Age related changes in striatal resting state functional connectivity in autism

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Aarthi ePadmanabhan

2013-11-01

Full Text Available Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity with resting state fMRI from late childhood to early adulthood (8-36 years, using a seed based functional connectivity method with the striatum. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to TD participants. In addition, ASD participants showed aberrant age-related changes in connectivity with anterior aspects of cerebellum, and posterior temporal regions (e.g. fusiform gyrus, inferior and superior temporal gyri. In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, atypical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which also may help clarify discrepant findings in the literature.

Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson’s disease

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Youngbin Kwak

2010-09-01

Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.

The Extended Fronto-Striatal Model of Obsessive Compulsive Disorder: Convergence from Event-Related Potentials, Neuropsychology and Neuroimaging

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Margherita eMelloni

2012-09-01

Full Text Available In this work, we explored convergent evidence supporting the fronto-striatal model of obsessive-compulsive disorder (FSMOCD and the contribution of event-related potential (ERP studies to this model. First, we considered minor modifications to the FSMOCD model based on neuroimaging and neuropsychological data. We noted the brain areas most affected in this disorder -anterior cingulate cortex (ACC, basal ganglia (BG and orbito-frontal cortex (OFC- and their related cognitive functions, such as monitoring and inhibition. Then, we assessed the ERPs that are directly related to the FSMOCD, including the error-related negativity (ERN, N200 and P600. Several OCD studies present enhanced ERN and N2 responses during conflict tasks as well as an enhanced P600 during working memory tasks. Evidence from ERP studies (especially regarding ERN and N200 amplitude enhancement, neuroimaging and neuropsychological findings suggests abnormal activity in the OFC, ACC and BG in OCD patients. Moreover, additional findings from these analyses suggest dorsolateral prefrontal and parietal cortex involvement, which might be related to executive function deficits. Thus, these convergent results suggest the existence of a self-monitoring imbalance involving inhibitory deficits and executive dysfunctions. OCD patients present an impaired ability to monitor, control, and inhibit intrusive thoughts, urges, feelings and behaviors. In the current model, this imbalance is triggered by an excitatory role of the BG (associated with cognitive or motor actions without volitional control and inhibitory activity of the OFC as well as excessive monitoring of the ACC to block excitatory impulses. This imbalance would interact with the reduced activation of the parietal-DLPC network, leading to executive dysfunction. ERP research may provide further insight regarding the temporal dynamics of action monitoring and executive functioning in OCD.

Increased cortico-striatal connectivity during motor practice contributes to the consolidation of motor memory in writer's cramp patients

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C. Gallea

2015-01-01

Full Text Available Sensorimotor representations of movements are created in the sensorimotor network through repeated practice to support successful and effortless performance. Writer's cramp (WC is a disorder acquired through extensive practice of finger movements, and it is likely associated with the abnormal acquisition of sensorimotor representations. We investigated (i the activation and connectivity changes in the brain network supporting the acquisition of sensorimotor representations of finger sequences in patients with WC and (ii the link between these changes and consolidation of motor performance 24 h after the initial practice. Twenty-two patients with WC and 22 age-matched healthy volunteers practiced a complex sequence with the right (pathological hand during functional MRI recording. Speed and accuracy were measured immediately before and after practice (day 1 and 24 h after practice (day 2. The two groups reached equivalent motor performance on day 1 and day 2. During motor practice, patients with WC had (i reduced hippocampal activation and hippocampal–striatal functional connectivity; and (ii overactivation of premotor–striatal areas, whose connectivity correlated with motor performance after consolidation. These results suggest that patients with WC use alternative networks to reach equiperformance in the acquisition of new motor memories.

Abnormal brain activation in excoriation (skin-picking) disorder

DEFF Research Database (Denmark)

Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R

2016-01-01

Background: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims: To probe the function of fronto-striatal circuitry in SPD. Method: Eighteen participants with SPD and 15 matched healthy controls undertook an executive...... encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. Conclusions: Abnormalities of neural regions...... involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive-compulsive spectrum disorders....

Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

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Jin, Chenwang; Zhang, Ting; Cai, Chenxi; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Zhang, Ming; Yuan, Kai

2016-09-01

Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.

Functional connectivity modeling of consistent cortico-striatal degeneration in Huntington's disease

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Imis Dogan

2015-01-01

Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis we identified core regions of consistent neurodegeneration in premanifest HD in the striatum and middle occipital gyrus (MOG. For early manifest HD convergent evidence of atrophy was most prominent in the striatum, motor cortex (M1 and inferior frontal junction (IFJ. The aim of the present study was to functionally characterize this topography of brain atrophy and to investigate differential connectivity patterns formed by consistent cortico-striatal atrophy regions in HD. Using areas of striatal and cortical atrophy at different disease stages as seeds, we performed task-free resting-state and task-based meta-analytic connectivity modeling (MACM. MACM utilizes the large data source of the BrainMap database and identifies significant areas of above-chance co-activation with the seed-region via the activation-likelihood-estimation approach. In order to delineate functional networks formed by cortical as well as striatal atrophy regions we computed the conjunction between the co-activation profiles of striatal and cortical seeds in the premanifest and manifest stages of HD, respectively. Functional characterization of the seeds was obtained using the behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the premanifest stage of HD showed common co-activation with a rather cognitive network including the striatum, anterior insula, lateral prefrontal, premotor, supplementary motor and parietal regions. A similar but more pronounced co-activation pattern, additionally including the medial prefrontal cortex and thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage. The striatum and M1 were functionally connected mainly to premotor and sensorimotor areas, posterior insula, putamen and thalamus. Behavioral characterization of the seeds confirmed that experiments

Distinct fronto-striatal couplings reveal the double-faced nature of response-outcome relations in instruction-based learning.

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Ruge, Hannes; Wolfensteller, Uta

2015-06-01

Higher species commonly learn novel behaviors by evaluating retrospectively whether actions have yielded desirable outcomes. By relying on explicit behavioral instructions, only humans can use an acquisition shortcut that prospectively specifies how to yield intended outcomes under the appropriate stimulus conditions. A recent and largely unexplored hypothesis suggests that striatal areas interact with lateral prefrontal cortex (LPFC) when novel behaviors are learned via explicit instruction, and that regional subspecialization exists for the integration of differential response-outcome contingencies into the current task model. Behaviorally, outcome integration during instruction-based learning has been linked to functionally distinct performance indices. This includes (1) compatibility effects, measured in a postlearning test procedure probing the encoding strength of outcome-response (O-R) associations, and (2) increasing response slowing across learning, putatively indicating active usage of O-R associations for the online control of goal-directed action. In the present fMRI study, we examined correlations between these behavioral indices and the dynamics of fronto-striatal couplings in order to mutually constrain and refine the interpretation of neural and behavioral measures in terms of separable subprocesses during outcome integration. We found that O-R encoding strength correlated with LPFC-putamen coupling, suggesting that the putamen is relevant for the formation of both S-R habits and habit-like O-R associations. By contrast, response slowing as a putative index of active usage of O-R associations correlated with LPFC-caudate coupling. This finding highlights the relevance of the caudate for the online control of goal-directed action also under instruction-based learning conditions, and in turn clarifies the functional relevance of the behavioral slowing effect.

A neurobehavioral examination of individuals with high-functioning autism and Asperger's disorder using a fronto-striatal model of dysfunction.

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Rinehart, Nicole J; Bradshaw, John L; Tonge, Bruce J; Brereton, Avril V; Bellgrove, Mark A

2002-06-01

The repetitive, stereotyped, and obsessive behaviors that characterize autism may in part be attributable to disruption of the region of the fronto-striatal system, which mediates executive abilities. Neuropsychological testing has shown that children with autism exhibit set-shifting deficiencies on tests such as the Wisconsin Card Sorting task but show normal inhibitory ability on variants of the Stroop color-word test. According to Minshew and Goldstein's multiple primary deficit theory, the complexity of the executive functioning task is important in determining the performance of individuals with autism. This study employed a visual-spatial task (with a Stroop-type component) to examine the integrity of executive functioning, in particular inhibition, in autism (n = 12) and Asperger's disorder (n = 12) under increasing levels of cognitive complexity. Whereas the Asperger's disorder group performed similarly to age- and IQ-matched control participants, even at the higher levels of cognitive complexity, the high-functioning autism group displayed inhibitory deficits specifically associated with increasing cognitive load.

Fronto-Limbic Brain Dysfunction during the Regulation of Emotion in Schizophrenia.

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Shaun M Eack

Full Text Available Schizophrenia is characterized by significant and widespread impairments in the regulation of emotion. Evidence is only recently emerging regarding the neural basis of these emotion regulation impairments, and few studies have focused on the regulation of emotion during effortful cognitive processing. To examine the neural correlates of deficits in effortful emotion regulation, schizophrenia outpatients (N = 20 and age- and gender-matched healthy volunteers (N = 20 completed an emotional faces n-back task to assess the voluntary attentional control subprocess of emotion regulation during functional magnetic resonance imaging. Behavioral measures of emotional intelligence and emotion perception were administered to examine brain-behavior relationships with emotion processing outcomes. Results indicated that patients with schizophrenia demonstrated significantly greater activation in the bilateral striatum, ventromedial prefrontal, and right orbitofrontal cortices during the effortful regulation of positive emotional stimuli, and reduced activity in these same regions when regulating negative emotional information. The opposite pattern of results was observed in healthy individuals. Greater fronto-striatal response to positive emotional distractors was significantly associated with deficits in facial emotion recognition. These findings indicate that abnormalities in striatal and prefrontal cortical systems may be related to deficits in the effortful emotion regulatory process of attentional control in schizophrenia, and may significantly contribute to emotion processing deficits in the disorder.

Anticipation-related brain connectivity in bipolar and unipolar depression: a graph theory approach.

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Manelis, Anna; Almeida, Jorge R C; Stiffler, Richelle; Lockovich, Jeanette C; Aslam, Haris A; Phillips, Mary L

2016-09-01

loss anticipation was characterized by denser top-down fronto-striatal and fronto-parietal connectivity in healthy control subjects, by bottom-up striatal-frontal connectivity in MDD, and by sparse connectivity lacking fronto-striatal connections in BDD. Win anticipation was characterized by dense connectivity of medial frontal with striatal and lateral frontal cortical regions in BDD, by sparser bottom-up striatum-medial frontal cortex connectivity in MDD, and by sparse connectivity in healthy control subjects. In summary, this is the first study to demonstrate that BDD and MDD with comparable levels of current depression differed from each other and healthy control subjects in density of connections, connectivity path length, and connectivity direction as a function of win or loss anticipation. These findings suggest that different neurobiological mechanisms may underlie aberrant anticipation processes in BDD and MDD, and that distinct therapeutic strategies may be required for these individuals to improve coping strategies during expectation of positive and negative outcomes. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.

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Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter; Hallett, Mark

2013-09-11

Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

Regional vulnerability of longitudinal cortical association connectivity

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Rafael Ceschin

2015-01-01

Full Text Available Preterm born children with spastic diplegia type of cerebral palsy and white matter injury or periventricular leukomalacia (PVL, are known to have motor, visual and cognitive impairments. Most diffusion tensor imaging (DTI studies performed in this group have demonstrated widespread abnormalities using averaged deterministic tractography and voxel-based DTI measurements. Little is known about structural network correlates of white matter topography and reorganization in preterm cerebral palsy, despite the availability of new therapies and the need for brain imaging biomarkers. Here, we combined novel post-processing methodology of probabilistic tractography data in this preterm cohort to improve spatial and regional delineation of longitudinal cortical association tract abnormalities using an along-tract approach, and compared these data to structural DTI cortical network topology analysis. DTI images were acquired on 16 preterm children with cerebral palsy (mean age 5.6 ± 4 and 75 healthy controls (mean age 5.7 ± 3.4. Despite mean tract analysis, Tract-Based Spatial Statistics (TBSS and voxel-based morphometry (VBM demonstrating diffusely reduced fractional anisotropy (FA reduction in all white matter tracts, the along-tract analysis improved the detection of regional tract vulnerability. The along-tract map-structural network topology correlates revealed two associations: (1 reduced regional posterior–anterior gradient in FA of the longitudinal visual cortical association tracts (inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiation, posterior thalamic radiation correlated with reduced posterior–anterior gradient of intra-regional (nodal efficiency metrics with relative sparing of frontal and temporal regions; and (2 reduced regional FA within frontal–thalamic–striatal white matter pathways (anterior limb/anterior thalamic radiation, superior longitudinal fasciculus and cortical spinal tract

Resting-State Connectivity Predicts Levodopa-Induced Dyskinesias in Parkinson's Disease

DEFF Research Database (Denmark)

Herz, Damian M.; Haagensen, Brian N.; Nielsen, Silas H.

2016-01-01

Background: Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood. Objectives: This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico-striatal connect......Background: Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood. Objectives: This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico......-striatal connectivity. Methods: Twelve PD patients with peak-of-dose dyskinesias and 12 patients without dyskinesias were withdrawn from dopaminergic medication. All patients received a single dose of fast-acting soluble levodopa and then underwent resting-state functional magnetic resonance imaging before any...... dyskinesias emerged. Levodopa-induced modulation of cortico-striatal resting-state connectivity was assessed between the putamen and the following 3 cortical regions of interest: supplementary motor area, primary sensorimotor cortex, and right inferior frontal gyrus. These functional connectivity measures...

Disruption of structure–function coupling in the schizophrenia connectome

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Luca Cocchi

2014-01-01

Full Text Available Neuroimaging studies have demonstrated that the phenomenology of schizophrenia maps onto diffuse alterations in large-scale functional and structural brain networks. However, the relationship between structural and functional deficits remains unclear. To answer this question, patients with established schizophrenia and matched healthy controls underwent resting-state functional and diffusion weighted imaging. The network-based statistic was used to characterize between-group differences in whole-brain functional connectivity. Indices of white matter integrity were then estimated to assess the structural correlates of the functional alterations observed in patients. Finally, group differences in the relationship between indices of functional and structural brain connectivity were determined. Compared to controls, patients with schizophrenia showed decreased functional connectivity and impaired white matter integrity in a distributed network encompassing frontal, temporal, thalamic, and striatal regions. In controls, strong interregional coupling in neural activity was associated with well-myelinated white matter pathways in this network. This correspondence between structure and function appeared to be absent in patients with schizophrenia. In two additional disrupted functional networks, encompassing parietal, occipital, and temporal cortices, the relationship between function and structure was not affected. Overall, results from this study highlight the importance of considering not only the separable impact of functional and structural connectivity deficits on the pathoaetiology of schizophrenia, but also the implications of the complex nature of their interaction. More specifically, our findings support the core nature of fronto-striatal, fronto-thalamic, and fronto-temporal abnormalities in the schizophrenia connectome.

A global network of RNA and protein interactions in Fronto Temporal Dementia

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Francesca eFontana

2015-03-01

Full Text Available Fronto Temporal Dementia (FTD is a neurodegenerative disorder characterized by degeneration of the fronto temporal lobes and abnormal protein inclusions. It exhibits a broad clinicopathological spectrum and has been linked to mutations in seven different genes. We will provide a picture, which connects the products of these genes, albeit diverse in nature and function, in a network. Despite the paucity of information available for some of these genes, we believe that RNA processing and post-transcriptional regulation of gene expression might constitute a common theme in the network. Recent studies have unraveled the role of mutations affecting the functions of RNA binding proteins and regulation of microRNAs. This review will combine all the recent findings on genes involved in the pathogenesis of FTD, highlighting the importance of a common network of interactions in order to study and decipher the heterogeneous clinical manifestations associated with FTD. This approach could be helpful for the research of potential therapeutic strategies.

Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling

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Yeunkum Lee

2017-06-01

Full Text Available Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3-overexpressing transgenic (TG mice that display manic-like behaviors. The results of transcriptome analysis suggested that mammalian target of rapamycin complex 1 (mTORC1 signaling may be the primary molecular signature altered in the Shank3 TG striatum. Indeed, we found that striatal mTORC1 activity, as measured by mTOR S2448 phosphorylation, was significantly decreased in the Shank3 TG mice compared to wild-type (WT mice. To elucidate the potential underlying mechanism, we re-analyzed previously reported protein interactomes, and detected a high connectivity between Shank3 and several upstream regulators of mTORC1, such as tuberous sclerosis 1 (TSC1, TSC2 and Ras homolog enriched in striatum (Rhes, via 94 common interactors that we denominated “Shank3-mTORC1 interactome”. We noticed that, among the 94 common interactors, 11 proteins were related to actin filaments, the level of which was increased in the dorsal striatum of Shank3 TG mice. Furthermore, we could co-immunoprecipitate Shank3, Rhes and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1 proteins from the striatal lysate of Shank3 TG mice. By comparing with the gene sets of psychiatric disorders, we also observed that the 94 proteins of Shank3-mTORC1 interactome were significantly associated with bipolar disorder (BD. Altogether, our results suggest a protein interaction-mediated connectivity between Shank3 and certain upstream

Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

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Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

2016-06-01

.409 ± 0.046; P = .016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877). These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Subcomponents and Connectivity of the Inferior Fronto-Occipital Fasciculus Revealed by Diffusion Spectrum Imaging Fiber Tracking

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Wu, Yupeng; Sun, Dandan; Wang, Yong; Wang, Yibao

2016-01-01

The definitive structure and functional role of the inferior fronto-occipital fasciculus (IFOF) are still controversial. In this study, we aimed to investigate the connectivity, asymmetry, and segmentation patterns of this bundle. High angular diffusion spectrum imaging (DSI) analysis was performed on 10 healthy adults and a 90-subject DSI template (NTU-90 Atlas). In addition, a new tractography approach based on the anatomic subregions and two regions of interest (ROI) was evaluated for the ...

Fronto-parietal and fronto-temporal theta phase synchronization for visual and auditory-verbal working memory.

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Kawasaki, Masahiro; Kitajo, Keiichi; Yamaguchi, Yoko

2014-01-01

In humans, theta phase (4-8 Hz) synchronization observed on electroencephalography (EEG) plays an important role in the manipulation of mental representations during working memory (WM) tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM.

Fronto-parietal and fronto-temporal theta phase synchronization for visual and auditory-verbal working memory

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Masahiro eKawasaki

2014-03-01

Full Text Available In humans, theta phase (4–8 Hz synchronization observed on electroencephalography (EEG plays an important role in the manipulation of mental representations during working memory (WM tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM.

Striatal morphology correlates with sensory abnormalities in unaffected relatives of cervical dystonia patients.

LENUS (Irish Health Repository)

Walsh, Richard A

2012-02-01

Structural grey matter abnormalities have been described in adult-onset primary torsion dystonia (AOPTD). Altered spatial discrimination thresholds are found in familial and sporadic AOPTD and in some unaffected relatives who may be non-manifesting gene carriers. Our hypothesis was that a subset of unaffected relatives with abnormal spatial acuity would have associated structural abnormalities. Twenty-eight unaffected relatives of patients with familial cervical dystonia, 24 relatives of patients with sporadic cervical dystonia and 27 control subjects were recruited. Spatial discrimination thresholds (SDTs) were determined using a grating orientation task. High-resolution magnetic resonance imaging (MRI) images (1.5 T) were analysed using voxel-based morphometry. Unaffected familial relatives with abnormal SDTs had reduced caudate grey matter volume (GMV) bilaterally relative to those with normal SDTs (right Z = 3.45, left Z = 3.81), where there was a negative correlation between SDTs and GMV (r = -0.76, r(2) = 0.58, p < 0.0001). Familial relatives also had bilateral sensory cortical expansion relative to unrelated controls (right Z = 4.02, left Z = 3.79). Unaffected relatives of patients with sporadic cervical dystonia who had abnormal SDTs had reduced putaminal GMV bilaterally compared with those with normal SDTs (right Z = 3.96, left Z = 3.45). Sensory abnormalities in some unaffected relatives correlate with a striatal substrate and may be a marker of genetic susceptibility in these individuals. Further investigation of grey matter changes as a candidate endophenotype may assist future genetic studies of dystonia.

Altered cortico-striatal-thalamic connectivity in relation to spatial working memory capacity in children with ADHD

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Kathryn L. Mills

2012-01-01

Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting state functional connectivity (rs-fcMRI studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical-striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD.Methods: We correlated the rs-fcMRI of five thalamic regions of interest with spatial span working memory scores in a sample of 67 children aged 7-11 years (ADHD and typically developing children; TDC. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7-11 years from the ADHD-200 dataset. Thalamic regions of interest were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus.Results/Conclusions: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype.

Alpha desynchronization and fronto­parietal connectivity during spatial working memory encoding deficits in ADHD: A simultaneous EEG­fMRI study

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Agatha Lenartowicz

2016-01-01

Full Text Available The underlying mechanisms of alpha band (8–12 Hz neural oscillations are of importance to the functioning of attention control systems as well as to neuropsychiatric conditions that are characterized by deficits of that system, such as attention deficit hyperactivity disorder (ADHD. The objectives of the present study were to test if visual encoding-related alpha event-related desynchronization (ERD correlates with fronto-parieto-occipital connectivity, and whether this is disrupted in ADHD during spatial working memory (SWM performance. We acquired EEG concurrently with fMRI in thirty boys (12–16 yrs. old, 15 with ADHD, during SWM encoding. Psychophysiological connectivity analyses indicated that alpha ERD during SWM encoding was associated with both occipital activation and fronto-parieto-occipital functional connectivity, a finding that expands on prior associations between alpha ERD and occipital activation. This finding provides novel support for the interpretation of alpha ERD (and the associated changes in occipital activation as a phenomenon that involves, and perhaps arises as a result of, top-down network interactions. Alpha ERD was associated less strongly with occipital activity, but associated more strongly with fronto-parieto-occipital connectivity in ADHD, consistent with a compensatory attentional response. Additionally, we illustrate that degradation of EEG data quality by MRI-amplified motion artifacts is robust to existing cleaning algorithms and is significantly correlated with hyperactivity symptoms and the ADHD Combined Type diagnosis. We conclude that persistent motion-related MR artifacts in EEG data can increase variance and introduce bias in interpretation of group differences in populations characterized by hypermobility — a clear limitation of current-state EEG-fMRI methodology.

Abnormal interhemispheric connectivity in male psychopathic offenders.

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Hoppenbrouwers, Sylco S; De Jesus, Danilo R; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J; Schutter, Dennis J L G

2014-01-01

Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.

Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.

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Fjell, Anders M; Sneve, Markus H; Storsve, Andreas B; Grydeland, Håkon; Yendiki, Anastasia; Walhovd, Kristine B

2016-03-01

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Motor tics evoked by striatal disinhibition in the rat

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Bronfeld, Maya; Yael, Dorin; Belelovsky, Katya; Bar-Gad, Izhar

2013-01-01

Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS). Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure—the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons' collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration, and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1–4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders. PMID:24065893

Functional segregation and integration within fronto-parietal networks.

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Parlatini, Valeria; Radua, Joaquim; Dell'Acqua, Flavio; Leslie, Anoushka; Simmons, Andy; Murphy, Declan G; Catani, Marco; Thiebaut de Schotten, Michel

2017-02-01

Experimental data on monkeys and functional studies in humans support the existence of a complex fronto-parietal system activating for cognitive and motor tasks, which may be anatomically supported by the superior longitudinal fasciculus (SLF). Advanced tractography methods have recently allowed the separation of the three branches of the SLF but are not suitable for their functional investigation. In order to gather comprehensive information about the functional organisation of these fronto-parietal connections, we used an innovative method, which combined tractography of the SLF in the largest dataset so far (129 participants) with 14 meta-analyses of functional magnetic resonance imaging (fMRI) studies. We found that frontal and parietal functions can be clustered into a dorsal spatial/motor network associated with the SLF I, and a ventral non-spatial/motor network associated with the SLF III. Further, all the investigated functions activated a middle network mostly associated with the SLF II. Our findings suggest that dorsal and ventral fronto-parietal networks are segregated but also share regions of activation, which may support flexible response properties or conscious processing. In sum, our novel combined approach provided novel findings on the functional organisation of fronto-parietal networks, and may be successfully applied to other brain connections. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Regional vulnerability of longitudinal cortical association connectivity: Associated with structural network topology alterations in preterm children with cerebral palsy.

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Ceschin, Rafael; Lee, Vince K; Schmithorst, Vince; Panigrahy, Ashok

2015-01-01

Preterm born children with spastic diplegia type of cerebral palsy and white matter injury or periventricular leukomalacia (PVL), are known to have motor, visual and cognitive impairments. Most diffusion tensor imaging (DTI) studies performed in this group have demonstrated widespread abnormalities using averaged deterministic tractography and voxel-based DTI measurements. Little is known about structural network correlates of white matter topography and reorganization in preterm cerebral palsy, despite the availability of new therapies and the need for brain imaging biomarkers. Here, we combined novel post-processing methodology of probabilistic tractography data in this preterm cohort to improve spatial and regional delineation of longitudinal cortical association tract abnormalities using an along-tract approach, and compared these data to structural DTI cortical network topology analysis. DTI images were acquired on 16 preterm children with cerebral palsy (mean age 5.6 ± 4) and 75 healthy controls (mean age 5.7 ± 3.4). Despite mean tract analysis, Tract-Based Spatial Statistics (TBSS) and voxel-based morphometry (VBM) demonstrating diffusely reduced fractional anisotropy (FA) reduction in all white matter tracts, the along-tract analysis improved the detection of regional tract vulnerability. The along-tract map-structural network topology correlates revealed two associations: (1) reduced regional posterior-anterior gradient in FA of the longitudinal visual cortical association tracts (inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiation, posterior thalamic radiation) correlated with reduced posterior-anterior gradient of intra-regional (nodal efficiency) metrics with relative sparing of frontal and temporal regions; and (2) reduced regional FA within frontal-thalamic-striatal white matter pathways (anterior limb/anterior thalamic radiation, superior longitudinal fasciculus and cortical spinal tract) correlated with

Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

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Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

2013-01-01

Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

Abnormalities of Functional Brain Networks in Pathological Gambling: A Graph-Theoretical Approach

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Melanie eTschernegg

2013-09-01

Full Text Available Functional neuroimaging studies of pathological gambling demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in pathological gambling. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional MRI data in pathological gambling. We compared 19 patients with pathological gambling to 19 healthy controls using the Graph Analysis Toolbox (GAT. None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (SMA, reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients.These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that pathological gambling is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in pathological gambling cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders.

Functional brain imaging across development.

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Rubia, Katya

2013-12-01

The developmental cognitive neuroscience literature has grown exponentially over the last decade. This paper reviews the functional magnetic resonance imaging (fMRI) literature on brain function development of typically late developing functions of cognitive and motivation control, timing and attention as well as of resting state neural networks. Evidence shows that between childhood and adulthood, concomitant with cognitive maturation, there is progressively increased functional activation in task-relevant lateral and medial frontal, striatal and parieto-temporal brain regions that mediate these higher level control functions. This is accompanied by progressively stronger functional inter-regional connectivity within task-relevant fronto-striatal and fronto-parieto-temporal networks. Negative age associations are observed in earlier developing posterior and limbic regions, suggesting a shift with age from the recruitment of "bottom-up" processing regions towards "top-down" fronto-cortical and fronto-subcortical connections, leading to a more mature, supervised cognition. The resting state fMRI literature further complements this evidence by showing progressively stronger deactivation with age in anti-correlated task-negative resting state networks, which is associated with better task performance. Furthermore, connectivity analyses during the resting state show that with development increasingly stronger long-range connections are being formed, for example, between fronto-parietal and fronto-cerebellar connections, in both task-positive networks and in task-negative default mode networks, together with progressively lesser short-range connections, suggesting progressive functional integration and segregation with age. Overall, evidence suggests that throughout development between childhood and adulthood, there is progressive refinement and integration of both task-positive fronto-cortical and fronto-subcortical activation and task-negative deactivation, leading to

Fronto-Temporal Connectivity Predicts ECT Outcome in Major Depression

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Amber M. Leaver

2018-03-01

Full Text Available BackgroundElectroconvulsive therapy (ECT is arguably the most effective available treatment for severe depression. Recent studies have used MRI data to predict clinical outcome to ECT and other antidepressant therapies. One challenge facing such studies is selecting from among the many available metrics, which characterize complementary and sometimes non-overlapping aspects of brain function and connectomics. Here, we assessed the ability of aggregated, functional MRI metrics of basal brain activity and connectivity to predict antidepressant response to ECT using machine learning.MethodsA radial support vector machine was trained using arterial spin labeling (ASL and blood-oxygen-level-dependent (BOLD functional magnetic resonance imaging (fMRI metrics from n = 46 (26 female, mean age 42 depressed patients prior to ECT (majority right-unilateral stimulation. Image preprocessing was applied using standard procedures, and metrics included cerebral blood flow in ASL, and regional homogeneity, fractional amplitude of low-frequency modulations, and graph theory metrics (strength, local efficiency, and clustering in BOLD data. A 5-repeated 5-fold cross-validation procedure with nested feature-selection validated model performance. Linear regressions were applied post hoc to aid interpretation of discriminative features.ResultsThe range of balanced accuracy in models performing statistically above chance was 58–68%. Here, prediction of non-responders was slightly higher than for responders (maximum performance 74 and 64%, respectively. Several features were consistently selected across cross-validation folds, mostly within frontal and temporal regions. Among these were connectivity strength among: a fronto-parietal network [including left dorsolateral prefrontal cortex (DLPFC], motor and temporal networks (near ECT electrodes, and/or subgenual anterior cingulate cortex (sgACC.ConclusionOur data indicate that pattern classification of multimodal f

Time Processing in Children with Tourette's Syndrome

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Vicario, Carmelo Mario; Martino, Davide; Spata, Felice; Defazio, Giovanni; Giacche, Roberta; Martino, Vito; Rappo, Gaetano; Pepi, Anna Maria; Silvestri, Paola Rosaria; Cardona, Francesco

2010-01-01

Background: Tourette syndrome (TS) is characterized by dysfunctional connectivity between prefrontal cortex and sub-cortical structures, and altered meso-cortical and/or meso-striatal dopamine release. Since time processing is also regulated by fronto-striatal circuits and modulated by dopaminergic transmission, we hypothesized that time…

Hypercholesterolemia causes psychomotor abnormalities in mice and alterations in cortico-striatal biogenic amine neurotransmitters: Relevance to Parkinson's disease.

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Paul, Rajib; Choudhury, Amarendranath; Chandra Boruah, Dulal; Devi, Rajlakshmi; Bhattacharya, Pallab; Choudhury, Manabendra Dutta; Borah, Anupom

2017-09-01

The symptoms of Parkinson's disease (PD) include motor behavioral abnormalities, which appear as a result of the extensive loss of the striatal biogenic amine, dopamine. Various endogenous molecules, including cholesterol, have been put forward as putative contributors in the pathogenesis of PD. Earlier reports have provided a strong link between the elevated level of plasma cholesterol (hypercholesterolemia) and onset of PD. However, the role of hypercholesterolemia on brain functions in terms of neurotransmitter metabolism and associated behavioral manifestations remain elusive. We tested in Swiss albino mice whether hypercholesterolemia induced by high-cholesterol diet would affect dopamine and serotonin metabolism in discrete brain regions that would precipitate in psychomotor behavioral manifestations. High-cholesterol diet for 12 weeks caused a significant increase in blood total cholesterol level, which validated the model as hypercholesterolemic. Tests for akinesia, catalepsy, swimming ability and gait pattern (increased stride length) have revealed that hypercholesterolemic mice develop motor behavioral abnormalities, which are similar to the behavioral phenotypes of PD. Moreover, hypercholesterolemia caused depressive-like behavior in mice, as indicated by the increased immobility time in the forced swim test. We found a significant depletion of dopamine in striatum and serotonin in cortex of hypercholesterolemic mice. The significant decrease in tyrosine hydroxylase immunoreactivity in striatum supports the observed depleted level dopamine in striatum, which is relevant to the pathophysiology of PD. In conclusion, hypercholesterolemia-induced depleted levels of cortical and striatal biogenic amines reported hereby are similar to the PD pathology, which might be associated with the observed psychomotor behavioral abnormalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased insula-putamen connectivity in X-linked dystonia-parkinsonism

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Anne J. Blood

2018-01-01

Full Text Available Preliminary evidence from postmortem studies of X-linked dystonia-parkinsonism (XDP suggests tissue loss may occur first and/or most severely in the striatal striosome compartment, followed later by cell loss in the matrix compartment. However, little is known about how this relates to pathogenesis and pathophysiology. While MRI cannot visualize these striatal compartments directly in humans, differences in relative gradients of afferent cortical connectivity across compartments (weighted toward paralimbic versus sensorimotor cortex, respectively can be used to infer potential selective loss in vivo. In the current study we evaluated relative connectivity of paralimbic versus sensorimotor cortex with the caudate and putamen in 17 individuals with XDP and 17 matched controls. Although caudate and putamen volumes were reduced in XDP, there were no significant reductions in either “matrix-weighted”, or “striosome-weighted” connectivity. In fact, paralimbic connectivity with the putamen was elevated, rather than reduced, in XDP. This was driven most strongly by elevated putamen connectivity with the anterior insula. There was no relationship of these findings to disease duration or striatal volume, suggesting insula and/or paralimbic connectivity in XDP may develop abnormally and/or increase in the years before symptom onset.

Multimodal Neuroimaging of Fronto-limbic Structure and Function Associated with Suicide Attempts in Adolescents and Young Adults with Bipolar Disorder

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Johnston, Jennifer A. Y.; Wang, Fei; Liu, Jie; Blond, Benjamin N.; Wallace, Amanda; Liu, Jiacheng; Spencer, Linda; Cox Lippard, Elizabeth T.; Purves, Kirstin L.; Landeros-Weisenberger, Angeli; Hermes, Eric; Pittman, Brian; Zhang, Sheng; King, Robert; Martin, Andrés; Oquendo, Maria A.; Blumberg, Hilary P.

2018-01-01

Objective Bipolar disorder is associated with high risk for suicide behavior that often develops in adolescence/young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents/young adults with bipolar disorder with and without history of suicide attempts combines structural, diffusion tensor and functional magnetic resonance imaging methods to investigate implicated abnormalities in structural and functional connectivity within fronto-limbic systems. Method Participants with bipolar disorder included 26 with a prior suicide attempt and 42 without attempts. Regional gray matter volume, white matter integrity and functional connectivity during processing of emotional stimuli were compared between groups and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Results Compared to the non-attempter group, the attempter group showed reductions in gray matter volume in orbitofrontal cortex, hippocampus and cerebellum; white matter integrity in uncinate fasciculus, ventral frontal and right cerebellum regions; and amygdala functional connectivity to left ventral and right rostral prefrontal cortex (pAdolescent/young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral fronto-limbic neural system subserving emotion regulation. Among suicide attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicide ideation and attempt lethality. PMID:28135845

Q-Ball of Inferior Fronto-Occipital Fasciculus and Beyond

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Amirbekian, Bagrat; Berger, Mitchel S.; Henry, Roland G.

2014-01-01

The inferior fronto-occipital fasciculus (IFOF) is historically described as the longest associative bundle in the human brain and it connects various parts of the occipital cortex, temporo-basal area and the superior parietal lobule to the frontal lobe through the external/extreme capsule complex. The exact functional role and the detailed anatomical definition of the IFOF are still under debate within the scientific community. In this study we present a fiber tracking dissection of the right and left IFOF by using a q-ball residual-bootstrap reconstruction of High-Angular Resolution Diffusion Imaging (HARDI) data sets in 20 healthy subjects. By defining a single seed region of interest on the coronal fractional anisotropy (FA) color map of each subject, we investigated all the pathways connecting the parietal, occipital and posterior temporal cortices to the frontal lobe through the external/extreme capsule. In line with recent post-mortem dissection studies we found more extended anterior-posterior association connections than the “classical” fronto-occipital representation of the IFOF. In particular the pathways we evidenced showed: a) diffuse projections in the frontal lobe, b) fronto-parietal lobes connections trough the external capsule in almost all the subjects and c) widespread connections in the posterior regions. Our study represents the first consistent in vivo demonstration across a large group of individuals of these novel anterior and posterior terminations of the IFOF detailed described only by post-mortem anatomical dissection. Furthermore our work establishes the feasibility of consistent in vivo mapping of this architecture with independent in vivo methodologies. In conclusion q-ball tractography dissection supports a more complex definition of IFOF, which includes several subcomponents likely underlying specific function. PMID:24945305

Q-ball of inferior fronto-occipital fasciculus and beyond.

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Eduardo Caverzasi

Full Text Available The inferior fronto-occipital fasciculus (IFOF is historically described as the longest associative bundle in the human brain and it connects various parts of the occipital cortex, temporo-basal area and the superior parietal lobule to the frontal lobe through the external/extreme capsule complex. The exact functional role and the detailed anatomical definition of the IFOF are still under debate within the scientific community. In this study we present a fiber tracking dissection of the right and left IFOF by using a q-ball residual-bootstrap reconstruction of High-Angular Resolution Diffusion Imaging (HARDI data sets in 20 healthy subjects. By defining a single seed region of interest on the coronal fractional anisotropy (FA color map of each subject, we investigated all the pathways connecting the parietal, occipital and posterior temporal cortices to the frontal lobe through the external/extreme capsule. In line with recent post-mortem dissection studies we found more extended anterior-posterior association connections than the "classical" fronto-occipital representation of the IFOF. In particular the pathways we evidenced showed: a diffuse projections in the frontal lobe, b fronto-parietal lobes connections trough the external capsule in almost all the subjects and c widespread connections in the posterior regions. Our study represents the first consistent in vivo demonstration across a large group of individuals of these novel anterior and posterior terminations of the IFOF detailed described only by post-mortem anatomical dissection. Furthermore our work establishes the feasibility of consistent in vivo mapping of this architecture with independent in vivo methodologies. In conclusion q-ball tractography dissection supports a more complex definition of IFOF, which includes several subcomponents likely underlying specific function.

Functional neural networks underlying response inhibition in adolescents and adults.

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Stevens, Michael C; Kiehl, Kent A; Pearlson, Godfrey D; Calhoun, Vince D

2007-07-19

This study provides the first description of neural network dynamics associated with response inhibition in healthy adolescents and adults. Functional and effective connectivity analyses of whole brain hemodynamic activity elicited during performance of a Go/No-Go task were used to identify functionally integrated neural networks and characterize their causal interactions. Three response inhibition circuits formed a hierarchical, inter-dependent system wherein thalamic modulation of input to premotor cortex by fronto-striatal regions led to response suppression. Adolescents differed from adults in the degree of network engagement, regional fronto-striatal-thalamic connectivity, and network dynamics. We identify and characterize several age-related differences in the function of neural circuits that are associated with behavioral performance changes across adolescent development.

Optimized gamma synchronization enhances functional binding of fronto-parietal cortices in mathematically gifted adolescents during deductive reasoning

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Li eZhang

2014-06-01

Full Text Available As enhanced fronto-parietal network has been suggested to support reasoning ability of math-gifted adolescents, the main goal of this EEG source analysis is to investigate the temporal binding of the gamma-band (30-60Hz synchronization between frontal and parietal cortices in adolescents with exceptional mathematical ability, including the functional connectivity of gamma neurocognitive network, the temporal dynamics of fronto-parietal network (phase-locking durations and network lability in time domain, and the self-organized criticality of synchronizing oscillation. Compared with the average-ability subjects, the math-gifted adolescents show a highly integrated fronto-parietal network due to distant gamma phase-locking oscillations, which is indicated by lower modularity of the global network topology, more connector bridges between the frontal and parietal cortices and less connector hubs in the sensorimotor cortex. The time-domain analysis finds that, while maintaining more stable phase dynamics of the fronto-parietal coupling, the math-gifted adolescents are characterized by more extensive fronto-parietal connection reconfiguration. The results from sample fitting in the power-law model further find that the phase-locking durations in the math-gifted brain abides by a wider interval of the power-law distribution. This phase-lock distribution mechanism could represent a relatively optimized pattern for the functional binding of frontal-parietal network, which underlies stable fronto-parietal connectivity and increases flexibility of timely network reconfiguration.

Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease.

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Singh, Arun; Mewes, Klaus; Gross, Robert E; DeLong, Mahlon R; Obeso, José A; Papa, Stella M

2016-08-23

Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

Impaired development of cortico-striatal synaptic connectivity in a cell culture model of Huntington's disease.

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Buren, Caodu; Parsons, Matthew P; Smith-Dijak, Amy; Raymond, Lynn A

2016-03-01

Huntington's disease (HD) is a genetically inherited neurodegenerative disease caused by a mutation in the gene encoding the huntingtin protein. This mutation results in progressive cell death that is particularly striking in the striatum. Recent evidence indicates that early HD is initially a disease of the synapse, in which subtle alterations in synaptic neurotransmission, particularly at the cortico-striatal (C-S) synapse, can be detected well in advance of cell death. Here, we used a cell culture model in which striatal neurons are co-cultured with cortical neurons, and monitored the development of C-S connectivity up to 21days in vitro (DIV) in cells cultured from either the YAC128 mouse model of HD or the background strain, FVB/N (wild-type; WT) mice. Our data demonstrate that while C-S connectivity in WT co-cultures develops rapidly and continuously from DIV 7 to 21, YAC128 C-S connectivity shows no significant growth from DIV 14 onward. Morphological and electrophysiological data suggest that a combination of pre- and postsynaptic mechanisms contribute to this effect, including a reduction in both the postsynaptic dendritic arborization and the size and replenishment rate of the presynaptic readily releasable pool of excitatory vesicles. Moreover, a chimeric culture strategy confirmed that the most robust impairment in C-S connectivity was only observed when mutant huntingtin was expressed both pre- and postsynaptically. In all, our data demonstrate a progressive HD synaptic phenotype in this co-culture system that may be exploited as a platform for identifying promising therapeutic strategies to prevent early HD-associated synaptopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controls.

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Halari, Rozmin; Simic, Mima; Pariante, Carmine M; Papadopoulos, Andrew; Cleare, Anthony; Brammer, Michael; Fombonne, Eric; Rubia, Katya

2009-03-01

There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naïve adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naïve adolescents with a first-episode of MDD aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.

Altered resting-state effective connectivity of fronto-parietal motor control systems on the primary motor network following stroke

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Inman, Cory S.; James, G. Andrew; Hamann, Stephan; Rajendra, Justin K.; Pagnoni, Giuseppe; Butler, Andrew J.

2011-01-01

Previous brain imaging work suggests that stroke alters the effective connectivity (the influence neural regions exert upon each other) of motor execution networks. The present study examines the intrinsic effective connectivity of top-down motor control in stroke survivors (n=13) relative to healthy participants (n=12). Stroke survivors exhibited significant deficits in motor function, as assessed by the Fugl-Meyer Motor Assessment. We used structural equation modeling (SEM) of resting-state fMRI data to investigate the relationship between motor deficits and the intrinsic effective connectivity between brain regions involved in motor control and motor execution. An exploratory adaptation of SEM determined the optimal model of motor execution effective connectivity in healthy participants, and confirmatory SEM assessed stroke survivors’ fit to that model. We observed alterations in spontaneous resting-state effective connectivity from fronto-parietal guidance systems to the motor network in stroke survivors. More specifically, diminished connectivity was found in connections from the superior parietal cortex to primary motor cortex and supplementary motor cortex. Furthermore, the paths demonstrated large individual variance in stroke survivors but less variance in healthy participants. These findings suggest that characterizing the deficits in resting-state connectivity of top-down processes in stroke survivors may help optimize cognitive and physical rehabilitation therapies by individually targeting specific neural pathway. PMID:21839174

ADHD- and Medication-Related Brain Activation Effects in Concordantly Affected Parent-Child Dyads with ADHD

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Epstein, Jeffery N.; Casey, B. J.; Tonev, Simon T.; Davidson, Matthew C.; Reiss, Allan L.; Garrett, Amy; Hinshaw, Stephen P.; Greenhill, Laurence L.; Glover, Gary; Shafritz, Keith M.; Vitolo, Alan; Kotler, Lisa A.; Jarrett, Matthew A.; Spicer, Julie

2007-01-01

Background: Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological…

Dopamine, fronto-striato-thalamic circuits and risk for psychosis.

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Dandash, Orwa; Pantelis, Christos; Fornito, Alex

2017-02-01

A series of parallel, integrated circuits link distinct regions of prefrontal cortex with specific nuclei of the striatum and thalamus. Dysfunction of these fronto-striato-thalamic systems is thought to play a major role in the pathogenesis of psychosis. In this review, we examine evidence from human and animal investigations that dysfunction of a specific dorsal fronto-striato-thalamic circuit, linking the dorsolateral prefrontal cortex, dorsal (associative) striatum, and mediodorsal nucleus of the thalamus, is apparent across different stages of psychosis, including prior to the onset of a first episode, suggesting that it represents a candidate risk biomarker. We consider how abnormalities at distinct points in the circuit may give rise to the pattern of findings seen in patient populations, and how these changes relate to disruptions in dopamine, glutamate and GABA signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Functional development of fronto-striato-parietal networks associated with time perception

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Anna eSmith

2011-11-01

Full Text Available Compared to our understanding of the functional maturation of executive functions, little is known about the neurofunctional development of perceptive functions. Time perception develops during late adolescence, underpinning many functions including motor and verbal processing, as well as late maturing higher order cognitive skills such as forward planning and future-related decision-making. Nothing, however, is known about the neurofunctional changes associated with time perception from childhood to adulthood. Using functional magnetic resonance imaging we explored the effects of age on the brain activation and functional connectivity of 32 male participants from 10 to 53 years of age during a time discrimination task that required the discrimination of temporal intervals of seconds differing by several hundred milliseconds. Increasing development was associated with progressive activation increases within left lateralised dorsolateral and inferior fronto-parieto-striato-thalamic brain regions. Furthermore, despite comparable task performance, adults showed increased functional connectivity between inferior/dorsolateral interhemispheric fronto-frontal activation as well as between inferior fronto-parietal regions compared with adolescents. Activation in caudate, specifically, was associated with both increasing age and better temporal discrimination. Progressive decreases in activation with age were observed in ventromedial prefrontal cortex, limbic regions and cerebellum. The findings demonstrate age-dependent developmentally dissociated neural networks for time discrimination. With increasing age there is progressive recruitment of later maturing left hemispheric and lateralised fronto-parieto-striato-thalamic networks, known to mediate time discrimination in adults, while earlier developing brain regions such as ventromedial prefrontal cortex, limbic and paralimbic areas and cerebellum subserve fine-temporal processing functions in children

Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

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Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

2017-05-01

According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis.

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Dandash, Orwa; Harrison, Ben J; Adapa, Ram; Gaillard, Raphael; Giorlando, Francesco; Wood, Stephen J; Fletcher, Paul C; Fornito, Alex

2015-02-01

The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral 'limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal 'associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness.

Alterations in Striatal Circuits Underlying Addiction-Like Behaviors.

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Kim, Hyun Jin; Lee, Joo Han; Yun, Kyunghwa; Kim, Joung-Hun

2017-06-30

Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

Cerebral Correlates of Abnormal Emotion Conflict Processing in Euthymic Bipolar Patients: A Functional MRI Study.

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Favre, Pauline; Polosan, Mircea; Pichat, Cédric; Bougerol, Thierry; Baciu, Monica

2015-01-01

Patients with bipolar disorder experience cognitive and emotional impairment that may persist even during the euthymic state of the disease. These persistent symptoms in bipolar patients (BP) may be characterized by disturbances of emotion regulation and related fronto-limbic brain circuitry. The present study aims to investigate the modulation of fronto-limbic activity and connectivity in BP by the processing of emotional conflict. Fourteen euthymic BP and 13 matched healthy subjects (HS) underwent functional magnetic resonance imaging (fMRI) while performing a word-face emotional Stroop task designed to dissociate the monitoring/generation of emotional conflict from its resolution. Functional connectivity was determined by means of psychophysiological interaction (PPI) approach. Relative to HS, BP were slower to process incongruent stimuli, reflecting higher amount of behavioral interference during emotional Stroop. Furthermore, BP showed decreased activation of the right dorsolateral prefrontal cortex (DLPFC) during the monitoring and a lack of bilateral amygdala deactivation during the resolution of the emotional conflict. In addition, during conflict monitoring, BP showed abnormal positive connectivity between the right DLPFC and several regions of the default mode network. Overall, our results highlighted dysfunctional processing of the emotion conflict in euthymic BP that may be subtended by abnormal activity and connectivity of the DLPFC during the conflict monitoring, which, in turn, leads to failure of amygdala deactivation during the resolution of the conflict. Emotional dysregulation in BP may be underpinned by a lack of top-down cognitive control and a difficulty to focus on the task due to persistent self-oriented attention.

Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

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Jessica Ann Wojtalik

2016-01-01

Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

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Arnsten, Amy F T; Rubia, Katya

2012-04-01

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence

PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

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Xu, Benjamin; Sandrini, Marco; Wang, Wen-Tung; Smith, Jason F; Sarlls, Joelle E; Awosika, Oluwole; Butman, John A; Horwitz, Barry; Cohen, Leonardo G

2016-09-01

Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder.

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Sundram, Frederick; Deeley, Quinton; Sarkar, Sagari; Daly, Eileen; Latham, Richard; Craig, Michael; Raczek, Malgorzata; Fahy, Tom; Picchioni, Marco; Barker, Gareth J; Murphy, Declan G M

2012-02-01

Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is not clear whether WM abnormalities are restricted to this tract or are or more widespread, including other tracts which are involved in connectivity with the frontal lobe. We performed whole brain voxel-based analyses on WM fractional anisotropy (FA) and mean diffusivity (MD) maps acquired with DT-MRI to compare 15 adults with ASPD and healthy age, handedness and IQ-matched controls. Also, within ASPD subjects we related differences in FA and MD to measures of psychopathy. Significant WM FA reduction and MD increases were found respectively in ASPD subjects relative to controls. FA was bilaterally reduced in the genu of corpus callosum while in the right frontal lobe FA reduction was found in the UF, inferior fronto-occipital fasciculus (IFOF), anterior corona radiata and anterior limb and genu of the internal capsule. These differences negatively correlated with measures of psychopathy. Also in the right frontal lobe, increased MD was found in the IFOF and UF, and the corpus callosum and anterior corona radiata. There was a significant positive correlation between MD and psychopathy scores. The present study confirms a previous report of reduced FA in the UF. Additionally, we report for the first time, FA deficits in tracts involved in interhemispheric as well as frontal lobe connectivity in conjunction with MD increases in the frontal lobe. Hence, we provide evidence of significant WM microstructural abnormalities in frontal brain regions in ASPD and psychopathy

Whole-brain structural connectivity in dyskinetic cerebral palsy and its association with motor and cognitive function.

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Ballester-Plané, Júlia; Schmidt, Ruben; Laporta-Hoyos, Olga; Junqué, Carme; Vázquez, Élida; Delgado, Ignacio; Zubiaurre-Elorza, Leire; Macaya, Alfons; Póo, Pilar; Toro, Esther; de Reus, Marcel A; van den Heuvel, Martijn P; Pueyo, Roser

2017-09-01

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system. Hum Brain Mapp 38:4594-4612, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia.

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Jeong, Bumseok; Wible, Cynthia G; Hashimoto, Ryu-ichiro; Kubicki, Marek

2009-12-01

Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. 2009 Wiley-Liss, Inc.

DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.

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Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2013-01-01

The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

Dysregulation of striatal projection neurons in Parkinson's disease.

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Beck, Goichi; Singh, Arun; Papa, Stella M

2018-03-01

The loss of nigrostriatal dopamine (DA) is the primary cause of motor dysfunction in Parkinson's disease (PD), but the underlying striatal mechanisms remain unclear. In spite of abundant literature portraying structural, biochemical and plasticity changes of striatal projection neurons (SPNs), in the past there has been a data vacuum from the natural human disease and its close model in non-human primates. Recently, single-cell recordings in advanced parkinsonian primates have generated new insights into the altered function of SPNs. Currently, there are also human data that provide direct evidence of profoundly dysregulated SPN activity in PD. Here, we review primate recordings that are impacting our understanding of the striatal dysfunction after DA loss, particularly through the analysis of physiologic correlates of parkinsonian motor behaviors. In contrast to recordings in rodents, data obtained in primates and patients demonstrate similar major abnormalities of the spontaneous SPN firing in the alert parkinsonian state. Furthermore, these studies also show altered SPN responses to DA replacement in the advanced parkinsonian state. Clearly, there is yet much to learn about the striatal discharges in PD, but studies using primate models are contributing unique information to advance our understanding of pathophysiologic mechanisms.

Latent and Abnormal Functional Connectivity Circuits in Autism Spectrum Disorder.

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Chen, Shuo; Xing, Yishi; Kang, Jian

2017-01-01

Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD.

Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

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Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

2013-06-01

Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

Self-face recognition shares brain regions active during proprioceptive illusion in the right inferior fronto-parietal superior longitudinal fasciculus III network.

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Morita, Tomoyo; Saito, Daisuke N; Ban, Midori; Shimada, Koji; Okamoto, Yuko; Kosaka, Hirotaka; Okazawa, Hidehiko; Asada, Minoru; Naito, Eiichi

2017-04-21

Proprioception is somatic sensation that allows us to sense and recognize position, posture, and their changes in our body parts. It pertains directly to oneself and may contribute to bodily awareness. Likewise, one's face is a symbol of oneself, so that visual self-face recognition directly contributes to the awareness of self as distinct from others. Recently, we showed that right-hemispheric dominant activity in the inferior fronto-parietal cortices, which are connected by the inferior branch of the superior longitudinal fasciculus (SLF III), is associated with proprioceptive illusion (awareness), in concert with sensorimotor activity. Herein, we tested the hypothesis that visual self-face recognition shares brain regions active during proprioceptive illusion in the right inferior fronto-parietal SLF III network. We scanned brain activity using functional magnetic resonance imaging while twenty-two right-handed healthy adults performed two tasks. One was a proprioceptive illusion task, where blindfolded participants experienced a proprioceptive illusion of right hand movement. The other was a visual self-face recognition task, where the participants judged whether an observed face was their own. We examined whether the self-face recognition and the proprioceptive illusion commonly activated the inferior fronto-parietal cortices connected by the SLF III in a right-hemispheric dominant manner. Despite the difference in sensory modality and in the body parts involved in the two tasks, both tasks activated the right inferior fronto-parietal cortices, which are likely connected by the SLF III, in a right-side dominant manner. Here we discuss possible roles for right inferior fronto-parietal activity in bodily awareness and self-awareness. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Abnormal topological organization of the white matter network in Mandarin speakers with congenital amusia.

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Zhao, Yanxin; Chen, Xizhuo; Zhong, Suyu; Cui, Zaixu; Gong, Gaolang; Dong, Qi; Nan, Yun

2016-05-23

Congenital amusia is a neurogenetic disorder that mainly affects the processing of musical pitch. Brain imaging evidence indicates that it is associated with abnormal structural and functional connections in the fronto-temporal region. However, a holistic understanding of the anatomical topology underlying amusia is still lacking. Here, we used probabilistic diffusion tensor imaging tractography and graph theory to examine whole brain white matter structural connectivity in 31 Mandarin-speaking amusics and 24 age- and IQ-matched controls. Amusics showed significantly reduced global connectivity, as indicated by the abnormally decreased clustering coefficient (Cp) and increased normalized shortest path length (λ) compared to the controls. Moreover, amusics exhibited enhanced nodal strength in the right inferior parietal lobule relative to controls. The co-existence of the lexical tone deficits was associated with even more deteriorated global network efficiency in amusics, as suggested by the significant correlation between the increments in normalized shortest path length (λ) and the insensitivity in lexical tone perception. Our study is the first to reveal reduced global connectivity efficiency in amusics as well as an increase in the global connectivity cost due to the co-existed lexical tone deficits. Taken together these results provide a holistic perspective on the anatomical substrates underlying congenital amusia.

Fronto-parietal and fronto-temporal theta phase synchronization for visual and auditory-verbal working memory

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Masahiro eKawasaki; Masahiro eKawasaki; Masahiro eKawasaki; Keiichi eKitajo; Keiichi eKitajo; Yoko eYamaguchi

2014-01-01

In humans, theta phase (4–8 Hz) synchronization observed on electroencephalography (EEG) plays an important role in the manipulation of mental representations during working memory (WM) tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from...

Subcomponents and connectivity of the inferior fronto-occipital fasciculus revealed by diffusion spectrum imaging fiber tracking

Directory of Open Access Journals (Sweden)

Yupeng Wu

2016-09-01

Full Text Available The definitive structure and functional role of the inferior fronto-occipital fasciculus (IFOF are still controversial. In this study, we aimed to investigate the connectivity, asymmetry and segmentation patterns of this bundle. High angular diffusion spectrum imaging (DSI analysis was performed on ten healthy adults and a 90-subject DSI template (NTU-90 Atlas. In addition, a new tractography approach based on the anatomic subregions and two regions of interest (ROI was evaluated for the fiber reconstructions. More widespread anterior-posterior connections than previous standard definition of the IFOF were found. This distinct pathway demonstrated a greater inter-subjects connective variability with a maximum of 40% overlap in its central part. The statistical results revealed no asymmetry between the left and right hemispheres and no significant differences existed in distributions of the IFOF according to sex. In addition, five subcomponents within the IFOF were identified according to the frontal areas of originations. As the subcomponents passed through the anterior floor of the external capsule, the fibers radiated to the posterior terminations. The most common connection patterns of the subcomponents were as follows: IFOF-I, from frontal polar cortex to occipital pole, inferior occipital lobe, middle occipital lobe, superior occipital lobe and pericalcarine; IFOF-II, from orbito-frontal cortex to occipital pole, inferior occipital lobe, middle occipital lobe, superior occipital lobe and pericalcarine; IFOF-III, from inferior frontal gyrus to inferior occipital lobe, middle occipital lobe, superior occipital lobe, occipital pole and pericalcarine; IFOF-IV, from middle frontal gyrus to occipital pole and inferior occipital lobe; IFOF-V, from superior frontal gyrus to occipital pole, inferior occipital lobe and middle occipital lobe. Our work demonstrates the feasibility of high resolution diffusion tensor tractography with sufficient

Subcomponents and Connectivity of the Inferior Fronto-Occipital Fasciculus Revealed by Diffusion Spectrum Imaging Fiber Tracking

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Wu, Yupeng; Sun, Dandan; Wang, Yong; Wang, Yibao

2016-01-01

The definitive structure and functional role of the inferior fronto-occipital fasciculus (IFOF) are still controversial. In this study, we aimed to investigate the connectivity, asymmetry, and segmentation patterns of this bundle. High angular diffusion spectrum imaging (DSI) analysis was performed on 10 healthy adults and a 90-subject DSI template (NTU-90 Atlas). In addition, a new tractography approach based on the anatomic subregions and two regions of interest (ROI) was evaluated for the fiber reconstructions. More widespread anterior-posterior connections than previous “standard” definition of the IFOF were found. This distinct pathway demonstrated a greater inter-subjects connective variability with a maximum of 40% overlap in its central part. The statistical results revealed no asymmetry between the left and right hemispheres and no significant differences existed in distributions of the IFOF according to sex. In addition, five subcomponents within the IFOF were identified according to the frontal areas of originations. As the subcomponents passed through the anterior floor of the external capsule, the fibers radiated to the posterior terminations. The most common connection patterns of the subcomponents were as follows: IFOF-I, from frontal polar cortex to occipital pole, inferior occipital lobe, middle occipital lobe, superior occipital lobe, and pericalcarine; IFOF-II, from orbito-frontal cortex to occipital pole, inferior occipital lobe, middle occipital lobe, superior occipital lobe, and pericalcarine; IFOF-III, from inferior frontal gyrus to inferior occipital lobe, middle occipital lobe, superior occipital lobe, occipital pole, and pericalcarine; IFOF-IV, from middle frontal gyrus to occipital pole, and inferior occipital lobe; IFOF-V, from superior frontal gyrus to occipital pole, inferior occipital lobe, and middle occipital lobe. Our work demonstrates the feasibility of high resolution diffusion tensor tractography with sufficient sensitivity

Subcomponents and Connectivity of the Inferior Fronto-Occipital Fasciculus Revealed by Diffusion Spectrum Imaging Fiber Tracking.

Science.gov (United States)

Wu, Yupeng; Sun, Dandan; Wang, Yong; Wang, Yibao

2016-01-01

The definitive structure and functional role of the inferior fronto-occipital fasciculus (IFOF) are still controversial. In this study, we aimed to investigate the connectivity, asymmetry, and segmentation patterns of this bundle. High angular diffusion spectrum imaging (DSI) analysis was performed on 10 healthy adults and a 90-subject DSI template (NTU-90 Atlas). In addition, a new tractography approach based on the anatomic subregions and two regions of interest (ROI) was evaluated for the fiber reconstructions. More widespread anterior-posterior connections than previous "standard" definition of the IFOF were found. This distinct pathway demonstrated a greater inter-subjects connective variability with a maximum of 40% overlap in its central part. The statistical results revealed no asymmetry between the left and right hemispheres and no significant differences existed in distributions of the IFOF according to sex. In addition, five subcomponents within the IFOF were identified according to the frontal areas of originations. As the subcomponents passed through the anterior floor of the external capsule, the fibers radiated to the posterior terminations. The most common connection patterns of the subcomponents were as follows: IFOF-I, from frontal polar cortex to occipital pole, inferior occipital lobe, middle occipital lobe, superior occipital lobe, and pericalcarine; IFOF-II, from orbito-frontal cortex to occipital pole, inferior occipital lobe, middle occipital lobe, superior occipital lobe, and pericalcarine; IFOF-III, from inferior frontal gyrus to inferior occipital lobe, middle occipital lobe, superior occipital lobe, occipital pole, and pericalcarine; IFOF-IV, from middle frontal gyrus to occipital pole, and inferior occipital lobe; IFOF-V, from superior frontal gyrus to occipital pole, inferior occipital lobe, and middle occipital lobe. Our work demonstrates the feasibility of high resolution diffusion tensor tractography with sufficient sensitivity to

Prolonged striatal disinhibition as a chronic animal model of tic disorders.

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Vinner, Esther; Israelashvili, Michal; Bar-Gad, Izhar

2017-12-01

Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABA A antagonists into the striatum, leading to temporary disinhibition. The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Multimodal FMRI resting-state functional connectivity in granulin mutations: the case of fronto-parietal dementia.

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Enrico Premi

Full Text Available BACKGROUND: Monogenic dementias represent a great opportunity to trace disease progression from preclinical to symptomatic stages. Frontotemporal Dementia related to Granulin (GRN mutations presents a specific framework of brain damage, involving fronto-temporal regions and long inter-hemispheric white matter bundles. Multimodal resting-state functional MRI (rs-fMRI is a promising tool to carefully describe disease signature from the earliest disease phase. OBJECTIVE: To define local connectivity alterations in GRN related pathology moving from the presymptomatic (asymptomatic GRN mutation carriers to the clinical phase of the disease (GRN- related Frontotemporal Dementia. METHODS: Thirty-one GRN Thr272fs mutation carriers (14 patients with Frontotemporal Dementia and 17 asymptomatic carriers and 38 healthy controls were recruited. Local connectivity measures (Regional Homogeneity (ReHo, Fractional Amplitude of Low Frequency Fluctuation (fALFF and Degree Centrality (DC were computed, considering age and gender as nuisance variables as well as the influence of voxel-level gray matter atrophy. RESULTS: Asymptomatic GRN carriers had selective reduced ReHo in the left parietal region and increased ReHo in frontal regions compared to healthy controls. Considering Frontotemporal Dementia patients, all measures (ReHo, fALFF and DC were reduced in inferior parietal, frontal lobes and posterior cingulate cortex. Considering GRN mutation carriers, an inverse correlation with age in the posterior cingulate cortex, inferior parietal lobule and orbitofrontal cortex was found. CONCLUSIONS: GRN pathology is characterized by functional brain network alterations even decades before the clinical onset; they involve the parietal region primarily and then spread to the anterior regions of the brain, supporting the concept of molecular nexopathies.

Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia

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Jovana eBelic

2016-03-01

Full Text Available We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the healthy state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

Connectivity and functional profiling of abnormal brain structures in pedophilia.

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Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-06-01

Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

Resting-state EEG oscillatory dynamics in fragile X syndrome: abnormal functional connectivity and brain network organization.

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Melle J W van der Molen

Full Text Available Disruptions in functional connectivity and dysfunctional brain networks are considered to be a neurological hallmark of neurodevelopmental disorders. Despite the vast literature on functional brain connectivity in typical brain development, surprisingly few attempts have been made to characterize brain network integrity in neurodevelopmental disorders. Here we used resting-state EEG to characterize functional brain connectivity and brain network organization in eight males with fragile X syndrome (FXS and 12 healthy male controls. Functional connectivity was calculated based on the phase lag index (PLI, a non-linear synchronization index that is less sensitive to the effects of volume conduction. Brain network organization was assessed with graph theoretical analysis. A decrease in global functional connectivity was observed in FXS males for upper alpha and beta frequency bands. For theta oscillations, we found increased connectivity in long-range (fronto-posterior and short-range (frontal-frontal and posterior-posterior clusters. Graph theoretical analysis yielded evidence of increased path length in the theta band, suggesting that information transfer between brain regions is particularly impaired for theta oscillations in FXS. These findings are discussed in terms of aberrant maturation of neuronal oscillatory dynamics, resulting in an imbalance in excitatory and inhibitory neuronal circuit activity.

Abnormal anatomical connectivity between the amygdala and orbitofrontal cortex in conduct disorder.

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Luca Passamonti

Full Text Available Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD. Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD.Diffusion Tensor Imaging (DTI was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA, an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography.Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction. Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts.These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.

Altered Intrinsic Functional Connectivity in Language-Related Brain Regions in Association with Verbal Memory Performance in Euthymic Bipolar Patients

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David E. J. Linden

2013-09-01

Full Text Available Potential abnormalities in the structure and function of the temporal lobes have been studied much less in bipolar disorder than in schizophrenia. This may not be justified because language-related symptoms, such as pressured speech and flight of ideas, and cognitive deficits in the domain of verbal memory are amongst the hallmark of bipolar disorder (BD, and contribution of temporal lobe dysfunction is therefore likely. In the current study, we examined resting-state functional connectivity (FC between the auditory cortex (Heschl’s gyrus [HG], planum temporale [PT] and whole brain using seed correlation analysis in n = 21 BD euthymic patients and n = 20 matched healthy controls and associated it with verbal memory performance. In comparison to controls BD patients showed decreased functional connectivity between Heschl’s gyrus and planum temporale and the left superior and middle temporal gyrus. Additionally, fronto-temporal functional connectivity with the right inferior frontal/precentral gyrus and the insula was increased in patients. Verbal episodic memory deficits in the investigated sample of BD patients and language-related symptoms might therefore be associated with a diminished FC within the auditory/temporal gyrus and a compensatory fronto-temporal pathway.

Magnetization transfer imaging identifies basal ganglia abnormalities in adult ADHD that are invisible to conventional T1 weighted voxel-based morphometry

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Arjun Sethi

2017-01-01

Full Text Available In childhood, Attention Deficit Hyperactivity Disorder (ADHD is reliably associated with reduced volume of the striatum. In contrast, striatal abnormalities are infrequently detected in voxel-based morphometry (VBM neuroimaging studies of adults with ADHD. This discrepancy has been suggested to reflect normalisation of striatal morphology with age and prolonged treatment of symptoms. If so, this would indicate that while striatal abnormalities are linked to symptom expression in childhood, they cannot explain the persistence of these symptoms in adulthood. However, this may not be case. Instead, we hypothesized that the lack of evidence for striatal abnormalities in adult ADHD may reflect poor sensitivity of typical (T1-weighted neuroimaging to detect subcortical differences. To address this, we acquired both magnetisation transfer (MT saturation maps optimised for subcortical contrast, and conventional T1-weighted images in 30 adults with ADHD and 30 age, IQ, gender and handedness-matched controls. Using VBM of both datasets, we demonstrate volumetric reductions within the left ventral striatum on MT that are not observed on identically pre-processed T1-weighted images from the same participants. Nevertheless, both techniques reported similar sensitivity to cortical abnormalities in the right inferior parietal lobe. Additionally, we show that differences in striatal iron may potentially explain this reduced sensitivity of T1-weighted images in adults. Together, these findings indicate that prior VBM studies reporting no abnormalities in striatal volume in adult ADHD might have been compromised by the methodological insensitivity of T1-weighted VBM to subcortical differences, and that structural abnormalities of the striatum in ADHD do indeed persist into adulthood.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

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Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

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Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

2014-01-01

Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

Altered cingulo-striatal function underlies reward drive deficits in schizophrenia.

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Park, Il Ho; Chun, Ji Won; Park, Hae-Jeong; Koo, Min-Seong; Park, Sunyoung; Kim, Seok-Hyeong; Kim, Jae-Jin

2015-02-01

Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Abnormal Brain Connectivity Spectrum Disorders Following Thimerosal Administration

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David A. Geier

2017-03-01

Full Text Available Background: Autism spectrum disorder (ASD, tic disorder (TD, and hyperkinetic syndrome of childhood (attention deficit disorder [ADD]/attention deficit hyperactivity disorder [ADHD] are disorders recently defined as abnormal connectivity spectrum disorders (ACSDs because they show a similar pattern of abnormal brain connectivity. This study examines whether these disorders are associated with exposure to thimerosal, a mercury (Hg-based preservative. Methods: A hypothesis testing case-control study evaluated the Vaccine Safety Datalink for the potential dose-dependent odds ratios (ORs for diagnoses of ASD, TD, and ADD/ADHD compared to controls, following exposure to Hg from thimerosal-containing Haemophilus influenzae type b vaccines administrated within the first 15 months of life. Febrile seizures, cerebral degeneration, and unspecified disorders of metabolism, which are not biologically plausibly linked to thimerosal, were examined as control outcomes. Results: On a per 25 μg Hg basis, cases diagnosed with ASD (OR = 1.493, TD (OR = 1.428, or ADD/ADHD (OR = 1.503 were significantly (P < .001 more likely than controls to have received increased Hg exposure. Similar relationships were observed when separated by gender. Cases diagnosed with control outcomes were no more likely than controls to have received increased Hg exposure. Conclusion: The results suggest that Hg exposure from thimerosal is significantly associated with the ACSDs of ASD, TD, and ADD/ADHD.

Bilateral fronto-parietal integrity in young chronic cigarette smokers: a diffusion tensor imaging study.

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Yanhui Liao

Full Text Available Cigarette smoking continues to be the leading cause of preventable morbidity and mortality in China and other countries. Previous studies have demonstrated gray matter loss in chronic smokers. However, only a few studies assessed the changes of white matter integrity in this group. Based on those previous reports of alterations in white matter integrity in smokers, the aim of this study was to examine the alteration of white matter integrity in a large, well-matched sample of chronic smokers and non-smokers.Using in vivo diffusion tensor imaging (DTI to measure the differences of whole-brain white matter integrity between 44 chronic smoking subjects (mean age, 28.0±5.6 years and 44 healthy age- and sex-matched comparison non-smoking volunteers (mean age, 26.3±5.8 years. DTI was performed on a 3-Tesla Siemens scanner (Allegra; Siemens Medical System. The data revealed that smokers had higher fractional anisotropy (FA than healthy non-smokers in almost symmetrically bilateral fronto-parietal tracts consisting of a major white matter pathway, the superior longitudinal fasciculus (SLF.We found the almost symmetrically bilateral fronto-parietal whiter matter changes in a relatively large sample of chronic smokers. These findings support the hypothesis that chronic cigarette smoking involves alterations of bilateral fronto-parietal connectivity.

Fronto-Parietal Network Reconfiguration Supports the Development of Reasoning Ability.

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Wendelken, Carter; Ferrer, Emilio; Whitaker, Kirstie J; Bunge, Silvia A

2016-05-01

The goal of this fMRI study was to examine how well developmental improvements in reasoning ability can be explained by changes in functional connectivity between specific nodes in prefrontal and parietal cortices. To this end, we examined connectivity within the lateral fronto-parietal network (LFPN) and its relation to reasoning ability in 132 children and adolescents aged 6-18 years, 56 of whom were scanned twice over the course of 1.5 years. Developmental changes in strength of connections within the LFPN were most prominent in late childhood and early adolescence. Reasoning ability was related to functional connectivity between left rostrolateral prefrontal cortex (RLPFC) and inferior parietal lobule (IPL), but only among 12-18-year olds. For 9-11-year olds, reasoning ability was most strongly related to connectivity between left and right RLPFC; this relationship was mediated by working memory. For 6-8-year olds, significant relationships between connectivity and performance were not observed; in this group, processing speed was the primary mediator of improvement in reasoning ability. We conclude that different connections best support reasoning at different points in development and that RLPFC-IPL connectivity becomes an important predictor of reasoning during adolescence. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Nature or Nurture? Determining the Heritability of Human Striatal Dopamine Function: an [18F]-DOPA PET Study

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Stokes, Paul R A; Shotbolt, Paul; Mehta, Mitul A; Turkheimer, Eric; Benecke, Aaf; Copeland, Caroline; Turkheimer, Federico E; Lingford-Hughes, Anne R; Howes, Oliver D

2013-01-01

Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions. PMID:23093224

Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

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Sarpal, Deepak K; Robinson, Delbert G; Fales, Christina; Lencz, Todd; Argyelan, Miklos; Karlsgodt, Katherine H; Gallego, Juan A; John, Majnu; Kane, John M; Szeszko, Philip R; Malhotra, Anil K

2017-10-01

Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (drugs. Functional connectivity maps of the striatum were generated and examined in relation to DUP as a covariate. Mediation analyses were performed on a composite measure of corticostriatal connectivity derived from the significant results of our DUP analysis. We found that longer DUP correlated with worse response to treatment as well as overall decreased functional connectivity between striatal nodes and specific regions within frontal and parietal cortices. Moreover, the relationship between DUP and treatment response was significantly mediated by corticostriatal connectivity. Our results indicate that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. Future prospective studies are necessary to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.

Abnormal systemic venous connection possibly associated with a persistent right umbilical vein; a case report

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Smevik Bjarne

2004-04-01

Full Text Available Abstract Background Abnormal venous connections involving a persistent right umbilical vein are rare. In a minority of cases the liver is entirely bypassed and the condition is associated with multiple congenital malformations. Case presentation The described case illustrates a systemic venous drainage that was severely abnormal in a newborn girl with a truncus arteriosus type II congenital heart defect. Injection of contrast medium through the umbilical vein catheter revealed a very peculiar venous connection that passed anterio-laterally through the right hemithorax before crossing in an oblique fashion towards the superior vena cava. Conclusions This venous drainage may be the result of a persistent right umbilical vein connecting with the superior vena cava.

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

2014-01-01

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. PMID:25280970

Is it Worth the Effort? Novel Insights into Obesity-Associated Alterations in Cost-Benefit Decision-Making

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Mathar, David; Horstmann, Annette; Pleger, Burkhard; Villringer, Arno; Neumann, Jane

2016-01-01

Cost-benefit decision-making entails the process of evaluating potential actions according to the trade-off between the expected reward (benefit) and the anticipated effort (costs). Recent research revealed that dopaminergic transmission within the fronto-striatal circuitry strongly modulates cost-benefit decision-making. Alterations within the dopaminergic fronto-striatal system have been associated with obesity, but little is known about cost-benefit decision-making differences in obese com...

Role of contingency in striatal response to incentive in adolescents with anxiety.

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Benson, Brenda E; Guyer, Amanda E; Nelson, Eric E; Pine, Daniel S; Ernst, Monique

2015-03-01

This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive behavioral and neural responses to higher value rewards with correct performance. This hypersensitivity to highly valued (salient) actions suggests that the value of actions is determined not only by outcome magnitude, but also by the degree to which the outcome is contingent on correct performance. Thus, contingency and incentive value might each modulate reward responses in unique ways in anxiety. Using fMRI with a monetary reward task, striatal response to cue anticipation is compared in 18 clinically anxious and 20 healthy adolescents. This task manipulates orthogonally reward contingency and incentive value. Findings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specifically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilaterally stronger to low than to high incentive in anxious adolescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy adolescents. These findings may reflect exaggerated concern about performance and/or alterations of striatal coding of reward value in anxious adolescents. Abnormalities in reward function in anxiety may have treatment implications.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder.

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Hassel, Stefanie; Almeida, Jorge R; Frank, Ellen; Versace, Amelia; Nau, Sharon A; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2009-11-01

The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. BD individuals scored significantly higher on these spectrum measures than healthy individuals (pright PFC activity to intense happy faces (pright caudate nucleus activity to neutral faces (pright ventral putamen activity to intense happy (pabuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

Gray matter abnormalities in patients with narcissistic personality disorder.

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Schulze, Lars; Dziobek, Isabel; Vater, Aline; Heekeren, Hauke R; Bajbouj, Malek; Renneberg, Babette; Heuser, Isabella; Roepke, Stefan

2013-10-01

Despite the relevance of narcissistic personality disorder (NPD) in clinical settings, there is currently no empirical data available regarding the neurobiological correlates of NPD. In the present study, we performed a voxel-based morphometric analysis to provide initial insight into local abnormalities of gray matter (GM) volume. Structural brain images were obtained from patients with NPD (n = 17) and a sample of healthy controls (n = 17) matched regarding age, gender, handedness, and intelligence. Groups were compared with regard to global brain tissue volumes and local abnormalities of GM volume. Regions-of-interest analyses were calculated for the anterior insula. Relative to the control group, NPD patients had smaller GM volume in the left anterior insula. Independent of group, GM volume in the left anterior insula was positively related to self-reported emotional empathy. Complementary whole-brain analyses yielded smaller GM volume in fronto-paralimbic brain regions comprising the rostral and median cingulate cortex as well as dorsolateral and medial parts of the prefrontal cortex. Here we provide the first empirical evidence for structural abnormalities in fronto-paralimbic brain regions of patients with NPD. The results are discussed in the context of NPD patients' restricted ability for emotional empathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Thalamocortical functional connectivity in Lennox-Gastaut syndrome is abnormally enhanced in executive-control and default-mode networks.

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Warren, Aaron E L; Abbott, David F; Jackson, Graeme D; Archer, John S

2017-12-01

To identify abnormal thalamocortical circuits in the severe epilepsy of Lennox-Gastaut syndrome (LGS) that may explain the shared electroclinical phenotype and provide potential treatment targets. Twenty patients with a diagnosis of LGS (mean age = 28.5 years) and 26 healthy controls (mean age = 27.6 years) were compared using task-free functional magnetic resonance imaging (MRI). The thalamus was parcellated according to functional connectivity with 10 cortical networks derived using group-level independent component analysis. For each cortical network, we assessed between-group differences in thalamic functional connectivity strength using nonparametric permutation-based tests. Anatomical locations were identified by quantifying spatial overlap with a histologically informed thalamic MRI atlas. In both groups, posterior thalamic regions showed functional connectivity with visual, auditory, and sensorimotor networks, whereas anterior, medial, and dorsal thalamic regions were connected with networks of distributed association cortex (including the default-mode, anterior-salience, and executive-control networks). Four cortical networks (left and right executive-control network; ventral and dorsal default-mode network) showed significantly enhanced thalamic functional connectivity strength in patients relative to controls. Abnormal connectivity was maximal in mediodorsal and ventrolateral thalamic nuclei. Specific thalamocortical circuits are affected in LGS. Functional connectivity is abnormally enhanced between the mediodorsal and ventrolateral thalamus and the default-mode and executive-control networks, thalamocortical circuits that normally support diverse cognitive processes. In contrast, thalamic regions connecting with primary and sensory cortical networks appear to be less affected. Our previous neuroimaging studies show that epileptic activity in LGS is expressed via the default-mode and executive-control networks. Results of the present study suggest that

Increased ventral-striatal activity during monetary decision making is a marker of problem poker gambling severity.

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Brevers, Damien; Noël, Xavier; He, Qinghua; Melrose, James A; Bechara, Antoine

2016-05-01

The aim of this study was to examine the impact of different neural systems on monetary decision making in frequent poker gamblers, who vary in their degree of problem gambling. Fifteen frequent poker players, ranging from non-problem to high-problem gambling, and 15 non-gambler controls were scanned using functional magnetic resonance imaging (fMRI) while performing the Iowa Gambling Task (IGT). During IGT deck selection, between-group fMRI analyses showed that frequent poker gamblers exhibited higher ventral-striatal but lower dorsolateral prefrontal and orbitofrontal activations as compared with controls. Moreover, using functional connectivity analyses, we observed higher ventral-striatal connectivity in poker players, and in regions involved in attentional/motor control (posterior cingulate), visual (occipital gyrus) and auditory (temporal gyrus) processing. In poker gamblers, scores of problem gambling severity were positively associated with ventral-striatal activations and with the connectivity between the ventral-striatum seed and the occipital fusiform gyrus and the middle temporal gyrus. Present results are consistent with findings from recent brain imaging studies showing that gambling disorder is associated with heightened motivational-reward processes during monetary decision making, which may hamper one's ability to moderate his level of monetary risk taking. © 2015 Society for the Study of Addiction.

Temporal abnormalities in children with developmental dyscalculia.

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Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Annamaria; Pavan, Andrea; Martino, Davide

2012-01-01

Recent imaging studies have associated Developmental dyscalculia (DD) to structural and functional alterations corresponding Parietal and the Prefrontal cortex (PFC). Since these areas were shown also to be involved in timing abilities, we hypothesized that time processing is abnormal in DD. We compared time processing abilities between 10 children with pure DD (8 years old) and 11 age-matched healthy children. Results show that the DD group underestimated duration of a sub-second scale when asked to perform a time comparison task. The timing abnormality observed in our DD participants is consistent with evidence of a shared fronto-parietal neural network for representing time and quantity.

White-matter tract abnormalities and antisocial behavior: A systematic review of diffusion tensor imaging studies across development

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Rebecca Waller

2017-01-01

Full Text Available Antisocial behavior (AB, including aggression, violence, and theft, is thought be underpinned by abnormal functioning in networks of the brain critical to emotion processing, behavioral control, and reward-related learning. To better understand the abnormal functioning of these networks, research has begun to investigate the structural connections between brain regions implicated in AB using diffusion tensor imaging (DTI, which assesses white-matter tract microstructure. This systematic review integrates findings from 22 studies that examined the relationship between white-matter microstructure and AB across development. In contrast to a prior hypothesis that AB is associated with greater diffusivity specifically in the uncinate fasciculus, findings suggest that adult AB is associated with greater diffusivity across a range of white-matter tracts, including the uncinate fasciculus, inferior fronto-occipital fasciculus, cingulum, corticospinal tract, thalamic radiations, and corpus callosum. The pattern of findings among youth studies was inconclusive with both higher and lower diffusivity found across association, commissural, and projection and thalamic tracts.

Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease

International Nuclear Information System (INIS)

Tanaka, Yasuhiro; Meguro, Kenichi; Yamaguchi, Satoshi

2003-01-01

Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D 2 receptor density in Alzheimer's disease (AD). Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [ 11 C]raclopride (D 2 antagonist). The uptake of [ 11 C]raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The AD patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg). There was a significant inverse Spearman's correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients. Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD. (author)

Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

International Nuclear Information System (INIS)

Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun

2007-01-01

We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging

Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

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Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2007-07-01

We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging.

Professional training in creative writing is associated with enhanced fronto-striatal activity in a literary text continuation task.

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Erhard, K; Kessler, F; Neumann, N; Ortheil, H-J; Lotze, M

2014-10-15

The aim of the present study was to explore brain activities associated with creativity and expertise in literary writing. Using functional magnetic resonance imaging (fMRI), we applied a real-life neuroscientific setting that consisted of different writing phases (brainstorming and creative writing; reading and copying as control conditions) to well-selected expert writers and to an inexperienced control group. During creative writing, experts showed cerebral activation in a predominantly left-hemispheric fronto-parieto-temporal network. When compared to inexperienced writers, experts showed increased left caudate nucleus and left dorsolateral and superior medial prefrontal cortex activation. In contrast, less experienced participants recruited increasingly bilateral visual areas. During creative writing activation in the right cuneus showed positive association with the creativity index in expert writers. High experience in creative writing seems to be associated with a network of prefrontal (mPFC and DLPFC) and basal ganglia (caudate) activation. In addition, our findings suggest that high verbal creativity specific to literary writing increases activation in the right cuneus associated with increased resources obtained for reading processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Abnormal rich club organization and impaired correlation between structural and functional connectivity in migraine sufferers.

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Li, Kang; Liu, Lijun; Yin, Qin; Dun, Wanghuan; Xu, Xiaolin; Liu, Jixin; Zhang, Ming

2017-04-01

Because of the unique position of the topologically central role of densely interconnected brain hubs, our study aimed to investigate whether these regions and their related connections would be particularly vulnerable to migraine. In our study, we explored the rich club structure and its role in global functional dynamics in 30 patients with migraine without aura and 30 healthy controls. DTI and resting fMRI were used to construct structural connectivity (SC) and functional connectivity (FC) networks. An independent replication data set of 26 patients and 26 controls was included to replicate and validate significant findings. As compared with the controls, the structural networks of patients exhibited altered rich club organization with higher level of feeder connection density, abnormal small-world organization with increased global efficiency and decreased strength of SC-FC coupling. As these abnormal topological properties and headache attack duration exhibited a significant association with increased density of feeder connections, our results indicated that migraine may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher 'bridgeness' with non-rich club regions, which may increase the integration among pain-related brain circuits with more excitability but less inhibition for the modulation of migraine.

Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

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Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

2016-03-01

Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

Olfactory identification deficits and associated response inhibition in obsessive-compulsive disorder: on the scent of the orbitofronto-striatal model.

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Bersani, Giuseppe; Quartini, Adele; Ratti, Flavia; Pagliuca, Giulio; Gallo, Andrea

2013-11-30

Olfactory identification ability implicates the integrity of the orbitofrontal cortex (OFC). The fronto-striatal circuits including the OFC have been involved in the neuropathology of Obsessive Compulsive Disorder (OCD). However, only a few studies have examined olfactory function in patients with OCD. The Brief Smell Identification Test (B-SIT) and tests from the Cambridge Neuropsychological Automated Battery (CANTAB) were administered to 25 patients with OCD and to 21 healthy matched controls. OCD patients showed a significant impairment in olfactory identification ability as well as widely distributed cognitive deficits in visual memory, executive functions, attention, and response inhibition. The degree of behavioural impairment on motor impulsivity (prolonged response inhibition Stop-Signal Reaction Time) strongly correlated with the B-SIT score. Our study is the first to indicate a shared OFC pathological neural substrate underlying olfactory identification impairment, impulsivity, and OCD. Deficits in visual memory, executive functions and attention further indicate that regions outside of the orbitofronto-striatal loop may be involved in this disorder. Such results may help delineate the clinical complexity of OCD and support more targeted investigations and interventions. In this regard, research on the potential diagnostic utility of olfactory identification deficits in the assessment of OCD would certainly be useful. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

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Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

2009-01-01

Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

Abnormal ventral tegmental area-anterior cingulate cortex connectivity in Parkinson's disease with depression.

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Wei, Luqing; Hu, Xiao; Yuan, Yonggui; Liu, Weiguo; Chen, Hong

2018-07-16

Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease. The present study used resting-state fMRI and seed-based functional connectivity of putative dopaminergic midbrain regions (i.e., substantia nigra (SN) and ventral tegmental area (VTA)) to investigate the circuit-related abnormalities in PD with depression. The results showed that depressed PD (DPD) patients relative to healthy controls (HC) and non-depressed PD (NDPD) patients had increased functional connectivity between VTA and anterior cingulate cortex (ACC), demonstrating that dysfunctional mesocorticolimbic dopaminergic neurotransmission may be associated with depression in PD. Compared with HC, DPD and NDPD patients showed increased functional connectivity from SN to sensorimotor cortex, validating that alterations in the nigrostriatal circuitry could be responsible for cardinal motor features in PD. In addition, aberrant connectivity between VTA and ACC was correlated with the severity of depression in PD patients, further supporting that abnormal mesocorticolimbic system may account for depressive symptoms in PD. These results have provided potential circuit-level biomarkers of depression in PD, and suggested that resting state functional connectivity of midbrain dopaminergic nuclei may be useful for understanding the underlying pathology in PD with depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Naïve Adolescents at High Risk for Psychosis

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Dean, Derek J.; Teulings, Hans-Leo; Caligiuri, Michael; Mittal, Vijay A.

2013-01-01

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of impaired neuromodulation of dopamine in fronto-striatal pathways. The traditional methods for identifying movement abnormalities include observer-based reports and force stability gauges. The drawbacks of these methods are long training times for raters, experimenter bias, large site differences in instrumental apparatus, and suboptimal reliability. Taking these drawbacks into account has guided the development of better standardized and more efficient procedures to examine movement abnormalities through handwriting analysis software and tablet. Individuals at risk for psychosis showed significantly more dysfluent pen movements (a proximal measure for dyskinesia) in a handwriting task. Handwriting kinematics offers a great advance over previous methods of assessing dyskinesia, which could clearly be beneficial for understanding the etiology of psychosis. PMID:24300590

Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

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Serra, Laura; Silvestri, Gabriella; Petrucci, Antonio; Basile, Barbara; Masciullo, Marcella; Makovac, Elena; Torso, Mario; Spanò, Barbara; Mastropasqua, Chiara; Harrison, Neil A; Bianchi, Maria L E; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2014-05-01

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel

Forgetting the best when predicting the worst: Preliminary observations on neural circuit function in adolescent social anxiety

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Johanna M. Jarcho

2015-06-01

Full Text Available Social anxiety disorder typically begins in adolescence, a sensitive period for brain development, when increased complexity and salience of peer relationships requires novel forms of social learning. Disordered social learning in adolescence may explain how brain dysfunction promotes social anxiety. Socially anxious adolescents (n = 15 and adults (n = 19 and non-anxious adolescents (n = 24 and adults (n = 32 predicted, then received, social feedback from high and low-value peers while undergoing functional magnetic resonance imaging (fMRI. A surprise recall task assessed memory biases for feedback. Neural correlates of social evaluation prediction errors (PEs were assessed by comparing engagement to expected and unexpected positive and negative feedback. For socially anxious adolescents, but not adults or healthy participants of either age group, PEs elicited heightened striatal activity and negative fronto-striatal functional connectivity. This occurred selectively to unexpected positive feedback from high-value peers and corresponded with impaired memory for social feedback. While impaired memory also occurred in socially-anxious adults, this impairment was unrelated to brain-based PE activity. Thus, social anxiety in adolescence may relate to altered neural correlates of PEs that contribute to impaired learning about social feedback. Small samples necessitate replication. Nevertheless, results suggest that the relationship between learning and fronto-striatal function may attenuate as development progresses.

Striatal dopamine D2/3 receptor availability in treatment resistant depression.

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Bart P de Kwaasteniet

Full Text Available Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3 receptor (D2/3R binding has not been investigated in TRD subjects. We used [(123I]IBZM single photon emission computed tomography (SPECT to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group and 15 matched healthy controls. Results showed no significant difference (p = 0.75 in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics relative to TRD patients and healthy controls (p<0.001 but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.

Abnormal white matter integrity in chronic users of codeine-containing cough syrups: a tract-based spatial statistics study.

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Qiu, Y-W; Su, H-H; Lv, X-F; Jiang, G-H

2015-01-01

Codeine-containing cough syrups have become one of the most popular drugs of abuse in young people in the world. Chronic codeine-containing cough syrup abuse is related to impairments in a broad range of cognitive functions. However, the potential brain white matter impairment caused by chronic codeine-containing cough syrup abuse has not been reported previously. Our aim was to investigate abnormalities in the microstructure of brain white matter in chronic users of codeine-containing syrups and to determine whether these WM abnormalities are related to the duration of the use these syrups and clinical impulsivity. Thirty chronic codeine-containing syrup users and 30 matched controls were evaluated. Diffusion tensor imaging was performed by using a single-shot spin-echo-planar sequence. Whole-brain voxelwise analysis of fractional anisotropy was performed by using tract-based spatial statistics to localize abnormal WM regions. The Barratt Impulsiveness Scale 11 was surveyed to assess participants' impulsivity. Volume-of-interest analysis was used to detect changes of diffusivity indices in regions with fractional anisotropy abnormalities. Abnormal fractional anisotropy was extracted and correlated with clinical impulsivity and the duration of codeine-containing syrup use. Chronic codeine-containing syrup users had significantly lower fractional anisotropy in the inferior fronto-occipital fasciculus of the bilateral temporo-occipital regions, right frontal region, and the right corona radiata WM than controls. There were significant negative correlations among fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the right superior corona radiata WM and Barratt Impulsiveness Scale total scores, and between the right frontal region of the inferior fronto-occipital fasciculus and nonplan impulsivity scores in chronic codeine-containing syrup users. There was also a significant negative correlation between fractional

Striatal abnormalities in trichotillomania: A multi-site MRI analysis

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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.

Virtual dissection and comparative connectivity of the superior longitudinal fasciculus in chimpanzees and humans

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Hecht, Erin E.; Gutman, David A.; Bradley, Bruce A.; Preuss, Todd M.; Stout, Dietrich

2015-01-01

Many of the behavioral capacities that distinguish humans from other primates rely on fronto-parietal circuits. The superior longitudinal fasciculus (SLF) is the primary white matter tract connecting lateral frontal with lateral parietal regions; it is distinct from the arcuate fasciculus, which interconnects the frontal and temporal lobes. Here we report a direct, quantitative comparison of SLF connectivity using virtual in vivo dissection of the SLF in chimpanzees and humans. SLF I, the superior-most branch of the SLF, showed similar patterns of connectivity between humans and chimpanzees, and was proportionally volumetrically larger in chimpanzees. SLF II, the middle branch, and SLF III, the inferior-most branch, showed species differences in frontal connectivity. In humans, SLF II showed greater connectivity with dorsolateral prefrontal cortex, whereas in chimps SLF II showed greater connectivity with the inferior frontal gyrus. SLF III was right-lateralized and proportionally volumetrically larger in humans, and human SLF III showed relatively reduced connectivity with dorsal premotor cortex and greater extension into the anterior inferior frontal gyrus, especially in the right hemisphere. These results have implications for the evolution of fronto-parietal functions including spatial attention to observed actions, social learning, and tool use, and are in line with previous research suggesting a unique role for the right anterior inferior frontal gyrus in the evolution of human fronto-parietal network architecture. PMID:25534109

Abnormal Resting-State Functional Connectivity in Progressive Supranuclear Palsy and Corticobasal Syndrome

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Komal Bharti

2017-06-01

Full Text Available BackgroundPathological and MRI-based evidence suggests that multiple brain structures are likely to be involved in functional disconnection between brain areas. Few studies have investigated resting-state functional connectivity (rsFC in progressive supranuclear palsy (PSP and corticobasal syndrome (CBS. In this study, we investigated within- and between-network rsFC abnormalities in these two conditions.MethodsTwenty patients with PSP, 11 patients with CBS, and 16 healthy subjects (HS underwent a resting-state fMRI study. Resting-state networks (RSNs were extracted to evaluate within- and between-network rsFC using the Melodic and FSLNets software packages.ResultsIncreased within-network rsFC was observed in both PSP and CBS patients, with a larger number of RSNs being involved in CBS. Within-network cerebellar rsFC positively correlated with mini-mental state examination scores in patients with PSP. Compared to healthy volunteers, PSP and CBS patients exhibit reduced functional connectivity between the lateral visual and auditory RSNs, with PSP patients additionally showing lower functional connectivity between the cerebellar and insular RSNs. Moreover, rsFC between the salience and executive-control RSNs was increased in patients with CBS compared to HS.ConclusionThis study provides evidence of functional brain reorganization in both PSP and CBS. Increased within-network rsFC could represent a higher degree of synchronization in damaged brain areas, while between-network rsFC abnormalities may mainly reflect degeneration of long-range white matter fibers.

Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction.

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Hu, Yuzheng; Salmeron, Betty Jo; Gu, Hong; Stein, Elliot A; Yang, Yihong

2015-06-01

Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood. To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction. A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status. Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining

Loss of Balance between Striatal Feedforward Inhibition and Corticostriatal Excitation Leads to Tremor.

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Oran, Yael; Bar-Gad, Izhar

2018-02-14

Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats before and after selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum. The tremor was accompanied by coherent oscillations in the local field potential (LFP). Individual neuron activity patterns became oscillatory and coherent in the tremor frequency. Striatal neurons, but not GP neurons, displayed additional temporal, nonoscillatory correlations. The subsequent reduction in the corticostriatal input following muscimol injection to the corresponding somatotopic location in the primary motor cortex led to disruption of the tremor and a reduction of the LFP oscillations and individual neuron's phase-locked activity. The breakdown of the normal balance of excitation and inhibition in the striatum has been shown previously to be related to different motor abnormalities. Our results further indicate that the balance between excitatory corticostriatal input and feedforward FSI inhibition is sufficient to break down the striatal decorrelation process and generate oscillations resulting in rest tremor typical of multiple basal ganglia disorders. SIGNIFICANCE STATEMENT Fast-spiking interneurons (FSIs) play a key role in normal striatal processing by exerting powerful inhibitory control over the network. FSI malfunctions have been associated with abnormal processing of information within the striatum that leads to multiple movement disorders. Here, we study the changes in neuronal activity and movement kinematics following selective inhibition of these

Electrical and chemical transmission between striatal GABAergic output neurones in rat brain slices

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Venance, Laurent; Glowinski, Jacques; Giaume, Christian

2004-01-01

Basal ganglia are interconnected subcortical nuclei, connected to the thalamus and all cortical areas involved in sensory motor control, limbic functions and cognition. The striatal output neurones (SONs), the major striatal population, are believed to act as detectors and integrators of distributed patterns of cerebral cortex inputs. Despite the key role of SONs in cortico-striatal information processing, little is known about their local interactions. Here, we report the existence and characterization of electrical and GABAergic transmission between SONs in rat brain slices. Tracer coupling (biocytin) incidence was high during the first two postnatal weeks and then decreased (postnatal days (P) 5–25, 60%; P25–30, 29%; n = 61). Electrical coupling was observed between 27% of SON pairs (coupling coefficient: 3.1 ± 0.3%, n = 89 at P15) and as shown by single-cell RT-PCR, several connexin (Cx) mRNAs were found to be expressed (Cx31.1, Cx32, Cx36 and Cx47). GABAergic synaptic transmission (abolished by bicuculline, a GABAA receptor antagonist) observed in 19% of SON pairs (n = 62) was reliable (mean failure rate of 6 ± 3%), precise (variation coefficient of latency, 0.06), strong (IPSC amplitudes of 38 ± 12 pA) and unidirectional. Interestingly, electrical and chemical transmission were mutually exclusive. These results suggest that preferential networks of electrically and chemically connected SONs, might be involved in the channelling of cortico-basal ganglia information processing. PMID:15235091

Concomitant Appearance of Pisa Syndrome and Striatal Hand in Parkinson’s Disease

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Sanjay Pandey

2011-10-01

Full Text Available Pisa syndrome is (PS usually seen in patients receiving antipsychotic drugs and characterised by lateral flexion of trunk and axial dystonia. It is believed that antipsychotic drugs lead to dopamine blockage causing PS. We describe a Parkinson’s disease patient who was doing well with levodopa/carbidopa for 3 years and developed lateral flexion of trunk. His abnormal posture used to completely improve upon lying down position. He also had striatal hand deformity suggestive of focal dystonia.

Functional connectivity between prefrontal and parietal cortex drives visuo-spatial attention shifts.

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Heinen, Klaartje; Feredoes, Eva; Ruff, Christian C; Driver, Jon

2017-05-01

It is well established that the frontal eye-fields (FEF) in the dorsal attention network (DAN) guide top-down selective attention. In addition, converging evidence implies a causal role for the FEF in attention shifting, which is also known to recruit the ventral attention network (VAN) and fronto-striatal regions. To investigate the causal influence of the FEF as (part of) a central hub between these networks, we applied thetaburst transcranial magnetic stimulation (TBS) off-line, combined with functional magnetic resonance (fMRI) during a cued visuo-spatial attention shifting paradigm. We found that TBS over the right FEF impaired performance on a visual discrimination task in both hemifields following attention shifts, while only left hemifield performance was affected when participants were cued to maintain the focus of attention. These effects recovered ca. 20min post stimulation. Furthermore, particularly following attention shifts, TBS suppressed the neural signal in bilateral FEF, right inferior and superior parietal lobule (IPL/SPL) and bilateral supramarginal gyri (SMG). Immediately post stimulation, functional connectivity was impaired between right FEF and right SMG as well as right putamen. Importantly, the extent of decreased connectivity between right FEF and right SMG correlated with behavioural impairment following attention shifts. The main finding of this study demonstrates that influences from right FEF on SMG in the ventral attention network causally underly attention shifts, presumably by enabling disengagement from the current focus of attention. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations.

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Sharott, Andrew; Vinciati, Federica; Nakamura, Kouichi C; Magill, Peter J

2017-10-11

Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on "direct pathway" SPNs (dSPNs) and "indirect pathway" SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine

Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

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Nicola J Platt

Full Text Available Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn, cause familial Parkinson's disease (PD. Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA signalling. In addition A53Tα-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Tα-syn, and explored whether A53Tα-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Tα-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction.

Pharmacological treatment of tics in Gilles de la Tourette Syndrome

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Andrea E. Cavanna

2011-12-01

Full Text Available Tourette syndrome is a neurodevelopmental disorder characterised by the chronic presence of multiple motor tics (e.g. eye blinking, shoulder shrugging, etc. and at least one vocal/phonic tic (e.g. grunting or sniffing. The clinical picture of patients with Tourette syndrome is often complicated by tic-related behavioural problems and associated psychopathology. The pathophysiology of Tourette syndrome is poorly understood, however converging evidence from neuroimaging studies suggests abnormalities within the fronto-striatal pathways. The pharmacological management of the tic symptoms focuses on the dopaminergic and noradrenergic pathways and aims to improve the health-related quality of life of patients.

Abnormal Functional Connectivity of Frontopolar Subregions in Treatment-Nonresponsive Major Depressive Disorder.

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Fettes, Peter W; Moayedi, Massieh; Dunlop, Katharine; Mansouri, Farrokh; Vila-Rodriguez, Fidel; Giacobbe, Peter; Davis, Karen D; Lam, Raymond W; Kennedy, Sidney H; Daskalakis, Zafiris J; Blumberger, Daniel M; Downar, Jonathan

2018-04-01

Approximately 30% of patients with major depressive disorder develop treatment-nonresponsive depression (TNRD); novel interventions targeting the substrates of this illness population are desperately needed. Convergent evidence from lesion, stimulation, connectivity, and functional neuroimaging studies implicates the frontopolar cortex (FPC) as a particularly important region in TNRD pathophysiology; regions functionally connected to the FPC, once identified, could present favorable targets for novel brain stimulation treatments. We recently published a parcellation of the FPC based on diffusion tensor imaging data, identifying distinct medial and lateral subregions. Here, we applied this parcellation to resting-state functional magnetic resonance imaging scans obtained in 56 patients with TNRD and 56 matched healthy control subjects. In patients, the medial FPC showed reduced connectivity to the anterior midcingulate cortex and insula. The left lateral FPC showed reduced connectivity to the right lateral orbitofrontal cortex and increased connectivity to the fusiform gyri. In addition, TNRD symptom severity correlated significantly with connectivity of the left lateral FPC subregion to a medial orbitofrontal cortex region of the classical reward network. Taken together, these findings suggest that changes in FPC subregion connectivity may underlie several dimensions of TNRD pathology, including changes in reward/positive valence, nonreward/negative valence, and cognitive control domains. Nodes of functional networks showing abnormal connectivity to the FPC could be useful in generating novel candidates for therapeutic brain stimulation in TNRD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Selective increase of auditory cortico-striatal coherence during auditory-cued Go/NoGo discrimination learning.

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Andreas L. Schulz

2016-01-01

Full Text Available Goal directed behavior and associated learning processes are tightly linked to neuronal activity in the ventral striatum. Mechanisms that integrate task relevant sensory information into striatal processing during decision making and learning are implicitly assumed in current reinforcementmodels, yet they are still weakly understood. To identify the functional activation of cortico-striatal subpopulations of connections during auditory discrimination learning, we trained Mongolian gerbils in a two-way active avoidance task in a shuttlebox to discriminate between falling and rising frequency modulated tones with identical spectral properties. We assessed functional coupling by analyzing the field-field coherence between the auditory cortex and the ventral striatum of animals performing the task. During the course of training, we observed a selective increase of functionalcoupling during Go-stimulus presentations. These results suggest that the auditory cortex functionally interacts with the ventral striatum during auditory learning and that the strengthening of these functional connections is selectively goal-directed.

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

Modulation of fronto-parietal connections during the rubber hand illusion

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Karabanov, Anke Ninija; Ritterband-Rosenbaum, Anina; Christensen, Mark Schram

2017-01-01

Accumulating evidence suggests that parieto-frontal connections play a role in adjusting body ownership during the Rubber Hand Illusion (RHI). Using a motor version of the rubber hand illusion paradigm, we applied single-site and dual-site transcranial magnetic stimulation (TMS) to investigate...... and during three RHI conditions: a) agency and ownership, b) agency but no ownership and c) neither agency nor ownership. Parietal-motor communication differed among experimental conditions. The induction of action ownership was associated with an inhibitory parietal-to-motor connectivity, which...... cortico-spinal and parietal-frontal connectivity during perceived rubber hand ownership. Healthy volunteers received a conditioning TMS pulse over left anterior intraparietal sulcus (aIPS) and a test TMS pulse over left primary motor cortex (M1). Motor Evoked Potentials (MEPs) were recorded at rest...

A prospective study of diffusion weighted magnetic resonance imaging abnormalities in patients with cluster of seizures and status epilepticus.

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Jabeen, S A; Cherukuri, Pavankumar; Mridula, Rukmini; Harshavardhana, K R; Gaddamanugu, Padmaja; Sarva, Sailaja; Meena, A K; Borgohain, Rupam; Jyotsna Rani, Y

2017-04-01

To study the frequency, imaging characteristics, and clinical predictors for development of periictal diffusion weighted MRI abnormalities. We prospectively analyzed electro clinical and imaging characteristic of adult patients with cluster of seizures or status epilepticus between November 2013 and November 2015, in whom the diffusion weighted imaging was done within 24h after the end of last seizure (clinical or electrographic). There were thirty patients who fulfilled the inclusion and exclusion criteria. Twenty patients (66%) had periictal MRI abnormalities. Nine patients (34%) did not have any MRI abnormality. All the patients with PMA had abnormalities on diffusion weighted imaging (DWI). Hippocampal abnormalities were seen in nine (53%), perisylvian in two (11.7%), thalamic in five (30%), splenium involvement in two (11.7%) and cortical involvement (temporo-occipital, parieto-occipital, temporo-parietal, fronto-parietal and fronto-temporal) in sixteen (94.1%) patients. Complete reversal of DWI changes was noted in sixteen (80%) patients and four (20%) patients showed partial resolution of MRI abnormalities. Mean duration of seizures was significantly higher among patients with PMA (59.11+20.97h) compared to those without MRI changes (27.33+9.33h) (pstatus epilepticus and were highly concordant with clinical semiology and EEG activity. Patients with longer duration of seizures/status were more likely to have PMA. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences in functional connectivity between alcohol dependence and internet gaming disorder.

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Han, Ji Won; Han, Doug Hyun; Bolo, Nicolas; Kim, BoAh; Kim, Boong Nyun; Renshaw, Perry F

2015-02-01

Internet gaming disorder (IGD) and alcohol dependence (AD) have been reported to share clinical characteristics including craving and over-engagement despite negative consequences. However, there are also clinical factors that differ between individuals with IGD and those with AD in terms of chemical intoxication, prevalence age, and visual and auditory stimulation. We assessed brain functional connectivity within the prefrontal, striatum, and temporal lobe in 15 patients with IGD and in 16 patients with AD. Symptoms of depression, anxiety, and the attention deficit hyperactivity disorder were assessed in patients with IGD and in patients with AD. Both AD and IGD subjects have positive functional connectivity between the dorsolateral prefrontal cortex (DLPFC), cingulate, and cerebellum. In addition, both groups have negative functional connectivity between the DLPFC and the orbitofrontal cortex. However, the AD subjects have positive functional connectivity between the DLPFC, temporal lobe and striatal areas while IGD subjects have negative functional connectivity between the DLPFC, temporal lobe and striatal areas. AD and IGD subjects may share deficits in executive function, including problems with self-control and adaptive responding. However, the negative connectivity between the DLPFC and the striatal areas in IGD subjects, different from the connectivity observed in AD subjects, may be due to the earlier prevalence age, different comorbid diseases as well as visual and auditory stimulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differences in functional connectivity between alcohol dependence and internet gaming disorder

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Han, Ji Won; Han, Doug Hyun; Bolo, Nicolas; Kim, BoAh; Kim, Boong Nyun; Renshaw, Perry F.

2017-01-01

Introduction Internet gaming disorder (IGD) and alcohol dependence (AD) have been reported to share clinical characteristics including craving and over-engagement despite negative consequences. However, there are also clinical factors that differ between individuals with IGD and those with AD in terms of chemical intoxication, prevalence age, and visual and auditory stimulation. Methods We assessed brain functional connectivity within the prefrontal, striatum, and temporal lobe in 15 patients with IGD and in 16 patients with AD. Symptoms of depression, anxiety, and the attention deficit hyperactivity disorder were assessed in patients with IGD and in patients with AD. Results Both AD and IGD subjects have positive functional connectivity between the dorsolateral prefrontal cortex (DLPFC), cingulate, and cerebellum. In addition, both groups have negative functional connectivity between the DLPFC and the orbitofrontal cortex. However, the AD subjects have positive functional connectivity between the DLPFC, temporal lobe and striatal areas while IGD subjects have negative functional connectivity between the DLPFC, temporal lobe and striatal areas. Conclusions AD and IGD subjects may share deficits in executive function, including problems with self-control and adaptive responding. However, the negative connectivity between the DLPFC and the striatal areas in IGD subjects, different from the connectivity observed in AD subjects, may be due to the earlier prevalence age, different comorbid diseases as well as visual and auditory stimulation. PMID:25282597

Identifying abnormal connectivity in patients using Dynamic Causal Modelling of fMRI responses.

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Mohamed L Seghier

2010-08-01

Full Text Available Functional imaging studies of brain damaged patients offer a unique opportunity to understand how sensori-motor and cognitive tasks can be carried out when parts of the neural system that support normal performance are no longer available. In addition to knowing which regions a patient activates, we also need to know how these regions interact with one another, and how these inter-regional interactions deviate from normal. Dynamic Causal Modelling (DCM offers the opportunity to assess task-dependent interactions within a set of regions. Here we review its use in patients when the question of interest concerns the characterisation of abnormal connectivity for a given pathology. We describe the currently available implementations of DCM for fMRI responses, varying from the deterministic bilinear models with one-state equation to the stochastic nonlinear models with two-state equations. We also highlight the importance of the new Bayesian model selection and averaging tools that allow different plausible models to be compared at the single subject and group level. These procedures allow inferences to be made at different levels of model selection, from features (model families to connectivity parameters. Following a critical review of previous DCM studies that investigated abnormal connectivity we propose a systematic procedure that will ensure more flexibility and efficiency when using DCM in patients. Finally, some practical and methodological issues crucial for interpreting or generalising DCM findings in patients are discussed.

DISC1 and striatal volume: a potential risk phenotype for mental illness

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M. Mallar eChakravarty

2012-06-01

Full Text Available Disrupted-in-schizophrenia 1 was originally discovered in a large Scottish family with abnormally high rates of severe mental illness, including schizophrenia, bipolar disorder, and depression. An accumulating body of evidence from genetic, postmortem, and animal data supports a role for DISC1 in different forms of mental illness. DISC1 may play an important role in determining structure and function of several brain regions. One brain region of particular importance for several mental disorders is the striatum, and DISC1 mutant mice have demonstrated an increase in dopamine (D2 receptors in this structure. However, association between DISC1 functional polymorphisms and striatal structure have not been examined in humans to our knowledge. We, therefore hypothesized that there would be a relationship between human striatal volume and DISC1 genotype, specifically in the Leu607Phe (rs6675281 and Ser704Cys (rs821618 single nucleotide polymorphisms. We tested our hypothesis by automatically identifying the striatum in fifty-four healthy volunteers recruited for this study. We also performed an exploratory analysis of cortical thickness, cortical surface area, and structure volume. Our results demonstrate that Phe allele carriers have larger striatal volume bilaterally (left striatum: p=0.017; right striatum: p=0.016. From the exploratory analyses we found that Phe carriers also had larger right hemisphere volumes and right occipital lobe surface area (p=0.014 compared to LeuLeu homozygotes (p=0.0074. However, these exploratory findings do not survive a conservative correction for multiple comparisons. Our findings demonstrate that a functional DISC1 variant influences striatal volumes. Taken together with animal data that this gene influences D2 receptor levels in striatum, a key risk pathway for mental illnesses such as schizophrenia and bipolar disorder may be conferred via DISC1’s effects on the striatum .

Enhanced prefrontal-amygdala connectivity following childhood adversity as a protective mechanism against internalizing in adolescence.

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Herringa, Ryan J; Burghy, Cory A; Stodola, Diane E; Fox, Michelle E; Davidson, Richard J; Essex, Marilyn J

2016-07-01

Much research has focused on the deleterious neurobiological effects of childhood adversity that may underlie internalizing disorders. While most youth show emotional adaptation following adversity, the corresponding neural mechanisms remain poorly understood. In this longitudinal community study, we examined the associations among childhood family adversity, adolescent internalizing symptoms, and their interaction on regional brain activation and amygdala/hippocampus functional connectivity during emotion processing in 132 adolescents. Consistent with prior work, childhood adversity predicted heightened amygdala reactivity to negative, but not positive, images in adolescence. However, amygdala reactivity was not related to internalizing symptoms. Furthermore, childhood adversity predicted increased fronto-amygdala connectivity to negative, but not positive, images, yet only in lower internalizing adolescents. Childhood adversity also predicted increased fronto-hippocampal connectivity to negative images, but was not moderated by internalizing. These findings were unrelated to adolescence adversity or externalizing symptoms, suggesting specificity to childhood adversity and adolescent internalizing. Together, these findings suggest that adaptation to childhood adversity is associated with augmentation of fronto-subcortical circuits specifically for negative emotional stimuli. Conversely, insufficient enhancement of fronto-amygdala connectivity, with increasing amygdala reactivity, may represent a neural signature of vulnerability for internalizing by late adolescence. These findings implicate early childhood as a critical period in determining the brain's adaptation to adversity, and suggest that even normative adverse experiences can have significant impact on neurodevelopment and functioning. These results offer potential neural mechanisms of adaptation and vulnerability which could be used in the prediction of risk for psychopathology following childhood

Abnormal laughter-like vocalisations replacing speech in primary progressive aphasia

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Rohrer, Jonathan D.; Warren, Jason D.; Rossor, Martin N.

2009-01-01

We describe ten patients with a clinical diagnosis of primary progressive aphasia (PPA) (pathologically confirmed in three cases) who developed abnormal laughter-like vocalisations in the context of progressive speech output impairment leading to mutism. Failure of speech output was accompanied by increasing frequency of the abnormal vocalisations until ultimately they constituted the patient's only extended utterance. The laughter-like vocalisations did not show contextual sensitivity but occurred as an automatic vocal output that replaced speech. Acoustic analysis of the vocalisations in two patients revealed abnormal motor features including variable note duration and inter-note interval, loss of temporal symmetry of laugh notes and loss of the normal decrescendo. Abnormal laughter-like vocalisations may be a hallmark of a subgroup in the PPA spectrum with impaired control and production of nonverbal vocal behaviour due to disruption of fronto-temporal networks mediating vocalisation. PMID:19435636

Altered striatal and pallidal connectivity in cervical dystonia

NARCIS (Netherlands)

Delnooz, C.C.S.; Pasman, J.W; Beckmann, C.F.; Warrenburg, B.P.C. van de

2015-01-01

Cervical dystonia is a neurological movement disorder characterized by involuntary, abnormal movements of the head and neck. Injecting the overactive muscles with botulinum toxin is the gold standard treatment, supported by good evidence (Delnooz and van de Warrenburg in Ther Adv Neurol Disord

Fronto-orbital feminization technique. A surgical strategy using fronto-orbital burring with or without eggshell technique to optimize the risk/benefit ratio.

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Villepelet, A; Jafari, A; Baujat, B

2018-05-04

The demand for facial feminization is increasing in transsexual patients. Masculine foreheads present extensive supraorbital bossing with a more acute glabellar angle, whereas female foreheads show softer features. The aim of this article is to describe our surgical technique for fronto-orbital feminization. The mask-lift technique is an upper face-lift. It provides rejuvenation by correcting collapsed features, and fronto-orbital feminization through burring of orbital rims and lateral canthopexies. Depending on the size of the frontal sinus and the thickness of its anterior wall, frontal remodeling is achieved using simple burring or by means of the eggshell technique. Orbital remodeling comprises a superolateral orbital opening, a reduction of ridges and a trough at the lateral orbital rim to support the lateral canthopexy. Frontal, corrugator and procerus myectomies, plus minimal scalp excision, complete the surgery. Our technique results in significant, natural-looking feminization. No complications were observed in our series of patients. The eggshell technique is an alternative to bone flap on over-pneumatized sinus. Fronto-orbital feminization fits into a wider surgical strategy. It can be associated to rhinoplasty, genioplasty, mandibular angle remodeling, face lift and laryngoplasty. Achieving facial feminization in 2 or 3 stages improves psychological and physiological tolerance. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls.

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Cristina Solé-Padullés

Full Text Available Schizophrenia (SZ and bipolar disorder (BD share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27, offspring of patients with BD (N = 39 and offspring of community control parents (N = 40. We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.

The rate of urinary tract abnormalities and the functional state of kidneys in relation to the degree of connective tissue dysplasia in children

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T. A. Kryganova

2016-01-01

Full Text Available The paper is devoted to the study of the rate of urinary tract abnormalities and kidney functions in children with mild, moderate, and severe connective tissue dysplasia. Severe connective tissue dysplasia was found to prevail in children with urinary tract abnormalities and to be characterized by a variety of urodynamic urinary tract abnormalities. Urinary system infection occurred equally frequently in both patient groups and its rate did not depend on the degree of the dysplasia. Some children with severe connective dysplasia were noted to have diminished renal filtration function. High-grade vesicoureteral reflux, tubular disorders as nocturias, and lowered urine osmolarity were more common in children with severe dysplasia. Hypertension was seen equally often in both patient groups, no matter what the degree of connective tissue dysplasia.

Abnormal functional connectivity of the medial cortex in euthymic bipolar II disorder.

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Marchand, William R; Lee, James N; Johnson, Susanna; Gale, Phillip; Thatcher, John

2014-06-03

This project utilized functional MRI (fMRI) and a motor activation paradigm to investigate neural circuitry in euthymic bipolar II disorder. We hypothesized that circuitry involving the cortical midline structures (CMS) would demonstrate abnormal functional connectivity. Nineteen subjects with recurrent bipolar disorder and 18 controls were studied using fMRI and a motor activation paradigm. We used functional connectivity analyses to identify circuits with aberrant connectivity. We found increased functional connectivity among bipolar subjects compared to healthy controls in two CMS circuits. One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus and the right medial frontal gyrus and surrounding region. Our results indicate that CMS circuit dysfunction persists in the euthymic state and thus may represent trait pathology. Future studies should address whether these circuits contribute to relapse of illness. Our results also suggest the possibility that aberrations of superior frontal circuitry may impact default mode network and cognitive processes. Published by Elsevier Inc.

Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

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Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

2017-12-13

A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.

New insights in the homotopic and heterotopic connectivity of the frontal portion of the human corpus callosum revealed by microdissection and diffusion tractography.

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De Benedictis, Alessandro; Petit, Laurent; Descoteaux, Maxime; Marras, Carlo Efisio; Barbareschi, Mattia; Corsini, Francesco; Dallabona, Monica; Chioffi, Franco; Sarubbo, Silvio

2016-12-01

Extensive studies revealed that the human corpus callosum (CC) plays a crucial role in providing large-scale bi-hemispheric integration of sensory, motor and cognitive processing, especially within the frontal lobe. However, the literature lacks of conclusive data regarding the structural macroscopic connectivity of the frontal CC. In this study, a novel microdissection approach was adopted, to expose the frontal fibers of CC from the dorsum to the lateral cortex in eight hemispheres and in one entire brain. Post-mortem results were then combined with data from advanced constrained spherical deconvolution in 130 healthy subjects. We demonstrated as the frontal CC provides dense inter-hemispheric connections. In particular, we found three types of fronto-callosal fibers, having a dorso-ventral organization. First, the dorso-medial CC fibers subserve homotopic connections between the homologous medial cortices of the superior frontal gyrus. Second, the ventro-lateral CC fibers subserve homotopic connections between lateral frontal cortices, including both the middle frontal gyrus and the inferior frontal gyrus, as well as heterotopic connections between the medial and lateral frontal cortices. Third, the ventro-striatal CC fibers connect the medial and lateral frontal cortices with the contralateral putamen and caudate nucleus. We also highlighted an intricate crossing of CC fibers with the main association pathways terminating in the lateral regions of the frontal lobes. This combined approach of ex vivo microdissection and in vivo diffusion tractography allowed demonstrating a previously unappreciated three-dimensional architecture of the anterior frontal CC, thus clarifying the functional role of the CC in mediating the inter-hemispheric connectivity. Hum Brain Mapp 37:4718-4735, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A review on functional and structural brain connectivity in numerical cognition

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Korbinian eMoeller

2015-05-01

Full Text Available Only recently has the complex anatomo-functional system underlying numerical cognition become accessible to evaluation in the living brain. We identified 26 studies investigating brain connectivity in numerical cognition. Despite considerable heterogeneity regarding methodological approaches, populations investigated, and assessment procedures implemented, the results provided largely converging evidence regarding the underlying brain connectivity involved in numerical cognition. Analyses of both functional/effective as well as structural connectivity have consistently corroborated the assumption that numerical cognition is subserved by a fronto-parietal network including (intraparietal as well as (prefrontal cortex sites. Evaluation of structural connectivity has indicated the involvement of fronto-parietal association fibers encompassing the superior longitudinal fasciculus dorsally and the external capsule/extreme capsule system ventrally. Additionally, commissural fibers seem to connect the bilateral intraparietal sulci when number magnitude information is processed. Finally, the identification of projection fibers such as the superior corona radiata indicates connections between cortex and basal ganglia as well as the thalamus in numerical cognition. Studies on functional/effective connectivity further indicated a specific role of the hippocampus. These specifications of brain connectivity augment the triple-code model of number processing and calculation with respect to how grey matter areas associated with specific number-related representations may work together.

[18F]fallypride characterization of striatal and extrastriatal D2/3 receptors in Parkinson's disease.

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Stark, Adam J; Smith, Christopher T; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Donahue, Manus J; Kessler, Robert M; Deutch, Ariel Y; Zald, David H; Claassen, Daniel O

2018-01-01

Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D 2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D 2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D 2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [ 18 F]fallypride, a high affinity D 2/3 receptor ligand, to measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BP ND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D 2/3 receptors, where reduced BP ND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D 2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D 2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.

Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

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Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho; Seppaenen, Marko; Noponen, Tommi

2014-01-01

Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [ 123 I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

Impulsivity in Parkinson’s Disease Is Associated With Alterations in Affective and Sensorimotor Striatal Networks

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Marit F. L. Ruitenberg

2018-04-01

Full Text Available A subset of patients with Parkinson’s disease (PD experiences problems with impulse control, characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of such impulse control disorders (ICDs in PD. We collected resting-state functional connectivity and structural MRI data from 21 PD patients with ICDs and 30 patients without such disorders. To assess impulsivity, all patients completed the Barratt Impulsiveness Scale and performed an information-gathering task. MRI results demonstrated substantial differences in neural characteristics between PD patients with and without ICDs. Results showed that impulsivity was linked to alterations in affective basal ganglia circuitries. Specifically, reduced frontal–striatal connectivity and GPe volume were associated with more impulsivity. We suggest that these changes affect decision making and result in a preference for risky or inappropriate actions. Results further showed that impulsivity was linked to alterations in sensorimotor striatal networks. Enhanced connectivity within this network and larger putamen volume were associated with more impulsivity. We propose that these changes affect sensorimotor processing such that patients have a greater propensity to act. Our findings suggest that the two mechanisms jointly contribute to impulsive behaviors in PD.

Parsing Heterogeneous Striatal Activity

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Kae Nakamura

2017-05-01

Full Text Available The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder.

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Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E; Brammer, Michael; Fletcher, Paul C; Bullmore, Edward T; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G M

2013-08-06

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of "cortical separation distances" to assess the global and local intrinsic "wiring costs" of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical "connectivity" in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms.

Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.

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Yun, Kangsun; Perantoni, Alan O

The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme. The conditional mutants fail to form a normal renal medulla but no longer exhibit duplex kidney formation. Approximately 1/3 of the mutants develop hydronephrosis in the kidneys either uni- or bilaterally when using Dll1Cre. The abnormal kidney phenotype becomes prominent at E16.5, which approximates the time when urine production begins in the mouse embryonic kidney, and is associated with a dramatic increase in apoptosis only in mutant kidneys with hydronephrosis. Methylene blue dye injection and histologic examination reveal that aberrant cell death likely results from urine toxicity due to an abnormal ureter-bladder connection. This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection. Published by Elsevier B.V.

Abnormal brain connectivity in first-episode psychosis: A diffusion MRI tractography study of the corpus callosum

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Price, Gary; Cercignani, Mara; Parker, Geoffrey J.M.; Altmann, Daniel R.; Barnes, Thomas R.E.; Barker, Gareth J.; Joyce, Eileen M.; Ron, Maria A.

2007-01-01

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the clinical manifestations of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail and we present here a study of patients with first-episode psychosis using this technique. We selected the corpus callosum for this study because there is evidence that it is abnormal in schizophrenia. In addition, the topographical organization of its fibers makes it possible to relate focal abnormalities to specific cortical regions. Eighteen patients with first-episode psychosis and 21 healthy subjects took part in the study. A probabilistic tractography algorithm (PICo) was used to study fractional anisotropy (FA). Seed regions were placed in the genu and splenium to track fiber tracts traversing these regions, and a multi-threshold approach to study the probability of connection was used. Multiple linear regressions were used to explore group differences. FA, a measure of tract coherence, was reduced in tracts crossing the genu, and to a lesser degree the splenium, in patients compared with controls. FA was also lower in the genu in females across both groups, but there was no gender-by-group interaction. The FA reduction in patients may be due to aberrant myelination or axonal abnormalities, but the similar tract volumes in the two groups suggest that severe axonal loss is unlikely at this stage of the illness. PMID:17275337

Abnormalities of white matter microstructure in unmedicated obsessive-compulsive disorder and changes after medication.

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Qing Fan

Full Text Available BACKGROUND: Abnormalities of myelin integrity have been reported in obsessive-compulsive disorder (OCD using multi-parameter maps of diffusion tensor imaging (DTI. However, it was still unknown to what degree these abnormalities might be affected by pharmacological treatment. OBJECTIVE: To investigate whether the abnormalities of white matter microstructure including myelin integrity exist in OCD and whether they are affected by medication. METHODOLOGY AND PRINCIPAL FINDINGS: Parameter maps of DTI, including fractional anisotropy (FA, axial diffusivity (AD, radial diffusivity (RD and mean diffusivity (MD, were acquired from 27 unmedicated OCD patients (including 13 drug-naïve individuals and 23 healthy controls. Voxel-based analysis was then performed to detect regions with significant group difference. We compared the DTI-derived parameters of 15 patients before and after 12-week Selective Serotonin Reuptake Inhibitor (SSRI therapies. Significant differences of DTI-derived parameters were observed between OCD and healthy groups in multiple structures, mainly within the fronto-striato-thalamo-cortical loop. An increased RD in combination with no change in AD among OCD patients was found in the left medial superior frontal gyrus, temporo-parietal lobe, occipital lobe, striatum, insula and right midbrain. There was no statistical difference in DTI-derived parameters between drug-naive and previously medicated OCD patients. After being medicated, OCD patients showed a reduction in RD of the left striatum and right midbrain, and in MD of the right midbrain. CONCLUSION: Our preliminary findings suggest that abnormalities of white matter microstructure, particularly in terms of myelin integrity, are primarily located within the fronto-striato-thalamo-cortical circuit of individuals with OCD. Some abnormalities may be partly reversed by SSRI treatment.

Interaction of language, auditory and memory brain networks in auditory verbal hallucinations.

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Ćurčić-Blake, Branislava; Ford, Judith M; Hubl, Daniela; Orlov, Natasza D; Sommer, Iris E; Waters, Flavie; Allen, Paul; Jardri, Renaud; Woodruff, Peter W; David, Olivier; Mulert, Christoph; Woodward, Todd S; Aleman, André

2017-01-01

Auditory verbal hallucinations (AVH) occur in psychotic disorders, but also as a symptom of other conditions and even in healthy people. Several current theories on the origin of AVH converge, with neuroimaging studies suggesting that the language, auditory and memory/limbic networks are of particular relevance. However, reconciliation of these theories with experimental evidence is missing. We review 50 studies investigating functional (EEG and fMRI) and anatomic (diffusion tensor imaging) connectivity in these networks, and explore the evidence supporting abnormal connectivity in these networks associated with AVH. We distinguish between functional connectivity during an actual hallucination experience (symptom capture) and functional connectivity during either the resting state or a task comparing individuals who hallucinate with those who do not (symptom association studies). Symptom capture studies clearly reveal a pattern of increased coupling among the auditory, language and striatal regions. Anatomical and symptom association functional studies suggest that the interhemispheric connectivity between posterior auditory regions may depend on the phase of illness, with increases in non-psychotic individuals and first episode patients and decreases in chronic patients. Leading hypotheses involving concepts as unstable memories, source monitoring, top-down attention, and hybrid models of hallucinations are supported in part by the published connectivity data, although several caveats and inconsistencies remain. Specifically, possible changes in fronto-temporal connectivity are still under debate. Precise hypotheses concerning the directionality of connections deduced from current theoretical approaches should be tested using experimental approaches that allow for discrimination of competing hypotheses. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Can understanding the neurobiology of body dysmorphic disorder (BDD) inform treatment?

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Rossell, Susan L; Harrison, Ben J; Castle, David

2015-08-01

We aim to provide a clinically focused review of the neurobiological literature in body dysmorphic disorder (BDD), with a focus on structural and functional neuroimaging. There has been a recent influx of studies examining the underlying neurobiology of BDD using structural and functional neuroimaging methods. Despite obvious symptom similarities with obsessive-compulsive disorder (OCD), no study to date has directly compared the two groups using neuroimaging techniques. Studies have established that there are limbic and visual cortex abnormalities in BDD, in contrast to fronto-striatal differences in OCD. Such data suggests affect or visual training maybe useful in BDD. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Abnormal white matter structural connectivity in treatment-naïve young adults with borderline personality disorder.

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Gan, J; Yi, J; Zhong, M; Cao, X; Jin, X; Liu, W; Zhu, X

2016-12-01

The pathogenesis of borderline personality disorder (BPD) is not well understood. We examined the microstructure of white matter in patients with BPD. Treatment-naïve young adult with BPD (N = 30) and young-adult healthy controls (HCs; N = 31) were subjected diffusion tensor imaging (DTI). Microstructural parameters were analyzed via tract-based spatial statistics (TBSS) and post hoc tractography. TBSS analysis revealed that, relative to the HC group, the BPD group had significantly lower fractional anisotropy (FA) values in the genu and body of the corpus callosum (CC), right superior corona radiate, right anterior corona radiate, as well as higher radial diffusivity (RD) in the left anterior thalamic radiation. Tractography showed that FA values of fiber bundles passing through the fornix were significantly reduced in BPD group relative to HCs. No significant correlations were observed between clinical symptom and DTI indices in BPD group (FDR corrected). Focal microstructural alterations were found in BPD group, mainly in the limbic system and CC. The present findings support the fronto-limbic disconnectivity hypothesis and suggest that abnormal maturation of white matter structures may play an important role in mechanism of BPD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fronto-Orbital Advancement and Total Calvarial Remodelling for Craniosynostosis

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Haq, E. U.; Aman, S.; Tammimy, M. S.; Ahmad, R. S.

2014-01-01

Objective: To describe the results of fronto-orbital advancement and remodelling for craniosynostosis in children. Study Design: Case series. Place and Duration of Study: Department of Plastic Surgery, Combined Military Hospital, Rawalpindi, from June 2009 to June 2012. Methodology: All the patients with cranial suture synostosis operated were included in the study. Those patients who were lost to follow-up were excluded. Variables considered were age, gender, type of synostosis, intracranial pressure, and history of previous surgeries for the same problem. Outcome measures were studied in terms of improvement of skull measurements (anteroposterior and bicoronal), duration of surgery, hospital stay, blood transfusions, complications and parents satisfaction. Results: A total of 36 patients were included in the study. Male to female ratio was 3:1. The age ranged from 5 to 54 months. Thirty two patients presented with non-syndromic and four with syndromic craniosynostosis. Fronto orbital advancement and total calvarial remodelling was done in 26 and 10 patients respectively. There was improvement in the skull measurements and the parents were satisfied in all cases with the skull shape. Complications occurred in 11.1% including chest and wound infection and one death. Conclusion: Fronto-orbital advancement and remodelling is an effective procedure for the correction of craniosynostosis, however, individual cases may require other procedures like total calvarial remodelling. (author)

Abnormal amygdala connectivity in patients with primary insomnia: evidence from resting state fMRI.

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Huang, Zhaoyang; Liang, Peipeng; Jia, Xiuqin; Zhan, Shuqin; Li, Ning; Ding, Yan; Lu, Jie; Wang, Yuping; Li, Kuncheng

2012-06-01

Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Abnormal amygdala connectivity in patients with primary insomnia: Evidence from resting state fMRI

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Huang Zhaoyang; Liang Peipeng; Jia Xiuqin; Zhan Shuqin; Li Ning; Ding Yan; Lu Jie; Wang Yuping; Li Kuncheng

2012-01-01

Background: Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Methods: Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. Results: We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). Conclusions: The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients.

Widespread structural brain changes in OCD: a systematic review of voxel-based morphometry studies.

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Piras, Federica; Piras, Fabrizio; Chiapponi, Chiara; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

2015-01-01

The most widely accepted model of obsessive-compulsive disorder (OCD) assumes brain abnormalities in the "affective circuit", mainly consisting of volume reduction in the medial orbitofrontal, anterior cingulate and temporolimbic cortices, and tissue expansion in the striatum and thalamus. The advent of whole-brain, voxel-based morphometry (VBM) has provided increasing evidence that regions outside the "affective" orbitofronto-striatal circuit are involved in OCD. Nevertheless, potential confounds from the different image analysis methods, as well as other factors, such as patients' medication and comorbidity status, may limit generalization of results. In the present paper, we systematically reviewed the whole-brain VBM literature on OCD by focussing specifically on degree of consistency between studies, extent to which findings have been replicated and interrelation between clinical variables and OCD anatomy, a potentially crucial factor that has been systematically examined only in a limited number of studies. The PubMed database was searched through February 2012. A total of 156 studies were identified; 18 of them fulfilled the inclusion/exclusion criteria and included 511 patients and 504 controls. Results support the notion that the brain alterations responsible for OCD are represented at the network level, and that widespread structural abnormalities may contribute to neurobiological vulnerability to OCD. Apart from defects in regions within the classic "affective" circuit, volume reduction of the cortical source of the dorsolateral (DL) prefronto-striatal "executive" circuit (dorsomedial, DL, ventrolateral and frontopolar prefrontal cortices), and of reciprocally connected regions (temporo-parieto-occipital associative areas) is consistently described in OCD patients. Moreover, increased volume of the internal capsule and reduced frontal and parietal white matter volumes may account for altered anatomical connectivity in fronto-subcortical circuitry

Global actions of nicotine on the striatal microcircuit.

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Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús; Hernández-Martinez, Ricardo; Rueda-Orozco, Pavel; Galarraga, Elvira; Drucker-Colín, René; Bargas, José

2013-01-01

what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

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Gross, Noah B; Duncker, Patrick C; Marshall, John F

2011-11-01

Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

Morphological and glucose metabolism abnormalities in alcoholic Korsakoff's syndrome: group comparisons and individual analyses.

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Anne-Lise Pitel

Full Text Available BACKGROUND: Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS. Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. METHODOLOGY/PRINCIPAL FINDINGS: Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and (18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. CONCLUSIONS/SIGNIFICANCE: These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker.

Global actions of nicotine on the striatal microcircuit

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Victor E Plata

2013-11-01

Full Text Available The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA, the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

Failing to learn from negative prediction errors: Obesity is associated with alterations in a fundamental neural learning mechanism.

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Mathar, David; Neumann, Jane; Villringer, Arno; Horstmann, Annette

2017-10-01

Prediction errors (PEs) encode the difference between expected and actual action outcomes in the brain via dopaminergic modulation. Integration of these learning signals ensures efficient behavioral adaptation. Obesity has recently been linked to altered dopaminergic fronto-striatal circuits, thus implying impairments in cognitive domains that rely on its integrity. 28 obese and 30 lean human participants performed an implicit stimulus-response learning paradigm inside an fMRI scanner. Computational modeling and psycho-physiological interaction (PPI) analysis was utilized for assessing PE-related learning and associated functional connectivity. We show that human obesity is associated with insufficient incorporation of negative PEs into behavioral adaptation even in a non-food context, suggesting differences in a fundamental neural learning mechanism. Obese subjects were less efficient in using negative PEs to improve implicit learning performance, despite proper coding of PEs in striatum. We further observed lower functional coupling between ventral striatum and supplementary motor area in obese subjects subsequent to negative PEs. Importantly, strength of functional coupling predicted task performance and negative PE utilization. These findings show that obesity is linked to insufficient behavioral adaptation specifically in response to negative PEs, and to associated alterations in function and connectivity within the fronto-striatal system. Recognition of neural differences as a central characteristic of obesity hopefully paves the way to rethink established intervention strategies: Differential behavioral sensitivity to negative and positive PEs should be considered when designing intervention programs. Measures relying on penalization of unwanted behavior may prove less effective in obese subjects than alternative approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unilateral proptosis revealing a fronto-ethmoidal mucocele.

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Lajmi, Houda; Hmaied, Wassim; Ben Jalel, Wady; Ben Romdhane, Khaoula; Chelly, Zied; El Fekih, Lamia

2017-06-01

Backgroud: The fronto-ethmoidal mucocele is a benign condition leading commonly to limited eye movement or ocular pain but it could also induce visual acuity impairment by compressing the optic nerve Aim: To discuss, through a case report, different ophthalmologic manifestations of the fronto-ethmoidalmucocele. Reported case: A 46-years-old man with no general history consulted for a bilateral ocular redness and itching. He reported, however, a mild protrusion of his left globe evolving for oneyear. The clinical examination revealed a unilateral proptosis in the left eye with a discrete limitation of theadduction. A brain and orbital computer tomography (CT)and a magnetic resonance imaging(MRI)revealed a grade I exophthalmos caused by an oval formation of fluid density in the left anterior and posterior ethmoidal cells in addition to the frontal sinus,driving theeyeball and internal oculomotor muscles back and out.The patient was referred to otorhinolaryngology department for a precocious surgical management. The ophtalmologic manifestations of the disease depend on the location, the size of the formation and involvement of adjacent structures. The loss of vision and the apex syndrome due to the compressionof the ocular globe are the most serious complications.

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions.

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Cohen, Michael S; Rissman, Jesse; Suthana, Nanthia A; Castel, Alan D; Knowlton, Barbara J

2014-06-01

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system coactivates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to assess how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants' selectivity index, which measures how close participants were to their optimal point total, given the number of items recalled. Greater selectivity scores were associated with greater differences in the activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during the encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items.

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions

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Cohen, Michael S.; Rissman, Jesse; Suthana, Nanthia A.; Castel, Alan D.; Knowlton, Barbara J.

2014-01-01

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system co-activates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to examine how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants’ selectivity index, a measure of how close participants were to their optimal point total given the number of items recalled. Greater selectivity scores were associated with greater differences in activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items. PMID:24683066

Striatal dysfunction in attention deficit and hyperkinetic disorder

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Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

1989-01-01

We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD

Striatal dysfunction in attention deficit and hyperkinetic disorder

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Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

1989-01-01

We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates.

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Singh, Arun; Jenkins, Meagan A; Burke, Kenneth J; Beck, Goichi; Jenkins, Andrew; Scimemi, Annalisa; Traynelis, Stephen F; Papa, Stella M

2018-01-23

Dopamine (DA) loss in Parkinson's disease (PD) alters the function of striatal projection neurons (SPNs) and causes motor deficits, but DA replacement can induce further abnormalities. A key pathological change in animal models and patients is SPN hyperactivity; however, the role of glutamate in altered DA responses remains elusive. We tested the effect of locally applied AMPAR or NMDAR antagonists on glutamatergic signaling in SPNs of parkinsonian primates. Following a reduction in basal hyperactivity by antagonists at either receptor, DA inputs induced SPN firing changes that were stable during the entire motor response, in clear contrast with the typically unstable effects. The SPN activity reduction over an extended putamenal area controlled the release of involuntary movements in the "on" state and therefore improved motor responses to DA replacement. These results demonstrate the pathophysiological role of upregulated SPN activity and support strategies to reduce striatal glutamate signaling for PD therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The alcoholic brain: neural bases of impaired reward-based decision-making in alcohol use disorders.

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Galandra, Caterina; Basso, Gianpaolo; Cappa, Stefano; Canessa, Nicola

2018-03-01

Neuroeconomics is providing insights into the neural bases of decision-making in normal and pathological conditions. In the neuropsychiatric domain, this discipline investigates how abnormal functioning of neural systems associated with reward processing and cognitive control promotes different disorders, and whether such evidence may inform treatments. This endeavor is crucial when studying different types of addiction, which share a core promoting mechanism in the imbalance between impulsive subcortical neural signals associated with immediate pleasurable outcomes and inhibitory signals mediated by a prefrontal reflective system. The resulting impairment in behavioral control represents a hallmark of alcohol use disorders (AUDs), a chronic relapsing disorder characterized by excessive alcohol consumption despite devastating consequences. This review aims to summarize available magnetic resonance imaging (MRI) evidence on reward-related decision-making alterations in AUDs, and to envision possible future research directions. We review functional MRI (fMRI) studies using tasks involving monetary rewards, as well as MRI studies relating decision-making parameters to neurostructural gray- or white-matter metrics. The available data suggest that excessive alcohol exposure affects neural signaling within brain networks underlying adaptive behavioral learning via the implementation of prediction errors. Namely, weaker ventromedial prefrontal cortex activity and altered connectivity between ventral striatum and dorsolateral prefrontal cortex likely underpin a shift from goal-directed to habitual actions which, in turn, might underpin compulsive alcohol consumption and relapsing episodes despite adverse consequences. Overall, these data highlight abnormal fronto-striatal connectivity as a candidate neurobiological marker of impaired choice in AUDs. Further studies are needed, however, to unveil its implications in the multiple facets of decision-making.

Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments

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Jill R. Crittenden

2011-09-01

Full Text Available The striatum is composed principally of GABAergic, medium spiny projection neurons (MSNs that can be categorized based on their gene expression, electrophysiological profiles and input-output circuits. Major subdivisions of MSN populations include 1 those in ventromedial and dorsolateral striatal regions, 2 those giving rise to the direct and indirect pathways, and 3 those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input-output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in

The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer's Disease Patients.

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Liu, Xiaozheng; Chen, Wei; Tu, Yunhai; Hou, Hongtao; Huang, Xiaoyan; Chen, Xingli; Guo, Zhongwei; Bai, Guanghui; Chen, Wei

2018-01-01

Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer's disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.

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Zhu, Xi; Helpman, Liat; Papini, Santiago; Schneier, Franklin; Markowitz, John C; Van Meter, Page E; Lindquist, Martin A; Wager, Tor D; Neria, Yuval

2017-07-01

Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed. © 2016 Wiley Periodicals, Inc.

Major depressive disorder is associated with abnormal interoceptive activity and functional connectivity in the insula.

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Avery, Jason A; Drevets, Wayne C; Moseman, Scott E; Bodurka, Jerzy; Barcalow, Joel C; Simmons, W Kyle

2014-08-01

Somatic complaints and altered interoceptive awareness are common features in the clinical presentation of major depressive disorder (MDD). Recently, neurobiological evidence has accumulated demonstrating that the insula is one of the primary cortical structures underlying interoceptive awareness. Abnormal interoceptive representation within the insula may thus contribute to the pathophysiology and symptomatology of MDD. We compared functional magnetic resonance imaging blood oxygenation level-dependent responses between 20 unmedicated adults with MDD and 20 healthy control participants during a task requiring attention to visceral interoceptive sensations and also assessed the relationship of this blood oxygenation level-dependent response to depression severity, as rated using the Hamilton Depression Rating Scale. Additionally, we examined between-group differences in insula resting-state functional connectivity and its relationship to Hamilton Depression Rating Scale ratings of depression severity. Relative to the healthy control subjects, unmedicated MDD subjects exhibited decreased activity bilaterally in the dorsal mid-insula cortex (dmIC) during interoception. Activity within the insula during the interoceptive attention task was negatively correlated with both depression severity and somatic symptom severity in depressed subjects. Major depressive disorder also was associated with greater resting-state functional connectivity between the dmIC and limbic brain regions implicated previously in MDD, including the amygdala, subgenual prefrontal cortex, and orbitofrontal cortex. Moreover, functional connectivity between these regions and the dmIC was positively correlated with depression severity. Major depressive disorder and the somatic symptoms of depression are associated with abnormal interoceptive representation within the insula. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Successful group psychotherapy of depression in adolescents alters fronto-limbic resting-state connectivity.

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Straub, J; Metzger, C D; Plener, P L; Koelch, M G; Groen, G; Abler, B

2017-02-01

Current resting state imaging findings support suggestions that the neural signature of depression and therefore also its therapy should be conceptualized as a network disorder rather than a dysfunction of specific brain regions. In this study, we compared neural connectivity of adolescent patients with depression (PAT) and matched healthy controls (HC) and analysed pre-to-post changes of seed-based network connectivities in PAT after participation in a cognitive behavioral group psychotherapy (CBT). 38 adolescents (30 female; 19 patients; 13-18 years) underwent an eyes-closed resting-state scan. PAT were scanned before (pre) and after (post) five sessions of CBT. Resting-state functional connectivity was analysed in a seed-based approach for right-sided amygdala and subgenual anterior cingulate cortex (sgACC). Symptom severity was assessed using the Beck Depression Inventory Revision (BDI-II). Prior to group CBT, between groups amygdala and sgACC connectivity with regions of the default mode network was stronger in the patients group relative to controls. Within the PAT group, a similar pattern significantly decreased after successful CBT. Conversely, seed-based connectivity with affective regions and regions processing cognition and salient stimuli was stronger in HC relative to PAT before CBT. Within the PAT group, a similar pattern changed with CBT. Changes in connectivity correlated with the significant pre-to-post symptom improvement, and pre-treatment amygdala connectivity predicted treatment response in depressed adolescents. Sample size and missing long-term follow-up limit the interpretability. Successful group psychotherapy of depression in adolescents involved connectivity changes in resting state networks to that of healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

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Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

2011-03-01

Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

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Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho [University of Turku and Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Seppaenen, Marko [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland); Noponen, Tommi [University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland)

2014-10-15

Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [{sup 123}I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

Corticostriatal Connectivity in Antisocial Personality Disorder by MAO-A Genotype and Its Relationship to Aggressive Behavior.

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Kolla, Nathan J; Dunlop, Katharine; Meyer, Jeffrey H; Downar, Jonathan

2018-05-09

The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucleotide tandem repeat polymorphisms, have been shown to differentially affect brain functional connectivity in healthy humans. However, it is currently unknown whether these same polymorphisms influence resting-state brain activity in clinical conditions. Given its high burden on society and strong connection to violent behavior, antisocial personality disorder is a logical condition to study, since in vivo markers of monoamine oxidase A brain enzyme are reduced in key affect-modulating regions, and striatal levels of monoamine oxidase A show a relation with the functional connectivity of this same region. We utilized monoamine oxidase A genotyping and seed-to-voxel-based functional connectivity to investigate the relationship between genotype and corticostriatal connectivity in 21 male participants with severe antisocial personality disorder and 19 male healthy controls. Dorsal striatal connectivity to the frontal pole and anterior cingulate gyrus differentiated antisocial personality disorder subjects and healthy controls by monoamine oxidase A genotype. Furthermore, the linear relationship of proactive aggression to superior ventral striatal-angular gyrus functional connectivity differed by monoamine oxidase A genotype in the antisocial personality disorder groups. These results suggest that monoamine oxidase A genotype may affect corticostriatal connectivity in antisocial personality disorder and that these functional connections may also underlie use of proactive aggression in a genotype-specific manner.

Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398.

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Lane, E L; Cheetham, S; Jenner, P

2008-01-01

The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed. The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

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Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

2017-01-01

Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

Observing complex action sequences: The role of the fronto-parietal mirror neuron system.

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Molnar-Szakacs, Istvan; Kaplan, Jonas; Greenfield, Patricia M; Iacoboni, Marco

2006-11-15

A fronto-parietal mirror neuron network in the human brain supports the ability to represent and understand observed actions allowing us to successfully interact with others and our environment. Using functional magnetic resonance imaging (fMRI), we wanted to investigate the response of this network in adults during observation of hierarchically organized action sequences of varying complexity that emerge at different developmental stages. We hypothesized that fronto-parietal systems may play a role in coding the hierarchical structure of object-directed actions. The observation of all action sequences recruited a common bilateral network including the fronto-parietal mirror neuron system and occipito-temporal visual motion areas. Activity in mirror neuron areas varied according to the motoric complexity of the observed actions, but not according to the developmental sequence of action structures, possibly due to the fact that our subjects were all adults. These results suggest that the mirror neuron system provides a fairly accurate simulation process of observed actions, mimicking internally the level of motoric complexity. We also discuss the results in terms of the links between mirror neurons, language development and evolution.

Childhood maltreatment and combat posttraumatic stress differentially predict fear-related fronto-subcortical connectivity.

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Birn, Rasmus M; Patriat, Rémi; Phillips, Mary L; Germain, Anne; Herringa, Ryan J

2014-10-01

Adult posttraumatic stress disorder (PTSD) has been characterized by altered fear-network connectivity. Childhood trauma is a major risk factor for adult PTSD, yet its contribution to fear-network connectivity in PTSD remains unexplored. We examined, within a single model, the contribution of childhood maltreatment, combat exposure, and combat-related posttraumatic stress symptoms (PTSS) to resting-state connectivity (rs-FC) of the amygdala and hippocampus in military veterans. Medication-free male veterans (n = 27, average 26.6 years) with a range of PTSS completed resting-state fMRI. Measures including the Clinician-Administered PTSD Scale (CAPS), Childhood Trauma Questionnaire (CTQ), and Combat Exposure Scale (CES) were used to predict rs-FC using multilinear regression. Fear-network seeds included the amygdala and hippocampus. Amygdala: CTQ predicted lower connectivity to ventromedial prefrontal cortex (vmPFC), but greater anticorrelation with dorsal/lateral PFC. CAPS positively predicted connectivity to insula, and loss of anticorrelation with dorsomedial/dorsolateral (dm/dl)PFC. Hippocampus: CTQ predicted lower connectivity to vmPFC, but greater anticorrelation with dm/dlPFC. CES predicted greater anticorrelation, whereas CAPS predicted less anticorrelation with dmPFC. Childhood trauma, combat exposure, and PTSS differentially predict fear-network rs-FC. Childhood maltreatment may weaken ventral prefrontal-subcortical circuitry important in automatic fear regulation, but, in a compensatory manner, may also strengthen dorsal prefrontal-subcortical pathways involved in more effortful emotion regulation. PTSD symptoms, in turn, appear to emerge with the loss of connectivity in the latter pathway. These findings suggest potential mechanisms by which developmental trauma exposure leads to adult PTSD, and which brain mechanisms are associated with the emergence of PTSD symptoms. © 2014 Wiley Periodicals, Inc.

Alterations in the microstructure of white matter in children and adolescents with Tourette syndrome measured using tract-based spatial statistics and probabilistic tractography.

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Sigurdsson, Hilmar P; Pépés, Sophia E; Jackson, Georgina M; Draper, Amelia; Morgan, Paul S; Jackson, Stephen R

2018-04-12

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by repetitive and intermittent motor and vocal tics. TS is thought to reflect fronto-striatal dysfunction and the aetiology of the disorder has been linked to widespread alterations in the functional and structural integrity of the brain. The aim of this study was to assess white matter (WM) abnormalities in a large sample of young patients with TS in comparison to a sample of matched typically developing control individuals (CS) using diffusion MRI. The study included 35 patients with TS (3 females; mean age: 14.0 ± 3.3) and 35 CS (3 females; mean age: 13.9 ± 3.3). Diffusion MRI data was analysed using tract-based spatial statistics (TBSS) and probabilistic tractography. Patients with TS demonstrated both marked and widespread decreases in axial diffusivity (AD) together with altered WM connectivity. Moreover, we showed that tic severity and the frequency of premonitory urges (PU) were associated with increased connectivity between primary motor cortex (M1) and the caudate nuclei, and increased information transfer between M1 and the insula, respectively. This is to our knowledge the first study to employ both TBSS and probabilistic tractography in a sample of young patients with TS. Our results contribute to the limited existing literature demonstrating altered connectivity in TS and confirm previous results suggesting in particular, that altered insular function contributes to increased frequency of PU. Copyright © 2018. Published by Elsevier Ltd.

Novel in silico multivariate mapping of intrinsic and anticorrelated connectivity to neurocognitive functional maps supports the maturational hypothesis of ADHD.

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de Lacy, Nina; Kodish, Ian; Rachakonda, Srinivas; Calhoun, Vince D

2018-04-22

From childhood to adolescence, strengthened coupling in frontal, striatal and parieto-temporal regions associated with cognitive control, and increased anticorrelation between task-positive and task-negative circuits, subserve the reshaping of behavior. ADHD is a common condition peaking in adolescence and regressing in adulthood, with a wide variety of cognitive control deficits. Alternate hypotheses of ADHD emphasize lagging circuitry refinement versus categorical differences in network function. However, quantifying the individual circuit contributions to behavioral findings, and relative roles of maturational versus categorical effects, is challenging in vivo or in meta-analyses using task-based paradigms within the same pipeline, given the multiplicity of neurobehavioral functions implicated. To address this, we analyzed 46 positively-correlated and anticorrelated circuits in a multivariate model in resting-state data from 504 age- and gender-matched youth, and created a novel in silico method to map individual quantified effects to reverse inference maps of 8 neurocognitive functions consistently implicated in ADHD, as well as dopamine and hyperactivity. We identified only age- and gender-related effects in intrinsic connectivity, and found that maturational refinement of circuits in youth with ADHD occupied 3-10x more brain locations than in typical development, with the footprint, effect size and contribution of individual circuits varying substantially. Our analysis supports the maturational hypothesis of ADHD, suggesting lagging connectivity reorganization within specific subnetworks of fronto-parietal control, ventral attention, cingulo-opercular, temporo-limbic and cerebellar sub-networks contribute across neurocognitive findings present in this complex condition. We present the first analysis of anti-correlated connectivity in ADHD and suggest new directions for exploring residual and non-responsive symptoms. © 2018 Wiley Periodicals, Inc.

Evidence for anomalous network connectivity during working memory encoding in schizophrenia: an ICA based analysis.

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Shashwath A Meda

2009-11-01

Full Text Available Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by "functional connectivity" analyses.We used independent component analysis (ICA to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct "normal" encoding-related working memory networks compared to controls. These encoding networks comprised 1 left posterior parietal-left dorsal/ventrolateral prefrontal cortex, cingulate, basal ganglia, 2 right posterior parietal, right dorsolateral prefrontal cortex and 3 default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001 and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase.This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia.

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Bernstein, Hans-Gert; Jauch, Esther; Dobrowolny, Henrik; Mawrin, Christian; Steiner, Johann; Bogerts, Bernhard

2016-09-01

Profound white matter abnormalities have repeatedly been described in schizophrenia, which involve the altered expression of numerous oligodendrocyte-associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a key susceptibility factor in schizophrenia, have recently been shown to be expressed by oligodendroglial cells and to negatively regulate oligodendrocyte differentiation and maturation. To learn more about the putative role(s) of oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in postmortem brains of patients with schizophrenia. Compared with controls (N = 12) and cases with undifferentiated/residual schizophrenia (N = 6), there was a significantly increased density of DISC1-expressing glial cells in paranoid schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment. Pathophysiologically, over-expression of DISC1 protein(s) in white matter oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia. Moreover, it might significantly contribute to cell cycle abnormalities as well as to deficits in oligodendroglial cell differentiation and maturation found in schizophrenia.

Deafferentation-Induced Plasticity of Visual Callosal Connections: Predicting Critical Periods and Analyzing Cortical Abnormalities Using Diffusion Tensor Imaging

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Jaime F. Olavarria

2012-01-01

Full Text Available Callosal connections form elaborate patterns that bear close association with striate and extrastriate visual areas. Although it is known that retinal input is required for normal callosal development, there is little information regarding the period during which the retina is critically needed and whether this period correlates with the same developmental stage across species. Here we review the timing of this critical period, identified in rodents and ferrets by the effects that timed enucleations have on mature callosal connections, and compare it to other developmental milestones in these species. Subsequently, we compare these events to diffusion tensor imaging (DTI measurements of water diffusion anisotropy within developing cerebral cortex. We observed that the relationship between the timing of the critical period and the DTI-characterized developmental trajectory is strikingly similar in rodents and ferrets, which opens the possibility of using cortical DTI trajectories for predicting the critical period in species, such as humans, in which this period likely occurs prenatally. Last, we discuss the potential of utilizing DTI to distinguish normal from abnormal cerebral cortical development, both within the context of aberrant connectivity induced by early retinal deafferentation, and more generally as a potential tool for detecting abnormalities associated with neurodevelopmental disorders.

Mediating Role of the Reward Network in the Relationship between the Dopamine Multilocus Genetic Profile and Depression

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Liang Gong

2017-09-01

Full Text Available Multiple genetic loci in the dopamine (DA pathway have been associated with depression symptoms in patients with major depressive disorder (MDD. However, the neural mechanisms underlying the polygenic effects of the DA pathway on depression remain unclear. We used an imaging genetic approach to investigate the polygenic effects of the DA pathway on the reward network in MDD. Fifty-three patients and 37 cognitively normal (CN subjects were recruited and underwent resting-state functional magnetic resonance imaging (R-fMRI scans. Multivariate linear regression analysis was employed to measure the effects of disease and multilocus genetic profile scores (MGPS on the reward network, which was constructed using the nucleus accumbens (NAc functional connectivity (NAFC network. DA-MGPS was widely associated within the NAFC network, mainly in the inferior frontal cortex, insula, hypothalamus, superior temporal gyrus, and occipital cortex. The pattern of DA-MGPS effects on the fronto-striatal pathway differed in MDD patients compared with CN subjects. More importantly, NAc-putamen connectivity mediates the association between DA MGPS and anxious depression traits in MDD patients. Our findings suggest that the DA multilocus genetic profile makes a considerable contribution to the reward network and anxious depression in MDD patients. These results expand our understanding of the pathophysiology of polygenic effects underlying brain network abnormalities in MDD.

Altered neural reward and loss processing and prediction error signalling in depression

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Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela

2015-01-01

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression. PMID:25567763

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

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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.

Behavioral sensitivity of temporally modulated striatal neurons

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George ePortugal

2011-07-01

Full Text Available Recent investigations into the neural mechanisms that underlie temporal perception have revealed that the striatum is an important contributor to interval timing processes, and electrophysiological recording studies have shown that the firing rates of striatal neurons are modulated by the time in a trial at which an operant response is made. However, it remains unclear whether striatal firing rate modulations are related to the passage of time alone (i.e., whether temporal information is represented in an abstract manner independent of other attributes of biological importance, or whether this temporal information is embedded within striatal activity related to co-occurring contextual information, such as motor behaviors. This study evaluated these two hypotheses by recording from striatal neurons while rats performed a temporal production task. Rats were trained to respond at different nosepoke apertures for food reward under two simultaneously active reinforcement schedules: a variable-interval (VI-15 sec schedule and a fixed-interval (FI-15 sec schedule of reinforcement. Responding during a trial occurred in a sequential manner composing 3 phases; VI responding, FI responding, VI responding. The vast majority of task-sensitive striatal neurons (95% varied their firing rates associated with equivalent behaviors (e.g., periods in which their snout was held within the nosepoke across these behavioral phases, and 96% of cells varied their firing rates for the same behavior within a phase, thereby demonstrating their sensitivity to time. However, in a direct test of the abstract timing hypothesis, 91% of temporally modulated hold cells were further modulated by the overt motor behaviors associated with transitioning between nosepokes. As such, these data are inconsistent with the striatum representing time in an abstract’ manner, but support the hypothesis that temporal information is embedded within contextual and motor functions of the

No association between striatal dopamine transporter binding and body mass index

DEFF Research Database (Denmark)

van de Giessen, Elsmarieke; Hesse, Swen; Caan, Matthan W A

2013-01-01

Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine...... transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated....

[Neuromolecular mechanism of the superiority illusion].

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Yamada, Makiko

2014-01-01

The majority of individuals evaluate themselves as above average. This is a cognitive bias called "the superiority illusion". This illusory self-evaluation helps us to have hopes for the future, and has been central to the process of human evolution. Possessing this illusion is also important for mental health, as depressed people appear to have a more realistic perception of themselves, dubbed "depressive realism". Our recent study revealed the spontaneous brain activity and central dopaminergic neurotransmission that generate this illusion, using resting-state fMRI and PET. A functional connectivity between the frontal cortex and striatum, regulated by inhibitory dopaminergic neurotransmission, determines individual levels of the superiority illusion. We further revealed that blocking the dopamine transporter, which enhanced the level of dopamine, increased the degree of the superiority illusion. These findings suggest that dopamine acts on striatal dopamine receptors to suppress fronto-striatal functional connectivity, leading to disinhibited, heuristic, approaches to positive self-evaluation. These findings help us to understand how this key aspect of the human mind is biologically determined, and will suggest treatments for depressive symptoms by targeting specific molecules and neural circuits.

Bayesian network analysis reveals alterations to default mode network connectivity in individuals at risk for Alzheimer's disease.

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Li, Rui; Yu, Jing; Zhang, Shouzi; Bao, Feng; Wang, Pengyun; Huang, Xin; Li, Juan

2013-01-01

Alzheimer's disease (AD) is associated with abnormal functioning of the default mode network (DMN). Functional connectivity (FC) changes to the DMN have been found in patients with amnestic mild cognitive impairment (aMCI), which is the prodromal stage of AD. However, whether or not aMCI also alters the effective connectivity (EC) of the DMN remains unknown. We employed a combined group independent component analysis (ICA) and Bayesian network (BN) learning approach to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17 controls, in order to establish the EC pattern of DMN, and to evaluate changes occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence degree across DMN regions, which were organized into two closely interacting subsystems. Compared to controls, the aMCI group showed altered directed connectivity weights between DMN regions in the fronto-parietal, temporo-frontal, and temporo-parietal pathways. The aMCI group also exhibited altered regional convergence degree in the right inferior parietal lobule. Moreover, we found EC changes in DMN regions in aMCI were correlated with regional FC levels, and the connectivity metrics were associated with patients' cognitive performance. This study provides novel sights into our understanding of the functional architecture of the DMN and adds to a growing body of work demonstrating the importance of the DMN as a mechanism of aMCI.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

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Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Does human presynaptic striatal dopamine function predict social conformity?

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Stokes, Paul R A; Benecke, Aaf; Puraite, Julita; Bloomfield, Michael A P; Shotbolt, Paul; Reeves, Suzanne J; Lingford-Hughes, Anne R; Howes, Oliver; Egerton, Alice

2014-03-01

Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D₂/₃ receptor availability. This may reflect an association between SDR and D₂/₃ receptor expression, synaptic dopamine levels or a combination of the two. In this study, we used a [¹⁸F]-DOPA positron emission tomography (PET) image database to investigate whether SDR is associated with presynaptic dopamine function. Striatal [¹⁸F]-DOPA uptake, (k(i)(cer), min⁻¹), was determined in two independent healthy participant cohorts (n=27 and 19), by Patlak analysis using a cerebellar reference region. SDR was assessed using the revised Eysenck Personality Questionnaire (EPQ-R) Lie scale, and IM and SDE were measured using the Paulhus Deception Scales. No significant associations were detected between Lie, SDE or IM scores and striatal [¹⁸F]-DOPA k(i)(cer). These results indicate that presynaptic striatal dopamine function is not associated with social conformity and suggests that social conformity may be associated with striatal D₂/₃ receptor expression rather than with synaptic dopamine levels.

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

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Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek

2016-01-01

Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study.

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Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-24

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed.

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

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Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-01

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983

Abnormal Functional Connectivity of Anterior Cingulate Cortex in Patients With Primary Insomnia: A Resting-State Functional Magnetic Resonance Imaging Study

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Chao-Qun Yan

2018-06-01

Full Text Available Background: Recently, there have been many reports about abnormalities regarding structural and functional brain connectivity of the patients with primary insomnia. However, the alterations in functional interaction between the left and right cerebral hemispheres have not been well understood. The resting-state fMRI approach, which reveals spontaneous neural fluctuations in blood-oxygen-level-dependent signals, offers a method to quantify functional interactions between the hemispheres directly.Methods: We compared interhemispheric functional connectivity (FC between 26 patients with primary insomnia (48.85 ± 12.02 years and 28 healthy controls (49.07 ± 11.81 years using a voxel-mirrored homotopic connectivity (VMHC method. The patients with primary insomnia and healthy controls were matched for age, gender, and education. Brain regions, which had significant differences in VMHC maps between the primary insomnia and healthy control groups, were defined as seed region of interests. A seed-based approach was further used to reveal significant differences of FC between the seeds and the whole contralateral hemisphere.Results: The patients with primary insomnia showed higher VMHC than healthy controls in the anterior cingulate cortex (ACC bilaterally. The seed-based analyses demonstrated increased FC between the left ACC and right thalamus (and the right ACC and left orbitofrontal cortex in patients with primary insomnia, revealing abnormal connectivity between the two cerebral hemispheres. The VMHC values in the ACC were positively correlated with the time to fall asleep and Self-Rating Depression Scale scores (SDS.Conclusions: The results demonstrate that there is abnormal interhemispheric resting-state FC in the brain regions of patients with primary insomnia, especially in the ACC. Our finding demonstrates valid evidence that the ACC is an area of interest in the neurobiology of primary insomnia.

Adversity in childhood linked to elevated striatal dopamine function in adulthood

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Egerton, A.; Valmaggia, L. R.; Howes, O. D.; Day, F.; Chaddock, C. A.; Allen, P.; Winton-Brown, T. T.; Bloomfield, M. A. P.; Bhattacharyya, S.; Chilcott, J.; Lappin, J. M.; Murray, R. M.; McGuire, P.

2016-01-01

Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and he...

QEEG and LORETA in Teenagers With Conduct Disorder and Psychopathic Traits.

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Calzada-Reyes, Ana; Alvarez-Amador, Alfredo; Galán-García, Lídice; Valdés-Sosa, Mitchell

2017-05-01

Few studies have investigated the impact of the psychopathic traits on the EEG of teenagers with conduct disorder (CD). To date, there is no other research studying low-resolution brain electromagnetic tomography (LORETA) technique using quantitative EEG (QEEG) analysis in adolescents with CD and psychopathic traits. To find electrophysiological differences specifically related to the psychopathic traits. The current investigation compares the QEEG and the current source density measures between adolescents with CD and psychopathic traits and adolescents with CD without psychopathic traits. The resting EEG activity and LORETA for the EEG fast spectral bands were evaluated in 42 teenagers with CD, 25 with and 17 without psychopathic traits according to the Antisocial Process Screening Device. All adolescents were assessed using the DSM-IV-TR criteria. The EEG visual inspection characteristics and the use of frequency domain quantitative analysis techniques (narrow band spectral parameters) are described. QEEG analysis showed a pattern of beta activity excess on the bilateral frontal-temporal regions and decreases of alpha band power on the left central-temporal and right frontal-central-temporal regions in the psychopathic traits group. Current source density calculated at 17.18 Hz showed an increase within fronto-temporo-striatal regions in the psychopathic relative to the nonpsychopathic traits group. These findings indicate that QEEG analysis and techniques of source localization may reveal differences in brain electrical activity among teenagers with CD and psychopathic traits, which was not obvious to visual inspection. Taken together, these results suggest that abnormalities in a fronto-temporo-striatal network play a relevant role in the neurobiological basis of psychopathic behavior.

Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

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Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

2016-10-01

Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. Copyright © 2016. Published by Elsevier Ltd.

Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study.

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Sanefuji, Masafumi; Craig, Michael; Parlatini, Valeria; Mehta, Mitul A; Murphy, Declan G; Catani, Marco; Cerliani, Leonardo; Thiebaut de Schotten, Michel

2017-01-01

Two core symptoms characterize Attention Deficit Hyperactivity Disorder (ADHD) subtypes: inattentiveness and hyperactivity-impulsivity. While previous brain imaging research investigated ADHD as if it was a homogenous condition, its two core symptoms may originate from different brain mechanisms. We, therefore, hypothesized that the functional connectivity of cortico-striatal and attentional networks would be different between ADHD subtypes. We studied 165 children (mean age 10.93 years; age range, 7-17 year old) diagnosed as having ADHD based on their revised Conner's rating scale score and 170 typical developing individuals (mean age 11.46 years; age range, 7-17 year old) using resting state functional fMRI. Groups were matched for age, IQ and head motion during the MRI acquisition. We fractionated the ADHD group into predominantly inattentive, hyperactive-impulsive and combined subtypes based on their revised Conner's rating scale score. We then analyzed differences in resting state functional connectivity of the cortico-striatal and attentional networks between these subtypes. We found a double dissociation of functional connectivity in the cortico-striatal and ventral attentional networks, reflecting the subtypes of the ADHD participants. Particularly, the hyperactive-impulsive subtype was associated with increased connectivity in cortico-striatal network, whereas the inattentive subtype was associated with increased connectivity in the right ventral attention network. Our study demonstrated for the first time a right lateralized, double dissociation between specific networks associated with hyperactivity-impulsivity and inattentiveness in ADHD children, providing a biological basis for exploring symptom dimensions and revealing potential targets for more personalized treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

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Worbe, Yulia; Marrakchi-Kacem, Linda; Lecomte, Sophie; Valabregue, Romain; Poupon, Fabrice; Guevara, Pamela; Tucholka, Alan; Mangin, Jean-François; Vidailhet, Marie; Lehericy, Stephane; Hartmann, Andreas; Poupon, Cyril

2015-02-01

-frontal cortex, inferior frontal, temporo-parietal junction, medial temporal and frontal pole also had enhanced structural connectivity with the striatum and thalamus in patients with Gilles de la Tourette syndrome. In addition, the cortico-striatal pathways were characterized by elevated fractional anisotropy and diminished radial diffusivity, suggesting microstructural axonal abnormalities of white matter in Gilles de la Tourette syndrome. These changes were more prominent in females with Gilles de la Tourette syndrome compared to males and were not related to the current medication status. Taken together, our data showed widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways in patients with Gilles de la Tourette, which likely result from abnormal brain development in this syndrome. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

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Carmela Giampà

2010-10-01

Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

Integrated analysis of gray and white matter alterations in attention-deficit/hyperactivity disorder

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Winke Francx

2016-01-01

Conclusions: Our results replicate and extend previous unimodal structural MRI findings by demonstrating that prefrontal, parietal, and occipital areas, as well as fronto-striatal and fronto-limbic systems are implicated in ADHD. By including multiple modalities, sensitivity for between-participant effects is increased, as shared variance across modalities is modeled. The convergence of modality-specific findings in our results suggests that different aspects of brain structure share underlying pathophysiology and brings us closer to a biological characterization of ADHD.

Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

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Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

2013-01-01

Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

Mucocele fronto-ethmoïdale geante avec extension intracranienne ...

African Journals Online (AJOL)

Mucocele fronto-ethmoïdale geante avec extension intracranienne: a propos d'un cas et revue de la litterature. A Kabre, DS Zabsonre, Y Haro. Abstract. Les mucocèles sont des pseudotumeurs kystiques développées aux dépens des sinus paranasaux. D'évolution lente et silencieuse elles se révèlent le plus souvent par ...

Fronto-parietal coding of goal-directed actions performed by artificial agents.

Science.gov (United States)

Kupferberg, Aleksandra; Iacoboni, Marco; Flanagin, Virginia; Huber, Markus; Kasparbauer, Anna; Baumgartner, Thomas; Hasler, Gregor; Schmidt, Florian; Borst, Christoph; Glasauer, Stefan

2018-03-01

With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto-parietal brain areas. The extent to which these areas are activated when observing artificial agents indicates the naturalness and easiness of interaction. Previous studies indicated that fronto-parietal activity does not depend on whether the agent is human or artificial. However, it is unknown whether this activity is modulated by observing grasping (self-related action) and pointing actions (other-related action) performed by an artificial agent depending on the action goal. Therefore, we designed an experiment in which subjects observed human and artificial agents perform pointing and grasping actions aimed at two different object categories suggesting different goals. We found a signal increase in the bilateral inferior parietal lobule and the premotor cortex when tool versus food items were pointed to or grasped by both agents, probably reflecting the association of hand actions with the functional use of tools. Our results show that goal attribution engages the fronto-parietal network not only for observing a human but also a robotic agent for both self-related and social actions. The debriefing after the experiment has shown that actions of human-like artificial agents can be perceived as being goal-directed. Therefore, humans will be able to interact with service robots intuitively in various domains such as education, healthcare, public service, and entertainment. © 2017 Wiley Periodicals, Inc.

Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses.

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Gay, Charles W; Robinson, Michael E; Lai, Song; O'Shea, Andrew; Craggs, Jason G; Price, Donald D; Staud, Roland

2016-02-01

Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

Striatal volume predicts level of video game skill acquisition.

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Erickson, Kirk I; Boot, Walter R; Basak, Chandramallika; Neider, Mark B; Prakash, Ruchika S; Voss, Michelle W; Graybiel, Ann M; Simons, Daniel J; Fabiani, Monica; Gratton, Gabriele; Kramer, Arthur F

2010-11-01

Video game skills transfer to other tasks, but individual differences in performance and in learning and transfer rates make it difficult to identify the source of transfer benefits. We asked whether variability in initial acquisition and of improvement in performance on a demanding video game, the Space Fortress game, could be predicted by variations in the pretraining volume of either of 2 key brain regions implicated in learning and memory: the striatum, implicated in procedural learning and cognitive flexibility, and the hippocampus, implicated in declarative memory. We found that hippocampal volumes did not predict learning improvement but that striatal volumes did. Moreover, for the striatum, the volumes of the dorsal striatum predicted improvement in performance but the volumes of the ventral striatum did not. Both ventral and dorsal striatal volumes predicted early acquisition rates. Furthermore, this early-stage correlation between striatal volumes and learning held regardless of the cognitive flexibility demands of the game versions, whereas the predictive power of the dorsal striatal volumes held selectively for performance improvements in a game version emphasizing cognitive flexibility. These findings suggest a neuroanatomical basis for the superiority of training strategies that promote cognitive flexibility and transfer to untrained tasks.

Emotion-induced loss aversion and striatal-amygdala coupling in low-anxious individuals.

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Charpentier, Caroline J; De Martino, Benedetto; Sim, Alena L; Sharot, Tali; Roiser, Jonathan P

2016-04-01

Adapting behavior to changes in the environment is a crucial ability for survival but such adaptation varies widely across individuals. Here, we asked how humans alter their economic decision-making in response to emotional cues, and whether this is related to trait anxiety. Developing an emotional decision-making task for functional magnetic resonance imaging, in which gambling decisions were preceded by emotional and non-emotional primes, we assessed emotional influences on loss aversion, the tendency to overweigh potential monetary losses relative to gains. Our behavioral results revealed that only low-anxious individuals exhibited increased loss aversion under emotional conditions. This emotional modulation of decision-making was accompanied by a corresponding emotion-elicited increase in amygdala-striatal functional connectivity, which correlated with the behavioral effect across participants. Consistent with prior reports of 'neural loss aversion', both amygdala and ventral striatum tracked losses more strongly than gains, and amygdala loss aversion signals were exaggerated by emotion, suggesting a potential role for this structure in integrating value and emotion cues. Increased loss aversion and striatal-amygdala coupling induced by emotional cues may reflect the engagement of adaptive harm-avoidance mechanisms in low-anxious individuals, possibly promoting resilience to psychopathology. © The Author (2015). Published by Oxford University Press.

Cerebro-fronto-facial syndrome type 3 with polymicrogyria: a clinical presentation of Baraitser-Winter syndrome.

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Eker, Hatice Koçak; Derinkuyu, Betül Emine; Ünal, Sevim; Masliah-Planchon, Julien; Drunat, Séverine; Verloes, Alain

2014-01-01

Baraitser-Winter syndrome (BRWS) is a rare condition affecting the development of the brain and the face. The most common characteristics are unusual facial appearance including hypertelorism and ptosis, ocular colobomas, hearing loss, impaired neuronal migration and intellectual disability. BRWS is caused by mutations in the ACTB and ACTG1 genes. Cerebro-fronto-facial syndrome (CFFS) is a clinically heterogeneous condition with distinct facial dysmorphism, and brain abnormalities. Three subtypes are identified. We report a female infant with striking facial features and brain anomalies (included polymicrogyria) that fit into the spectrum of the CFFS type 3 (CFFS3). She also had minor anomalies on her hands and feet, heart and kidney malformations, and recurrent infections. DNA investigations revealed c.586C>T mutation (p.Arg196Cys) in ACTB. This mutation places this patient in the spectrum of BRWS. The same mutation has been detected in a polymicrogyric patient reported previously in literature. We expand the malformation spectrum of BRWS/CFFS3, and present preliminary findings for phenotype-genotype correlation in this spectrum. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS).

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San Juan, Juan; Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

2017-01-01

Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom

Tinnitus alters resting state functional connectivity (RSFC in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS.

Directory of Open Access Journals (Sweden)

Juan San Juan

Full Text Available Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex and non-region of interest (adjacent non-auditory cortices and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz, broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to

Impaired pitch perception and memory in congenital amusia: the deficit starts in the auditory cortex.

Science.gov (United States)

Albouy, Philippe; Mattout, Jérémie; Bouet, Romain; Maby, Emmanuel; Sanchez, Gaëtan; Aguera, Pierre-Emmanuel; Daligault, Sébastien; Delpuech, Claude; Bertrand, Olivier; Caclin, Anne; Tillmann, Barbara

2013-05-01

Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a melodic contour task and an easier transposition task); they had to indicate whether sequences of six tones (presented in pairs) were the same or different. Behavioural data indicated that in comparison with control participants, amusics' short-term memory was impaired for the melodic contour task, but not for the transposition task. The major finding was that pitch processing and short-term memory deficits can be traced down to amusics' early brain responses during encoding of the melodic information. Temporal and frontal generators of the N100m evoked by each note of the melody were abnormally recruited in the amusic brain. Dynamic causal modelling of the N100m further revealed decreased intrinsic connectivity in both auditory cortices, increased lateral connectivity between auditory cortices as well as a decreased right fronto-temporal backward connectivity in amusics relative to control subjects. Abnormal functioning of this fronto-temporal network was also shown during the retention interval and the retrieval of melodic information. In particular, induced gamma oscillations in right frontal areas were decreased in amusics during the retention interval. Using voxel-based morphometry, we confirmed morphological brain anomalies in terms of white and grey matter concentration in the right inferior frontal gyrus and the right superior temporal gyrus in the amusic brain. The convergence between functional and structural brain differences strengthens the hypothesis of abnormalities in the fronto-temporal pathway of the amusic brain. Our data provide first evidence of altered functioning of the auditory cortices during pitch

Family Matters: imaging the vulnerability for schizophrenia

NARCIS (Netherlands)

Leeuw, M. de

2015-01-01

Schizophrenia is a highly heritable psychiatric disorder that is characterized by impairments in the fronto-striatal network underlying cognitive deficits. Subjects who are at increased familial risk such as siblings and offspring of schizophrenia patients, also show cognitive impairments

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function

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Olga Laporta-Hoyos

2017-01-01

Conclusion: The widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult.

Exogenous vs. endogenous attention: Shifting the balance of fronto-parietal activity.

Science.gov (United States)

Meyer, Kristin N; Du, Feng; Parks, Emily; Hopfinger, Joseph B

2018-03-01

Despite behavioral and electrophysiological evidence for dissociations between endogenous (voluntary) and exogenous (reflexive) attention, fMRI results have yet to consistently and clearly differentiate neural activation patterns between these two types of attention. This study specifically aimed to determine whether activity in the dorsal fronto-parietal network differed between endogenous and exogenous conditions. Participants performed a visual discrimination task in endogenous and exogenous attention conditions while undergoing fMRI scanning. Analyses revealed robust and bilateral activation throughout the dorsal fronto-parietal network for each condition, in line with many previous results. In order to investigate possible differences in the balance of neural activity within this network with greater sensitivity, a priori regions of interest (ROIs) were selected for analysis, centered on the frontal eye fields (FEF) and intraparietal sulcus (IPS) regions identified in previous studies. The results revealed a significant interaction between region, condition, and hemisphere. Specifically, in the left hemisphere, frontal areas were more active than parietal areas, but only during endogenous attention. Activity in the right hemisphere, in contrast, remained relatively consistent for these regions across conditions. Analysis of this activity over time indicates that this left-hemispheric regional imbalance is present within the FEF early, at 3-6.5 s post-stimulus presentation, whereas a regional imbalance in the exogenous condition is not evident until 6.5-8 s post-stimulus presentation. Overall, our results provide new evidence that although the dorsal fronto-parietal network is indeed associated with both types of attentional orienting, regions of the network are differentially engaged over time and across hemispheres depending on the type of attention. Copyright © 2018 Elsevier Ltd. All rights reserved.

MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

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Weihmuller, F B; O'Dell, S J; Marshall, J F

1992-06-01

Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

Science.gov (United States)

Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

2010-01-01

Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

Reduced striatal D2 receptor binding in myoclonus-dystonia

International Nuclear Information System (INIS)

Beukers, R.J.; Weisscher, N.; Tijssen, M.A.J.; Booij, J.; Zijlstra, F.; Amelsvoort, T.A.M.J. van

2009-01-01

To study striatal dopamine D 2 receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using 123 I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D 2 receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out. (orig.)

An inquiry into the semiquantitative parameters of striatal dopamine receptor imaging

International Nuclear Information System (INIS)

Cao Guoxiang; Tan Tianzhi; Kuang Anren; Liang Zhenglu

1998-01-01

Purpose: To inquire into the optimal striatal reference region for nonspecific IBZM uptake in brain dopamine receptor imaging. Methods: Using in vivo data from rats, the authors compared the results of 125 I-iodobenzamide ( 125 I-IBZM) striatal specific binding that were respectively obtained taking cerebellum and frontal cortex as striatal reference region of nonspecific uptake of ligand. Results: Radioiodination labelled IBZM bound stereoselectively and reversibly to striatal D2 receptors. Frontal cortex and cerebellum showed rapid uptake and rapid washout of ligand. When cerebellar uptake was used as a reference of nonspecific uptake in striatum, IBZM saturation could not be demonstrated. But when the frontal cortex was used as reference region, saturation could be demonstrated with B max = 44 pmol/g striatum tissue. The percentage of haloperidol replacement and the percentage of uptake difference between striatum and other brain regions which were derived from competitive inhibition experiments with a large does of spiperone or haloperidol, suggested that the cerebellar uptake underestimated nonspecific uptake in the striatum while frontal cortex was an appropriate reference region for nonspecific uptake of ligand in striatum. Conclusions: For the calculation of specific IBZM binding and other semiquantitative parameters of striatal dopamine D2 receptor imaging, frontal cortex would be the nonspecific reference region of choice

Sortilin-Mediated Endocytosis Determines Levels of the Fronto-Temporal Dementia Protein, Progranulin

DEFF Research Database (Denmark)

Hu, Fenghua; Padukkavidana, Thihan; Vægter, Christian Bjerggaard

2010-01-01

The most common inherited form of Fronto-Temporal Lobar Degeneration (FTLD) known stems from Progranulin (GRN) mutation, and exhibits TDP-43 plus ubiquitin protein aggregates in brain. Despite the causative role of GRN haploinsufficiency in FTLD-TDP, the neurobiology of this secreted glycoprotein...

Activity in the fronto-parietal network indicates numerical inductive reasoning beyond calculation: An fMRI study combined with a cognitive model.

Science.gov (United States)

Liang, Peipeng; Jia, Xiuqin; Taatgen, Niels A; Borst, Jelmer P; Li, Kuncheng

2016-05-19

Numerical inductive reasoning refers to the process of identifying and extrapolating the rule involved in numeric materials. It is associated with calculation, and shares the common activation of the fronto-parietal regions with calculation, which suggests that numerical inductive reasoning may correspond to a general calculation process. However, compared with calculation, rule identification is critical and unique to reasoning. Previous studies have established the central role of the fronto-parietal network for relational integration during rule identification in numerical inductive reasoning. The current question of interest is whether numerical inductive reasoning exclusively corresponds to calculation or operates beyond calculation, and whether it is possible to distinguish between them based on the activity pattern in the fronto-parietal network. To directly address this issue, three types of problems were created: numerical inductive reasoning, calculation, and perceptual judgment. Our results showed that the fronto-parietal network was more active in numerical inductive reasoning which requires more exchanges between intermediate representations and long-term declarative knowledge during rule identification. These results survived even after controlling for the covariates of response time and error rate. A computational cognitive model was developed using the cognitive architecture ACT-R to account for the behavioral results and brain activity in the fronto-parietal network.

PROGRANULIN MUTATIONS AFFECTS BRAIN OSCILLATORY ACTIVITY IN FRONTO-TEMPORAL DEMENTIA

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Davide Vito Moretti

2016-02-01

Full Text Available Background: mild cognitive impairment (MCI is a clinical stage indicating a prodromal phase of dementia. This practical concept could be used also for fronto-temporal dementia (FTD. Progranulin (PGRN has been recently recognized as a useful diagnostic biomarker for fronto-temporal lobe degeneration (FTLD due to GRN null mutations. Electroencephalography (EEG is a reliable tool in detecting brain networks changes. The working hypothesis of the present study is that EEG oscillations could detect different modifications among FTLD stages (FTD-MCI versus overt FTD as well as differences between GRN mutation carriers versus non carriers in patients with overt FTD. Methods: EEG in all patients and PGRN dosage in patients with a clear FTD were detected. The cognitive state has been investigated through mini mental state examination (MMSE. Results: MCI-FTD showed a significant lower spectral power in both alpha and theta oscillations as compared to overt FTD. GRN mutations carriers affected by FTLD show an increase in high alpha and decrease in theta oscillations as compared to non-carriers.Conclusion: EEG frequency rhythms are sensible to different stage of FTD and could detect changes in brain oscillatory activity affected by GRN mutations

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction.

Science.gov (United States)

Illa, Miriam; Brito, Verónica; Pla, Laura; Eixarch, Elisenda; Arbat-Plana, Ariadna; Batallé, Dafnis; Muñoz-Moreno, Emma; Crispi, Fatima; Udina, Esther; Figueras, Francesc; Ginés, Silvia; Gratacós, Eduard

2017-10-12

The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR. © 2017 S. Karger AG, Basel.

Structural and functional connectivity underlying grey matter covariance: impact of developmental insult.

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Paquola, Casey; Bennett, Maxwell; Lagopoulos, Jim

2018-05-15

Structural covariance networks (SCNs) may offer unique insights into the developmental impact of childhood maltreatment because they are thought to reflect coordinated maturation of distinct grey matter regions. T1-weighted magnetic resonance images were acquired from 121 young people with emerging mental illness. Diffusion weighted and resting state functional imaging was also acquired from a random subset of the participants (n=62). Ten study-specific SCNs were identified using a whole brain grey matter independent component analysis. The effects of childhood maltreatment and age on average grey matter density and the expression of each SCN were calculated. Childhood maltreatment was linked to age-related decreases in grey matter density across a SCN that overlapped with the default mode and fronto-parietal networks. Resting state functional connectivity and structural connectivity were calculated in the study-specific SCN and across the whole brain. Grey matter covariance was significantly correlated with rsFC across the SCN, and rsFC fully mediated the relationship between grey matter covariance and structural connectivity in the non-maltreated group. A unique association of grey matter covariance with structural connectivity was detected amongst individuals with a history of childhood maltreatment. Perturbation of grey matter development across the default mode and fronto-parietal networks following childhood maltreatment may have significant implications for mental well-being, given the networks' roles in self-referential activity. Cross-modal comparisons suggest reduced grey matter following childhood maltreatment could arise from deficient functional activity earlier in life.

Reward processing dysfunction in ventral striatum and orbitofrontal cortex in Parkinson's disease

NARCIS (Netherlands)

du Plessis, Stéfan; Bossert, Meija; Vink, Matthijs; van den Heuvel, Leigh; Bardien, Soraya; Emsley, Robin; Buckle, Chanelle; Seedat, Soraya; Carr, Jonathan

BACKGROUND: Parkinson's disease is a growing concern as the longevity of the world's population steadily increases. Both ageing and Parkinson's disease have an impact on dopamine neurotransmission. It is therefore important to investigate their relative impact on the fronto-striatal reward system.

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

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Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

2018-01-01

Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

Motivational Tuning of Fronto-Subthalamic Connectivity Facilitates Control of Action Impulses

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Herz, Damian M.; Christensen, Mark S.; Bruggemann, Norbert

2014-01-01

It is critical for survival to quickly respond to environmental stimuli with the most appropriate action. This task becomes most challenging when response tendencies induced by relevant and irrelevant stimulus features are in conflict, and have to be resolved in real time. Inputs from the pre...... for fast and accurate responses. These effects were mediated by enhanced activation and connectivity of the IFG–STN pathway. These results provide causal evidence for a pivotal role of the IFG–STN pathway during action control. Additionally, they suggest a parallel rather than hierarchical organization...

A small number of abnormal brain connections predicts adult autism spectrum disorder.

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Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez, José E; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

2016-04-14

Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.

Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability.

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Damasceno, Alfredo; Damasceno, Benito Pereira; Cendes, Fernando

2016-05-01

MRI studies have shown gray-matter abnormalities in fatigued multiple sclerosis (MS) patients. However, given that physical disability is highly correlated to MS fatigue, it is often difficult to disentangle its effect in these MRI findings. The objective of this research paper is to investigate gray-matter damage in mildly disabled MS patients, addressing which variables were better related to fatigue while controlling for physical disability and depression. Forty-nine relapsing-remitting MS (RRMS) patients and 30 controls underwent MRI (3T). Fatigue was assessed using the Fatigue Severity Scale (FSS). Multivariate logistic regression was performed to assess the contribution of clinical and MRI metrics to fatigue. Statistical analyses were performed controlling for disability and depression. Fatigue was present in 22 (44.9%) patients. FSS score was highly correlated with EDSS (p = 0.00001). Patients with fatigue had lower brain cortical and subcortical gray-matter volumes. However, after controlling for EDSS, only the caudate and the accumbens volumes remained statistically significant. Fatigued MS patients have a global cortical and subcortical gray-matter atrophy that seems largely related to higher physical disability. However, striatal structures involved in effort-reward functions exhibited smaller volumes in fatigued patients, independently of physical disability and depressive symptoms, supporting the theory of cortico-striatal network impairment in MS fatigue. © The Author(s), 2015.

Effects of exercise on depressive behavior and striatal levels of norepinephrine, serotonin and their metabolites in sleep-deprived mice.

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Daniele, Thiago Medeiros da Costa; de Bruin, Pedro Felipe Carvalhedo; Rios, Emiliano Ricardo Vasconcelos; de Bruin, Veralice Meireles Sales

2017-08-14

Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo

DEFF Research Database (Denmark)

Hansen, Henrik H; Weikop, Pia; Mikkelsen, Maria D

2017-01-01

Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener ...... by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo....

Diffusion Tensor Imaging Tractography Reveals Disrupted White Matter Structural Connectivity Network in Healthy Adults with Insomnia Symptoms

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Feng-Mei Lu

2017-11-01

Full Text Available Neuroimaging studies have revealed that insomnia is characterized by aberrant neuronal connectivity in specific brain regions, but the topological disruptions in the white matter (WM structural connectivity networks remain largely unknown in insomnia. The current study uses diffusion tensor imaging (DTI tractography to construct the WM structural networks and graph theory analysis to detect alterations of the brain structural networks. The study participants comprised 30 healthy subjects with insomnia symptoms (IS and 62 healthy subjects without IS. Both the two groups showed small-world properties regarding their WM structural connectivity networks. By contrast, increased local efficiency and decreased global efficiency were identified in the IS group, indicating an insomnia-related shift in topology away from regular networks. In addition, the IS group exhibited disrupted nodal topological characteristics in regions involving the fronto-limbic and the default-mode systems. To our knowledge, this is the first study to explore the topological organization of WM structural network connectivity in insomnia. More importantly, the dysfunctions of large-scale brain systems including the fronto-limbic pathways, salience network and default-mode network in insomnia were identified, which provides new insights into the insomnia connectome. Topology-based brain network analysis thus could be a potential biomarker for IS.

Stimulant treatment history predicts frontal-striatal structural connectivity in adolescents with attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

Schweren, L. J. S.; Hartman, C. A.; Zwiers, M. P.; Heslenfeld, D. J.; Franke, B.; Oosterlaan, J.; Buitelaar, J. K.; Hoekstra, P. J.

Diffusion tensor imaging (DTI) has revealed white matter abnormalities in individuals with attention-deficit/hyperactivity disorder (ADHD). Stimulant treatment may affect such abnormalities. The current study investigated associations between long-term stimulant treatment and white matter integrity

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

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Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

2016-01-01

Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

Measurement of striatal dopamine metabolism with 6-[18F]-fluoro-L-dopa and PET

International Nuclear Information System (INIS)

Kuwabara, Y.; Otsuka, M.; Ichiya, Y.; Yoshikai, T.; Fukumura, T.; Masuda, K.; Kato, M.; Taniwaki, T.

1992-01-01

Striatal dopamine metabolism was studied with 6-[ 18 F]-fluoro-L-dopa ( 18 F-DOPA) and PET. The subjects were normal controls, and patients with Parkinson's disease (PD), parkinsonism, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease (HD) and other cerebral disorders. Cerebral glucose metabolism (CMRGlc) was also measured in these patients. Striatal dopamine metabolism was evaluated by the relative striatal uptake of 18 F-DOPA referring cerebellum (S/C ratio). In normal controls, the S/C ratio was 2.82 ± 0.32 (n = 6, mean ± SD) at 120 min after injection of 18 F-DOPA. The S/C ratio was low in patients with PD, parkinsonism, MSA and PSP compared to the normal controls and thus coincident with the symptoms of parkinsonism due to decrease in striatal dopamine concentration. The decrease in the striatal CMRGlc was also observed in patients with parkinsonism and PSP, and it was preserved in patients with PD, thus representing that more neurons were damaged in patients with parkinsonism and PSP than in patients with PD. A patient with AD having symptoms of parkinsonism also showed a decrease in S/C ratio. In a patient with HD, the striatal CMRGlc sharply decreased, but the S/C ratio was normal. The measurements of striatal dopamine and glucose metabolism with PET may be useful for studying the pathophysiological mechanism in patients with cerebral disorders. (author)

Functional alterations of fronto-limbic circuit and default mode network systems in first-episode, drug-naïve patients with major depressive disorder: A meta-analysis of resting-state fMRI data.

Science.gov (United States)

Zhong, Xue; Pu, Weidan; Yao, Shuqiao

2016-12-01

The neurobiological mechanisms of depression are increasingly being explored through resting-state brain imaging studies. However, resting-state fMRI findings have varied, perhaps because of differences between study populations, which included the disorder course and medication use. The aim of our study was to integrate studies of resting-state fMRI and explore the alterations of abnormal brain activity in first-episode, drug-naïve patients with major depressive disorder. Relevant imaging reports in English were searched, retrieved, selected and subjected to analysis by activation likelihood estimation, a coordinate-based meta-analysis technique (final sample, 31 studies). Coordinates extracted from the original reports were assigned to two categories based on effect directionality. Compared with healthy controls, the first-episode, medication-naïve major depressive disorder patients showed decreased brain activity in the dorsolateral prefrontal cortex, superior temporal gyrus, posterior precuneus, and posterior cingulate, as well as in visual areas within the occipital lobe, lingual gyrus, and fusiform gyrus, and increased activity in the putamen and anterior precuneus. Not every study that has reported relevant data met the inclusion criteria. Resting-state functional alterations were located mainly in the fronto-limbic system, including the dorsolateral prefrontal cortex and putamen, and in the default mode network, namely the precuneus and superior/middle temporal gyrus. Abnormal functional alterations of the fronto-limbic circuit and default mode network may be characteristic of first-episode, drug-naïve major depressive disorder patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroticism is linked to microstructural left-right asymmetry of fronto-limbic fibre tracts in adolescents with opposite effects in boys and girls.

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Madsen, Kathrine Skak; Jernigan, Terry L; Vestergaard, Martin; Mortensen, Erik Lykke; Baaré, William F C

2018-06-01

Neuroticism is a fundamental personality trait that reflects a tendency to experience heightened negative affect and susceptibility to stress. Negative emotionality has been associated with fronto-limbic brain structures and connecting fibre tracts. The major fibre tracts connecting the frontal and limbic brain regions are the cingulum bundle and uncinate fasciculus. We previously found that healthy adults with higher neuroticism scores had decreased left relative to right fractional anisotropy (FA) of the cingulum. Both cingulum and uncinate fasciculus FA increases throughout childhood and into early adulthood. Since adolescence is associated with an increased incidence of anxiety and mood disorders, for which neuroticism is a known risk factor, the question arises whether the association between neuroticism and fronto-limbic white matter microstructure asymmetry is already present in children and adolescents or whether such relationship emerges during this age period. To address this question, we assessed 72 typically-developing 10-to-15 year-olds with diffusion-weighted imaging on a 3 T magnetic resonance scanner. Neuroticism was assessed with the Junior Eysenck Personality Questionnaire. FA and parallel and perpendicular diffusivity measures were extracted for cingulum, uncinate fasciculus as well as the white matter underlying the ventromedial prefrontal cortex. Higher neuroticism scores were associated with decreased left relative to right cingulum FA in boys, while in girls, higher neuroticism scores were associated with increased left relative to right cingulum and ventromedial prefrontal white matter FA, indicating that there are sex differences in the neural correlates of neuroticism. Our findings suggest that the link between neuroticism and frontal-limbic white matter microstructure asymmetry likely predates early adolescence. Future studies need to elucidate the significance of the observed sex differences in the neural correlates of neuroticism

Control of striatal signaling by G protein regulators

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Keqiang eXie

2011-08-01

Full Text Available Signaling via heterotrimeric G proteins plays a crucial role in modulating the responses of striatal neurons that ultimately shape core behaviors mediated by the basal ganglia circuitry, such as reward valuation, habit formation and movement coordination. Activation of G-protein-coupled receptors (GPCRs by extracellular signals activates heterotrimeric G proteins by promoting the binding of GTP to their α subunits. G proteins exert their effects by influencing the activity of key effector proteins in this region, including ion channels, second messenger enzymes and protein kinases. Striatal neurons express a staggering number of GPCRs whose activation results in the engagement of downstream signaling pathways and cellular responses with unique profiles but common molecular mechanisms. Studies over the last decade have revealed that the extent and duration of GPCR signaling are controlled by a conserved protein family named Regulator of G protein Signaling (RGS. RGS proteins accelerate GTP hydrolysis by the α subunits of G proteins, thus promoting deactivation of GPCR signaling. In this review, we discuss the progress made in understanding the roles of RGS proteins in controlling striatal G protein signaling and providing integration and selectivity of signal transmission. We review evidence on the formation of a macromolecular complex between RGS proteins and other components of striatal signaling pathways, their molecular regulatory mechanisms and impacts on GPCR signaling in the striatum obtained from biochemical studies and experiments involving genetic mouse models. Special emphasis is placed on RGS9-2, a member of the RGS family that is highly enriched in the striatum and plays critical roles in drug addiction and motor control.

Fractal analysis of striatal dopamine re-uptake sites

International Nuclear Information System (INIS)

Kuikka, J.T.; Bergstroem, K.A.; Tiihonen, J.; Raesaenen, P.; Karhu, J.

1997-01-01

Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane ([ 123 I]β-CIT). The mean fractal dimension was 1.15±0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19±0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab

Fractal analysis of striatal dopamine re-uptake sites

Energy Technology Data Exchange (ETDEWEB)

Kuikka, J.T.; Bergstroem, K.A. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Tiihonen, J.; Raesaenen, P. [Department of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Karhu, J. [Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio (Finland)

1997-09-01

Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ([{sup 123}I]{beta}-CIT). The mean fractal dimension was 1.15{+-}0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19{+-}0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab.

Diminished fronto-limbic functional connectivity in child sexual offenders.

Science.gov (United States)

Kneer, Jonas; Borchardt, Viola; Kärgel, Christian; Sinke, Christopher; Massau, Claudia; Tenbergen, Gilian; Ponseti, Jorge; Walter, Henrik; Beier, Klaus M; Schiffer, Boris; Schiltz, Kolja; Walter, Martin; Kruger, Tillmann H C

2018-02-22

Child sexual abuse and neglect have been related to an increased risk for the development of a wide range of behavioral, psychological, and sexual problems and increased rates of suicidal behavior. Contrary to the large amount of research focusing on the negative mental health consequences of child sexual abuse, very little is known about the characteristics of child sexual offenders and the neuronal underpinnings contributing to child sexual offending. This study investigates differences in resting state functional connectivity (rs-FC) between non-pedophilic child sexual offenders (N = 20; CSO-P) and matched healthy controls (N = 20; HC) using a seed-based approach. The focus of this investigation of rs-FC in CSO-P was put on prefrontal and limbic regions highly relevant for emotional and behavioral processing. Results revealed a significant reduction of rs-FC between the right centromedial amygdala and the left dorsolateral prefrontal cortex in child sexual offenders compared to controls. Given that, in the healthy brain, there is a strong top-down inhibitory control of prefrontal over limbic structures, these results suggest that diminished rs-FC between the amygdala and the dorsolateral prefrontal cortex and may foster sexual deviance and sexual offending. A profound understanding of these concepts should contribute to a better understanding of the occurrence of child sexual offending, as well as further development of more differentiated and effective interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

The clinical differentiation of fronto-temporal dementia from psychiatric disease

OpenAIRE

Panegyres, Peter K; Graves, Angela; Frencham, Kate AR

2007-01-01

Objective Frontal and/or temporal lobar atrophy (F/TA) is sometimes detected on neuroimaging in patients with psychiatric disease. This observation leads to difficulty in distinguishing whether patients have fronto-temporal dementia (FTD) or psychiatric illness. This paper sets out to develop clinical profiles that might be useful at first presentation to distinguish these two populations. Methods 29 patients were selected from a database of 250 current patients attending young onset dementia...

Tourette's Syndrome: Performance on Tests of Behavioural Inhibition, Working Memory and Gambling

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Crawford, Sarah; Channon, Shelley; Robertson, Mary M.

2005-01-01

Background: Tourette's syndrome (TS) is a neurodevelopmental disorder associated with fronto-striatal dysfunction. There is debate as to the extent to which TS is associated with cognitive impairment. Some authors argue that any impairments seen are attributable to comorbid psychiatric symptomatology, whilst others have suggested that…

Left hemisphere structural connectivity abnormality in pediatric hydrocephalus patients following surgery

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Weihong Yuan

2016-01-01

Edition (ABAS-II]. However, one global network measure (global efficiency and two regional network measures in the insula (local efficiency and between centrality tested at 3-month post-surgery were found to correlate with GAC score tested at 12-month post-surgery with statistical significance (all p < 0.05, corrected. Our data showed that the structural connectivity analysis based on DTI and graph theory was sensitive in detecting both global and regional network abnormality when the analysis was conducted in the left hemisphere only. This approach provides a new avenue enabling the application of advanced neuroimaging analysis methods in quantifying brain damage in children with hydrocephalus surgically treated with programmable shunts.

Dynamic Amygdala Influences on the Fronto-Striatal Brain Mechanisms Involved in Self-Control of Impulsive Desires.

Science.gov (United States)

Krämer, Bernd; Gruber, Oliver

2015-01-01

Human decisions are guided by a variety of motivational factors, such as immediate rewards, long-term goals, and emotions. We used functional magnetic resonance imaging to investigate the dynamic functional interactions between the amygdala, the nucleus accumbens, and the prefrontal cortex that underlie the influences of emotions, desires, and rationality on human decisions. We found that increased functional connectivity between the amygdala and the nucleus accumbens facilitated the approach of an immediate reward in the presence of emotional information. Further, increased functional interactions of the anteroventral prefrontal cortex with the amygdala and the nucleus accumbens were associated with rational decisions in dilemma situations. These findings support previous animal studies by demonstrating that emotional signals from the amygdala and goal-oriented information from prefrontal cortices interface in the nucleus accumbens to guide human decisions and reward-directed actions. © 2015 S. Karger AG, Basel.

Fronto-parietal network oscillations reveal relationship between working memory capacity and cognitive control

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Rasa eGulbinaite

2014-09-01

Full Text Available Executive-attention theory proposes a close relationship between working memory capacity (WMC and cognitive control abilities. However, conflicting results are documented in the literature, with some studies reporting that individual variations in WMC predict differences in cognitive control and trial-to-trial control adjustments (operationalized as the size of the congruency effect and congruency sequence effects, respectively, while others report no WMC-related differences. We hypothesized that brain network dynamics might be a more sensitive measure of WMC-related differences in cognitive control abilities. Thus, in the present study, we measured human EEG during the Simon task to characterize WMC-related differences in the neural dynamics of conflict processing and adaptation to conflict. Although high- and low-WMC individuals did not differ behaviorally, there were substantial WMC-related differences in theta (4-8 Hz and delta (1-3 Hz connectivity in fronto-parietal networks. Group differences in local theta and delta power were relatively less pronounced. These results suggest that the relationship between WMC and cognitive control abilities is more strongly reflected in large-scale oscillatory network dynamics than in spatially localized activity or in behavioral task performance.

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.

Functional connectivity disruption in neonates with prenatal marijuana exposure

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Karen eGrewen

2015-11-01

Full Text Available Prenatal marijuana exposure (PME is linked to neurobehavioral and cognitive impairments, however findings in childhood and adolescence are inconsistent. Type-1 cannabinoid receptors (CB1R modulate fetal neurodevelopment, mediating PME effects on growth of functional circuitry sub-serving behaviors critical for academic and social success. The purpose of this study was to investigate the effects of prenatal marijuana on development of early brain functional circuitry prior to prolonged postnatal environmental influences. We measured resting state functional connectivity during unsedated sleep in infants at 2-6 weeks (+MJ: 20 with PME in combination with nicotine, alcohol, opiates, and/or SSRI; -MJ: 23 exposed to the same other drugs without marijuana, CTR: 20 drug free controls. Connectivity of subcortical seed regions with high fetal CB1R expression was examined. Marijuana-specific differences were observed in insula and three striatal connections: anterior insula – cerebellum, right caudate – cerebellum, right caudate – right fusiform gyrus/inferior occipital, left caudate – cerebellum. +MJ neonates had hypoconnectivity in all clusters compared with -MJ and CTR groups. Altered striatal connectivity to areas involved in visual spatial and motor learning, attention, and in fine-tuning of motor outputs involved in movement and language production may contribute to neurobehavioral deficits reported in this at-risk group. Disrupted anterior insula connectivity may contribute to altered integration of interoceptive signals with salience estimates, motivation, decision-making, and later drug use. Compared with CTRs, both +MJ and -MJ groups demonstrated hyperconnectivity of left amygdala seed with orbital frontal cortex and hypoconnectivity of posterior thalamus seed with hippocampus, suggesting vulnerability to multiple drugs in these circuits.

Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?

OpenAIRE

Hughes, J R; Bowes, S G; Leeman, A L; O'Neill, C J; Deshmukh, A A; Nicholson, P W; Dobbs, S M; Dobbs, R J

1990-01-01

1. Normally during walking, the heel strikes the ground before the forefoot. Abnormalities of foot strike in idiopathic Parkinson's disease may be amenable to therapy: objective measurements may reveal response which is not clinically apparent. Occult changes in foot strike leading to instability may parallel the normal, age-related loss of striatal dopamine. 2. The nature of foot strike was studied using pedobarography in 160 healthy volunteers, aged 15 to 91 years. Although 16% of strikes w...

Episodic Memory Encoding Interferes with Reward Learning and Decreases Striatal Prediction Errors

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Braun, Erin Kendall; Daw, Nathaniel D.

2014-01-01

Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. PMID:25378157

Dopamine D4 Receptor Gene Associated with the Frontal-Striatal-Cerebellar Loop in Children with ADHD: A Resting-State fMRI Study.

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Qian, Andan; Wang, Xin; Liu, Huiru; Tao, Jiejie; Zhou, Jiejie; Ye, Qiong; Li, Jiance; Yang, Chuang; Cheng, Jingliang; Zhao, Ke; Wang, Meihao

2018-03-21

Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.

Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

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Marion Ortner

2016-09-01

Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

Time course of the involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum in emotional prosody perception.

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Marjolijn Hoekert

Full Text Available In verbal communication, not only the meaning of the words convey information, but also the tone of voice (prosody conveys crucial information about the emotional state and intentions of others. In various studies right frontal and right temporal regions have been found to play a role in emotional prosody perception. Here, we used triple-pulse repetitive transcranial magnetic stimulation (rTMS to shed light on the precise time course of involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum. We hypothesized that information would be processed in the right anterior superior temporal gyrus before being processed in the right fronto-parietal operculum. Right-handed healthy subjects performed an emotional prosody task. During listening to each sentence a triplet of TMS pulses was applied to one of the regions at one of six time points (400-1900 ms. Results showed a significant main effect of Time for right anterior superior temporal gyrus and right fronto-parietal operculum. The largest interference was observed half-way through the sentence. This effect was stronger for withdrawal emotions than for the approach emotion. A further experiment with the inclusion of an active control condition, TMS over the EEG site POz (midline parietal-occipital junction, revealed stronger effects at the fronto-parietal operculum and anterior superior temporal gyrus relative to the active control condition. No evidence was found for sequential processing of emotional prosodic information from right anterior superior temporal gyrus to the right fronto-parietal operculum, but the results revealed more parallel processing. Our results suggest that both right fronto-parietal operculum and right anterior superior temporal gyrus are critical for emotional prosody perception at a relatively late time period after sentence onset. This may reflect that emotional cues can still be ambiguous at the beginning of sentences, but become

Time course of the involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum in emotional prosody perception.

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Hoekert, Marjolijn; Bais, Leonie; Kahn, René S; Aleman, André

2008-05-21

In verbal communication, not only the meaning of the words convey information, but also the tone of voice (prosody) conveys crucial information about the emotional state and intentions of others. In various studies right frontal and right temporal regions have been found to play a role in emotional prosody perception. Here, we used triple-pulse repetitive transcranial magnetic stimulation (rTMS) to shed light on the precise time course of involvement of the right anterior superior temporal gyrus and the right fronto-parietal operculum. We hypothesized that information would be processed in the right anterior superior temporal gyrus before being processed in the right fronto-parietal operculum. Right-handed healthy subjects performed an emotional prosody task. During listening to each sentence a triplet of TMS pulses was applied to one of the regions at one of six time points (400-1900 ms). Results showed a significant main effect of Time for right anterior superior temporal gyrus and right fronto-parietal operculum. The largest interference was observed half-way through the sentence. This effect was stronger for withdrawal emotions than for the approach emotion. A further experiment with the inclusion of an active control condition, TMS over the EEG site POz (midline parietal-occipital junction), revealed stronger effects at the fronto-parietal operculum and anterior superior temporal gyrus relative to the active control condition. No evidence was found for sequential processing of emotional prosodic information from right anterior superior temporal gyrus to the right fronto-parietal operculum, but the results revealed more parallel processing. Our results suggest that both right fronto-parietal operculum and right anterior superior temporal gyrus are critical for emotional prosody perception at a relatively late time period after sentence onset. This may reflect that emotional cues can still be ambiguous at the beginning of sentences, but become more apparent half

Abnormal temporal lobe white matter as a biomarker for genetic risk of bipolar disorder.

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Mahon, Katie; Burdick, Katherine E; Ikuta, Toshikazu; Braga, Raphael J; Gruner, Patricia; Malhotra, Anil K; Szeszko, Philip R

2013-01-15

Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD (n=26), unaffected siblings of patients with BD (n=15), and healthy volunteers (n=27) to identify WM biomarkers of genetic risk. The FA differed significantly (punaffected siblings>BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Regulation of dopamine synthesis and release in striatal and prefrontal cortical brain slices

International Nuclear Information System (INIS)

Wolf, M.E.

1986-01-01

Brain slices were used to investigate the role of nerve terminal autoreceptors in modulating dopamine (DA) synthesis and release in striatum and prefrontal cortex. Accumulation of dihydroxyphenylalanine (DOPA) was used as an index of tyrosine hydroxylation in vitro. Nomifensine, a DA uptake blocker, inhibited DOPA synthesis in striatal but not prefrontal slices. This effect was reversed by the DA antagonist sulpiride, suggesting it involved activation of DA receptors by elevated synaptic levels of DA. The autoreceptor-selective agonist EMD-23-448 also inhibited striatal but not prefrontal DOPA synthesis. DOPA synthesis was stimulated in both brain regions by elevated K + , however only striatal synthesis could be further enhanced by sulpiride. DA release was measured by following the efflux of radioactivity from brain slices prelabeled with [ 3 H]-DA. EMD-23-448 and apomorphine inhibited, while sulpiride enhanced, the K + -evoked overflow of radioactivity from both striatal and prefrontal cortical slices. These findings suggest that striatal DA nerve terminals possess autoreceptors which modulate tyrosine hydroxylation as well as autoreceptors which modulate release. Alternatively, one site may be coupled to both functions through distinct transduction mechanisms. In contrast, autoreceptors on prefrontal cortical terminals appear to regulate DA release but not DA synthesis

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

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Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

2010-02-22

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

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Alessandro Bertolino

2010-02-01

Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

HIV infection results in ventral-striatal reward system hypo-activation during cue processing

NARCIS (Netherlands)

Plessis, Stéfan du; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

2015-01-01

OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to

Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: Development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain

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Peng, Yu-Hao; Heintz, Ryan; Wang, Zhuo; Guo, Yumei; Myers, Kalisa; Scremin, Oscar; Maarek, Jean-Michel; Holschneider, Daniel

2014-12-01

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex--changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic

Right hemisphere dominance during spatial selective attention and target detection occurs outside the dorsal fronto-parietal network

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Shulman, Gordon L.; Pope, Daniel L. W.; Astafiev, Serguei V.; McAvoy, Mark P.; Snyder, Abraham Z.; Corbetta, Maurizio

2010-01-01

Spatial selective attention is widely considered to be right hemisphere dominant. Previous functional magnetic resonance imaging (fMRI) studies, however, have reported bilateral blood-oxygenation-level-dependent (BOLD) responses in dorsal fronto-parietal regions during anticipatory shifts of attention to a location (Kastner et al., 1999; Corbetta et al., 2000; Hopfinger et al., 2000). Right-lateralized activity has mainly been reported in ventral fronto-parietal regions for shifts of attention to an unattended target stimulus (Arrington et al., 2000; Corbetta et al., 2000). However, clear conclusions cannot be drawn from these studies because hemispheric asymmetries were not assessed using direct voxel-wise comparisons of activity in left and right hemispheres. Here, we used this technique to measure hemispheric asymmetries during shifts of spatial attention evoked by a peripheral cue stimulus and during target detection at the cued location. Stimulus-driven shifts of spatial attention in both visual fields evoked right-hemisphere dominant activity in temporo-parietal junction (TPJ). Target detection at the attended location produced a more widespread right hemisphere dominance in frontal, parietal, and temporal cortex, including the TPJ region asymmetrically activated during shifts of spatial attention. However, hemispheric asymmetries were not observed during either shifts of attention or target detection in the dorsal fronto-parietal regions (anterior precuneus, medial intraparietal sulcus, frontal eye fields) that showed the most robust activations for shifts of attention. Therefore, right hemisphere dominance during stimulus-driven shifts of spatial attention and target detection reflects asymmetries in cortical regions that are largely distinct from the dorsal fronto-parietal network involved in the control of selective attention. PMID:20219998

Atomoxetine restores the response inhibition network in Parkinson’s disease

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Rae, Charlotte L.; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E.; Jones, P. Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

2016-01-01

stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson’s disease. PMID:27343257

Abnormal Functional Connectivity of Resting State Network Detection Based on Linear ICA Analysis in Autism Spectrum Disorder.

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Bi, Xia-An; Zhao, Junxia; Xu, Qian; Sun, Qi; Wang, Zhigang

2018-01-01

Some functional magnetic resonance imaging (fMRI) researches in autism spectrum disorder (ASD) patients have shown that ASD patients have significant impairment in brain response. However, few researchers have studied the functional structure changes of the eight resting state networks (RSNs) in ASD patients. Therefore, research on statistical differences of RSNs between 42 healthy controls (HC) and 50 ASD patients has been studied using linear independent component analysis (ICA) in this paper. Our researches showed that there was abnormal functional connectivity (FC) of RSNs in ASD patients. The RSNs with the decreased FC and increased FC in ASD patients included default mode network (DMN), central executive network (CEN), core network (CN), visual network (VN), self-referential network (SRN) compared to HC. The RSNs with the increased FC in ASD patients included auditory network (AN), somato-motor network (SMN). The dorsal attention network (DAN) in ASD patients showed the decreased FC. Our findings indicate that the abnormal FC in RSNs extensively exists in ASD patients. Our results have important contribution for the study of neuro-pathophysiological mechanisms in ASD patients.

Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease

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Rosa M Villalba

2011-08-01

Full Text Available Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD. Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011. The concept of tripartite synapses (TS was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a. Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD

Molecular substrates of action control in cortico-striatal circuits.

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Shiflett, Michael W; Balleine, Bernard W

2011-09-15

The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

The role of striatal NMDA receptors in drug addiction.

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Ma, Yao-Ying; Cepeda, Carlos; Cui, Cai-Lian

2009-01-01

The past decade has witnessed an impressive accumulation of evidence indicating that the excitatory amino acid glutamate and its receptors, in particular the N-methyl-D-aspartate (NMDA) receptor subtype, play an important role in drug addiction. Various lines of research using animal models of drug addiction have demonstrated that drug-induced craving is accompanied by significant upregulation of NR2B subunit expression. Furthermore, selective blockade of NR2B-containing NMDA receptors in the striatum, especially in the nucleus accumbens (NAc) can inhibit drug craving and reinstatement. The purpose of this review is to examine the role of striatal NMDA receptors in drug addiction. After a brief description of glutamatergic innervation and NMDA receptor subunit distribution in the striatum, we discuss potential mechanisms to explain the role of striatal NMDA receptors in drug addiction by elucidating signaling cascades involved in the regulation of subunit expression and redistribution, phosphorylation of receptor subunits, as well as activation of intracellular signals triggered by drug experience. Understanding the mechanisms regulating striatal NMDA receptor changes in drug addiction will provide more specific and rational targets to counteract the deleterious effects of drug addiction.

[3H]Dopamine accumulation and release from striatal slices in young, mature and senescent rats

International Nuclear Information System (INIS)

Thompson, J.M.

1981-01-01

Examinations of [ 3 H]dopamine ([ 3 H]DA) release following KCl or amphetamine administration in striatal slices from young (7 month), mature (12 month) and senescent (24 month) Wistar rats showed no age-related changes. Further, the amount of [ 3 H]DA accumulated in the striatal slices showed no changes with age. Thus, previously reported age-related deficits in motor behavior (i.e. rotational) are not produced by changes in striatal DA accumulation or release. (Auth.)

Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models.

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Thiele, Sherri L; Chen, Betty; Lo, Charlotte; Gertler, Tracey S; Warre, Ruth; Surmeier, James D; Brotchie, Jonathan M; Nash, Joanne E

2014-11-01

Parkinsonian symptoms arise due to over-activity of the indirect striatal output pathway, and under-activity of the direct striatal output pathway. l-DOPA-induced dyskinesia (LID) is caused when the opposite circuitry problems are established, with the indirect pathway becoming underactive, and the direct pathway becoming over-active. Here, we define synaptic plasticity abnormalities in these pathways associated with parkinsonism, symptomatic benefits of l-DOPA, and LID. We applied spike-timing dependent plasticity protocols to cortico-striatal synapses in slices from 6-OHDA-lesioned mouse models of parkinsonism and LID, generated in BAC transgenic mice with eGFP targeting the direct or indirect output pathways, with and without l-DOPA present. In naïve mice, bidirectional synaptic plasticity, i.e. LTP and LTD, was induced, resulting in an EPSP amplitude change of approximately 50% in each direction in both striatal output pathways, as shown previously. In parkinsonism and dyskinesia, both pathways exhibited unidirectional plasticity, irrespective of stimulation paradigm. In parkinsonian animals, the indirect pathway only exhibited LTP (LTP protocol: 143.5±14.6%; LTD protocol 177.7±22.3% of baseline), whereas the direct pathway only showed LTD (LTP protocol: 74.3±4.0% and LTD protocol: 63.3±8.7%). A symptomatic dose of l-DOPA restored bidirectional plasticity on both pathways to levels comparable to naïve animals (Indirect pathway: LTP protocol: 124.4±22.0% and LTD protocol: 52.1±18.5% of baseline. Direct pathway: LTP protocol: 140.7±7.3% and LTD protocol: 58.4±6.0% of baseline). In dyskinesia, in the presence of l-DOPA, the indirect pathway exhibited only LTD (LTP protocol: 68.9±21.3% and LTD protocol 52.0±14.2% of baseline), whereas in the direct pathway, only LTP could be induced (LTP protocol: 156.6±13.2% and LTD protocol 166.7±15.8% of baseline). We conclude that normal motor control requires bidirectional plasticity of both striatal outputs

Altered retrieval of melodic information in congenital amusia: insights from dynamic causal modeling of MEG data.

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Albouy, Philippe; Mattout, Jérémie; Sanchez, Gaëtan; Tillmann, Barbara; Caclin, Anne

2015-01-01

Congenital amusia is a neuro-developmental disorder that primarily manifests as a difficulty in the perception and memory of pitch-based materials, including music. Recent findings have shown that the amusic brain exhibits altered functioning of a fronto-temporal network during pitch perception and short-term memory. Within this network, during the encoding of melodies, a decreased right backward frontal-to-temporal connectivity was reported in amusia, along with an abnormal connectivity within and between auditory cortices. The present study investigated whether connectivity patterns between these regions were affected during the short-term memory retrieval of melodies. Amusics and controls had to indicate whether sequences of six tones that were presented in pairs were the same or different. When melodies were different only one tone changed in the second melody. Brain responses to the changed tone in "Different" trials and to its equivalent (original) tone in "Same" trials were compared between groups using Dynamic Causal Modeling (DCM). DCM results confirmed that congenital amusia is characterized by an altered effective connectivity within and between the two auditory cortices during sound processing. Furthermore, right temporal-to-frontal message passing was altered in comparison to controls, with notably an increase in "Same" trials. An additional analysis in control participants emphasized that the detection of an unexpected event in the typically functioning brain is supported by right fronto-temporal connections. The results can be interpreted in a predictive coding framework as reflecting an abnormal prediction error sent by temporal auditory regions towards frontal areas in the amusic brain.

Altered retrieval of melodic information in congenital amusia: Insights from Dynamic Causal Modeling of MEG data

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Philippe eAlbouy

2015-02-01

Full Text Available Congenital amusia is a neuro-developmental disorder that primarily manifests as a difficulty in the perception and memory of pitch-based materials, including music. Recent findings have shown that the amusic brain exhibits altered functioning of a fronto-temporal network during pitch perception and memory. Within this network, during the encoding of melodies, a decreased right backward frontal-to-temporal connectivity was reported in amusia, along with an abnormal connectivity within and between auditory cortices. The present study investigated whether connectivity patterns between these regions were affected during the retrieval of melodies. Amusics and controls had to indicate whether sequences of six tones that were presented in pairs were the same or different. When melodies were different only one tone changed in the second melody. Brain responses to the changed tone in Different trials and to its equivalent (original tone in Same trials were compared between groups using Dynamic Causal Modeling (DCM. DCM results confirmed that congenital amusia is characterized by an altered effective connectivity within and between the two auditory cortices during sound processing. Furthermore, right temporal-to-frontal message passing was altered in comparison to controls, with an increase in Same trials and a decrease in Different trials. An additional analysis in control participants emphasized that the detection of an unexpected event in the typically functioning brain is supported by right fronto-temporal connections. The results can be interpreted in a predictive coding framework as reflecting an abnormal prediction error sent by temporal auditory regions towards frontal areas in the amusic brain.

The neuropsychopharmacology of fronto-executive function: monoaminergic modulation.

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Robbins, T W; Arnsten, A F T

2009-01-01

We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and shifting, reversal learning, and response inhibition are compared in rodents, nonhuman primates, and humans using, in a behavioral context, several techniques ranging from microiontophoresis and single-cell electrophysiological recording to pharmacologic functional magnetic resonance imaging. Dissociable effects of drugs and neurotoxins affecting these monoamine systems suggest new ways of conceptualizing state-dependent fronto-executive functions, with implications for understanding the molecular genetic basis of mental illness and its treatment.

Differentiating neural reward responsiveness in autism versus ADHD

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Gregor Kohls

2014-10-01

Full Text Available Although attention deficit hyperactivity disorders (ADHD and autism spectrum disorders (ASD share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC. A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ASD. Shared dysfunction was characterized by fronto-striato-parietal hypoactivation in both clinical groups when money was at stake. Interestingly, lower neural activation within parietal circuitry was associated with higher autistic traits across the entire study sample. In sum, the present findings concur with the assumption that both ASD and ADHD display distinct and shared neural dysfunction in response to reward.

Chest Abnormalities in Juvenile-Onset Mixed Connective Tissue Disease: Assessment with High-Resolution Computed Tomography and Pulmonary Function Tests

International Nuclear Information System (INIS)

Aaloekken, T.M.; Mynarek, G.; Kolbenstvedt, A.; Lilleby, V.; Foerre, Oe.; Soeyseth, V.; Pripp, A.H.; Johansen, B.

2009-01-01

Background: Mixed connective tissue disease (MCTD) is associated with several chest manifestations. Only a few studies have focused on chest manifestations in juvenile-onset MCTD (jMCTD), and the true prevalence of pulmonary abnormalities on high-resolution computed tomography (HRCT) in these patients is unknown. Purpose: To investigate the occurrence of pulmonary abnormalities in jMCTD with particular reference to interstitial lung disease (ILD), and to evaluate a possible association between pulmonary findings and disease-related variables. Material and Methods: Twenty-four childhood-onset MCTD patients with median disease duration of 10.5 years (range 1-21 years) were investigated in a cross-sectional study by means of HRCT, pulmonary function tests (PFT), and clinical assessment. Results: Discrete ILD was identified in six patients (25%). Median extent of ILD was 2.0%, and all except one of the patients had very mild disease in which 5% or less of the parenchyma was affected. The CT features of fibrosis were mainly microcystic and fine intralobular. The most frequently abnormal PFT was carbon monoxide uptake from the lung, which was abnormal in 33% of the patients. PFT and disease duration were not significantly associated with HRCT findings of ILD. Conclusion: The prevalence of ILD in childhood-onset MCTD patients was lower than previously believed. In most of the patients with ILD, the findings were subtle and without clinical correlation. The results suggest a low extent of ILD in childhood-onset MCTD, even after long-term disease duration

Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

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Wimmer, G Elliott; Braun, Erin Kendall; Daw, Nathaniel D; Shohamy, Daphna

2014-11-05

Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. Copyright © 2014 the authors 0270-6474/14/3414901-12$15.00/0.

In vivo neurochemical characterization of clothianidin induced striatal dopamine release.

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Faro, L R F; Oliveira, I M; Durán, R; Alfonso, M

2012-12-16

Clothianidin (CLO) is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine the neurochemical basis for CLO-induced striatal dopamine release using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of CLO (3.5mM), produced an increase in both spontaneous (2462 ± 627% with respect to basal values) and KCl-evoked (4672 ± 706% with respect to basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium, and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin (TTX). To investigate the involvement of dopamine transporter (DAT), the effect of CLO was observed in presence of nomifensine. The coadministration of CLO and nomifensine produced an additive effect on striatal dopamine release. The results suggest that the effect of CLO on striatal dopamine release is predominantly mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not by a mechanism mediated by dopamine transporter. Published by Elsevier Ireland Ltd.

Fronto-limbic novelty processing in acute psychosis: disrupted relationship with memory performance and potential implications for delusions

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Björn H Schott

2015-06-01

Full Text Available Recent concepts have highlighted the role of the hippocampus and adjacent medial temporal lobe (MTL in positive symptoms like delusions in schizophrenia. In healthy individuals, the MTL is critically involved in the detection and encoding of novel information. Here, we aimed to investigate whether dysfunctional novelty processing by the MTL might constitute a potential neural mechanism contributing to the pathophysiology of delusions, using functional magnetic resonance imaging (fMRI in 16 unmedicated patients with paranoid schizophrenia and 20 age-matched healthy controls. All patients experienced positive symptoms at time of participation. Participants performed a visual target detection task with complex scene stimuli in which novel and familiar rare stimuli were presented randomly intermixed with a standard and a target picture. Presentation of novel relative to familiar images was associated with hippocampal activation in both patients and healthy controls, but only healthy controls showed a positive relationship between novelty-related hippocampal activation and recognition memory performance after 24 hours. Patients, but not controls, showed a robust neural response in the orbitofrontal cortex (OFC during presentation of novel stimuli. Functional connectivity analysis in the patients further revealed a novelty-related increase of functional connectivity of both the hippocampus and the OFC with the rostral anterior cingulate cortex (rACC and the ventral striatum. Notably, delusions correlated positively with the difference of the functional connectivity of the hippocampus versus the OFC with the rACC. Taken together, our results suggest that alterations of fronto-limbic novelty processing may contribute to the pathophysiology of delusions in patients with acute psychosis.

Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

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Kolko, M; Bruhn, T; Christensen, Thomas

1999-01-01

The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10...... no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.......5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards...

Adversity in childhood linked to elevated striatal dopamine function in adulthood.

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Egerton, Alice; Valmaggia, Lucia R; Howes, Oliver D; Day, Fern; Chaddock, Christopher A; Allen, Paul; Winton-Brown, Toby T; Bloomfield, Michael A P; Bhattacharyya, Sagnik; Chilcott, Jack; Lappin, Julia M; Murray, Robin M; McGuire, Philip

2016-10-01

Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63=2.92; P=0.005), and unstable family arrangements (T57=2.80; P=0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Striatal dopamine release codes uncertainty in pathological gambling

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Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

2012-01-01

Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [11C]raclopride to measure...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

Striatal dopamine release codes uncertainty in pathological gambling

DEFF Research Database (Denmark)

Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

2012-01-01

Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C......]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

Elevated functional connectivity in a striatal-amygdala circuit in pathological gamblers.

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Jan Peters

Full Text Available Both substance-based addiction and behavioural impulse control disorders (ICDs have been associated with dysfunctions of the ventral striatum. Recent studies using functional connectivity techniques have revealed increased coupling of the ventral striatum with other limbic regions such as amygdala and orbitofrontal cortex in patients with substance abuse disorders and attention-deficit hyperactivity disorder. In the present study, we re-analyzed previously published functional magnetic resonance imaging data acquired in pathological gamblers and controls during value-based decision-making to investigate whether PG is associated with similar functional connectivity effects. In line with previous studies in other ICDs, we observed reliable increases in functional coupling between striatum and bilateral amygdala in gamblers vs. controls. Implications of these findings for neural models of self-control and addiction are discussed.

Observational learning of new movement sequences is reflected in fronto-parietal coherence.

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Jurjen van der Helden

Full Text Available Mankind is unique in her ability for observational learning, i.e. the transmission of acquired knowledge and behavioral repertoire through observation of others' actions. In the present study we used electrophysiological measures to investigate brain mechanisms of observational learning. Analysis investigated the possible functional coupling between occipital (alpha and motor (mu rhythms operating in the 10 Hz frequency range for translating "seeing" into "doing". Subjects observed movement sequences consisting of six consecutive left or right hand button presses directed at one of two target-buttons for subsequent imitation. Each movement sequence was presented four times, intervened by short pause intervals for sequence rehearsal. During a control task subjects observed the same movement sequences without a requirement for subsequent reproduction. Although both alpha and mu rhythms desynchronized during the imitation task relative to the control task, modulations in alpha and mu power were found to be largely independent from each other over time, arguing against a functional coupling of alpha and mu generators during observational learning. This independence was furthermore reflected in the absence of coherence between occipital and motor electrodes overlaying alpha and mu generators. Instead, coherence analysis revealed a pair of symmetric fronto-parietal networks, one over the left and one over the right hemisphere, reflecting stronger coherence during observation of movements than during pauses. Individual differences in fronto-parietal coherence were furthermore found to predict imitation accuracy. The properties of these networks, i.e. their fronto-parietal distribution, their ipsilateral organization and their sensitivity to the observation of movements, match closely with the known properties of the mirror neuron system (MNS as studied in the macaque brain. These results indicate a functional dissociation between higher order areas for

[Endoscopically assisted fronto-orbitary correction in trigonocephaly].

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Hinojosa, J; Esparza, J; García-Recuero, I; Romance, A

2007-01-01

The development of multidisciplinar Units for Craneofacial Surgery has led to a considerable decrease in morbidity even in the cases of more complex craniofacial syndromes. The use of minimally invasive techniques for the correction of some of these malformations allows the surgeon to minimize the incidence of complications by means of a decrease in the surgical time, blood salvage and shortening of postoperative hospitalization in comparison to conventional craniofacial techniques. Simple and milder craniosynostosis are best approached by these techniques and render the best results. Different osteotomies resembling standard fronto-orbital remodelling besides simple suturectomies and the use of postoperative cranial orthesis may improve the final aesthetic appearence. In endoscopic treatment of trigonocephaly the use of preauricular incisions achieves complete pterional resection, lower lateral orbital osteotomies and successful precoronal frontal osteotomies to obtain long lasting and satisfactory outcomes.

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

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Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

2010-01-01

Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

International Nuclear Information System (INIS)

Dwoskin, L.P.; Peris, J.; Yasuda, R.P.; Philpott, K.; Zahniser, N.R.

1988-01-01

Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [ 3 H]DA, modulation of [ 3 H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [ 3 H]spiperone binding assays. 31 references, 2 figures, 1 table

Abnormal functional connectivity of the amygdala in first-episode and untreated adult major depressive disorder patients with different ages of onset.

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Ye, Jing; Shen, Zonglin; Xu, Xiufeng; Yang, Shuran; Chen, Wei; Liu, Xiaoyan; Lu, Yi; Liu, Fang; Lu, Jin; Li, Na; Sun, Xuejin; Cheng, Yuqi

2017-03-01

Major depressive disorder (MDD) is a common mental disorder with high morbidity. As a part of the limbic system, the amygdala is important in the processing of emotional information. Structural and functional connectivity (FC) abnormalities in the amygdala have been observed in MDD patients. The present study was carried out to identify the features of amygdala FC in adult MDD patients with different ages of onset. Sixty-nine first-episode and untreated MDD patients and 81 healthy controls (CTLs) were included in this study and underwent 3D structural imaging and resting-state functional MRI scanning. The patients and CTLs were divided into two groups according to age of onset: young adult (abnormal resting-state FC with other regions compared with matched controls. However, in old adult patients, compared with matched controls, the right amygdala showed more abnormal changes in the resting-state FC with other regions. MDD patients with different ages of onset showed different changes in the structure and FC of the amygdala. These results might help us to understand the high heterogeneity of MDD.

Multimodal magnetic resonance imaging study of treatment-naïve adults with attention-deficit/hyperactivity disorder.

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Tiffany M Chaim

Full Text Available BACKGROUND: Attention-Deficit/Hiperactivity Disorder (ADHD is a prevalent disorder, but its neuroanatomical circuitry is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI and diffusion tensor imaging (DTI studies available to date have found heterogeneous results. This may be at least partly attributable to some well-known technical limitations of the conventional voxel-based methods usually employed to analyze such neuroimaging data. Moreover, there is a great paucity of imaging studies of adult ADHD to date that have excluded patients with history of use of stimulant medication. METHODS: A newly validated method named optimally-discriminative voxel-based analysis (ODVBA was applied to multimodal (structural and DTI MRI data acquired from 22 treatment-naïve ADHD adults and 19 age- and gender-matched healthy controls (HC. RESULTS: Regarding DTI data, we found higher fractional anisotropy in ADHD relative to HC encompassing the white matter (WM of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus; reductions in trace (a measure of diffusivity in ADHD relative to HC were also found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi. Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter (GM in the right angular gyrus, and increased GM in the right supplementary motor area and superior frontal gyrus. CONCLUSIONS: Our results suggest that adult ADHD is associated

Multimodal Magnetic Resonance Imaging Study of Treatment-Naïve Adults with Attention-Deficit/Hyperactivity Disorder

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Chaim, Tiffany M.; Zhang, Tianhao; Zanetti, Marcus V.; da Silva, Maria Aparecida; Louzã, Mário R.; Doshi, Jimit; Serpa, Mauricio H.; Duran, Fabio L. S.; Caetano, Sheila C.; Davatzikos, Christos; Busatto, Geraldo F.

2014-01-01

Background Attention-Deficit/Hiperactivity Disorder (ADHD) is a prevalent disorder, but its neuroanatomical circuitry is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies available to date have found heterogeneous results. This may be at least partly attributable to some well-known technical limitations of the conventional voxel-based methods usually employed to analyze such neuroimaging data. Moreover, there is a great paucity of imaging studies of adult ADHD to date that have excluded patients with history of use of stimulant medication. Methods A newly validated method named optimally-discriminative voxel-based analysis (ODVBA) was applied to multimodal (structural and DTI) MRI data acquired from 22 treatment-naïve ADHD adults and 19 age- and gender-matched healthy controls (HC). Results Regarding DTI data, we found higher fractional anisotropy in ADHD relative to HC encompassing the white matter (WM) of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus; reductions in trace (a measure of diffusivity) in ADHD relative to HC were also found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi. Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter (GM) in the right angular gyrus, and increased GM in the right supplementary motor area and superior frontal gyrus. Conclusions Our results suggest that adult ADHD is associated with

Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in L-DOPA-treated rats.

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Azkona, Garikoitz; Sagarduy, Ainhoa; Aristieta, Asier; Vazquez, Nerea; Zubillaga, Verónica; Ruíz-Ortega, José Angel; Pérez-Navarro, Esther; Ugedo, Luisa; Sánchez-Pernaute, Rosario

2014-04-01

Dopamine replacement with l-DOPA is the most effective therapy in Parkinson's disease. However, with chronic treatment, half of the patients develop an abnormal motor response including dyskinesias. The specific molecular mechanisms underlying dyskinesias are not fully understood. In this study, we used a well-characterized animal model to first establish the molecular differences between rats that did and did not develop dyskinesias. We then investigated the molecular substrates implicated in the anti-dyskinetic effect of buspirone, a 5HT1A partial agonist. Striatal protein expression profile of dyskinetic animals revealed increased levels of the dopamine receptor (DR)D3, ΔFosB and phospho (p)CREB, as well as an over-activation of the DRD1 signalling pathway, reflected by elevated ratios of phosphorylated DARPP32 and ERK2. Buspirone reduced the abnormal involuntary motor response in dyskinetic rats in a dose-dependent fashion. Buspirone (4 mg/kg) dramatically reduced the presence and severity of dyskinesias (by 83%) and normalized DARPP32 and ERK2 phosphorylation ratios, while the increases in DRD3, ΔFosB and pCREB observed in dyskinetic rats were not modified. Pharmacological experiments combining buspirone with 5HT1A and DRD3 antagonists confirmed that normalization of both pDARPP32 and pERK2 is required, but not sufficient, for blocking dyskinesias. The correlation between pDARPP32 ratio and dyskinesias was significant but not strong, pointing to the involvement of convergent factors and signalling pathways. Our results suggest that in dyskinetic rats DRD3 striatal over-expression could be instrumental in the activation of DRD1-downstream signalling and demonstrate that the anti-dyskinetic effect of buspirone in this model is correlated with DRD1 pathway normalization. Copyright © 2013 Elsevier Ltd. All rights reserved.

Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

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Stéphanie Bissonnette

Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

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.

Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

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Nicolai Franzmeier

2017-08-01

Full Text Available Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44. Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education and better maintenance of memory in mild cognitive impairment (MCI. Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC and in an independent validation sample (23 MCI/32 HC. Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN, but positively correlated with the dorsal-attention network (DAN. Greater education predicted stronger LFC-DMN-connectivity (anti-correlation and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.

Analyzing the association between functional connectivity of the brain and intellectual performance

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Pamplona, Gustavo S. P.; Santos Neto, Gérson S.; Rosset, Sara R. E.; Rogers, Baxter P.; Salmon, Carlos E. G.

2015-01-01

Measurements of functional connectivity support the hypothesis that the brain is composed of distinct networks with anatomically separated nodes but common functionality. A few studies have suggested that intellectual performance may be associated with greater functional connectivity in the fronto-parietal network and enhanced global efficiency. In this fMRI study, we performed an exploratory analysis of the relationship between the brain's functional connectivity and intelligence scores derived from the Portuguese language version of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of 29 people, born and raised in Brazil. We examined functional connectivity between 82 regions, including graph theoretic properties of the overall network. Some previous findings were extended to the Portuguese-speaking population, specifically the presence of small-world organization of the brain and relationships of intelligence with connectivity of frontal, pre-central, parietal, occipital, fusiform and supramarginal gyrus, and caudate nucleus. Verbal comprehension was associated with global network efficiency, a new finding. PMID:25713528

Analyzing the association between functional connectivity of the brain and intellectual performance

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Gustavo Santo Pedro Pamplona

2015-02-01

Full Text Available Measurements of functional connectivity support the hypothesis that the brain is composed of distinct networks with anatomically separated nodes but common functionality. A few studies have suggested that intellectual performance may be associated with greater functional connectivity in the fronto-parietal network and enhanced global efficiency. In this fMRI study, we performed an exploratory analysis of the relationship between the brain's functional connectivity and intelligence scores derived from the Portuguese language version of the Wechsler Adult Intelligence Scale (WAIS-III in a sample of 29 people, born and raised in Brazil. We examined functional connectivity between 82 regions, including graph theoretic properties of the overall network. Some previous findings were extended to the Portuguese-speaking population, specifically the presence of small-world organization of the brain and relationships of intelligence with connectivity of frontal, pre-central, parietal, occipital, fusiform and supramarginal gyrus and caudate nucleus. Verbal comprehension was associated with global network efficiency, a new finding.

Recognition memory span in autopsy-confirmed Dementia with Lewy Bodies and Alzheimer's Disease.

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Salmon, David P; Heindel, William C; Hamilton, Joanne M; Vincent Filoteo, J; Cidambi, Varun; Hansen, Lawrence A; Masliah, Eliezer; Galasko, Douglas

2015-08-01

Evidence from patients with amnesia suggests that recognition memory span tasks engage both long-term memory (i.e., secondary memory) processes mediated by the diencephalic-medial temporal lobe memory system and working memory processes mediated by fronto-striatal systems. Thus, the recognition memory span task may be particularly effective for detecting memory deficits in disorders that disrupt both memory systems. The presence of unique pathology in fronto-striatal circuits in Dementia with Lewy Bodies (DLB) compared to AD suggests that performance on the recognition memory span task might be differentially affected in the two disorders even though they have quantitatively similar deficits in secondary memory. In the present study, patients with autopsy-confirmed DLB or AD, and Normal Control (NC) participants, were tested on separate recognition memory span tasks that required them to retain increasing amounts of verbal, spatial, or visual object (i.e., faces) information across trials. Results showed that recognition memory spans for verbal and spatial stimuli, but not face stimuli, were lower in patients with DLB than in those with AD, and more impaired relative to NC performance. This was despite similar deficits in the two patient groups on independent measures of secondary memory such as the total number of words recalled from long-term storage on the Buschke Selective Reminding Test. The disproportionate vulnerability of recognition memory span task performance in DLB compared to AD may be due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes. Assessment of recognition memory span may contribute to the ability to distinguish between DLB and AD relatively early in the course of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adrenergic receptor-mediated modulation of striatal firing patterns.

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Ohta, Hiroyuki; Kohno, Yu; Arake, Masashi; Tamura, Risa; Yukawa, Suguru; Sato, Yoshiaki; Morimoto, Yuji; Nishida, Yasuhiro; Yawo, Hiromu

2016-11-01

Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α 1 -AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α 1 -ARs work in opposition controlling the striatal firing initiation and the firing increment. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Disturbed Interhemispheric Functional Connectivity Rather than Structural Connectivity in Irritable Bowel Syndrome

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Rongfeng Qi

2016-12-01

Full Text Available Neuroimaging studies have demonstrated that irritable bowel syndrome (IBS—a relapsing functional bowel disorder—presents with disrupted brain connections. However, little is known about the alterations of interhemispheric functional connectivity and underlying structural connectivity in IBS. This study combined resting-state functional magnetic resonance imaging (MRI and diffusion tensor imaging (DTI to investigate changes in interhemispheric coordination in IBS patients. Resting-state functional and structural magnetic resonance images were acquired from 65 IBS patients and 67 healthy controls (matched for age, sex and educational level. Interhemispheric voxel-mirrored homotopic connectivity (VMHC was calculated and compared between groups. Homotopic regions showing abnormal VMHC in patients were targeted as regions of interest for analysis of DTI tractography. The fractional anisotropy, fiber number, and fiber length were compared between groups. Statistical analysis was also performed by including anxiety and depression as covariates to evaluate their effect. A Pearson correlation analysis between abnormal interhemispheric connectivity and clinical indices of IBS patients was performed. Compared to healthy controls, IBS patients had higher interhemispheric functional connectivity between bilateral thalami, cuneus, posterior cingulate cortices, lingual gyri and inferior occipital/cerebellum lobes, as well as lower interhemispheric functional connectivity between bilateral ventral anterior cingulate cortices (vACC and inferior parietal lobules (IPL. The inclusion of anxiety and depression as covariates abolished VMHC difference in vACC. Microstructural features of white matter tracts connecting functionally abnormal regions did not reveal any differences between the groups. VMHC values in vACC negatively correlated with the quality of life scores of patients. In conclusion, this study provides preliminary evidence of the disrupted

Emotion Regulation and Complex Brain Networks: Association Between Expressive Suppression and Efficiency in the Fronto-Parietal Network and Default-Mode Network

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Junhao Pan

2018-03-01

Full Text Available Emotion regulation (ER refers to the “implementation of a conscious or non-conscious goal to start, stop or otherwise modulate the trajectory of an emotion” (Etkin et al., 2015. Whereas multiple brain areas have been found to be involved in ER, relatively little is known about whether and how ER is associated with the global functioning of brain networks. Recent advances in brain connectivity research using graph-theory based analysis have shown that the brain can be organized into complex networks composed of functionally or structurally connected brain areas. Global efficiency is one graphic metric indicating the efficiency of information exchange among brain areas and is utilized to measure global functioning of brain networks. The present study examined the relationship between trait measures of ER (expressive suppression (ES and cognitive reappraisal (CR and global efficiency in resting-state functional brain networks (the whole brain network and ten predefined networks using structural equation modeling (SEM. The results showed that ES was reliably associated with efficiency in the fronto-parietal network and default-mode network. The finding advances the understanding of neural substrates of ER, revealing the relationship between ES and efficient organization of brain networks.

Altered resting-state functional connectivity of the frontal-striatal reward system in social anxiety disorder.

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Manning, Joshua; Reynolds, Gretchen; Saygin, Zeynep M; Hofmann, Stefan G; Pollack, Mark; Gabrieli, John D E; Whitfield-Gabrieli, Susan

2015-01-01

We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.

Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder.

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Noordermeer, Siri D S; Luman, Marjolein; Greven, Corina U; Veroude, Kim; Faraone, Stephen V; Hartman, Catharina A; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan K; Heslenfeld, Dirk J; Oosterlaan, Jaap

2017-11-01

Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Three groups, 16 ± 3.5 years of age (mean ± SD; range 7-29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome.

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Larsen, Kit Melissa; Mørup, Morten; Birknow, Michelle Rosgaard; Fischer, Elvira; Hulme, Oliver; Vangkilde, Anders; Schmock, Henriette; Baaré, William Frans Christiaan; Didriksen, Michael; Olsen, Line; Werge, Thomas; Siebner, Hartwig R; Garrido, Marta I

2018-01-30

22q11.2 deletion syndrome (22q11.2DS) is one of the most common copy number variants and confers a markedly increased risk for schizophrenia. As such, 22q11.2DS is a homogeneous genetic liability model which enables studies to delineate functional abnormalities that may precede disease onset. Mismatch negativity (MMN), a brain marker of change detection, is reduced in people with schizophrenia compared to healthy controls. Using dynamic causal modelling (DCM), previous studies showed that top-down effective connectivity linking the frontal and temporal cortex is reduced in schizophrenia relative to healthy controls in MMN tasks. In the search for early risk-markers for schizophrenia we investigated the neural basis of change detection in a group with 22q11.2DS. We recorded high-density EEG from 19 young non-psychotic 22q11.2 deletion carriers, as well as from 27 healthy non-carriers with comparable age distribution and sex ratio, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Despite finding no significant reduction in the MMN responses, whole-scalp spatiotemporal analysis of responses to the tones revealed a greater fronto-temporal N1 component in the 22q11.2 deletion carriers. DCM showed reduced intrinsic connection within right primary auditory cortex as well as in the top-down, connection from the right inferior frontal gyrus to right superior temporal gyrus for 22q11.2 deletion carriers although not surviving correction for multiple comparison. We discuss these findings in terms of reduced adaptation and a general increased sensitivity to tones in 22q11.2DS. Copyright © 2018. Published by Elsevier B.V.

Baseline frontostriatal-limbic connectivity predicts reward-based memory formation.

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Hamann, Janne M; Dayan, Eran; Hummel, Friedhelm C; Cohen, Leonardo G

2014-12-01

Reward mediates the acquisition and long-term retention of procedural skills in humans. Yet, learning under rewarded conditions is highly variable across individuals and the mechanisms that determine interindividual variability in rewarded learning are not known. We postulated that baseline functional connectivity in a large-scale frontostriatal-limbic network could predict subsequent interindividual variability in rewarded learning. Resting-state functional MRI was acquired in two groups of subjects (n = 30) who then trained on a visuomotor procedural learning task with or without reward feedback. We then tested whether baseline functional connectivity within the frontostriatal-limbic network predicted memory strength measured immediately, 24 h and 1 month after training in both groups. We found that connectivity in the frontostriatal-limbic network predicted interindividual variability in the rewarded but not in the unrewarded learning group. Prediction was strongest for long-term memory. Similar links between connectivity and reward-based memory were absent in two control networks, a fronto-parieto-temporal language network and the dorsal attention network. The results indicate that baseline functional connectivity within the frontostriatal-limbic network successfully predicts long-term retention of rewarded learning. © 2014 Wiley Periodicals, Inc.

Transient and steady-state selection in the striatal microcircuit

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Adam eTomkins

2014-01-01

Full Text Available Although the basal ganglia have been widely studied and implicated in signal processing and action selection, little information is known about the active role the striatal microcircuit plays in action selection in the basal ganglia-thalamo-cortical loops. To address this knowledge gap we use a large scale three dimensional spiking model of the striatum, combined with a rate coded model of the basal ganglia-thalamo-cortical loop, to asses the computational role the striatum plays in action selection. We identify a robust transient phenomena generated by the striatal microcircuit, which temporarily enhances the difference between two competing cortical inputs. We show that this transient is sufficient to modulate decision making in the basal ganglia-thalamo-cortical circuit. We also find that the transient selection originates from a novel adaptation effect in single striatal projection neurons, which is amenable to experimental testing. Finally, we compared transient selection with models implementing classical steady-state selection. We challenged both forms of model to account for recent reports of paradoxically enhanced response selection in Huntington's Disease patients. We found that steady-state selection was uniformly impaired under all simulated Huntington's conditions, but transient selection was enhanced given a sufficient Huntington's-like increase in NMDA receptor sensitivity. Thus our models provide an intriguing hypothesis for the mechanisms underlying the paradoxical cognitive improvements in manifest Huntington's patients.

Effort-Based Reinforcement Processing and Functional Connectivity Underlying Amotivation in Medicated Patients with Depression and Schizophrenia.

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Park, Il Ho; Lee, Boung Chul; Kim, Jae-Jin; Kim, Joong Il; Koo, Min-Seung

2017-04-19

Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso-striatal-prefrontal pathway. We found that integrated reward and effort values of low effort-positive reinforcement and high effort-negative reinforcement were behaviorally anticipated and represented in the putamen and medial orbitofrontal cortex activities. Patients with schizophrenia and depression did not show anticipation-related and work-related reaction time reductions, respectively. Greater amotivation severity correlated with smaller work-related putamen activity changes according to reward type in schizophrenia and effort level in depression. Patients with schizophrenia showed feedback-related putamen hyperactivity of low effort compared with healthy controls and depressed patients. The strength of medial orbitofrontal-striatal functional connectivity predicted work-related reaction time reduction of high effort negative reinforcement in healthy controls and amotivation severity in both patients with schizophrenia and those with depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared with healthy controls and patients with schizophrenia. These results indicate that amotivation in depression and schizophrenia involves different pathophysiology in the prefrontal-striatal circuitry. SIGNIFICANCE STATEMENT Amotivation is present in both depression and schizophrenia

Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers.

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Brasted, P J; Döbrössy, M D; Robbins, T W; Dunnett, S B

1998-08-01

The dorsal striatum plays a crucial role in mediating voluntary movement. Excitotoxic striatal lesions in rats have previously been shown to impair the initiation but not the execution of movement in a choice reaction time task in an automated lateralised nose-poke apparatus (the "nine-hole box"). Conversely, when a conceptually similar reaction time task has been applied in a conventional operant chamber (or "Skinner box"), striatal lesions have been seen to impair the execution rather than the initiation of the lateralised movement. The present study was undertaken to compare directly these two results by training the same group of rats to perform a choice reaction time task in the two chambers and then comparing the effects of a unilateral excitotoxic striatal lesion in both chambers in parallel. Particular attention was paid to adopting similar parameters and contingencies in the control of the task in the two test chambers. After striatal lesions, the rats showed predominantly contralateral impairments in both tasks. However, they showed a deficit in reaction time in the nine-hole box but an apparent deficit in response execution in the Skinner box. This finding confirms the previous studies and indicates that differences in outcome are not simply attributable to procedural differences in the lesions, training conditions or tasks parameters. Rather, the pattern of reaction time deficit after striatal lesions depends critically on the apparatus used and the precise response requirements for each task.

Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.

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Karpuk, Nikolay; Burkovetskaya, Maria; Kielian, Tammy

2012-07-01

Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive G(i) increments vs. V(m), respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i), and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting G(i) was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation.

Cerebellar influence on motor cortex plasticity: behavioral implications for Parkinson’s disease

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Asha eKishore

2014-05-01

Full Text Available Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration and normal functioning of these net works. Strong topography-specific connections among the basal ganglia, cerebellum and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other’s plastic responses and functions. The defective striatal signaling in Parkinson’s disease (PD could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD.

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

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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)

Elevated Striatal Reactivity Across Monetary and Social Rewards in Bipolar I Disorder

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Dutra, Sunny J.; Cunningham, William A.; Kober, Hedy; Gruber, June

2016-01-01

Bipolar disorder (BD) is associated with increased reactivity to rewards and heightened positive affectivity. It is less clear to what extent this heightened reward sensitivity is evident across contexts and what the associated neural mechanisms might be. The present investigation employed both a monetary and social incentive delay task among adults with remitted BD type I (N=24) and a healthy non-psychiatric control group (HC; N=25) using fMRI. Both whole-brain and region-of-interest analyses revealed elevated ventral and dorsal striatal reactivity across monetary and social reward receipt, but not anticipation, in the BD group. Post-hoc analyses further suggested that greater striatal reactivity to reward receipt across monetary and social reward tasks predicted decreased self-reported positive affect when anticipating subsequent rewards in the HC, but not BD, group. Results point toward elevated striatal reactivity to reward receipt as a potential neural mechanism of reward reactivity. PMID:26390194

Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

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Cherubini, Marta; Ginés, Silvia

2017-01-01

Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

Distinctive striatal dopamine signaling after dieting and gastric bypass.

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Hankir, Mohammed K; Ashrafian, Hutan; Hesse, Swen; Horstmann, Annette; Fenske, Wiebke K

2015-05-01

Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

A new framework for cortico-striatal plasticity: behavioural theory meets in vitro data at the reinforcement-action interface.

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Kevin N Gurney

2015-01-01

Full Text Available Operant learning requires that reinforcement signals interact with action representations at a suitable neural interface. Much evidence suggests that this occurs when phasic dopamine, acting as a reinforcement prediction error, gates plasticity at cortico-striatal synapses, and thereby changes the future likelihood of selecting the action(s coded by striatal neurons. But this hypothesis faces serious challenges. First, cortico-striatal plasticity is inexplicably complex, depending on spike timing, dopamine level, and dopamine receptor type. Second, there is a credit assignment problem-action selection signals occur long before the consequent dopamine reinforcement signal. Third, the two types of striatal output neuron have apparently opposite effects on action selection. Whether these factors rule out the interface hypothesis and how they interact to produce reinforcement learning is unknown. We present a computational framework that addresses these challenges. We first predict the expected activity changes over an operant task for both types of action-coding striatal neuron, and show they co-operate to promote action selection in learning and compete to promote action suppression in extinction. Separately, we derive a complete model of dopamine and spike-timing dependent cortico-striatal plasticity from in vitro data. We then show this model produces the predicted activity changes necessary for learning and extinction in an operant task, a remarkable convergence of a bottom-up data-driven plasticity model with the top-down behavioural requirements of learning theory. Moreover, we show the complex dependencies of cortico-striatal plasticity are not only sufficient but necessary for learning and extinction. Validating the model, we show it can account for behavioural data describing extinction, renewal, and reacquisition, and replicate in vitro experimental data on cortico-striatal plasticity. By bridging the levels between the single synapse and

Reduced Striatal Dopamine Transporters in People with Internet Addiction Disorder

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Haifeng Hou

2012-01-01

Full Text Available In recent years, internet addiction disorder (IAD has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT levels measured by T99mc-TRODAT-1 single photon emission computed tomography (SPECT brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V and weight (W of bilateral corpus striatum as well as the T99mc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and the V, W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders.

Longitudinal changes in task-evoked brain responses in Parkinson’s disease patients with and without mild cognitive impairment

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Urban eEkman

2014-07-01

Full Text Available Cognitive deficits are common in Parkinson’s disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson’s disease patients with and without mild cognitive impairment.Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up compared 28 patients with Parkinson’s disease without mild cognitive impairment with 11 patients with Parkinson’s disease and mild cognitive impairment. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with mild cognitive impairment under-recruited bilateral medial prefrontal cortex, right putamen, and lateral parietal cortex at both time-points (main effect of group: p<0.001, uncorrected. Critically, a significant group-by-time interaction effect (p<0.001, uncorrected was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson’s disease and mild cognitive impairment between baseline and follow-up, while patients without mild cognitive impairment were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI.Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson’s disease and mild cognitive impairment. The longitudinal evolution of mild cognitive impairment in Parkinson’s disease translates into additional task

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

Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex and substantia nigra.

Science.gov (United States)

Snyder-Keller, A; Costantini, L C; Graber, D J

2001-01-01

Organotypic cultures of fetal or early postnatal striatum were used to assess striatal patch formation and maintenance in the presence or absence of dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in static culture on clear membrane inserts in Dulbecco's modified Eagle's medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day 12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex, which produced a dense dopaminergic innervation and a modest cortical innervation. Donors of striatal and cortical tissue were previously injected with bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal neurons destined to populate the patch compartment of the striatum. Patches of BrdU-immunoreactive cells were maintained in organotypic cultures of late prenatal (embryonic days 20-22) or early postnatal striatum in the absence of nigral dopaminergic or cortical glutamatergic influences. In slices taken from embryonic day 19 fetuses prior to the time of in vivo patch formation, patches were observed to form after 10 days in vitro, in 39% of nigral-striatal co-cultures compared to 6% of striatal slices cultured alone or in the presence of cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase immunoreactivity, were observed in the majority of nigral-striatal co-cultures. Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch distribution in nearly all cultures, which developed in embryonic day 19 cultures after at least six days in vitro. These findings indicate that striatal patch/matrix organization is maintained in organotypic culture, and can be induced to form in vitro in striatal slices removed from fetuses prior to the time of in vivo patch formation. Furthermore, dopaminergic innervation from co-cultured pieces of ventral mesencephalon enhances patch

Atomoxetine restores the response inhibition network in Parkinson's disease.

Science.gov (United States)

Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

2016-08-01

time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson's disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Electrophysiological signatures of atypical intrinsic brain connectivity networks in autism

Science.gov (United States)

Shou, Guofa; Mosconi, Matthew W.; Wang, Jun; Ethridge, Lauren E.; Sweeney, John A.; Ding, Lei

2017-08-01

Objective. Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network. Approach. Connectivity within individual ICNs (measured by spectral power) and between ICNs (measured by coherence) were examined at four canonical frequency bands via a time-frequency independent component analysis on high-density EEG, which were recorded from 20 ASD and 20 typical developing (TD) subjects during an eyes-closed resting state. Main results. Among twelve identified electrophysiological ICNs, individuals with ASD showed hyper-connectivity in individual ICNs and hypo-connectivity between ICNs. Functional connectivity alterations in ASD were more severe in the frontal lobe and the default mode network (DMN) and at low frequency bands. These functional connectivity measures also showed abnormal age-related associations in ICNs related to frontal, temporal and motor regions in ASD. Significance. Our findings suggest that ASD is characterized by the opposite directions of abnormalities (i.e. hypo- and hyper-connectivity) in the hierarchical structure of the whole brain network, with more impairments in the frontal lobe and the DMN at low frequency bands, which are critical for top-down control of sensory systems, as well as for both cognition and social skills.

The Functional Organisation of the Fronto-Temporal Language System: Evidence from Syntactic and Semantic Ambiguity

Science.gov (United States)

Rodd, Jennifer M.; Longe, Olivia A.; Randall, Billi; Tyler, Lorraine K.

2010-01-01

Spoken language comprehension is known to involve a large left-dominant network of fronto-temporal brain regions, but there is still little consensus about how the syntactic and semantic aspects of language are processed within this network. In an fMRI study, volunteers heard spoken sentences that contained either syntactic or semantic ambiguities…

Striatal hypometabolism in premanifest and manifest Huntington's disease patients

Energy Technology Data Exchange (ETDEWEB)

Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

2016-11-15

To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

Corticolimbic functional connectivity in adolescents with bipolar disorder.

Directory of Open Access Journals (Sweden)

Fei Wang

Full Text Available Convergent evidence supports regional dysfunction within a corticolimbic neural system that subserves emotional processing and regulation in adolescents and adults with bipolar disorder (BD, with abnormalities prominent within the amygdala and its major anterior paralimbic cortical connection sites including ventral anterior cingulate, orbitofrontal, insular and temporopolar cortices. Recent studies of adults with BD demonstrate abnormalities in the functional connectivity between the amygdala and anterior paralimbic regions suggesting an important role for the connections between these regions in the development of the disorder. This study tests the hypothesis that these functional connectivity abnormalities are present in adolescents with BD. Fifty-seven adolescents, twenty-one with BD and thirty-six healthy comparison (HC adolescents, participated in functional magnetic resonance imaging while processing emotional face stimuli. The BD and HC groups were compared in the strength of functional connectivity from amygdala to the anterior paralimbic cortical regions, and explored in remaining brain regions. Functional connectivity was decreased in the BD group, compared to the HC group, during processing of emotional faces in ventral anterior cingulate (VACC, orbitofrontal, insular and temporopolar cortices (p<0.005. Orbitofrontal and VACC findings for the happy condition, and additionally right insula for the neutral condition, survived multiple comparison correction. Exploratory analyses did not reveal additional regions of group differences. This study provides evidence for decreased functional connectivity between the amygdala and anterior paralimbic cortices in adolescents with BD. This suggests that amygdala-anterior paralimbic connectivity abnormalities are early features of BD that emerge at least by adolescence in the disorder.

Aspectos neuropsicológicos do transtorno obsessivo-compulsivo

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Leonardo Fontenelle

2001-10-01

Full Text Available Neuropsychology is contributing to elucidate the nature of brain dysfunction associated with obsessive-compulsive disorder (OCD. Neuropsychological studies of individuals with subclinical and clinical obsessive-compulsive symptoms are reviewed here. It was observed that OCD patients may display impaired "reality monitoring", memory for actions, non-verbal memory, visuo-spatial abilities, and executive functions. Some specific neuropsychological findings are associated with different clinical characteristics such as gender, duration of disease, severity of symptoms, and response to drug treatment. Comparative studies suggest that the neuropsychological dysfunction associated with OCD is significantly different from that seen in major depressive disorder or schizophrenia. However, many similarities were observed between patients with OCD and patients with social phobia, body dysmorphic disorder, and trichotillomania. Furthermore, studies suggest that certain neurochemical abnormalities may underlie particular neuropsychological dysfunctions found in OCD. Despite many heterogeneous results, the reviewed data seems to support the pathophysiological theory centered in the dysfunction of the fronto-striatal circuits in OCD.

Centrality of striatal cholinergic transmission in basal ganglia function

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Paola eBonsi

2011-02-01

Full Text Available Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction.Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson’s disease and dystonia.Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

Amygdala and dorsal anterior cingulate connectivity during an emotional working memory task in borderline personality disorder patients with interpersonal trauma history

Directory of Open Access Journals (Sweden)

Annegret eKrause-Utz

2014-10-01

Full Text Available Emotion dysregulation and stress-related cognitive disturbances including dissociation are key features of Borderline Personality Disorder (BPD. Previous research suggests that amygdala hyperreactivity along with a failure to activate frontal brain areas implicated in inhibitory control (e.g., anterior cingulate cortex, ACC may underlie core symptoms of BPD. However, studies investigating interactions of fronto-limbic brain areas during cognitive inhibition of interfering emotional stimuli in BPD patients are still needed. Moreover, very little is known about how dissociation modulates fronto-limbic connectivity during emotional distraction in BPD. We used Psychophysiological Interaction (PPI to analyse amygdala and dorsal ACC (dACC connectivity in 22 un-medicated BPD patients with interpersonal trauma history and 22 healthy controls (HC, who performed a working memory task, while either no distractors or neutral vs. negative interpersonal pictures were presented. A measure of state dissociation was used to predict amygdala as well as dACC connectivity in the BPD group. During emotional distraction, both groups showed disrupted amygdala connectivity with dorsolateral prefrontal cortex, which was more pronounced in the BPD group. Patients further showed stronger amygdala-hippocampus and dACC-insula connectivity during emotional interference and demonstrated a stronger coupling of the dACC with nodes of the default mode network (e.g. posterior cingulate. Dissociation positively predicted amygdala-dACC connectivity and negatively predicted dACC connectivity with insula and posterior cingulate. Our results suggest aberrant connectivity patterns involving brain regions associated with emotion processing, salience detection, and self-referential processes, which may be modulated by dissociation, in BPD. Findings might be related to difficulties in shifting attention away from external (distracting emotional stimuli as well as internal emotional states

Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: state versus trait vulnerability markers of depression in bipolar disorder.

Science.gov (United States)

Versace, Amelia; Thompson, Wesley K; Zhou, Donli; Almeida, Jorge R C; Hassel, Stefanie; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2010-03-01

Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. The BD versus HC showed significantly greater right amygdala-OFC FC (p relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001). In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC-FA relationships in BD and HC require further study. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

International Nuclear Information System (INIS)

Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

1988-01-01

We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

Abnormal resting-state functional connectivity study in unilateral pulsatile tinnitus patients with single etiology: A seed-based functional connectivity study

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Lv, Han [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Neuroradiology Division, Department of Radiology, Stanford University, CA, 94305 (United States); Zhao, Pengfei [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Liu, Zhaohui [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Li, Rui; Zhang, Ling; Wang, Peng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Yan, Fei [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Liu, Liheng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Wang, Guopeng; Zeng, Rong [Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Li, Ting [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Dong, Cheng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Gong, Shusheng, E-mail: gongss@ccmu.edu.cn [Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Wang, Zhenchang, E-mail: cjr.wzhch@vip.163.com [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China)

2016-11-15

Objective: Previous studies demonstrated altered regional neural activations in several brain areas in patients with pulsatile tinnitus (PT), especially indicating an important role of posterior cingulate cortex (PCC). However, few studies focused on the degree of functional connectivity (FC) of this area in PT patients. In this study, we will compare the FC of PCC in patients affected with this condition and normal controls by using resting-state functional magnetic resonance imaging (fMRI). Methods: Structural and functional MRI data were obtained from 36 unilateral PT patients with single etiology and 36 matched healthy controls. FC feature of the region of interest (PCC) were characterized using a seed-based correlation method with the voxels in the whole-brain. Results: Compared with healthy controls, patients showed significant decreased FC to the right middle temporal gyrus (MTG), right thalamus and bilateral insula. By contrast, PCC demonstrated increased functional connectivity between the precuneus, bilateral inferior parietal lobule and middle occipital gyrus. We also found correlations between the disease duration of PT and FC of PCC-right MTG (r = −0.616, p < 0.001). Conclusions: Unilateral PT patients could have abnormal FC to the PCC bilaterally in the brain. PCC, as a highly integrated brain area, is an example of nucleus that was involved in mediation between different neural networks. It might be a modulation core between visual network and auditory network. The decreased FC of MTG to PCC may indicate a down regulation of activity between PCC and auditory associated brain cortex. Decreased FC between limbic system (bilateral AI) and PCC may reflect the emotional message control in patient group. This study facilitated understanding of the underlying neuropathological process in patients with pulsatile tinnitus.

Abnormal resting-state functional connectivity study in unilateral pulsatile tinnitus patients with single etiology: A seed-based functional connectivity study

International Nuclear Information System (INIS)

Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

2016-01-01

Objective: Previous studies demonstrated altered regional neural activations in several brain areas in patients with pulsatile tinnitus (PT), especially indicating an important role of posterior cingulate cortex (PCC). However, few studies focused on the degree of functional connectivity (FC) of this area in PT patients. In this study, we will compare the FC of PCC in patients affected with this condition and normal controls by using resting-state functional magnetic resonance imaging (fMRI). Methods: Structural and functional MRI data were obtained from 36 unilateral PT patients with single etiology and 36 matched healthy controls. FC feature of the region of interest (PCC) were characterized using a seed-based correlation method with the voxels in the whole-brain. Results: Compared with healthy controls, patients showed significant decreased FC to the right middle temporal gyrus (MTG), right thalamus and bilateral insula. By contrast, PCC demonstrated increased functional connectivity between the precuneus, bilateral inferior parietal lobule and middle occipital gyrus. We also found correlations between the disease duration of PT and FC of PCC-right MTG (r = −0.616, p < 0.001). Conclusions: Unilateral PT patients could have abnormal FC to the PCC bilaterally in the brain. PCC, as a highly integrated brain area, is an example of nucleus that was involved in mediation between different neural networks. It might be a modulation core between visual network and auditory network. The decreased FC of MTG to PCC may indicate a down regulation of activity between PCC and auditory associated brain cortex. Decreased FC between limbic system (bilateral AI) and PCC may reflect the emotional message control in patient group. This study facilitated understanding of the underlying neuropathological process in patients with pulsatile tinnitus.

Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

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Kovacs, G L; Szabo, G; Telegdy, G [Institute of Pathophysiology, University Medical School, Szeged, Hungary; Penke, B [Institute of Medical Chemistry, University Medical School, Szeged, Hungary

1981-01-29

The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of ..cap alpha..-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of (/sup 3/H)DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10/sup -5/ M). Potassium-induced in vitro release of (/sup 3/H)DA from striatal slices was significantly increased by 10/sup -5/ M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions.

Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

International Nuclear Information System (INIS)

Kovacs, G.L.; Szabo, G.; Telegdy, G.; Penke, B.

1981-01-01

The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of α-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of [ 3 H]DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10 -5 M). Potassium-induced in vitro release of [ 3 H]DA from striatal slices was significantly increased by 10 -5 M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions. (Auth.)

Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies.

Science.gov (United States)

Kaasinen, Valtteri; Vahlberg, Tero

2017-12-01

A meta-analysis of 142 positron emission tomography and single photon emission computed tomography studies that have investigated striatal presynaptic dopamine function in Parkinson disease (PD) was performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L-amino-acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter and vesicular monoamine transporter 2 defects, suggesting upregulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear, but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. Ann Neurol 2017;82:873-882. © 2017 American Neurological Association.

Right Fronto-Temporal EEG can Differentiate the Affective Responses to Award-Winning Advertisements.

Science.gov (United States)

Wang, Regina W Y; Huarng, Shy-Peih; Chuang, Shang-Wen

2018-04-01

Affective engineering aims to improve service/product design by translating the customer's psychological feelings. Award-winning advertisements (AAs) were selected on the basis of the professional standards that consider creativity as a prerequisite. However, it is unknown if AA is related to satisfactory advertising performance among customers or only to the experts' viewpoints towards the advertisements. This issue in the field of affective engineering and design merits in-depth evaluation. We recruited 30 subjects and performed an electroencephalography (EEG) experiment while watching AAs and non-AAs (NAAs). The event-related potential (ERP) data showed that AAs evoked larger positive potentials 250-1400 [Formula: see text]ms after stimulus onset, particularly in the right fronto-temporal regions. The behavioral results were consistent with the professional recognition given to AAs by experts. The perceived levels of creativity and "product-like" quality were higher for the AAs than for the NAAs. Event-related spectral perturbation (ERSP) analysis further revealed statistically significant differences in the theta, alpha, beta, and gamma band activity in the right fronto-temporal regions between the AAs and NAAs. Our results confirm that EEG features from the time/frequency domains can differentiate affective responses to AAs at a neural circuit level, and provide scientific evidence to support the identification of AAs.

D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

Science.gov (United States)

Fazio, Leonardo; Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Romano, Raffaella; Gelao, Barbara; Ursini, Gianluca; Quarto, Tiziana; Lo Bianco, Luciana; Di Giorgio, Annabella; Mancini, Marina; Popolizio, Teresa; Rubini, Giuseppe; Bertolino, Alessandro

2011-02-14

Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease. Copyright © 2010 Elsevier Inc. All rights reserved.

Striatal [[sup 11]C]-N-methyl-spiperone binding in patients with focal dystonia (torticollis) using positron emission tomography

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Leenders, K [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Hartvig, P [Hospital Pharmacy, Univ. Hospital, Uppsala (Sweden); Forsgren, L; Holmgren, G; Almay, B [Dept. of Neurology, Umeaa Univ., Umeaa (Sweden); Eckernaes, S A [Dept. of Neurology, Univ. Hospital, Uppsala (Sweden); Lundqvist, H; Laangstroem, B [Uppsala Univ. PET-Center, Uppsala (Sweden)

1993-01-01

Specific binding of [[sup 11]C]-N-methyl-spiperone to striatal dopamine D2 receptors was assessed using positron emission tomography (PET) in 6 patients with adult-onset focal dystonia (predominantly spasmodic torticollis) and in 5 healthy subjects. No significant difference in average specific striatal tracer uptake between patients and healthy subjects was found. However, in the 5 patients showing lateralisation of clinical signs a trend to higher striatal tracer uptake in the contralateral hemisphere was observed. (authors).

Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis

OpenAIRE

Egerton, A.; Howes, O. D.; Houle, S.; McKenzie, K.; Valmaggia, L. R.; Bagby, M. R.; Tseng, H-H; Bloomfield, M. A. P.; Kenk, M.; Bhattacharyya, S.; Suridjan, I.; Chaddock, C. A.; Winton-Brown, T. T.; Allen, P.; Rusjan, P.

2017-01-01

Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case–control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capaci...

Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory.

Science.gov (United States)

Harding, Ian H; Yücel, Murat; Harrison, Ben J; Pantelis, Christos; Breakspear, Michael

2015-02-01

Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control. Copyright © 2014 Elsevier Inc. All rights reserved.

Fronto-parietal contributions to phonological processes in successful artificial grammar learning

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Dariya Goranskaya

2016-11-01

Full Text Available Sensitivity to regularities plays a crucial role in the acquisition of various linguistic features from spoken language input. Artificial grammar (AG learning paradigms explore pattern recognition abilities in a set of structured sequences (i.e. of syllables or letters. In the present study, we investigated the functional underpinnings of learning phonological regularities in auditorily presented syllable sequences. While previous neuroimaging studies either focused on functional differences between the processing of correct vs. incorrect sequences or between different levels of sequence complexity, here the focus is on the neural foundation of the actual learning success. During functional magnetic resonance imaging (fMRI, participants were exposed to a set of syllable sequences with an underlying phonological rule system, known to ensure performance differences between participants. We expected that successful learning and rule application would require phonological segmentation and phoneme comparison. As an outcome of four alternating learning and test fMRI sessions, participants split into successful learners and non-learners. Relative to non-learners, successful learners showed increased task-related activity in a fronto-parietal network of brain areas encompassing the left lateral premotor cortex as well as bilateral superior and inferior parietal cortices during both learning and rule application. These areas were previously associated with phonological segmentation, phoneme comparison and verbal working memory. Based on these activity patterns and the phonological strategies for rule acquisition and application, we argue that successful learning and processing of complex phonological rules in our paradigm is mediated via a fronto-parietal network for phonological processes.

Context-specific differences in fronto-parieto-occipital effective connectivity during short-term memory maintenance.

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Kundu, Bornali; Chang, Jui-Yang; Postle, Bradley R; Van Veen, Barry D

2015-07-01

Although visual short-term memory (VSTM) performance has been hypothesized to rely on two distinct mechanisms, capacity and filtering, the two have not been dissociated using network-level causality measures. Here, we hypothesized that behavioral tasks challenging capacity or distraction filtering would both engage a common network of areas, namely dorsolateral prefrontal cortex (dlPFC), superior parietal lobule (SPL), and occipital cortex, but would do so according to dissociable patterns of effective connectivity. We tested this by estimating directed connectivity between areas using conditional Granger causality (cGC). Consistent with our prediction, the results indicated that increasing mnemonic load (capacity) increased the top-down drive from dlPFC to SPL, and cGC in the alpha (8-14Hz) frequency range was a predominant component of this effect. The presence of distraction during encoding (filtering), in contrast, was associated with increased top-down drive from dlPFC to occipital cortices directly and from SPL to occipital cortices directly, in both cases in the beta (15-25Hz) range. Thus, although a common anatomical network may serve VSTM in different contexts, it does so via specific functions that are carried out within distinct, dynamically configured frequency channels. Copyright © 2015 Elsevier Inc. All rights reserved.

The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation

International Nuclear Information System (INIS)

Calvini, Piero; Rodriguez, Guido; Nobili, Flavio; Inguglia, Fabrizio; Mignone, Alessandro; Guerra, Ugo P.

2007-01-01

To design a novel algorithm (BasGan) for automatic segmentation of striatal 123 I-FP-CIT SPECT. The BasGan algorithm is based on a high-definition, three-dimensional (3D) striatal template, derived from Talairach's atlas. A blurred template, obtained by convolving the former with a 3D Gaussian kernel (FWHM = 10 mm), approximates striatal activity distribution. The algorithm performs translations and scale transformation on the bicommissural aligned image to set the striatal templates with standard size in an appropriate initial position. An optimization protocol automatically performs fine adjustments in the positioning of blurred templates to best match the radioactive counts, and locates an occipital ROI for background evaluation. Partial volume effect correction is included in the process of uptake computation of caudate, putamen and background. Experimental validation was carried out by means of six acquisitions of an anthropomorphic striatal phantom. The BasGan software was applied to a first set of patients with Parkinson's disease (PD) versus patients affected by essential tremor. A highly significant correlation was achieved between true binding potential and measured 123 I activity from the phantom. 123 I-FP-CIT uptake was significantly lower in all basal ganglia in the PD group versus controls with both BasGan and a conventional ROI method used for comparison, but particularly with the former. Correlations with the motor UPDRS score were far more significant with the BasGan. The novel BasGan algorithm automatically performs the 3D segmentation of striata. Because co-registered MRI is not needed, it can be used by all nuclear medicine departments, since it is freely available on the Web. (orig.)

Functional hierarchy underlies preferential connectivity disturbances in schizophrenia.

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Yang, Genevieve J; Murray, John D; Wang, Xiao-Jing; Glahn, David C; Pearlson, Godfrey D; Repovs, Grega; Krystal, John H; Anticevic, Alan

2016-01-12

Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.

Nitrofurantoin and congenital abnormalities

DEFF Research Database (Denmark)

Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik Toft

2001-01-01

or fetuses with Down’s syndrome (patient controls), 23 (2.8%) pregnant women were treated with nitrofurantoin. The above differences between population controls and cases may be connected with recall bias, because the case-control pair analysis did not indicate a teratogenic potential of nitrofurantoin use......Objective: To study human teratogenic potential of oral nitrofurantoin treatment during pregnancy. Materials and Methods: Pair analysis of cases with congenital abnormalities and matched population controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital...... during the second and the third months of gestation, i.e. in the critical period for major congenital abnormalities. Conclusion: Treatment with nitrofurantoin during pregnancy does not present detectable teratogenic risk to the fetus....

Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

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Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

2014-04-01

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

Assessment of striatal & postural deformities in patients with Parkinson's disease

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Sanjay Pandey

2016-01-01

Interpretation & conclusions: Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.

Secondary bilateral synchrony due to fronto-mesial lesions: an invasive recording study

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CUKIERT ARTHUR

1999-01-01

Full Text Available Frontal lobe epilepsies may present difficulties in focus localization in the pre-operative work-up for epilepsy surgery. This is specially true in patients with normal MRIs. We report on a 16 years-old girl that started with seizures by the age of 8 years. They were brief nocturnal episodes with automatisms such as bicycling and boxing. Seizure frequency ranged from 4-10 per night. Scalp EEG showed few right frontal convexity spiking and intense secondary bilateral syncrhony (SBS. High resolution MRI directed to the frontal lobes was normal. Ictal SPECT suggested a right fronto-lateral focus. Ictal video-EEG showed no focal onset. She was submitted to invasive recordings after subdural plates implantation. Electrodes covered all the frontal convexity and mesial surface bilaterally. Ictal recordings disclosed stereotyped seizures starting from the right mesial frontal. Using a high-resolution tool to measure intra and interhemispheric latencies, the timing and direction of seizure spread from the right fronto-mesial region were studied. Motor strip mapping was performed by means of electrical stimulation. She was submitted to a right frontal lobe resection, 1.5 cm ahead of the motor strip and has been seizure free since surgery (8 months. Pathological examination found a 4 mm area of cortical dysplasia. Invasive studies are needed to allow adequate localization in patients with non-localizatory non-invasive work-up and may lead to excellent results in relation to seizures after surgery.

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

Energy Technology Data Exchange (ETDEWEB)

Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

1988-01-01

We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder

OpenAIRE

Herbort, Maike C.; Soch, Joram; W?stenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, J?rgen; Walter, Henrik; Roepke, Stefan; Schott, Bj?rn H.

2016-01-01

Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BP...

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment.

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Robertson, Chelsea L; Ishibashi, Kenji; Chudzynski, Joy; Mooney, Larissa J; Rawson, Richard A; Dolezal, Brett A; Cooper, Christopher B; Brown, Amira K; Mandelkern, Mark A; London, Edythe D

2016-05-01

Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

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Tanda Koichi

2009-06-01

Full Text Available Abstract Background Neuronal nitric oxide synthase (nNOS is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice. Results nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice. Conclusion These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.

Blunted striatal response to monetary reward anticipation during smoking abstinence predicts lapse during a contingency-managed quit attempt.

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Sweitzer, Maggie M; Geier, Charles F; Denlinger, Rachel; Forbes, Erika E; Raiff, Bethany R; Dallery, Jesse; McClernon, F J; Donny, Eric C

2016-03-01

Tobacco smoking is associated with dysregulated reward processing within the striatum, characterized by hypersensitivity to smoking rewards and hyposensitivity to non-smoking rewards. This bias toward smoking reward at the expense of alternative rewards is further exacerbated by deprivation from smoking, which may contribute to difficulty maintaining abstinence during a quit attempt. We examined whether abstinence-induced changes in striatal processing of rewards predicted lapse likelihood during a quit attempt supported by contingency management (CM), in which abstinence from smoking was reinforced with money. Thirty-six non-treatment-seeking smokers participated in two functional MRI (fMRI) sessions, one following 24-h abstinence and one following smoking as usual. During each scan, participants completed a rewarded guessing task designed to elicit striatal activation in which they could earn smoking and monetary rewards delivered after the scan. Participants then engaged in a 3-week CM-supported quit attempt. As previously reported, 24-h abstinence was associated with increased striatal activation in anticipation of smoking reward and decreased activation in anticipation of monetary reward. Individuals exhibiting greater decrements in right striatal activation to monetary reward during abstinence (controlling for activation during non-abstinence) were more likely to lapse during CM (p reward. These results are consistent with a growing number of studies indicating the specific importance of disrupted striatal processing of non-drug reward in nicotine dependence and highlight the importance of individual differences in abstinence-induced deficits in striatal function for smoking cessation.

Reduced prefrontal connectivity in psychopathy.

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Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

2011-11-30

Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

Striatal response to reward anticipation: evidence for a systems-level intermediate phenotype for schizophrenia.

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Grimm, Oliver; Heinz, Andreas; Walter, Henrik; Kirsch, Peter; Erk, Susanne; Haddad, Leila; Plichta, Michael M; Romanczuk-Seiferth, Nina; Pöhland, Lydia; Mohnke, Sebastian; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Schäfer, Axel; Cichon, Sven; Nöthen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

2014-05-01

Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P systems-level functional phenotype is reliable (with intraclass correlation coefficients of 0.59-0.73), independent of local gray matter volume (with no corresponding group differences and no correlation to function, and with all uncorrected P values >.05), and affected by

Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age

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James N. Porter

2015-02-01

Full Text Available The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC imaging in 106 healthy individuals, ages 9–44. Broadly, the dorsal striatum (DS is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns and dorsal anterior cingulate cortex (dACC that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents’ unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices

International Nuclear Information System (INIS)

Eells, J.T.; Dubocovich, M.L.

1988-01-01

The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-alpha-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [ 3 H]dopamine and [ 3 H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [ 3 H]dopamine and [ 3 H]acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [ 3 H]norepinephrine or [ 3 H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions

Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

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Bossong, Matthijs G; Mehta, Mitul A; van Berckel, Bart N M; Howes, Oliver D; Kahn, René S; Stokes, Paul R A

2015-08-01

Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

Postural & striatal deformities in Parkinson`s disease: Are these rare?

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Sanjay Pandey

2016-01-01

Full Text Available Parkinson`s disease (PD is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.

Right fronto-limbic atrophy is associated with reduced empathy in refractory unilateral mesial temporal lobe epilepsy.

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Toller, Gianina; Adhimoolam, Babu; Rankin, Katherine P; Huppertz, Hans-Jürgen; Kurthen, Martin; Jokeit, Hennric

2015-11-01

Refractory mesial temporal lobe epilepsy (MTLE) is the most frequent focal epilepsy and is often accompanied by deficits in social cognition including emotion recognition, theory of mind, and empathy. Consistent with the neuronal networks that are crucial for normal social-cognitive processing, these impairments have been associated with functional changes in fronto-temporal regions. However, although atrophy in unilateral MTLE also affects regions of the temporal and frontal lobes that underlie social cognition, little is known about the structural correlates of social-cognitive deficits in refractory MTLE. In the present study, a psychometrically validated empathy questionnaire was combined with whole-brain voxel-based morphometry (VBM) to investigate the relationship between self-reported affective and cognitive empathy and gray matter volume in 55 subjects (13 patients with right MTLE, 9 patients with left MTLE, and 33 healthy controls). Consistent with the brain regions underlying social cognition, our results show that lower affective and cognitive empathy was associated with smaller volume in predominantly right fronto-limbic regions, including the right hippocampus, parahippocampal gyrus, thalamus, fusiform gyrus, inferior temporal gyrus, dorsomedial and dorsolateral prefrontal cortices, and in the bilateral midbrain. The only region that was associated with both affective and cognitive empathy was the right mesial temporal lobe. These findings indicate that patients with right MTLE are at increased risk for reduced empathy towards others' internal states and they shed new light on the structural correlates of impaired social cognition frequently accompanying refractory MTLE. In line with previous evidence from patients with neurodegenerative disease and stroke, the present study suggests that empathy depends upon the integrity of right fronto-limbic and brainstem regions and highlights the importance of the right mesial temporal lobe and midbrain

Striatal structure and its association with N-Acetylaspartate and glutamate in autism spectrum disorder and obsessive compulsive disorder

NARCIS (Netherlands)

Naaijen, Jilly; Zwiers, Marcel P.; Forde, Natalie J.; Williams, Steven C. R.; Durston, Sarah; Brandeis, Daniel; Glennon, Jeffrey C.; Franke, Barbara; Lythgoe, David J.; Buitelaar, Jan K.

Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often comorbid and are associated with changes in striatal volumes and N-Acetylaspartate (NAA) and glutamate levels. Here, we investigated the relation between dorsal striatal volume and NAA and glutamate levels. We

DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.

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Engmann, Olivia; Giralt, Albert; Gervasi, Nicolas; Marion-Poll, Lucile; Gasmi, Laila; Filhol, Odile; Picciotto, Marina R; Gilligan, Diana; Greengard, Paul; Nairn, Angus C; Hervé, Denis; Girault, Jean-Antoine

2015-12-07

Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.

Prefrontal cortex and striatal activation by feedback in Parkinson's disease

NARCIS (Netherlands)

Keitz, Martijn; Koerts, Janneke; Kortekaas, Rudie; Renken, Remco; de Jong, Bauke M.; Leenders, Klaus L.

2008-01-01

Positive feedbacks reinforce goal-directed behavior and evoke pleasure. in Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but also may lead to decreased positive feedback (reward) processing. This study investigates two types of positive feedback processing (monetary

Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

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Pan, Pedro Mario; Sato, João R; Salum, Giovanni A; Rohde, Luis A; Gadelha, Ary; Zugman, Andre; Mari, Jair; Jackowski, Andrea; Picon, Felipe; Miguel, Eurípedes C; Pine, Daniel S; Leibenluft, Ellen; Bressan, Rodrigo A; Stringaris, Argyris

2017-11-01

Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.

BDNF genotype modulates resting functional connectivity in children

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Moriah E Thomason

2009-11-01

Full Text Available A specific polymorphism of the brain-derived neurotrophic factor (BDNF gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined in the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within each of three resting networks: the default-mode, executive, and paralimbic networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because the BDNF met-allele has been linked to increased susceptibility to neuropsychiatric disorders, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. Additionally, we provide the first demonstration that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.

Fronto-striatal grey matter contributions to discrimination learning in Parkinson's disease

NARCIS (Netherlands)

O'Callaghan, C.; Moustafa, A.A.; de Wit, S.; Shine, J.M.; Robbins, T.W.; Lewis, S.J.G.; Hornberger, M.

2013-01-01

Discrimination learning deficits in Parkinson's disease (PD) have been well-established. Using both behavioral patient studies and computational approaches, these deficits have typically been attributed to dopamine imbalance across the basal ganglia. However, this explanation of impaired learning in

Abnormal Functional Connectivity Between Default and Salience Networks in Pediatric Bipolar Disorder.

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Lopez-Larson, Melissa P; Shah, Lubdha M; Weeks, Howard R; King, Jace B; Mallik, Atul K; Yurgelun-Todd, Deborah A; Anderson, Jeffrey S

2017-01-01

Pediatric bipolar disorder (PBD) (occurring prior to 18 years of age) is a developmental brain disorder that is among the most severe and disabling psychiatric conditions affecting youth. Despite increasing evidence that brain connectivity is atypical in adults with bipolar disorder, it is not clear how brain connectivity may be altered in youths with PBD. This cross-sectional resting-state functional magnetic resonance imaging study included 80 participants recruited over 4 years: 32 youths with PBD, currently euthymic (13 males; 15.1 years old), and 48 healthy control (HC) subjects (27 males; 14.5 years old). Functional connectivity between eight major intrinsic connectivity networks, along with connectivity measurements between 333 brain regions, was compared between PBD and HC subjects. Additionally, connectivity differences were evaluated between PBD and HC samples in negatively correlated connections, as defined by 839 subjects of the Human Connectome Project dataset. We found increased inter- but not intranetwork functional connectivity in PBD between the default mode and salience networks (p = .0017). Throughout the brain, atypical connections showed failure to develop anticorrelation with age during adolescence in PBD but not HC samples among connections that exhibit negative correlation in adulthood. Youths with PBD demonstrate reduced anticorrelation between default mode and salience networks. Further evaluation of the interaction between these networks is needed in development and with other mood states such as depression and mania to clarify if this atypical connectivity is a PBD trait biomarker. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Uncertainty, reward, and attention in the Bayesian brain

DEFF Research Database (Denmark)

Whiteley, Louise Emma

2008-01-01

results suggest that value a¿ects a fronto-striatal action selection network rather than directly impacting on sensory processing. Finally, we consider a major theoretical problem – the demonstrations of optimality that dominate the ¿eld have been obtained in tasks with a small number of objects...... in the focus of attention. When faced instead with a complex scene, the brain can’t be Bayes-optimal everywhere. We suggest that a general limitation on the representation of complex posteriors causes the brain to make approximations, which are then locally re¿ned by attention. This framework extends ideas...... of attention as Bayesian prior, and uni¿es apparently disparate attentional ‘bottlenecks’. We present simulations of three key paradigms, and discuss how such modelling could be extended to more detailed, neurally inspired settings. Broadening the Bayesian picture of perception and strengthening its connection...

Ventral striatal activity correlates with memory confidence for old- and new-responses in a difficult recognition test.

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Ulrike Schwarze

Full Text Available Activity in the ventral striatum has frequently been associated with retrieval success, i.e., it is higher for hits than correct rejections. Based on the prominent role of the ventral striatum in the reward circuit, its activity has been interpreted to reflect the higher subjective value of hits compared to correct rejections in standard recognition tests. This hypothesis was supported by a recent study showing that ventral striatal activity is higher for correct rejections than hits when the value of rejections is increased by external incentives. These findings imply that the striatal response during recognition is context-sensitive and modulated by the adaptive significance of "oldness" or "newness" to the current goals. The present study is based on the idea that not only external incentives, but also other deviations from standard recognition tests which affect the subjective value of specific response types should modulate striatal activity. Therefore, we explored ventral striatal activity in an unusually difficult recognition test that was characterized by low levels of confidence and accuracy. Based on the human uncertainty aversion, in such a recognition context, the subjective value of all high confident decisions is expected to be higher than usual, i.e., also rejecting items with high certainty is deemed rewarding. In an accompanying behavioural experiment, participants rated the pleasantness of each recognition response. As hypothesized, ventral striatal activity correlated in the current unusually difficult recognition test not only with retrieval success, but also with confidence. Moreover, participants indicated that they were more satisfied by higher confidence in addition to perceived oldness of an item. Taken together, the results are in line with the hypothesis that ventral striatal activity during recognition codes the subjective value of different response types that is modulated by the context of the recognition test.

Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible

International Nuclear Information System (INIS)

Booij, Jan; Bruin, Kora de; Win, Maartje M.L. de; Lavini, Cristina Mphil; Heeten, Gerard J. den; Habraken, Jan

2003-01-01

A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand 123 I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [ 123 I]FP-CIT binding ratios of the test/retest studies were 1.7 ± 0.2 and 1.6 ± 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [ 123 I]FP-CIT binding ratios in rats is highly reproducible

Atypical functional connectivity in autism spectrum disorder is associated with disrupted white matter microstructural organisation

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Jane eMcGrath

2013-09-01

Full Text Available Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were 1. to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM in ASD and 2. to examine the relationships between aberrant neural connectivity and behaviour in ASD. 22 individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19 and five paired regions: left caudate head, left caudate body, left uncus, left thalamus and left cuneus. Measures of WM microstructural organisation were extracted from these tracts. Fractional anisotropy reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant white matter microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute 1. to abnormal functional connectivity and 2. to atypical visuospatial processing in ASD.

Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of SKF38393.

NARCIS (Netherlands)

Saigusa, T.; Aono, Y.; Sekino, R.; Uchida, T.; Takada, K.; Oi, Y.; Koshikawa, N.; Cools, A.R.

2009-01-01

Like dexamphetamine, SKF38393 induces an increase in striatal dopamine efflux which is insensitive for tetrodotoxin, Ca(2+) independent and prevented by a dopamine transporter inhibitor. The dexamphetamine-induced striatal dopamine efflux originates from both the reserpine-sensitive vesicular

A Comparative study for striatal-direct and -indirect pathway neurons to DA depletion-induced lesion in a PD rat model.

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Zheng, Xuefeng; Wu, Jiajia; Zhu, Yaofeng; Chen, Si; Chen, Zhi; Chen, Tao; Huang, Ziyun; Wei, Jiayou; Li, Yanmei; Lei, Wanlong

2018-04-16

Striatal-direct and -indirect Pathway Neurons showed different vulnerability in basal ganglia disorders. Therefore, present study aimed to examine and compare characteristic changes of densities, protein and mRNA levels of soma, dendrites, and spines between striatal-direct and -indirect pathway neurons after DA depletion by using immunohistochemistry, Western blotting, real-time PCR and immunoelectron microscopy techniques. Experimental results showed that: 1) 6OHDA-induced DA depletion decreased the soma density of striatal-direct pathway neurons (SP+), but no significant changes for striatal-indirect pathway neurons (ENK+). 2) DA depletion resulted in a decline of dendrite density for both striatal-direct (D1+) and -indirect (D2+) pathway neurons, and D2+ dendritic density declined more obviously. At the ultrastructure level, the densities of D1+ and D2+ dendritic spines reduced in the 6OHDA groups compared with their control groups, but the density of D2+ dendritic spines reduced more significant than that of D1. 3) Striatal DA depletion down-regulated protein and mRNA expression levels of SP and D1, on the contrary, ENK and D2 protein and mRNA levels of indirect pathway neurons were up-regulated significantly. Present results suggested that indirect pathway neurons be more sensitive to 6OHDA-induced DA depletion. Copyright © 2018 Elsevier Ltd. All rights reserved.

Suppression of serotonin hyperinnervation does not alter the dysregulatory influences of dopamine depletion on striatal neuropeptide gene expression in rodent neonates.

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Basura, G J; Walker, P D

1999-10-15

Sixty days following neonatal dopamine depletion (>98%) with 6-hydroxydopamine, preprotachykinin and preprodynorphin mRNA levels were significantly reduced (67 and 78% of vehicle controls, respectively) in the anterior striatum as determined by in situ hybridization while preproenkephalin mRNA expression was elevated (133% of vehicle controls). Suppression of the serotonin hyperinnervation phenomenon in the dopamine-depleted rat with 5,7-dihydroxytryptamine yielded no significant alterations in reduced striatal preprotachykinin (66%) or preprodynorphin (64%) mRNA levels, while preproenkephalin mRNA expression remained significantly elevated (140%). These data suggest that striatal serotonin hyperinnervation does not contribute to the development of dysregulated striatal neuropeptide transmission in either direct or indirect striatal output pathways following neonatal dopamine depletion.

Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

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Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A; Quik, Maryka

2016-12-01

Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos + D2 MSNs and decreased c-Fos + non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. Copyright © 2016 Elsevier Inc. All rights reserved.

Preclinical cerebral network connectivity evidence of deficits in mild white matter lesions

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Ying eLiang

2016-02-01

Full Text Available White matter lesions (WMLs are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer’s disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity of three resting-state networks related to the changed cognitive domains: the default mode network (DMN and the bilateral fronto-parietal network (FPN. We also performed voxel-based morphometry analysis to compare whole-brain gray matter volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between functional connectivity and structural connectivity. We observed functional connectivity alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant gray matter atrophy difference was found. Furthermore, the right precuneus functional connectivity in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance.

Moral competence and brain connectivity: a resting-state fMRI study

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Jung, Wi Hoon; Prehn, Kristin; Fang, Zhuo; Korczykowski, Marc; Kable, Joseph W.; Rao, Hengyi; Robertson, Diana C.

2016-01-01

Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent operation of these networks. Our findings provide novel insights into how individual differences in moral judgment are associated with RSFC in brain circuits related to emotion processing and cognitive control. PMID:27456537

Modulating transcallosal and intra-hemispheric brain connectivity with tDCS: Implications for interventions in Aphasia.

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Zheng, Xin; Dai, Weiying; Alsop, David C; Schlaug, Gottfried

2016-07-25

Transcranial direct current stimulation (tDCS) can enhance or diminish cortical excitability levels depending on the polarity of the stimulation. One application of non-invasive brain-stimulation has been to modulate a possible inter-hemispheric disinhibition after a stroke. This disinhibition model has been developed mainly for the upper extremity motor system, but it is not known whether the language/speech-motor system shows a similar inter-hemispheric interaction. We aimed to examine physiological evidence of inter- and intra-hemispheric connectivity changes induced by tDCS of the right inferior frontal gyrus (IFG) using arterial-spin labeling (ASL) MRI. Using an MR-compatible DC-Stimulator, we applied anodal stimulation to the right IFG region of nine healthy adults while undergoing non-invasive cerebral blood flow imaging with arterial-spin labeling (ASL) before, during, and after the stimulation. All ASL images were then normalized and timecourses were extracted in regions of interest (ROIs), which were the left and right IFG regions, and the right supramarginal gyrus (SMG) in the inferior parietal lobule. Two additional ROIs (the right occipital lobe and the left fronto-orbital region) were taken as control regions. Using regional correlation coefficients as a surrogate marker of connectivity, we could show that inter-hemispheric connectivity (right IFG with left IFG) decreased significantly (p < 0.05; r-scores from 0.67 to 0.53) between baseline and post-stimulation, while the intra-hemispheric connectivity (right IFG with right SMG) increased significantly (p < 0.05;r-scores from 0.74 to 0.81). A 2 × 2 ANOVA found a significant main effect of HEMISPHERE (F(8) = 6.83, p < 0.01) and a significant HEMISPHERE-by-TIME interaction (F(8) = 4.24, p < 0.05) in connectivity changes. The correlation scores did not change significantly in the control region pairs (right IFG with right occipital and right IFG with left fronto-orbital) over

Recovery of resting brain connectivity ensuing mild traumatic brain injury

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Rose Dawn Bharath

2015-09-01

Full Text Available Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI. 25 subjects with mild head injury were longitudinally evaluated within 36 hours, 3 and 6 months using resting state functional connectivity (RSFC. Region of interest (ROI based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p<0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within three months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Initial imaging within 36 hours of injury revealed hyper connectivity predominantly involving the salience network and default mode network, which reduced at 3 months when lingual, inferior frontal and fronto-parietal networks revealed hyper connectivity. At six months all the evaluated networks revealed hyper connectivity and became comparable to the healthy controls. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3-6 months after injury. Hyper connectivity of several networks supported normal recovery in the first six months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.

Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine.

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Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

2016-10-11

The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R + -MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits.

Local functional connectivity suggests functional immaturity in children with attention-deficit/hyperactivity disorder.

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Marcos-Vidal, Luis; Martínez-García, Magdalena; Pretus, Clara; Garcia-Garcia, David; Martínez, Kenia; Janssen, Joost; Vilarroya, Oscar; Castellanos, Francisco X; Desco, Manuel; Sepulcre, Jorge; Carmona, Susanna

2018-06-01

Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age. © 2018 Wiley Periodicals, Inc.

Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer's Disease.

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Sánchez, Stella M; Abulafia, Carolina; Duarte-Abritta, Barbara; de Guevara, M Soledad Ladrón; Castro, Mariana N; Drucaroff, Lucas; Sevlever, Gustavo; Nemeroff, Charles B; Vigo, Daniel E; Loewenstein, David A; Villarreal, Mirta F; Guinjoan, Salvador M

2017-01-01

We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

What is said or how it is said makes a difference: role of the right fronto-parietal operculum in emotional prosody as revealed by repetitive TMS.

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van Rijn, Sophie; Aleman, André; van Diessen, Eric; Berckmoes, Celine; Vingerhoets, Guy; Kahn, René S

2005-06-01

Emotional signals in spoken language can be conveyed by semantic as well as prosodic cues. We investigated the role of the fronto-parietal operculum, a somatosensory area where the lips, tongue and jaw are represented, in the right hemisphere to detection of emotion in prosody vs. semantics. A total of 14 healthy volunteers participated in the present experiment, which involved transcranial magnetic stimulation (TMS) in combination with frameless stereotaxy. As predicted, compared with sham stimulation, TMS over the right fronto-parietal operculum differentially affected the reaction times for detection of emotional prosody vs. emotional semantics, showing that there is a dissociation at a neuroanatomical level. Detection of withdrawal emotions (fear and sadness) in prosody was delayed significantly by TMS. No effects of TMS were observed for approach emotions (happiness and anger). We propose that the right fronto-parietal operculum is not globally involved in emotion evaluation, but sensitive to specific forms of emotional discrimination and emotion types.

Striatal and extra-striatal dopamine transporter in cannabis and tobacco addiction: a high resolution PET study

International Nuclear Information System (INIS)

Leroy, C.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Ribeiro, M.J.; Trichard, Ch.; Karila, L.; Lukasiewicz, M.; Benyamina, A.; Reynaud, M.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Comtat, C.; Artiges, E.; Trichard, Ch.

2011-01-01

The dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long-term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extra-striatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age-matched subjects were compared: 11 healthy non-smoker subjects, 14 tobacco-dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [ 11 C]PE2I, a selective DAT radioligand. Region of interest and voxel-by-voxel approaches using a simplified reference tissue model were performed for the between-group comparison of DAT availability. Measurements in the dorsal striatum from both analyses were concordant and showed a mean 20% lower DAT availability in drug users compared with controls. Whole-brain analysis also revealed lower DAT availability in the ventral striatum, the midbrain, the middle cingulate and the thalamus (ranging from -15 to -30%). The DAT availability was slightly lower in all regions in CTS than in subjects who smoke tobacco only, but the difference does not reach a significant level. These results support the existence of a decrease in DAT availability associated with tobacco and cannabis addictions involving all dopaminergic brain circuits. These findings are consistent with the idea of a global decrease in cerebral DA activity in dependent subjects. (authors)

Enhanced striatal sensitivity to aversive reinforcement in adolescents versus adults.

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Galván, Adriana; McGlennen, Kristine M

2013-02-01

Neurodevelopmental changes in mesolimbic regions are associated with adolescent risk-taking behavior. Numerous studies have shown exaggerated activation in the striatum in adolescents compared with children and adults during reward processing. However, striatal sensitivity to aversion remains elusive. Given the important role of the striatum in tracking both appetitive and aversive events, addressing this question is critical to understanding adolescent decision-making, as both positive and negative factors contribute to this behavior. In this study, human adult and adolescent participants performed a task in which they received squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach in human adolescents. Compared with adults, adolescents showed greater behavioral and striatal sensitivity to both appetitive and aversive stimuli, an effect that was exaggerated in response to delivery of the aversive stimulus. Collectively, these findings contribute to understanding how neural responses to positive and negative outcomes differ between adolescents and adults and how they may influence adolescent behavior.

Decreased spontaneous eye blink rates in chronic cannabis users: evidence for striatal cannabinoid-dopamine interactions.

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Mikael A Kowal

Full Text Available Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR, a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

Transgenic mice expressing a Huntington s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

OpenAIRE

Hansson, Oskar; Petersén, Åsa; Leist, Marcel; Nicotera, Pierluigi; Castilho, Roger F.; Brundin, Patrik

1999-01-01

Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant HD gene mediates a slowly progressing striatal neurotoxicity is unknown. Glutamate receptor-mediated excitotoxicity has been hypothesized to contribute to the pathogenesis of HD. Here we show that transgenic HD mice expressing exon 1 of a human HD gene with an expanded number of CAG repeats (line R...

Abnormalities in structural covariance of cortical gyrification in schizophrenia.

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Palaniyappan, Lena; Park, Bert; Balain, Vijender; Dangi, Raj; Liddle, Peter

2015-07-01

The highly convoluted shape of the adult human brain results from several well-coordinated maturational events that start from embryonic development and extend through the adult life span. Disturbances in these maturational events can result in various neurological and psychiatric disorders, resulting in abnormal patterns of morphological relationship among cortical structures (structural covariance). Structural covariance can be studied using graph theory-based approaches that evaluate topological properties of brain networks. Covariance-based graph metrics allow cross-sectional study of coordinated maturational relationship among brain regions. Disrupted gyrification of focal brain regions is a consistent feature of schizophrenia. However, it is unclear if these localized disturbances result from a failure of coordinated development of brain regions in schizophrenia. We studied the structural covariance of gyrification in a sample of 41 patients with schizophrenia and 40 healthy controls by constructing gyrification-based networks using a 3-dimensional index. We found that several key regions including anterior insula and dorsolateral prefrontal cortex show increased segregation in schizophrenia, alongside reduced segregation in somato-sensory and occipital regions. Patients also showed a lack of prominence of the distributed covariance (hubness) of cingulate cortex. The abnormal segregated folding pattern in the right peri-sylvian regions (insula and fronto-temporal cortex) was associated with greater severity of illness. The study of structural covariance in cortical folding supports the presence of subtle deviation in the coordinated development of cortical convolutions in schizophrenia. The heterogeneity in the severity of schizophrenia could be explained in part by aberrant trajectories of neurodevelopment.

Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure.

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Pastura, Giuseppe; Doering, Thomas; Gasparetto, Emerson Leandro; Mattos, Paulo; Araújo, Alexandra Prüfer

2016-06-01

Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.

Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: A resting-state functional MRI study.

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Tian, Lin; Meng, Chun; Jiang, Ying; Tang, Qunfeng; Wang, Shuai; Xie, Xiyao; Fu, Xiangshuai; Jin, Chunhui; Zhang, Fuquan; Wang, Jidong

2016-04-03

Abnormal brain networks have been observed in patients with obsessive-compulsive disorder (OCD). However, detailed network hub and connectivity changes remained unclear in treatment-naive patients with OCD. Here, we sought to determine whether patients show hub-related connectivity changes in their whole-brain functional networks. We used resting-state functional magnetic resonance imaging data and voxel-based graph-theoretic analysis to investigate functional connectivity strength and hubs of whole-brain networks in 29 treatment-naive patients with OCD and 29 age- and gender-matched healthy controls. Correlation analysis was applied for potential associations with OCD symptom severity. OCD selectively targeted brain regions of higher functional connectivity strength than the average including brain network hubs, mainly distributed in the cortico-striato-thalamo-cortical (CSTC) circuits and additionally parietal, occipital, temporal and cerebellar regions. Moreover, affected functional connectivity strength in the cerebellum, the medial orbitofrontal cortex and superior occipital cortex was significantly associated with global OCD symptom severity. Our results provide the evidence about OCD-related brain network hub changes, not only in the CSTC circuits but more distributed in whole brain networks. Data suggest that whole brain network hub analysis is useful for understanding the pathophysiology of OCD. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

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Stevens, Michael C.; Haney-Caron, Emily

2012-01-01

Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is

Precentral gyrus functional connectivity signatures of autism

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Mary Beth eNebel

2014-05-01

Full Text Available Motor impairments are prevalent in children with autism spectrum disorders (ASD and are perhaps the earliest symptoms to develop. In addition, motor skills relate to the communicative/social deficits at the core of ASD diagnosis, and these behavioral deficits may reflect abnormal connectivity within brain networks underlying motor control and learning. Despite the fact that motor abnormalities in ASD are well-characterized, there remains a fundamental disconnect between the complexity of the clinical presentation of ASD and the underlying neurobiological mechanisms. In this study, we examined connectivity within and between functional subregions of a key component of the motor control network, the precentral gyrus, using resting state functional Magnetic Resonance Imaging data collected from a large, heterogeneous sample of individuals with ASD as well as neurotypical controls. We found that the strength of connectivity within and between distinct functional subregions of the precentral gyrus was related to ASD diagnosis and to the severity of ASD traits. In particular, connectivity involving the dorsomedial (lower limb/trunk subregion was abnormal in ASD individuals as predicted by models using a dichotomous variable coding for the presence of ASD, as well as models using symptom severity ratings. These findings provide further support for a link between motor and social/communicative abilities in ASD.

Detector for flow abnormalities in gaseous diffusion plant compressors

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Smith, S.F.; Castleberry, K.N.

1998-06-16

A detector detects a flow abnormality in a plant compressor which outputs a motor current signal. The detector includes a demodulator/lowpass filter demodulating and filtering the motor current signal producing a demodulated signal, and first, second, third and fourth bandpass filters connected to the demodulator/lowpass filter, and filtering the demodulated signal in accordance with first, second, third and fourth bandpass frequencies generating first, second, third and fourth filtered signals having first, second, third and fourth amplitudes. The detector also includes first, second, third and fourth amplitude detectors connected to the first, second, third and fourth bandpass filters respectively, and detecting the first, second, third and fourth amplitudes, and first and second adders connected to the first and fourth amplitude detectors and the second and third amplitude detectors respectively, and adding the first and fourth amplitudes and the second and third amplitudes respectively generating first and second added signals. Finally, the detector includes a comparator, connected to the first and second adders, and comparing the first and second added signals and detecting the abnormal condition in the plant compressor when the second added signal exceeds the first added signal by a predetermined value. 6 figs.

Electroencephalographic abnormalities in antisocial personality disorder.

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Calzada-Reyes, Ana; Alvarez-Amador, Alfredo; Galán-García, Lídice; Valdés-Sosa, Mitchell

2012-01-01

The presence of brain dysfunction in violent offenders has been frequently examined with inconsistent results. The aim of the study was to assess the EEG of 84 violent offenders by visual inspection and frequency-domain quantitative analysis in 84 violent prisoners. Low-resolution electromagnetic tomography (LORETA) was also employed for theta band of the EEG spectra. Antisocial personality disorder (ASPD) was present in 50 of the offenders and it was absent in the remaining 34. The prevalence of EEG abnormalities, by visual inspection, was similar for both the ASPD group (82%) and non-ASPD group (79%). The brain topography of these anomalies also did not differ between groups, in contrast to results of the EEG quantitative analysis (QEEG) and LORETA that showed remarkable regional differences between both groups. QEEG analysis showed a pattern of excess of theta-delta activities and decrease of alpha band on the right fronto-temporal and left temporo-parietal regions in the ASPD group. LORETA signified an increase of theta activity (5.08 Hz) in ASPD group relative to non-ASPD group within left temporal and parietal regions. Findings indicate that QEEG analysis and techniques of source localization may reveal differences in brain electrical activity among offenders with ASPD, which was not obvious to visual inspection. Copyright © 2011 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

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

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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.

Increased coherence among striatal regions in the theta range during attentive wakefulness

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G. Lepski

2012-08-01

Full Text Available The striatum, the largest component of the basal ganglia, is usually subdivided into associative, motor and limbic components. However, the electrophysiological interactions between these three subsystems during behavior remain largely unknown. We hypothesized that the striatum might be particularly active during exploratory behavior, which is presumably associated with increased attention. We investigated the modulation of local field potentials (LFPs in the striatum during attentive wakefulness in freely moving rats. To this end, we implanted microelectrodes into different parts of the striatum of Wistar rats, as well as into the motor, associative and limbic cortices. We then used electromyograms to identify motor activity and analyzed the instantaneous frequency, power spectra and partial directed coherence during exploratory behavior. We observed fine modulation in the theta frequency range of striatal LFPs in 92.5 ± 2.5% of all epochs of exploratory behavior. Concomitantly, the theta power spectrum increased in all striatal channels (P 0.7 between the primary motor cortex and the rostral part of the caudatoputamen nucleus, as well as among all striatal channels (P < 0.001. Conclusively, we observed a pattern of strong theta band activation in the entire striatum during attentive wakefulness, as well as a strong coherence between the motor cortex and the entire striatum. We suggest that this activation reflects the integration of motor, cognitive and limbic systems during attentive wakefulness.

Effect of in vitro gamma exposure on rat mesencephalic and striatal cellular types and processes length

International Nuclear Information System (INIS)

Coffigny, H.; Court, L.

1994-01-01

The isolated mesencephalic and striatal cells were irradiated in a dose-range of 0.25 to 3 Gy followed by 3 day of culture. The proportion of monopolar, bipolar, tripolar and multipolar cell population was not obviously modified by irradiation. The processes length was similar to controls, except after 3 Gy exposure, for monopolar and bipolar mesencephalic cells and the tripolar striatal cells where it was increased. In these populations, only cells with long processes seemed to survive. (author)

Morphological Abnormalities of Thalamic Subnuclei in Migraine

DEFF Research Database (Denmark)

Magon, Stefano; May, Arne; Stankewitz, Anne

2015-01-01

UNLABELLED: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging te...... is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling....... a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate.......9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine...

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.

Identification of an Abbreviated Test Battery for Detection of HIV-Associated Neurocognitive Impairment in an Early-Managed HIV-Infected Cohort

Science.gov (United States)

2012-11-01

within the fronto-striatal regions (e.g., processing speed) [5–7] than cortical dementias such as Alzheimer disease. As such, traditional cognitive...Part A, PASAT, and HVLT-R Learning avoids the requirement of having the color stimuli of the Stroop tests and replaces it with the Trail Making Test...assessment time points to avoid practice effect problems; however, this would require those who administer the tests to be trained on a wider range of

Dopamine D(1) receptor-mediated control of striatal acetylcholine release by endogenous dopamine.

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Acquas, E; Di Chiara, G

1999-10-27

The role of dopamine D(1) and D(2) receptors in the control of acetylcholine release in the dorsal striatum by endogenous dopamine was investigated by monitoring with microdialysis the effect of the separate or combined administration of the dopamine D(1) receptor antagonist, SCH 39166 ¿(-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride¿ (50 microg/kg subcutaneous (s.c.)), of the dopamine D(2)/D(3) receptor agonist, quinpirole (trans-(-)-4aR, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 microg/kg s.c.), and of the D(3) receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin -9-ol hydrochloride] (50 microg/kg s.c.), on in vivo dopamine and acetylcholine release. Microdialysis was performed with a Ringer containing low concentrations (0.01 microM) of the acetylcholinesterase inhibitor, neostigmine. Quinpirole (10 microg/kg s.c.) decreased striatal dopamine and acetylcholine release. Administration of PD 128,907 (50 microg/kg) decreased dopamine but failed to affect acetylcholine release. SCH 39166 (50 microg/kg s.c.) stimulated dopamine release and reduced acetylcholine release. Pretreatment with quinpirole reduced (5 microg/kg s.c.) or completely prevented (10 microg/kg s.c.) the stimulation of dopamine release elicited by SCH 39166 (50 microg/kg s.c.); on the other hand, pretreatment with quinpirole (5 and 10 microg/kg) potentiated the reduction of striatal acetylcholine release induced by SCH 39166 (50 microg/kg s.c.). Similarly, pretreatment with PD 128,907 (50 microg/kg) which prevented the increase of dopamine release induced by SCH 39166 (50 microg/kg), potentiated the reduction of striatal acetylcholine transmission elicited by SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907 influences in opposite manner the effect of SCH 39166 on striatal dopamine and

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

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Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

2014-02-01

Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

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Webber, Emily S; Mankin, David E; Cromwell, Howard C

2016-01-01

The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

Differences in number and distribution of striatal calbindin medium spiny neurons between a vocal-learner (Melopsittacus undulatus and a non-vocal learner bird (Colinus virginianus

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Elena eGarcia-Calero

2013-12-01

Full Text Available Striatal projecting neurons, known as medium spiny neurons (MSNs, segregate into two compartments called matrix and striosome in the mammalian striatum. The matrix domain is characterized by the presence of calbindin immunopositive (CB+ MSNs, not observed in the striosome subdivision. The existence of a similar CB+ MSN population has recently been described in two striatal structures in male zebra finch (a vocal learner bird: the striatal capsule and the Area X, a nucleus implicated in song learning. Female zebra finches show a similar pattern of CB+ MSNs than males in the developing striatum but loose these cells in juveniles and adult stages. In the present work we analyzed the existence and allocation of CB+MSNs in the striatal domain of the vocal learner bird budgerigar (representative of psittaciformes order and the non-vocal learner bird quail (representative of galliformes order. We studied the co-localization of CB protein with FoxP1, a transcription factor expressed in vertebrate striatal MSNs. We observed CB+ MSNs in the medial striatal domain of adult male and female budgerigars, although this cell type was missing in the potentially homologous nucleus for Area X in budgerigar. In quail, we observed CB+ cells in the striatal domain at developmental and adult stages but they did not co-localize with the MSN marker FoxP1. We also described the existence of the CB+ striatal capsule in budgerigar and quail and compared these results with the CB+ striatal capsule observed in juvenile zebra finches. Together, these results point out important differences in CB+MSN distribution between two representative species of vocal learner and non-vocal learner avian orders (respectively the budgerigar and the quail, but also between close vocal learner bird families.

Regional grey matter volume abnormalities in bulimia nervosa and binge-eating disorder.

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Schäfer, Axel; Vaitl, Dieter; Schienle, Anne

2010-04-01

This study investigated whether bulimia nervosa (BN) and binge-eating disorder (BED) are associated with structural brain abnormalities. Both disorders share the main symptom binge-eating, but are considered differential diagnoses. We attempted to identify alterations in grey matter volume (GMV) that are present in both psychopathologies as well as disorder-specific GMV characteristics. Such information can help to improve neurobiological models of eating disorders and their classification. A total of 50 participants (patients suffering from BN (purge type), BED, and normal-weight controls) underwent structural MRI scanning. GMV for specific brain regions involved in food/reinforcement processing was analyzed by means of voxel-based morphometry. Both patient groups were characterized by greater volumes of the medial orbitofrontal cortex (OFC) compared to healthy controls. In BN patients, who had increased ventral striatum volumes, body mass index and purging severity were correlated with striatal grey matter volume. Altogether, our data implicate a crucial role of the medial OFC in the studied eating disorders. The structural abnormality might be associated with dysfunctions in food reward processing and/or self-regulation. The bulimia-specific volume enlargement of the ventral striatum is discussed in the framework of negative reinforcement through purging and associated weight regulation. Copyright 2009 Elsevier Inc. All rights reserved.

Pramipexole Modulates Interregional Connectivity Within the Sensorimotor Network.

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Ye, Zheng; Hammer, Anke; Münte, Thomas F

2017-05-01

Pramipexole is widely prescribed to treat Parkinson's disease but has been reported to cause impulse control disorders such as pathological gambling. Recent neurocomputational models suggested that D2 agonists may distort functional connections between the striatum and the motor cortex, resulting in impaired reinforcement learning and pathological gambling. To examine how D2 agonists modulate the striatal-motor connectivity, we carried out a pharmacological resting-state functional magnetic resonance imaging study with a double-blind randomized within-subject crossover design. We analyzed the medication-induced changes of network connectivity and topology with two approaches, an independent component analysis (ICA) and a graph theoretical analysis (GTA). The ICA identified the sensorimotor network (SMN) as well as other classical resting-state networks. Within the SMN, the connectivity between the right caudate nucleus and other cortical regions was weaker under pramipexole than under placebo. The GTA measured the topological properties of the whole-brain network at global and regional levels. Both the whole-brain network under placebo and that under pramipexole were identified as small-world networks. The two whole-brain networks were similar in global efficiency, clustering coefficient, small-world index, and modularity. However, the degree of the right caudate nucleus decreased under pramipexole mainly due to the loss of the connectivity with the supplementary motor area, paracentral lobule, and precentral and postcentral gyrus of the SMN. The two network analyses consistently revealed that pramipexole weakened the functional connectivity between the caudate nucleus and the SMN regions.

Striatal fast-spiking interneurons: from firing patterns to postsynaptic impact

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Andreas eKlaus

2011-07-01

Full Text Available In the striatal microcircuit, fast-spiking (FS interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization, do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

Brain connectivity in pathological and pharmacological coma

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Quentin Noirhomme

2010-12-01

Full Text Available Recent studies in patients with disorders of consciousness (DOC tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the frontoparietal network. Functional neuroimaging studies have shown preserved albeit disconnected low level cortical activation in response to external stimulation in patients in a vegetative state or unresponsive wakefulness syndrome. While activation of these primary sensory cortices does not necessarily reflect conscious awareness, activation in higher order associative cortices in minimally conscious state patients seems to herald some residual perceptual awareness. PET studies have identified a metabolic dysfunction in a widespread fronto-parietal global neuronal workspace in DOC patients including the midline default mode network, ‘intrinsic’ system, and the lateral frontoparietal cortices or ‘extrinsic system’. Recent studies have investigated the relation of awareness to the functional connectivity within intrinsic and extrinsic networks, and with the thalami in both pathological and pharmacological coma. In brain damaged patients, connectivity in all default network areas was found to be non-linearly correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative, coma and brain dead patients. Anesthesia-induced loss of consciousness was also shown to correlate with a global decrease in cortico-cortical and thalamo-cortical connectivity in both intrinsic and extrinsic networks, but not in auditory or visual networks. In anesthesia, unconsciousness was also associated with a loss of cross-modal interactions between networks. These results suggest that conscious awareness critically depends on the functional integrity of thalamo-cortical and cortico-cortical frontoparietal connectivity within and between intrinsic and extrinsic brain networks.

Anatomical and electrophysiological changes in striatal TH interneurons after loss of the nigrostriatal dopaminergic pathway.

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Ünal, Bengi; Shah, Fulva; Kothari, Janish; Tepper, James M

2015-01-01

Using transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the tyrosine hydroxylase (TH) promoter, we have previously shown that there are approximately 3,000 striatal EGFP-TH interneurons per hemisphere in mice. Here, we report that striatal TH-EGFP interneurons exhibit a small, transient but significant increase in number after unilateral destruction of the nigrostriatal dopaminergic pathway. The increase in cell number is accompanied by electrophysiological and morphological changes. The intrinsic electrophysiological properties of EGFP-TH interneurons ipsilateral to 6-OHDA lesion were similar to those originally reported in intact mice except for a significant reduction in the duration of a characteristic depolarization induced plateau potential. There was a significant change in the distribution of the four previously described electrophysiologically distinct subtypes of striatal TH interneurons. There was a concomitant increase in the frequency of both spontaneous excitatory and inhibitory post-synaptic currents, while their amplitudes did not change. Nigrostriatal lesions did not affect somatic size or dendritic length or branching, but resulted in an increase in the density of proximal dendritic spines and spine-like appendages in EGFP-TH interneurons. The changes indicate that electrophysiology properties and morphology of striatal EGFP-TH interneurons depend on endogenous levels of dopamine arising from the nigrostriatal pathway. Furthermore, these changes may serve to help compensate for the changes in activity of spiny projection neurons that occur following loss of the nigrostriatal innervation in experimental or in early idiopathic Parkinson's disease by increasing feedforward GABAergic inhibition exerted by these interneurons.

A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

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Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

2017-01-01

Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia

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Meijboom, R.; Steketee, R.M.E.; Lugt, A. van der; Smits, M. [Erasmus MC - University Medical Centre, Radiology and Nuclear Medicine, Rotterdam (Netherlands); Koning, I. de [Erasmus MC - University Medical Centre, Neuropsychology, Rotterdam (Netherlands); Osse, R.J. [Erasmus MC - University Medical Centre, Psychiatry, Rotterdam (Netherlands); Jiskoot, L.C. [Erasmus MC - University Medical Centre, Neuropsychology, Rotterdam (Netherlands); Erasmus MC - University Medical Centre, Neurology, Rotterdam (Netherlands); Jong, F.J. de; Swieten, J.C. van [Erasmus MC - University Medical Centre, Neurology, Rotterdam (Netherlands)

2017-04-15

Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. (orig.)

Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia

International Nuclear Information System (INIS)

Meijboom, R.; Steketee, R.M.E.; Lugt, A. van der; Smits, M.; Koning, I. de; Osse, R.J.; Jiskoot, L.C.; Jong, F.J. de; Swieten, J.C. van

2017-01-01

Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. (orig.)

Device for diagnoising abnormalities of equipments

International Nuclear Information System (INIS)

Nakano, Hiroshi.

1986-01-01

Purpose: To measure the collision energy easily and at high accuracy by applying impact shocks at known collision energy from a simulated acoustic wave generator and using the generated acoustic signal as reference data. Constitution: A plurality of acoustic detectors are attached to the surface of a nuclear reactor pressure vessel. These acoustic detectors are connected respectively to an abnormality diagnosis device for equipments. Then, when metal obstacles collide against the inner surface of the reactor pressure vessel, acoustic signals generated upon collision are detected by the acoustic detectors and acoustic information thus obtained from the acoustic detectors determines the colliding position of the metal obstacles by means of the abnormality diagnosis device and then the collision energy is measured. In this case, by applying impact shocks at known collision energy near the colliding position of metal obstacles determined by the abnormality diagnosis device, collision energy can be determined at a higher accuracy. (Kawakami, Y.)

Reward inference by primate prefrontal and striatal neurons.

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Pan, Xiaochuan; Fan, Hongwei; Sawa, Kosuke; Tsuda, Ichiro; Tsukada, Minoru; Sakagami, Masamichi

2014-01-22

The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus-reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning.

Sexual dimorphism in striatal dopaminergic responses promotes monogamy in social songbirds.

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Tokarev, Kirill; Hyland Bruno, Julia; Ljubičić, Iva; Kothari, Paresh J; Helekar, Santosh A; Tchernichovski, Ofer; Voss, Henning U

2017-08-11

In many songbird species, males sing to attract females and repel rivals. How can gregarious, non-territorial songbirds such as zebra finches, where females have access to numerous males, sustain monogamy? We found that the dopaminergic reward circuitry of zebra finches can simultaneously promote social cohesion and breeding boundaries. Surprisingly, in unmated males but not in females, striatal dopamine neurotransmission was elevated after hearing songs. Behaviorally too, unmated males but not females persistently exchanged mild punishments in return for songs. Song reinforcement diminished when dopamine receptors were blocked. In females, we observed song reinforcement exclusively to the mate's song, although their striatal dopamine neurotransmission was only slightly elevated. These findings suggest that song-triggered dopaminergic activation serves a dual function in social songbirds: as low-threshold social reinforcement in males and as ultra-selective sexual reinforcement in females. Co-evolution of sexually dimorphic reinforcement systems can explain the coexistence of gregariousness and monogamy.

Phasic dopamine release drives rapid activation of striatal D2-receptors

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Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

2014-01-01

Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control.

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Christakou, Anastasia; Halari, Rozmin; Smith, Anna B; Ifkovits, Eve; Brammer, Mick; Rubia, Katya

2009-10-15

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

Faciobrachial dystonic seizures result from fronto-temporo-basalganglial network involvement.

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Iyer, Rajesh Shankar; Ramakrishnan, T C R; Karunakaran; Shinto, Ajit; Kamaleshwaran, Koramadai Karuppuswamy

2017-01-01

•Faciobrachial dystonic seizures (FBDS) are caused by autoantibodies to leucine-rich glioma-inactivated1 proteins, a component of the voltage-gated potassium channel complex (VGKC-complex) and precede the clinical presentation of limbic encephalitis.•The exact pathophysiology of FBDS is not known and whether they are seizures or movement disorder is still debated.•We suggest the fronto-temporo-basal ganglia network involving the medial frontal and temporal regions along with the corpus striatum and substantia nigra being responsible for the clinical phenomenon of FBDS.•The varied clinical, electrical and imaging features of FBDS in our cases and in the literature are best explained by involvement of this network.•Entrainment from any part of this network will result in similar clinical expression of FBDS, whereas other electro-clinical associations and duration depends on the extent of involvement of the network.

Activity in the fronto-parietal network indicates numerical inductive reasoning beyond calculation : An fMRI study combined with a cognitive model

NARCIS (Netherlands)

Liang, Peipeng; Jia, Xiuqin; Taatgen, Niels A; Borst, Jelmer P; Li, Kuncheng

2016-01-01

Numerical inductive reasoning refers to the process of identifying and extrapolating the rule involved in numeric materials. It is associated with calculation, and shares the common activation of the fronto-parietal regions with calculation, which suggests that numerical inductive reasoning may

Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson's Disease and the Temporal Regression of Striatal Tracer Uptake

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Fang, Yu-Hua Dean; Chiu, Shao-Chieh; Lu, Chin-Song; Weng, Yi-Hsin

2015-01-01

Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [99mTc]-TRODAT with SPECT imaging. Procedures. A normal [99mTc]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n = 365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R 2 = 0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients. PMID:26366413

Fully Automated Quantification of the Striatal Uptake Ratio of [(99m)Tc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson's Disease and the Temporal Regression of Striatal Tracer Uptake.

Science.gov (United States)

Fang, Yu-Hua Dean; Chiu, Shao-Chieh; Lu, Chin-Song; Yen, Tzu-Chen; Weng, Yi-Hsin

2015-01-01

We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [(99m)Tc]-TRODAT with SPECT imaging. A normal [(99m)Tc]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n = 365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R (2) = 0.84. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

Modulation of electric brain responses evoked by pitch deviants through transcranial direct current stimulation.

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Royal, Isabelle; Zendel, Benjamin Rich; Desjardins, Marie-Ève; Robitaille, Nicolas; Peretz, Isabelle

2018-01-31

Congenital amusia is a neurodevelopmental disorder, characterized by a difficulty detecting pitch deviation that is related to abnormal electrical brain responses. Abnormalities found along the right fronto-temporal pathway between the inferior frontal gyrus (IFG) and the auditory cortex (AC) are the likely neural mechanism responsible for amusia. To investigate the causal role of these regions during the detection of pitch deviants, we applied cathodal (inhibitory) transcranial direct current stimulation (tDCS) over right frontal and right temporal regions during separate testing sessions. We recorded participants' electrical brain activity (EEG) before and after tDCS stimulation while they performed a pitch change detection task. Relative to a sham condition, there was a decrease in P3 amplitude after cathodal stimulation over both frontal and temporal regions compared to pre-stimulation baseline. This decrease was associated with small pitch deviations (6.25 cents), but not large pitch deviations (200 cents). Overall, this demonstrates that using tDCS to disrupt regions around the IFG and AC can induce temporary changes in evoked brain activity when processing pitch deviants. These electrophysiological changes are similar to those observed in amusia and provide causal support for the connection between P3 and fronto-temporal brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Moral competence and brain connectivity: A resting-state fMRI study.

Science.gov (United States)

Jung, Wi Hoon; Prehn, Kristin; Fang, Zhuo; Korczykowski, Marc; Kable, Joseph W; Rao, Hengyi; Robertson, Diana C

2016-11-01

Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent operation of these networks. Our findings provide novel insights into how individual differences in moral judgment are associated with RSFC in brain circuits related to emotion processing and cognitive control. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison between piezosurgery and conventional osteotomy in cranioplasty with fronto-orbital advancement.

Science.gov (United States)

Martini, Markus; Röhrig, Andreas; Reich, Rudolf Hermann; Messing-Jünger, Martina

2017-03-01

Cranioplasty of patients with craniosynostosis requires rapid, precise and gentle osteotomy of the skull to avoid complications and benefit the healing process. The aim of this prospective clinical study was to compare two different methods of osteotomy. Piezosurgery and conventional osteotomy were compared using an oscillating saw and high speed drill while performing cranioplasties with fronto-orbital advancement. Thirty-four children who required cranioplasty with fronto-orbital advancement were recruited consecutively. The operations were conducted using piezosurgery or a conventional surgical technique, alternately. Operative time, blood count, CRP and transfusion rate, as well as soft tissue injuries, postoperative edema, pain development and secondary bone healing were investigated. The average age of patients was 9.7 months. The following indications for craniosynostosis were surgically corrected: trigonocephaly (23), anterior plagiocephaly (8), brachycephaly (1), and syndromic craniosynostosis (2). Piezosurgery was utilized in 18 cases. There were no group differences with regard to the incidence of soft tissue injuries (dura, periorbita), pain, swelling, blood loss or bony integration. The duration of osteotomy was significantly longer in the piezosurgery group, leading to slightly increased blood loss, while the postoperative CRP increase was higher using the conventional method. The piezosurgery method is a comparatively safe surgical method for conducting osteotomy during cranioplasty. With regard to soft tissue protection and postoperative clinical course, the same procedural precautions and controls are necessary as those needed for conventional methods. The osteotomy duration is considerably longer using piezosurgery, although it is accompanied by lower initial postoperative CRP values. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

Science.gov (United States)

Kita, Hitoshi; Kita, Takako

2011-07-13

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Aberrant cerebellar connectivity in motor and association networks in schizophrenia

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Ann K. Shinn

2015-03-01

Full Text Available Schizophrenia is a devastating illness characterized by disturbances in multiple domains. The cerebellum is involved in both motor and non-motor functions, and the cognitive dysmetria and dysmetria of thought models propose that abnormalities of the cerebellum may contribute to schizophrenia signs and symptoms. The cerebellum and cerebral cortex are reciprocally connected via a modular, closed-loop network architecture, but few schizophrenia neuroimaging studies have taken into account the topographical and functional heterogeneity of the cerebellum. In this study, using a previously defined 17-network cerebral cortical parcellation system as the basis for our functional connectivity seeds, we systematically investigated connectivity abnormalities within the cerebellum of 44 schizophrenia patients and 28 healthy control participants. We found selective alterations in cerebro-cerebellar functional connectivity. Specifically, schizophrenia patients showed decreased cerebro-cerebellar functional connectivity in higher level association networks (ventral attention, salience, control, and default mode networks relative to healthy control participants. Schizophrenia patients also showed increased cerebro-cerebellar connectivity in somatomotor and default mode networks, with the latter showing no overlap with the regions found to be hypoconnected within the same default mode network. Finally, we found evidence to suggest that somatomotor and default mode networks may be inappropriately linked in schizophrenia. The relationship of these dysconnectivities to schizophrenia symptoms, such as neurological soft signs and altered sense of agency, is discussed. We conclude that the cerebellum ought to be considered for analysis in all future studies of network abnormalities in SZ, and further suggest the cerebellum as a potential target for further elucidation, and possibly treatment, of the underlying mechanisms and network abnormalities producing symptoms of

Multi-Site Diagnostic Classification of Schizophrenia Using Discriminant Deep Learning with Functional Connectivity MRI

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Ling-Li Zeng

2018-04-01

Full Text Available Background: A lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia. Methods: A large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls. Findings: Accuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks. Interpretation: The findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the “disconnectivity” model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites. Keywords: Schizophrenia, Deep learning, Connectome, f

Multi-Site Diagnostic Classification of Schizophrenia Using Discriminant Deep Learning with Functional Connectivity MRI.

Science.gov (United States)

Zeng, Ling-Li; Wang, Huaning; Hu, Panpan; Yang, Bo; Pu, Weidan; Shen, Hui; Chen, Xingui; Liu, Zhening; Yin, Hong; Tan, Qingrong; Wang, Kai; Hu, Dewen

2018-04-01

A lack of a sufficiently large sample at single sites causes poor generalizability in automatic diagnosis classification of heterogeneous psychiatric disorders such as schizophrenia based on brain imaging scans. Advanced deep learning methods may be capable of learning subtle hidden patterns from high dimensional imaging data, overcome potential site-related variation, and achieve reproducible cross-site classification. However, deep learning-based cross-site transfer classification, despite less imaging site-specificity and more generalizability of diagnostic models, has not been investigated in schizophrenia. A large multi-site functional MRI sample (n = 734, including 357 schizophrenic patients from seven imaging resources) was collected, and a deep discriminant autoencoder network, aimed at learning imaging site-shared functional connectivity features, was developed to discriminate schizophrenic individuals from healthy controls. Accuracies of approximately 85·0% and 81·0% were obtained in multi-site pooling classification and leave-site-out transfer classification, respectively. The learned functional connectivity features revealed dysregulation of the cortical-striatal-cerebellar circuit in schizophrenia, and the most discriminating functional connections were primarily located within and across the default, salience, and control networks. The findings imply that dysfunctional integration of the cortical-striatal-cerebellar circuit across the default, salience, and control networks may play an important role in the "disconnectivity" model underlying the pathophysiology of schizophrenia. The proposed discriminant deep learning method may be capable of learning reliable connectome patterns and help in understanding the pathophysiology and achieving accurate prediction of schizophrenia across multiple independent imaging sites. Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.

Increased parietal circuit-breaker activity in delta frequency band and abnormal delta/theta band connectivity in salience network in hyperacusis subjects.

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Jae Joon Han

Full Text Available Recent studies have suggested that hyperacusis, an abnormal hypersensitivity to ordinary environmental sounds, may be characterized by certain resting-state cortical oscillatory patterns, even with no sound stimulus. However, previous studies are limited in that most studied subjects with other comorbidities that may have affected cortical activity. In this regard, to assess ongoing cortical oscillatory activity in idiopathic hyperacusis patients with no comorbidities, we compared differences in resting-state cortical oscillatory patterns between five idiopathic hyperacusis subjects and five normal controls. The hyperacusis group demonstrated significantly higher electrical activity in the right auditory-related cortex for the gamma frequency band and left superior parietal lobule (SPL for the delta frequency band versus the control group. The hyperacusis group also showed significantly decreased functional connectivity between the left auditory cortex (AC and left orbitofrontal cortex (OFC, between the left AC and left subgenual anterior cingulate cortex (sgACC for the gamma band, and between the right insula and bilateral dorsal anterior cingulate cortex (dACC and between the left AC and left sgACC for the theta band versus the control group. The higher electrical activity in the SPL may indicate a readiness of "circuit-breaker" activity to shift attention to forthcoming sound stimuli. Also, because of the disrupted salience network, consisting of the dACC and insula, abnormally increased salience to all sound stimuli may emerge, as a consequence of decreased top-down control of the AC by the dACC and dysfunctional emotional weight attached to auditory stimuli by the OFC. Taken together, abnormally enhanced attention and salience to forthcoming sound stimuli may render hyperacusis subjects hyperresponsive to non-noxious auditory stimuli.

The value of CT in the diagnosis of traumatic fronto-basal CSF fistulae

International Nuclear Information System (INIS)

Stoeter, P.; Ebeling, U.; Sankt Elisabethenkrankenhaus, Ravensburg

1982-01-01

In 20 patients with fronto-basal CSF fistulae, radiograms, tomograms and CTs in the axial and coronal projection were taken before operation. The evaluation showed that small fractures of the cribriform lamina could be demonstrated most clearly by CT with narrow coronal sections. Although the resolution properties of CT is still inferior to that of tomography for small osseous fissures, good CT results could be achieved by the better demonstration of accompanying mucosal swelling and/or small effusions. Fractures of the walls of the frontal sinuses, on the other hand, were shown better by tomography and those of the frontal calotte by normal radiograms. (orig.) [de

Chronic levodopa administration followed by a washout period increased number and induced phenotypic changes in striatal dopaminergic cells in MPTP-monkeys.

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Carla DiCaudo

Full Text Available In addition to the medium spiny neurons the mammalian striatum contains a small population of GABAergic interneurons that are immunoreactive for tyrosine hydroxylase (TH, which dramatically increases after lesions to the nigrostriatal pathway and striatal delivery of neurotrophic factors. The regulatory effect of levodopa (L-Dopa on the number and phenotype of these cells is less well understood. Eleven macaques (Macaca fascicularis were included. Group I (n = 4 received 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP and L-Dopa; Group II (n = 4 was treated with MPTP plus vehicle and Group III (n = 3 consist of intact animals (control group. L-Dopa and vehicle were given for 1 year and animals sacrificed 6 months later. Immunohistochemistry against TH was used to identify striatal and nigral dopaminergic cells. Double and triple labeling immunofluorescence was performed to detect the neurochemical characteristics of the striatal TH-ir cells using antibodies against: TH, anti-glutamate decarboxylase (GAD(67 anti-calretinin (CR anti-dopa decarboxylase (DDC and anti-dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32. The greatest density of TH-ir striatal cells was detected in the striatum of the L-Dopa treated monkeys and particularly in its associative territory. None of the striatal TH-ir cell expressed DARPP-32 indicating they are interneurons. The percentages of TH-ir cells that expressed GAD67 and DDC was approximately 50%. Interestingly, we found that in the L-Dopa group the number of TH/CR expressing cells was significantly reduced. We conclude that chronic L-Dopa administration produced a long-lasting increase in the number of TH-ir cells, even after a washout period of 6 months. L-Dopa also modified the phenotype of these cells with a significant reduction of the TH/CR phenotype in favor of an increased number of TH/GAD cells that do not express CR. We suggest that the increased number of striatal TH-ir cells might be involved

Effect of pharmacological interventions on the fronto-cingulo-parietal cognitive control network in psychiatric disorders: a transdiagnostic systematic review of fMRI studies

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Therese eVan Amelsvoort

2016-05-01

Full Text Available Executive function deficits such as working memory, decision-making, and attention problems are a common feature of several psychiatric disorders for which no satisfactory treatment exists. Here, we transdiagnostically investigate the effects of pharmacological interventions (other than methylphenidate on the fronto-cingulo-parietal cognitive control network, in order to identify functional brain markers for future pro-cognitive pharmacological interventions. 29 manuscripts investigated the effect of pharmacological treatment on executive function-related brain correlates in psychotic disorders (n=11, depression (n=4, bipolar disorder (n=4, ADHD (n=4, OCD (n=2, smoking dependence (n=2, alcohol dependence (n=1 and pathological gambling (n=1. In terms of impact on the fronto-cingulo-parietal networks, the preliminary evidence for catechol-o-methyl-transferase inhibitors, nicotinic receptor agonists and atomoxetine suggested was relatively consistent, the data for atypical antipsychotics and anticonvulsants moderate, and interpretation of the data for antidepressants was hampered by the employed study designs. Increased activity in task-relevant areas and decreased activity in task-irrelevant areas were the most common transdiagnostic effects of pharmacological treatment. These markers showed good positive and moderate negative predictive value. It is concluded that fronto-cingulo-parietal activity changes can serve as a marker for future pro-cognitive interventions. Future recommendations include the use of randomized double-blind designs and selective cholinergic and glutamatergic compounds.

The 2D:4D Marker and Different Forms of Internet Use Disorder

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Müller, Marko; Brand, Matthias; Mies, Julia; Lachmann, Bernd; Sariyska, Rayna Yordanova; Montag, Christian

2017-01-01

Internet use disorder (IUD) presents a growing problem worldwide. Among others, it manifests in loss of control over Internet usage and social problems due to problematic Internet use. Although IUD currently is not an official diagnosis in DSM-5 or ICD-10, mounting evidence suggests that IUD indeed could be categorized as a behavioral addiction. On a systemic neuroscientific level, IUD is well characterized and dysfunctions in the fronto-striatal-limbic loop have been observed in persons bein...

Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis.

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Zhong, Jidan; Nantes, Julia C; Holmes, Scott A; Gallant, Serge; Narayanan, Sridar; Koski, Lisa

2016-12-01

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting-state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting-state fMRI, T1-weighted and T2-weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease-related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting-state fMRI, T1-weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262-4275, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis.

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Egerton, Alice; Howes, Oliver D; Houle, Sylvain; McKenzie, Kwame; Valmaggia, Lucia R; Bagby, Michael R; Tseng, Huai-Hsuan; Bloomfield, Michael A P; Kenk, Miran; Bhattacharyya, Sagnik; Suridjan, Ivonne; Chaddock, Chistopher A; Winton-Brown, Toby T; Allen, Paul; Rusjan, Pablo; Remington, Gary; Meyer-Lindenberg, Andreas; McGuire, Philip K; Mizrahi, Romina

2017-03-01

Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

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.

Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

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Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

2015-02-01

Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

Connectivity Neurofeedback Training Can Differentially Change Functional Connectivity and Cognitive Performance.

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Yamashita, Ayumu; Hayasaka, Shunsuke; Kawato, Mitsuo; Imamizu, Hiroshi

2017-10-01

Advances in functional magnetic resonance imaging have made it possible to provide real-time feedback on brain activity. Neurofeedback has been applied to therapeutic interventions for psychiatric disorders. Since many studies have shown that most psychiatric disorders exhibit abnormal brain networks, a novel experimental paradigm named connectivity neurofeedback, which can directly modulate a brain network, has emerged as a promising approach to treat psychiatric disorders. Here, we investigated the hypothesis that connectivity neurofeedback can induce the aimed direction of change in functional connectivity, and the differential change in cognitive performance according to the direction of change in connectivity. We selected the connectivity between the left primary motor cortex and the left lateral parietal cortex as the target. Subjects were divided into 2 groups, in which only the direction of change (an increase or a decrease in correlation) in the experimentally manipulated connectivity differed between the groups. As a result, subjects successfully induced the expected connectivity changes in either of the 2 directions. Furthermore, cognitive performance significantly and differentially changed from preneurofeedback to postneurofeedback training between the 2 groups. These findings indicate that connectivity neurofeedback can induce the aimed direction of change in connectivity and also a differential change in cognitive performance. © The Author 2017. Published by Oxford University Press.

Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson’s Disease and the Temporal Regression of Striatal Tracer Uptake

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Yu-Hua Dean Fang

2015-01-01

Full Text Available Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging. Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n=365 and nPD subjects (28 healthy controls and 33 essential tremor patients were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR. The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R2=0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

Altered intrinsic connectivity of the auditory cortex in congenital amusia.

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Leveque, Yohana; Fauvel, Baptiste; Groussard, Mathilde; Caclin, Anne; Albouy, Philippe; Platel, Hervé; Tillmann, Barbara

2016-07-01

Congenital amusia, a neurodevelopmental disorder of music perception and production, has been associated with abnormal anatomical and functional connectivity in a right frontotemporal pathway. To investigate whether spontaneous connectivity in brain networks involving the auditory cortex is altered in the amusic brain, we ran a seed-based connectivity analysis, contrasting at-rest functional MRI data of amusic and matched control participants. Our results reveal reduced frontotemporal connectivity in amusia during resting state, as well as an overconnectivity between the auditory cortex and the default mode network (DMN). The findings suggest that the auditory cortex is intrinsically more engaged toward internal processes and less available to external stimuli in amusics compared with controls. Beyond amusia, our findings provide new evidence for the link between cognitive deficits in pathology and abnormalities in the connectivity between sensory areas and the DMN at rest. Copyright © 2016 the American Physiological Society.

Magnetic resonance imaging (MRI to study striatal iron accumulation in a rat model of Parkinson's disease.

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Ana Virel

Full Text Available Abnormal accumulation of iron is observed in neurodegenerative disorders. In Parkinson's disease, an excess of iron has been demonstrated in different structures of the basal ganglia and is suggested to be involved in the pathogenesis of the disease. Using the 6-hydroxydopamine (6-OHDA rat model of Parkinson's disease, the edematous effect of 6-OHDA and its relation with striatal iron accumulation was examined utilizing in vivo magnetic resonance imaging (MRI. The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images. Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities. The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers. Correlation analyses demonstrated a direct relation between the hyperintensities caused by the edema and the hypointensities caused by the accumulation of iron.

Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

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Bustamante, Juan-Carlos; Barrós-Loscertales, Alfonso; Costumero, Víctor; Fuentes-Claramonte, Paola; Rosell-Negre, Patricia; Ventura-Campos, Noelia; Llopis, Juan-José; Ávila, César

2014-09-01

Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

Striatal Dopamine Depletion Patterns and Early Non-Motor Burden in Parkinsons Disease.

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Su Jin Chung

Full Text Available The mechanism underlying non-motor symptoms in Parkinson's disease has not yet been elucidated. In this study, we hypothesized that Parkinson patients with more non-motor symptoms have a different pattern of striatal dopamine depletion, particularly in areas other than the sensorimotor striatum, compared to those with fewer non-motor symptoms.We conducted a prospective survey of the degree of non-motor symptoms (using the Korean version of the Non-Motor Symptoms Scale; K-NMSS in 151 patients with early-stage Parkinson's disease who had undergone a dopamine transporter PET scan as an initial diagnostic procedure. We classified the patients into two groups; high non-motor patients (HNM-PD; K-NMSS score ≥ 41 and low non-motor patients (LNM-PD.Patients in the HNM-PD group (n = 71 were older, had longer symptom duration, exhibited more severe motor deficits, and had been prescribed higher levodopa-equivalent doses at follow-up than those in the LNM-PD group. However, dopamine transporter binding to the striatal sub-regions and inter-sub-regional binding ratios were comparable between the two groups. A general linear model showed that the HNM-PD group had significantly more severe motor deficits than the LNM-PD group after controlling for age, gender, symptom duration, and dopamine transporter binding to the sensorimotor striatum.This study demonstrated that the pattern of striatal dopamine depletion does not contribute to early non-motor burden in Parkinson's disease. Our results suggest that LNM-PD patients may have a more benign course of motor symptom progression than HNM-PD patients.

Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function