence; Tanner, Colby; van Dongen, Eelco V.; Greven, Corina U.; Bralten, Janita; Zwiers, Marcel P.; Franke, Barbara; Heslenfeld, Dirk; Oosterlaan, Jaap; Hoekstra, Pieter J.; Hartman, Catharina A.; Groen, Wouter; Rommelse, Nanda; Buitelaar, Jan K.

2016-01-01

Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups. PMID:27806078

Decreased dopamine activity predicts relapse in methamphetamine abusers

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Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

2011-01-20

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

Decreased dopamine activity predicts relapse in methamphetamine abusers

International Nuclear Information System (INIS)

Wang, G.J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

2011-01-01

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and ( 11 C)raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

Neural signature of behavioural inhibition in women with bulimia nervosa.

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Skunde, Mandy; Walther, Stephan; Simon, Joe J; Wu, Mudan; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

2016-08-01

Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa. Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task. We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen). The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness. Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients.

Diffusion tensor imaging of the nigrostriatal fibers in Parkinson's disease.

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Zhang, Yu; Wu, I-Wei; Buckley, Shannon; Coffey, Christopher S; Foster, Eric; Mendick, Susan; Seibyl, John; Schuff, Norbert

2015-08-01

Parkinson's disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios. Diffusion tensor tractography was performed on 50 drug-naïve PD patients and 27 healthy control subjects from the international multicenter Parkinson's Progression Marker Initiative. Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD. © 2015 International Parkinson and Movement Disorder Society.

Neural signature of behavioural inhibition in women with bulimia nervosa

Science.gov (United States)

Skunde, Mandy; Walther, Stephan; Simon, Joe J.; Wu, Mudan; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

2016-01-01

Background Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa. Methods Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task. Results We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen). Limitations The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness. Conclusion Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients. PMID:27575858

Proton MR spectroscopic imaging of basal ganglia and thalamus in neurofibromatosis type 1: correlation with T2 hyperintensities

International Nuclear Information System (INIS)

Barbier, Charlotte; Barantin, Laurent; Chabernaud, Camille; Bertrand, Philippe; Sembely, Catherine; Sirinelli, Dominique; Castelnau, Pierre; Cottier, Jean-Philippe

2011-01-01

Neurofibromatosis type 1 (NF1) is frequently associated with hyperintense lesions on T2-weighted images called ''unidentified bright objects'' (UBO). To better characterize the functional significance of UBO, we investigate the basal ganglia and thalamus using spectroscopic imaging in children with NF1 and compare the results to anomalies observed on T2-weighted images. Magnetic resonance (MR) data of 25 children with NF1 were analyzed. On the basis of T2-weighted images analysis, two groups were identified: one with normal MR imaging (UBO- group; n = 10) and one with UBO (UBO+ group; n = 15). Within the UBO+ group, a subpopulation of patients (n = 5) only had lesions of the basal ganglia. We analyzed herein seven regions of interest (ROIs) for each side: caudate nucleus, capsulo-lenticular region, lateral and posterior thalamus, thalamus (lateral and posterior voxels combined), putamen, and striatum. For each ROI, a spectrum of the metabolites and their ratio was obtained. Patients with abnormalities on T2-weighted images had significantly lower NAA/Cr, NAA/Cho, and NAA/mI ratios in the lateral right thalamus compared with patients with normal T2. These abnormal spectroscopic findings were not observed in capsulo-lenticular regions that had UBO but in the thalamus region that was devoid of UBO. Multivoxel spectroscopic imaging using short-time echo showed spectroscopic abnormalities in the right thalamus of NF1 patients harboring UBO, which were mainly located in the basal ganglia. This finding could reflect the anatomical and functional interactions of these regions. (orig.)

Extracting the basal extracellular dopamine concentrations from the evoked responses: re-analysis of the dopamine kinetics.

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Chen, Kevin C; Budygin, Evgeny A

2007-08-15

Fast-scan cyclic voltammetry in conjunction with carbon fiber microelectrode has been used to study dopamine (DA) release and uptake mechanisms in rat brains because of the smaller size of the electrode and the subsecond resolution. Current voltammetry data were analyzed by a DA kinetic model assuming a zero baseline, which is in conflict with existing microdialysis findings and a recent claim of the striatal extracellular DA concentration at micromolar levels. This work applied a new analysis approach based on a modified DA kinetic model to analyze the kinetics of electrically evoked DA overflow in the caudate-putamen of anesthetized rats. The DA uptake parameters were fitted from the electrical stimulation phase, and subsequently used to calculate theoretical DA uptake rates. Comparison of the theoretical uptake rates with experimental clearance rates allows for the study of the tonic DA release process following electrical stimulations. Analyses of DA voltammetry data suggest that the locally averaged basal level of extracellular DA in the rat striatum might be confined between 95 and 220 nM. The disparate time scales in the clearance kinetics of endogenous and exogenous DA were investigated. Long-distance diffusion could only partially explain the slow clearance time course of exogenous DA. Model simulations and parameter analyses on evoked DA responses indicate that suppression of the nonevoked DA release process immediately following electrical stimulation cannot completely account for the rapid clearance of the electrically evoked DA. Inconsistency in the measured uptake strengths in the literature studying endogenous and exogenous DA remains to be investigated in the future.

Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a {sup 123}I-FP-CIT SPECT study

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Di Giuda, Daniela; Cocciolillo, Fabrizio; Bruno, Isabella; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Istituto di Medicina Nucleare, Rome (Italy); Camardese, Giovanni; Pucci, Lorella; Janiri, Luigi [Universita Cattolica del Sacro Cuore, Istituto di Psichiatria e Psicologia, Rome (Italy); Bentivoglio, Anna Rita; Guidubaldi, Arianna [Universita Cattolica del Sacro Cuore, Istituto di Neurologia, Rome (Italy); Fasano, Alfonso [Universita Cattolica del Sacro Cuore, Istituto di Neurologia, Rome (Italy); AFaR-Associazione Fatebenefratelli per la Ricerca, Rome (Italy)

2012-12-15

Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of {sup 123}I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity. Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific {sup 123}I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects. As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and {sup 123}I-FP-CIT uptake ratios in healthy subjects. We found association between presynaptic dopaminergic function and affective symptoms in different movement

Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I-FP-CIT SPECT study

International Nuclear Information System (INIS)

Di Giuda, Daniela; Cocciolillo, Fabrizio; Bruno, Isabella; Giordano, Alessandro; Camardese, Giovanni; Pucci, Lorella; Janiri, Luigi; Bentivoglio, Anna Rita; Guidubaldi, Arianna; Fasano, Alfonso

2012-01-01

Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of 123 I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity. Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific 123 I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects. As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and 123 I-FP-CIT uptake ratios in healthy subjects. We found association between presynaptic dopaminergic function and affective symptoms in different movement disorders. Interestingly, the

Value of dynamic susceptibility contrast perfusion MRI in the acute phase of transient global amnesia.

Directory of Open Access Journals (Sweden)

Alex Förster

Full Text Available Transient global amnesia (TGA is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET or single-photon emission computed tomography (SPECT. In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI in TGA in the acute phase.From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF and volume (CBV were generated and analyzed by use of Signal Processing In NMR-Software (SPIN. CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB Software Library (FSL.Five TGA patients were included (2 men, 3 women. On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus.Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI

Reward-modulated motor information in identified striatum neurons.

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Isomura, Yoshikazu; Takekawa, Takashi; Harukuni, Rie; Handa, Takashi; Aizawa, Hidenori; Takada, Masahiko; Fukai, Tomoki

2013-06-19

It is widely accepted that dorsal striatum neurons participate in either the direct pathway (expressing dopamine D1 receptors) or the indirect pathway (expressing D2 receptors), controlling voluntary movements in an antagonistically balancing manner. The D1- and D2-expressing neurons are activated and inactivated, respectively, by dopamine released from substantia nigra neurons encoding reward expectation. However, little is known about the functional representation of motor information and its reward modulation in individual striatal neurons constituting the two pathways. In this study, we juxtacellularly recorded the spike activity of single neurons in the dorsolateral striatum of rats performing voluntary forelimb movement in a reward-predictable condition. Some of these neurons were identified morphologically by a combination of juxtacellular visualization and in situ hybridization for D1 mRNA. We found that the striatal neurons exhibited distinct functional activations before and during the forelimb movement, regardless of the expression of D1 mRNA. They were often positively, but rarely negatively, modulated by expecting a reward for the correct motor response. The positive reward modulation was independent of behavioral differences in motor performance. In contrast, regular-spiking and fast-spiking neurons in any layers of the motor cortex displayed only minor and unbiased reward modulation of their functional activation in relation to the execution of forelimb movement. Our results suggest that the direct and indirect pathway neurons cooperatively rather than antagonistically contribute to spatiotemporal control of voluntary movements, and that motor information is subcortically integrated with reward information through dopaminergic and other signals in the skeletomotor loop of the basal ganglia.

Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts

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Cumming, P; Danielsen, E H; Vafaee, M

2001-01-01

, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers...... for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However...

Hippocampus, caudate nucleus and entorhinal cortex volumetric MRI measurements in discrimination between Alzheimer’s disease, mild cognitive impairment, and normal aging

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Rasha Elshafey

2014-06-01

Conclusion: Semi-automated MR volumetric measurements can be used to determine atrophy in hippocampus, caudate nucleus and entorhinal cortex which aided in discrimination of healthy elderly control subjects from subjects with AD and MCI and predict clinical decline of MCI leading to increase the efficiency of clinical treatments, delay institutionalization and improve cognition and behavioral symptoms.

Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: a possible role for plasticity in adenosine receptors

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Clark, Peter J.; Ghasem, Parsa R.; Mika, Agnieszka; Day, Heidi E.; Herrera, Jonathan J.; Greenwood, Benjamin N.; Fleshner, Monika

2014-01-01

Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was two-fold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance. PMID:25017571

5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

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Amodeo, D A; Rivera, E; Cook, E H; Sweeney, J A; Ragozzino, M E

2017-03-01

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT 2A receptor activity is altered in autism, while recent work indicates that systemic 5HT 2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT 2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT 2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT 2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT 2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT 2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Time-dependent regional brain distribution of methadone and naltrexone in the treatment of opioid addiction.

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Teklezgi, Belin G; Pamreddy, Annapurna; Baijnath, Sooraj; Kruger, Hendrik G; Naicker, Tricia; Gopal, Nirmala D; Govender, Thavendran

2018-02-14

Opioid addiction is a serious public health concern with severe health and social implications; therefore, extensive therapeutic efforts are required to keep users drug free. The two main pharmacological interventions, in the treatment of addiction, involve management with methadone an mu (μ)-opioid agonist and treatment with naltrexone, μ-opioid, kappa (κ)-opioid and delta (δ)-opioid antagonist. MET and NAL are believed to help individuals to derive maximum benefit from treatment and undergo a full recovery. The aim of this study was to determine the localization and distribution of MET and NAL, over a 24-hour period in rodent brain, in order to investigate the differences in their respective regional brain distributions. This would provide a better understanding of the role of each individual drug in the treatment of addiction, especially NAL, whose efficacy is controversial. Tissue distribution was determined by using mass spectrometric imaging (MSI), in combination with quantification via liquid chromatography tandem mass spectrometry. MSI image analysis showed that MET was highly localized in the striatal and hippocampal regions, including the nucleus caudate, putamen and the upper cortex. NAL was distributed with high intensities in the mesocorticolimbic system including areas of the cortex, caudate putamen and ventral pallidum regions. Our results demonstrate that MET and NAL are highly localized in the brain regions with a high density of μ-receptors, the primary sites of heroin binding. These areas are strongly implicated in the development of addiction and are the major pathways that mediate brain stimulation during reward. © 2018 Society for the Study of Addiction.

Neonatal ventral hippocampus lesion alters the dopamine content in the limbic regions in postpubertal rats.

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Alquicer, Glenda; Silva-Gómez, Adriana B; Peralta, Fernando; Flores, Gonzalo

2004-04-01

The neonatal ventral Hippocampus (nVH) lesion in rats has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. The schizophrenic patients tend to social isolation. In addition, considerable evidence from behavioral and neurochemistry studies strongly implicate the dopamine (DA) system and the medial part of the prefrontal cortex (mPFC) in the pathophysiology of the social isolation syndrome. In order to assess effects of the postweaning social isolation (pwSI) on the DA system of the nVH lesions, we investigated the DA content and its metabolite, DOPAC in different limbic subregions in rats postpubertally at postnatal day (P) 78 following nVH lesions at P7 with and without pwSI for 8 weeks. The DA and DOPAC were measured by HPLC with electrochemical detection. The nVH lesion induces increase in the DA content in the hippocampus with no effect in the mPFC, nucleus accumbens and caudate-putamen, while the pwSI induces major increase in the DA content in limbic subregions such as the mPFC, nucleus accumbens and hipocampus with opposite effect in the caudate-putamen. These results suggest that while pwSI has an effect in the postpubertal content of DA in both sham and nVH lesions in rats, the nVH-lesioned rats appear to be affected to a greater extent than the sham animals underscoring the influence of pwSI differences in the development of behaviors in the nVH-lesioned animals.

Significance of apparent diffusion coefficient measurement for the differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and Parkinson's disease: evaluation by 3.0-T MR imaging

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Tsukamoto, Kazumichi; Kanasaki, Yoshiko; Kakite, Suguru; Fujii, Shinya; Kaminou, Toshio; Ogawa, Toshihide; Matsusue, Eiji

2012-01-01

The clinical differentiation of Parkinson's disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) may be challenging, especially in their early stages. The aim of this study was to evaluate the utility of apparent diffusion coefficient (ADC) measurement to distinguish among these degenerative disorders. Twenty-five MSA, 20 PSP, and 17 PD patients and 18 healthy controls were retrospectively studied. Axial diffusion-weighted and T2-weighted images were obtained using a 3-T MR system. Regions of interest (ROIs) were precisely placed in the midbrain, pons, putamen, globus pallidus, caudate nucleus, thalamus, superior cerebellar peduncle, middle cerebellar peduncle, cerebellar white matter, and cerebellar dentate nucleus, and the regional ADC (rADC) value was calculated in each ROI. In MSA, rADC values in the pons, middle cerebellar peduncle, cerebellar white matter, and cerebellar dentate nucleus were significantly higher than in PSP, PD, and controls. Furthermore, rADC values in the posterior putamen were significantly higher in MSA than in PSP and controls. In PSP, rADC values were significantly higher in the globus pallidus and midbrain than in MSA, PD, and controls. Furthermore, rADC values in the caudate nucleus and superior cerebellar peduncle were significantly higher in PSP than in MSA and controls. In PD, there were no significant differences in the rADC values compared to in MSA, PSP, and controls in all regions. Evaluation of rADC values in characteristic lesions in MSA, PSP, and PD by placing ROIs using 3-T systems can provide useful additional information for differentiating these disorders. (orig.)

Grey matter volume loss is associated with specific clinical motor signs in Huntington's disease.

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Coppen, Emma M; Jacobs, Milou; van den Berg-Huysmans, Annette A; van der Grond, Jeroen; Roos, Raymund A C

2018-01-01

Motor disturbances are clinical hallmarks of Huntington's disease (HD) and involve chorea, dystonia, hypokinesia and visuomotor dysfunction. Investigating the association between specific motor signs and different regional volumes is important to understand the heterogeneity of HD. To investigate the motor phenotype of HD and associations with subcortical and cortical grey matter volume loss. Structural T1-weighted MRI scans of 79 HD patients and 30 healthy controls were used to calculate volumes of seven subcortical structures including the nucleus accumbens, hippocampus, thalamus, caudate nucleus, putamen, pallidum and amygdala. Multiple linear regression analyses, corrected for age, gender, CAG, MRI scan protocol and normalized brain volume, were performed to assess the relationship between subcortical volumes and different motor subdomains (i.e. eye movements, chorea, dystonia, hypokinesia/rigidity and gait/balance). Voxel-based morphometry analysis was used to investigate the relationship between cortical volume changes and motor signs. Subcortical volume loss of the accumbens nucleus, caudate nucleus, putamen, and pallidum were associated with higher chorea scores. No other subcortical region was significantly associated with motor symptoms after correction for multiple comparisons. Voxel-based cortical grey matter volume reductions in occipital regions were related with an increase in eye movement scores. In HD, chorea is mainly associated with subcortical volume loss, while eye movements are more related to cortical volume loss. Both subcortical and cortical degeneration has an impact on motor impairment in HD. This implies that there is a widespread contribution of different brain regions resulting in the clinical motor presentation seen in HD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuropeptide processing in regional brain slices: Effect of conformation and sequence

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Li, Z.W.; Bijl, W.A.; van Nispen, J.W.; Brendel, K.; Davis, T.P. (Univ. of Arizona, Tucson (USA))

1990-05-01

The central enzymatic stability of des-enkephalin-gamma-endorphin and its synthetic analogs (cycloN alpha 6, C delta 11)beta-endorphin-(6-17) and (Pro7, Lys(Ac)9)-beta-endorphin(6-17) was studied in vitro using a newly developed, regionally dissected rat brain slice, time course incubation procedure. Tissue slice viability was estimated as the ability of the brain slice to take up or release gamma-(3H)aminobutyric acid after high K+ stimulation. Results demonstrated stability of uptake/release up to 5 hr of incubation, suggesting tissue viability over this period. The estimated half-life of peptides based on the results obtained in our incubation protocol suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. A good correlation exists between the high enzyme activity of neutral endopeptidase and the rapid degradation of des-enkephalin-gamma-endorphin and (cycloN alpha 6, C delata 11)beta-endorphin-(6-17) in caudate putamen. Proline substitution combined with lysine acetylation appears to improve resistance to enzymatic metabolism in caudate putamen and hypothalamus. However, cyclization of des-enkephalin-gamma-endorphin forming an amide bond between the alpha-NH2 of the N-terminal threonine and the gamma-COOH of glutamic acid did not improve peptide stability in any brain region tested. The present study has shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of rat brain where peptides, peptidases and receptors are colocalized and that specific structural modifications can improve peptide stability.

Amphetamine sensitization alters reward processing in the human striatum and amygdala.

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Owen G O'Daly

Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

Liver parenchyma transection-first approach in hemihepatectomy with en bloc caudate lobectomy for hilar cholangiocarcinoma: A safe technique to secure favorable surgical outcomes.

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Kawabata, Yasunari; Hayashi, Hikota; Yano, Seiji; Tajima, Yoshitsugu

2017-06-01

Although hemihepatectomy with total caudate lobectomy (hemiHx-tc) is essential for the surgical treatment of hilar cholangiocarcinoma, the advantage of an anterior approach for hemiHx-tc has not been fully discussed technically; the significance of an anterior approach without liver mobilization for preventing infectious complications also remains unknown. The liver parenchyma transection-first approach (Hp-first) technique is an early transection of the hepatic parenchyma without mobilization of the liver that utilizes a modified liver-hanging maneuver to avoid damaging the future remnant liver. Between May 2010 and August 2016, a total of 40 consecutive patients underwent surgery for hilar cholangiocarcinoma. Of these, 19 patients underwent a conventional hemihepatectomy with total caudate lobectomy (cHx), while 21 patients received a Hp-first. The patients in the Hp-first group had significantly less intraoperative blood loss (P hilar cholangiocarcinoma because it resulted in improved surgical outcomes as compared with the conventional approach. © 2017 Wiley Periodicals, Inc.

Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

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Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

2017-10-06

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

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Christina Coughlan

2015-01-01

Full Text Available Epidemiological studies indicate exposures to the herbicide paraquat (PQ and fungicide maneb (MB are associated with increased risk of Parkinson’s disease (PD. Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg, MB (30 mg/kg, or the combination of PQ and MB (PQMB. Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.

Change of striatum dopaminergic transporter and content of dopamine in rats with experimental hyperthyroidism

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Lin Yansong; Wang Huicheng; Zhao Zhiying; Zhu Li; Zhang Yingqiang; Chen Zhengping

2009-01-01

Objective: The central dopamine system plays an important role in regulating movement and mood. In our routine clinical practice,we found that patients with hyperthyroidism often show tremor of their hands or legs. Meanwhile they also experienced emotional problems such as anxiety and depression. These reminded us that there might be close relationship between thyroid hormone and dopamine system. Based on our previous works, in this study we evaluated the change of striatum dopamine transporter (DAT) by using 99 Tc m -2β- [N, N'-bis (2-merecaptoethyl) ethylenediamino]methyl, 3β- (4-chlorophenyl) tropane (TRODAT-1) brain biodistribution, and the content of striatum dopamine and its metabolites 3.4-di-hydroxyphenylacetic (DOPAC) by high performace liquid chromatograph-electrochemical detection (HPLC-ECD) in rats with experimental hyperthyroidism. Methods: All 24 rats were randomly divided into two groups, thyroxin group were induced by daily thyroxin infusion for 14 d to be experimental hyperthyroidism, the others were control group which received saline infusion. The blood samples were randomly taken from thyroxine group and control group, and the concentration of TT 3 and TT 4 were detected by radioimmunoassay. After 14 d,both experimental (thyroxine group) and control group were further divided into 2 sub-groups. One was for evaluation of the function of striatum DAT by 99 Tc m -TRODAT-1 biodistribution study and the other was for HPIJC-ECD measurement of the concentration of dopamine and its metabolites DOPAC. Results: Significantly hyperactivity and weight loss [(223.90 ± 8.40) VS (261.60 ± 14.20)g, t=6.98. P 3 and TT 4 after thyroxin infusion was significantly elevated than that of before thyroxin infusion [(2.72 ± 0.29) V8(1.46 ± 0.17) nmol/L, t=10.51, P 3 , and TT 4 after saline infusion showed no statistical significance as compared with before saline infusion [(1.71 ± 0.20) vs (1.54 ± O.09) nmol/L, t=1.68. P>0.05 and (88.38 ± 6.76) vs (98.38 ± 9

Functional Specialization within the Striatum along Both the Dorsal/Ventral and Anterior/Posterior Axes during Associative Learning via Reward and Punishment

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Mattfeld, Aaron T.; Gluck, Mark A.; Stark, Craig E. L.

2011-01-01

The goal of the present study was to elucidate the role of the human striatum in learning via reward and punishment during an associative learning task. Previous studies have identified the striatum as a critical component in the neural circuitry of reward-related learning. It remains unclear, however, under what task conditions, and to what…

SELEKSI RUMPUT LAUT Kappaphycus striatum DALAM UPAYA PENINGKATAN LAJU PERTUMBUHAN BIBIT UNTUK BUDIDAYA

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Andi Parenrengi

2017-01-01

Full Text Available Budidaya rumput laut di Indonesia semakin berkembang seiring dengan peningkatan permintaan bahan baku industri untuk pasar domestik dan eksport. Rumput laut Kappaphycus striatum, salah satu spesies rumput laut komersil, telah intensif dibudidayakan di perairan pantai. Saat ini, masalah utama yang dihadapi pembudidaya adalah rendahnya kualitas bibit yang berasal dari hasil budidaya. Seleksi varietas merupakan salah satu metode yang diharapkan dapat meningkatkan laju pertumbuhan rumput laut. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh seleksi varietas terhadap pertumbuhan rumput laut sehingga dapat dilakukan produksi bibit unggul untuk keperluan budidaya. Budidaya rumput laut K. striatum telah dilakukan di Teluk Laikang, Kabupaten Takalar, Provinsi Sulawesi Selatan dengan menggunakan metode long line. Seleksi varietas dilakukan berdasarkan parameter laju pertumbuhan harian (LPH dan metode seleksi mengacu pada protokol seleksi yang telah dikembangkan pada rumput laut K. alvarezii. Hasil penelitian menunjukkan bahwa LPH bibit hasil seleksi lebih tinggi (P

BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain serotonin levels

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Fisher, Patrick M; Holst, Klaus K; Adamsen, Dea

2015-01-01

) polymorphism. We applied a linear latent variable model (LVM) using regional 5-HT4 binding values (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, allowing us to explicitly model brain-wide and region-specific genotype effects on 5-HT4 binding. Our data supported an LVM wherein...... specifically affects 5-HT4 binding in the neocortex. These findings implicate serotonin signaling as an important molecular mediator underlying the effects of BDNF val66met and 5-HTTLPR on behavior and related risk for neuropsychiatric illness in humans. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc....

Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

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Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

2008-04-01

Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

The development of the region of basal nuclei in fetus using MRI of high field

International Nuclear Information System (INIS)

Geng Hequn; Zhang Zhonghe; Liu Shuwei

2010-01-01

Objective: To study the developmental process of the region of basal nuclei of postmortem fetuses by 3.0 T and 7.0 T MRI. Methods: One hundred and thirty-one postmortem fetuses of 14 to 40 weeks of gestational age (GA) were scanned by 3.0 T MR, of which 11 fetuses of 14-27 weeks of GA were chosen and scanned by 7.0 T MR. The time when the structures in the region of basal nuclei could be detected and the changes of MR signal intensity were analyzed for MRI of different Tesla. Results: On 3.0 T MRI, the dorsal thalamus could be delineated as early as 14 weeks of GA. The germinal matrix, caudate nucleus, and putamen could be visualized as early as 15 weeks of GA. The globus pallidus could be described as early as 18 weeks of GA, and the internal capsule and external capsule could be shown as early as 20 weeks of GA. The signal of the caudate nucleus during 15-30 weeks of GA was relatively hypointense on T 1 WI and hyperintense on T 2 WI, but during 31-40 weeks of GA, it was relatively hyperintense on T 1 WI and hypointense on T 2 WI. The putamen had a relatively high signal intensity on T 1 WI and low signal intensity on T 2 WI during 15-17 weeks of GA, and it appeared patchy during 18-25 weeks of GA, then it had a relatively low signal intensity on T 1 WI and high signal intensity on T 2 WI during 26-30 weeks of GA, and during 31-40 weeks of GA, its signal intensity was relatively high on T 1 WI and low on T 2 WI. The globus pallidus had a relatively high signal intensity on T 1 WI and low signal intensity on T 2 WI during 20- 40 weeks of GA. Compared to the 3.0 T MRI, the T 2 images of 7.0 T MRI were more clear, and most structures in the region of basal nuclei could be clearly displayed as early as 16 weeks of GA, such as the germinal matrix, caudate nucleus, dorsal thalamus, putamen, globus pallidus, internal capsule, and extemal capsule. The claustrum could be delineated as early as 18 weeks of GA on 7.0 T MRI. Conclusions: 3.0 T MRI could show the development

The role of dopamine in the nucleus accumbens and striatum during sexual behavior in the female rat.

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Becker, J B; Rudick, C N; Jenkins, W J

2001-05-01

Dopamine in dialysate from the nucleus accumbens (NAcc) increases during sexual and feeding behavior and after administration of drugs of abuse, even those that do not directly activate dopaminergic systems (e.g., morphine or nicotine). These findings and others have led to hypotheses that propose that dopamine is rewarding, predicts that reinforcement will occur, or attributes incentive salience. Examining increases in dopamine in NAcc or striatum during sexual behavior in female rats provides a unique situation to study these relations. This is because, for the female rat, sexual behavior is associated with an increase in NAcc dopamine and conditioned place preference only under certain testing conditions. This experiment was conducted to determine what factors are important for the increase in dopamine in dialysate from NAcc and striatum during sexual behavior in female rats. The factors considered were the number of contacts by the male, the timing of contacts by the male, or the ability of the female to control contacts by the male. The results indicate that increased NAcc dopamine is dependent on the timing of copulatory stimuli, independent of whether the female rat is actively engaged in regulating this timing. For the striatum, the timing of copulatory behavior influences the magnitude of the increase in dopamine in dialysate, but other factors are also involved. We conclude that increased extracellular dopamine in the NAcc and striatum conveys qualitative or interpretive information about the rewarding value of stimuli. Sexual behavior in the female rat is proposed as a model to determine the role of dopamine in motivated behavior.

Arterial blood supply to the caudate lobe of the liver from the proximal branches of the right inferior phrenic artery in patients with recurrent hepatocellular carcinoma after chemoembolization

International Nuclear Information System (INIS)

Miyayama, Shiro; Yamashiro, Masashi; Shibata, Yoshihiro; Hashimoto, Masahiro; Yoshida, Miki; Tsuji, Kazunobu; Toshima, Fumihito; Matsui, Osamu

2012-01-01

The purpose of this study was to evaluate the arterial blood supply to the caudate lobe of the liver from the proximal branches of the right inferior phrenic artery (RIPA) in patients with recurrent hepatocellular carcinoma after transcatheter arterial chemoembolization (TACE). Thirteen patients, including 10 who had a history of TACE of the caudate artery (A1), underwent TACE of the proximal RIPA branches. Iodized oil distribution was evaluated by computed tomography (CT) 1-week after TACE. Angiographic findings were also evaluated. Previously embolized A1 was occluded (n=15) or attenuated (n=2). In one of three patients without A1 TACE, A1 was also attenuated. TACE was performed at the first branch of the proximal RIPA (n=8), the first branch of the anterior branch (n=6), and the first branch of the posterior branch (n=1), respectively. Iodized oil was mainly distributed into the dorsal part of the Siegel lobe (SP) (n=10), the caudate process (n=1), and both (n=2). In three of seven patients who had undergone serial RIPA angiography, RIPA parasitization to SP was suspected before A1 TACE. The proximal RIPA branches mainly supply the SP when A1 is attenuated. (author)

Haloperidol-induced changes in neuronal activity in the striatum of the freely moving rat

Directory of Open Access Journals (Sweden)

Dorin eYael

2013-12-01

Full Text Available The striatum is the main input structure of the basal ganglia, integrating input from the cerebral cortex and the thalamus, which is modulated by midbrain dopaminergic input. Dopamine modulators, including agonists and antagonists, are widely used to relieve motor and psychiatric symptoms in a variety of pathological conditions. Haloperidol, a dopamine D2 antagonist, is commonly used in multiple psychiatric conditions and motor abnormalities. This article reports the effects of haloperidol on the activity of three major striatal subpopulations: medium spiny projection neurons (MSNs, fast spiking interneurons (FSIs and tonically active neurons (TANs. We implanted multi-wire electrode arrays in the rat dorsal striatum and recorded the activity of multiple single units in freely moving animals before and after systemic haloperidol injection. Haloperidol decreased the firing rate of FSIs and MSNs while increasing their tendency to fire in an oscillatory manner in the high voltage spindle (HVS frequency range of 7-9 Hz. Haloperidol led to an increased firing rate of TANs but did not affect their non-oscillatory firing pattern and their typical correlated firing activity. Our results suggest that dopamine plays a key role in tuning both single unit activity and the interactions within and between different subpopulations in the striatum in a differential manner. These findings highlight the heterogeneous striatal effects of tonic dopamine regulation via D2 receptors which potentially enable the treatment of diverse pathological states associated with basal ganglia dysfunction.

Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

Science.gov (United States)

Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

2007-11-01

Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

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Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

2018-04-15

Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

Chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring of the striatum.

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Taylor, S B; Anglin, J M; Paode, P R; Riggert, A G; Olive, M F; Conrad, C D

2014-11-07

Chronic stress is an established risk factor in the development of addiction. Addiction is characterized by a progressive transition from casual drug use to habitual and compulsive drug use. The ability of chronic stress to facilitate the transition to addiction may be mediated by increased engagement of the neurocircuitries underlying habitual behavior and addiction. In the present study, striatal morphology was evaluated after 2 weeks of chronic variable stress in male Sprague-Dawley rats. Dendritic complexity of medium spiny neurons was visualized and quantified with Golgi staining in the dorsolateral and dorsomedial striatum, as well as in the nucleus accumbens core and shell. In separate cohorts, the effects of chronic stress on habitual behavior and the acute locomotor response to methamphetamine were also assessed. Chronic stress resulted in increased dendritic complexity in the dorsolateral striatum and nucleus accumbens core, regions implicated in habitual behavior and addiction, while decreased complexity was found in the nucleus accumbens shell, a region critical for the initial rewarding effects of drugs of abuse. Chronic stress did not affect dendritic complexity in the dorsomedial striatum. A parallel shift toward habitual learning strategies following chronic stress was also identified. There was an initial reduction in acute locomotor response to methamphetamine, but no lasting effect as a result of chronic stress exposure. These findings suggest that chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring in the striatum. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Ventral striatum activation to prosocial rewards predicts longitudinal declines in adolescent risk taking.

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Telzer, Eva H; Fuligni, Andrew J; Lieberman, Matthew D; Galván, Adriana

2013-01-01

Adolescence is a period of intensified emotions and an increase in motivated behaviors and passions. Evidence from developmental neuroscience suggests that this heightened emotionality occurs, in part, due to a peak in functional reactivity to rewarding stimuli, which renders adolescents more oriented toward reward-seeking behaviors. Most prior work has focused on how reward sensitivity may create vulnerabilities, leading to increases in risk taking. Here, we test whether heightened reward sensitivity may potentially be an asset for adolescents when engaged in prosocial activities. Thirty-two adolescents were followed over a one-year period to examine whether ventral striatum activation to prosocial rewards predicts decreases in risk taking over a year. Results show that heightened ventral striatum activation to prosocial stimuli relates to longitudinal declines in risk taking. Therefore, the very same neural region that has conferred vulnerability for adolescent risk taking may also be protective against risk taking. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dopamine transporter density by [99mTc]-TRODAT-1 SPECT and neurocognitive performance - a preliminary pilot study

International Nuclear Information System (INIS)

Shih, Ming C; Amaro, Edson Jr; Souza, Sayuri de E

2006-01-01

caudate DAT density and performance on verbal learning tasks. Caudate/putamen segmentation in a larger sample is being performed by this group and will potentially provide more information on the relationship between cognitive deficits and DAT loss (au)

Deficits in water maze performance and oxidative stress in the hippocampus and striatum induced by extremely low frequency magnetic field exposure.

Directory of Open Access Journals (Sweden)

Yonghua Cui

Full Text Available The exposures to extremely low frequency magnetic field (ELF-MF in our environment have dramatically increased. Epidemiological studies suggest that there is a possible association between ELF-MF exposure and increased risks of cardiovascular disease, cancers and neurodegenerative disorders. Animal studies show that ELF-MF exposure may interfere with the activity of brain cells, generate behavioral and cognitive disturbances, and produce deficits in attention, perception and spatial learning. Although, many research efforts have been focused on the interaction between ELF-MF exposure and the central nervous system, the mechanism of interaction is still unknown. In this study, we examined the effects of ELF-MF exposure on learning in mice using two water maze tasks and on some parameters indicative of oxidative stress in the hippocampus and striatum. We found that ELF-MF exposure (1 mT, 50 Hz induced serious oxidative stress in the hippocampus and striatum and impaired hippocampal-dependent spatial learning and striatum-dependent habit learning. This study provides evidence for the association between the impairment of learning and the oxidative stress in hippocampus and striatum induced by ELF-MF exposure.

Identification of Functional Clusters in the Striatum Using Infinite Relational Modeling

DEFF Research Database (Denmark)

Andersen, Kasper Winther; Madsen, Kristoffer Hougaard; Siebner, Hartwig

2011-01-01

In this paper we investigate how the Infinite Relational Model can be used to infer functional groupings of the human striatum using resting state fMRI data from 30 healthy subjects. The Infinite Relational Model is a non-parametric Bayesian method for infering community structure in complex netw...... and non-links in the graphs as missing. We find that the model is performing well above chance for all subjects....

Disrupted reinforcement signaling in the orbitofrontal cortex and caudate in youths with conduct disorder or oppositional defiant disorder and a high level of psychopathic traits.

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Finger, Elizabeth C; Marsh, Abigail A; Blair, Karina S; Reid, Marguerite E; Sims, Courtney; Ng, Pamela; Pine, Daniel S; Blair, R James R

2011-02-01

Dysfunction in the amygdala and orbitofrontal cortex has been reported in youths and adults with psychopathic traits. The specific nature of the functional irregularities within these structures remains poorly understood. The authors used a passive avoidance task to examine the responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. While performing the passive avoidance learning task, 15 youths with conduct disorder or oppositional defiant disorder plus a high level of psychopathic traits and 15 healthy subjects completed a 3.0-T fMRI scan. Relative to the comparison youths, the youths with a disruptive behavior disorder plus psychopathic traits showed less orbitofrontal responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as less caudate response to early stimulus-reinforcement exposure. There were no group differences in amygdala responsiveness to these two task measures, but amygdala responsiveness throughout the task was lower in the youths with psychopathic traits. Compromised sensitivity to early reinforcement information in the orbitofrontal cortex and caudate and to reward outcome information in the orbitofrontal cortex of youths with conduct disorder or oppositional defiant disorder plus psychopathic traits suggests that the integrated functioning of the amygdala, caudate, and orbitofrontal cortex may be disrupted. This provides a functional neural basis for why such youths are more likely to repeat disadvantageous decisions. New treatment possibilities are raised, as pharmacologic modulations of serotonin and dopamine can affect this form of learning.

Efferent projections of the dorsal ventricular ridge and the striatum in the Tegu lizard. Tupinambis nigropunctatus.

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Voneida, T J; Sligar, C M

1979-07-01

A H3 proline-leucine mixture was injected into the dorsal ventricular ridge (DVR) and striatum of the Tegu lizard in order to determine their efferent projections. The brains were processed according to standard radioautographic technique, and counterstained with cresyl violet. DVR projections were generally restricted to the telencephalon, while striatal projections were limited to diencephalic and mesencephalic structures. Thus the anterior DVR projects ipsilaterally to nuclei sphericus and lateralis amygdalae, striatum (ipsilateral and contralateral) ventromedial nucleus of the hypothalamus, nucleus accumbens, anterior olfactory nucleus, nucleus of the lateral olfactory tract and lateral pallium. Posterior DVR projections enter ipsilateral anterior olfactory nucleus, lateral and interstitial amygdalar nuclei, olfactory tubercle and bulb, nucleus of the lateral olfactory tract and a zone surrounding the ventromedial hypothalamic nucleus. Labeled axons from striatal injections pass caudally in the lateral forebrain bundle to enter (via dorsal peduncle) nuclei dorsomedialis, medialis posterior, entopeduncularis anterior, and a zone surrounding nucleus rotundus. Others join the ventral peduncle of LFB and enter ventromedial nucleus (thalami), while the remaining fibers continue caudally in the ventral peduncle to the mesencephalic prerubral field, central gray, substantia nigra, nucleus intercollicularis, reticular formation and pretectal nucleus posterodorsalis. These results are discussed in relation to the changing notions regarding terminology, classification and functions of dorsl ventricular ridge and striatum.

Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca^{2+} efflux in rat caudate nucleus and brain stem

OpenAIRE

PETROVIC, SNJEZANA; MILOSEVIC, MAJA; RISTIC-MEDIC, DANIJELA; VELICKOVIC, NATASA; DRAKULIC, DUNJA; GRKOVIC, IVANA; HORVAT, ANICA

2015-01-01

Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca^{2+} efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl_2 (0.6?0.75 µCi ^45CaCl_{2}) was used for Ca^{2+} transport monitoring. The results revealed that in the presence of ER antagonist 7\\alpha,17ß-[9[(4,4,5,5,5-...

Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

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Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

2014-12-01

Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

Regional Brain Activity in Abstinent Methamphetamine Dependent Males Following Cue Exposure.

Science.gov (United States)

Malcolm, Robert; Myrick, Hugh; Li, Xingbao; Henderson, Scott; Brady, Kathleen T; George, Mark S; See, Ronald E

Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied. Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5). Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (pcues, have increased brain activity in ventral striatum, caudate nucleus and medial frontal cortex which subserve craving, drug-seeking, and drug use.

Common genetic variants influence human subcortical brain structures

Science.gov (United States)

Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

2015-01-01

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

Common genetic variants influence human subcortical brain structures.

Science.gov (United States)

Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

2015-04-09

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

The effects of caffeine ingestion on cortical areas: functional imaging study.

Science.gov (United States)

Park, Chan-A; Kang, Chang-Ki; Son, Young-Don; Choi, Eun-Jung; Kim, Sang-Hoon; Oh, Seung-Taek; Kim, Young-Bo; Park, Chan-Woong; Cho, Zang-Hee

2014-05-01

The effect of caffeine as a cognitive enhancer is well known; however, caffeine-induced changes in the cortical regions are still not very clear. Therefore, in this study, we conducted an investigation of the activation and deactivation with blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and of metabolic activity change with positron emission tomography (PET) in the human brain. Fourteen healthy subjects performed a visuomotor task inducing attention with 3T MRI, and PET imaging was also carried out in seven subjects to determine the cerebral glucose metabolic changes of caffeine at rest. The result by fMRI showed increased BOLD activation in the left cerebellum, putamen, insula, thalamus and the right primary motor cortex, and decreased BOLD deactivation in the posterior medial and the left posterior lateral cortex. Also, the resting state PET data showed reduced metabolic activity in the putamen, caudate nucleus, insula, pallidum and posterior medial cortex. The common cortical regions between fMRI and PET, such as putamen, insula and posterior medial cortex, where significant changes occurred after caffeine ingestion, are well known to play an important role in cognitive function like attention. This result suggests that the effect of caffeine as a cognitive enhancer is derived by modulating the attentional areas. Copyright © 2014 Elsevier Inc. All rights reserved.

Glucose Injections into the Dorsal Hippocampus or Dorsolateral Striatum of Rats Prior to T-Maze Training: Modulation of Learning Rates and Strategy Selection

Science.gov (United States)

Canal, Clinton E.; Stutz, Sonja J.; Gold, Paul E.

2005-01-01

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial…

Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.

Science.gov (United States)

Xue, Bing; Chen, Elton C; He, Nan; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

2017-01-01

Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs. In addition, D1R and D2R coactivation recruited GluA1 and PKA preferentially to extrasynaptic sites. In sum, our in vivo data support an existence of a dynamic DA-ACh balance in the striatum which actively modulates GluA1 AMPAR phosphorylation and trafficking. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional inactivation of dorsal medial striatum alters behavioral flexibility and recognition process in mice.

Science.gov (United States)

Qiao, Yanhua; Wang, Xingyue; Ma, Lian; Li, Shengguang; Liang, Jing

2017-10-01

Deficits in behavioral flexibility and recognition memory are commonly observed in mental illnesses and neurodegenerative diseases. Abnormality of the striatum has been implicated in an association with the pathology of these diseases. However, the exact roles of striatal heterogeneous structures in these cognitive functions are still unknown. In the present study, we investigated the effects of suppressing neuronal activity in the dorsomedial striatum (DMStr) and nucleus accumbens core (NAcC) on reversal learning and novelty recognition in mice. In addition, the locomotor activity, anxiety-like behavior and social interaction were analyzed. Neuronal inactivation was performed by expressing lentivirus-mediated tetanus toxin (TeNT) in the target regions. The results showed that reversal learning was facilitated by neuronal inactivation in the DMStr but not the NAcC, which was attributable to accelerated extinction of acquired strategy but not to impaired memory retention. Furthermore, mice with NAcC inactivation spent more time exploring a novel object than a familiar one, comparable to control mice. In contrast, mice with DMStr inactivation exhibited no preference to a novel environment during the novel object or place recognition test. The DMStr mice also exhibited decreased anxiety level. No phenotypic effect was observed in the locomotion or social interaction in mice with either DMStr or NAcC inactivation. Altogether, these findings suggest that the DMStr but not the ventral area of the striatum plays a crucial role in learning and memory by coordinating spatial exploration as well as mediating information updating. Copyright © 2017 Elsevier Inc. All rights reserved.