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Sample records for subcallosal cingulate gyrus

  1. Impact of brain shift on subcallosal cingulate deep brain stimulation.

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    Choi, Ki Sueng; Noecker, Angela M; Riva-Posse, Patricio; Rajendra, Justin K; Gross, Robert E; Mayberg, Helen S; McIntyre, Cameron C

    2017-12-06

    Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is an emerging experimental therapy for treatment-resistant depression. New developments in SCC DBS surgical targeting are focused on identifying specific axonal pathways for stimulation that are estimated from preoperatively collected diffusion-weighted imaging (DWI) data. However, brain shift induced by opening burr holes in the skull may alter the position of the target pathways. Quantify the effect of electrode location deviations on tractographic representations for stimulating the target pathways using longitudinal clinical imaging datasets. Preoperative MRI and DWI data (planned) were coregistered with postoperative MRI (1 day, near-term) and CT (3 weeks, long-term) data. Brain shift was measured with anatomical control points. Electrode models corresponding to the planned, near-term, and long-term locations were defined in each hemisphere of 15 patients. Tractography analyses were performed using estimated stimulation volumes as seeds centered on the different electrode positions. Mean brain shift of 2.2 mm was observed in the near-term for the frontal pole, which resolved in the long-term. However, electrode displacements from the planned stereotactic target location were observed in the anterior-superior direction in both the near-term (mean left electrode shift: 0.43 mm, mean right electrode shift: 0.99 mm) and long-term (mean left electrode shift: 1.02 mm, mean right electrode shift: 1.47 mm). DBS electrodes implanted in the right hemisphere (second-side operated) were more displaced from the plan than those in the left hemisphere. These displacements resulted in 3.6% decrease in pathway activation between the electrode and the ventral striatum, but 2.7% increase in the frontal pole connection, compared to the plan. Remitters from six-month chronic stimulation had less variance in pathway activation patterns than the non-remitters. Brain shift is an important concern for SCC DBS

  2. Mapping the "Depression Switch" During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation.

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    Choi, Ki Sueng; Riva-Posse, Patricio; Gross, Robert E; Mayberg, Helen S

    2015-11-01

    The clinical utility of monitoring behavioral changes during intraoperative testing of subcallosal cingulate deep brain stimulation is unknown. To characterize the structural connectivity correlates of deep brain stimulation-evoked behavioral effects using probabilistic tractography in depression. Categorization of acute behavioral effects was conducted in 9 adults undergoing deep brain stimulation implantation surgery for chronic treatment-resistant depression in a randomized and blinded testing session at Emory University. Patients were studied from September 1, 2011, through June 30, 2013. Post hoc analyses of the structural tractography patterns mediating distinct categories of evoked behavioral effects were defined, including the best response overall. Data analyses were performed from May 1 through July 1, 2015. Categorization of stimulation-induced transient behavioral effects and delineation of the shared white matter tracts mediating response subtypes. Among the 9 patients, 72 active and 36 sham trials were recorded. The following stereotypical behavior patterns were identified: changes in interoceptive (noted changes in body state in 30 of 72 active and 4 of 36 sham trials) and in exteroceptive (shift in attention from patient to others in 9 of 72 active and 0 sham trials) awareness. The best response was a combination of exteroceptive and interoceptive changes at a single left contact for all 9 patients. Structural connectivity showed that the best response contacts had a pattern of connections to the bilateral ventromedial frontal cortex (via forceps minor and left uncinate fasciculus) and to the cingulate cortex (via left cingulum bundle), whereas behaviorally salient but nonbest contacts had only cingulate involvement. The involvement of the 3 white matter bundles during stimulation of the best contacts suggests a mechanism for the observed transient "depression switch." This analysis of transient behavior changes during intraoperative deep brain

  3. Compensatory shift of subcallosal area and paraterminal gyrus white matter parameters on DTI in patients with Alzheimer disease.

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    Kuchtova, Barbora; Wurst, Zdenek; Mrzílkova, Jana; Ibrahim, Ibrahim; Tintera, Jaroslav; Bartos, Ales; Musil, Vladimir; Kieslich, Karel; Zach, Petr

    2017-12-27

    Alzheimer disease is traditionally conceptualized as a disease of brain gray matter, however, studies with diffusion tensor imaging have demonstrated that Alzheimer disease also involves alterations in white matter integrity. We measured number of tracts, tracts length, tract volume, quantitative anisotropy and general fractional anisotropy of neuronal tracts in subcallosal area, paraterminal gyrus and fornix in patients with Alzheimer disease and healthy age-matched controls. Our hypothesis was that patients with Alzheimer disease should exhibit decrease in the integrity of these white matter structures that are crucial for semantic memory function. For our study were selected 24 patients with confirmed Alzheimer disease diagnosis and 24 healthy controls (AD center, Department of Neurology, Charles University, Prague, Czech Republic). Statistically significant differences between the patients with Alzheimer disease and the control group were found both on the left and right fornices but only concerning the tract numbers and tract length. The subcallosal area and paraterminal gyrus showed statistically significant differences between the patients with Alzheimer disease and the control group, but only on the left side and only associated with the tract volume and quantitative anisotropy. Our explanation for these findings lies in the severe hippocampal atrophy (and subsequent loss of function) with compensatory hypertrophy of the subcallosal area and paraterminal gyrus neuronal fibers that occurs in Alzheimer´s disease, as an adaptation to the loss of projection from the hippocampal formation via fornix. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Epilepsy surgery of the cingulate gyrus and the frontomesial cortex.

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    von Lehe, Marec; Wagner, Jan; Wellmer, Joerg; Clusmann, Hans; Kral, Thomas

    2012-04-01

    Epilepsy surgery involving the cingulate gyrus has been mostly presented as case reports, and larger series with long-term follow-up are not published yet. To report our experience with focal epilepsy arising from the cingulate gyrus and surrounding structures and its surgical treatment. Twenty-two patients (mean age, 36; range, 12-63) with a mean seizure history of 23 years (range, 2-52) were retrospectively analyzed. We report presurgical diagnostics, surgical strategy, and postoperative follow-up concerning functional morbidity and seizures (mean follow-up, 86 months; range, 25-174). Nineteen patients showed potential epileptogenic lesions on preoperative magnetic resonance imaging (MRI). All patients had noninvasive presurgical workup; 15 (68%) underwent invasive Video-electroencephalogram (EEG)-Monitoring. In 12 patients we performed extended lesionectomy according to MRI; an extension with regard to EEG results was done in 6 patients. In 4 patients, the resection was incomplete because of the involvement of eloquent areas according to functional mapping results. Eight pure cingulate resections (36%, 3 in the posterior cingulate gyrus) and 14 extended supracingular frontal resections were performed. Nine patients experienced temporary postoperative supplementary motor area syndrome after resection in the superior frontal gyrus. Two patients retained a persistent mild hand or leg paresis, respectively. Postoperatively, 62% of patients were seizure-free (International League Against Epilepsy [ILAE] 1), and 76% had a satisfactory seizure outcome (ILAE 1-3). Epilepsy surgery for lesions involving the cingulate gyrus represents a small fraction of all epilepsy surgery cases, with good seizure outcome and low rates of postoperative permanent deficits. In case of extended supracingular resection, supplementary motor area syndrome should be considered.

  5. Subcallosal Cingulate Connectivity in Anorexia Nervosa Patients Differs From Healthy Controls: A Multi-tensor Tractography Study.

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    Hayes, Dave J; Lipsman, Nir; Chen, David Q; Woodside, D Blake; Davis, Karen D; Lozano, Andres M; Hodaie, Mojgan

    2015-01-01

    Anorexia nervosa is characterized by extreme low body weight and alterations in affective processing. The subcallosal cingulate regulates affect through wide-spread white matter connections and is implicated in the pathophysiology of anorexia nervosa. We examined whether those with treatment refractory anorexia nervosa undergoing deep brain stimulation (DBS) of the subcallosal white matter (SCC) show: (1) altered anatomical SCC connectivity compared to healthy controls, (2) white matter microstructural changes, and (3) microstructural changes associated with clinically-measured affect. Diffusion magnetic resonance imaging (dMRI) and deterministic multi-tensor tractography were used to compare anatomical connectivity and microstructure in SCC-associated white matter tracts. Eight women with treatment-refractory anorexia nervosa were compared to 8 age- and sex-matched healthy controls. Anorexia nervosa patients also completed affect-related clinical assessments presurgically and 12 months post-surgery. (1) Higher (e.g., left parieto-occipital cortices) and lower (e.g., thalamus) connectivity in those with anorexia nervosa compared to controls. (2) Decreases in fractional anisotropy, and alterations in axial and radial diffusivities, in the left fornix crus, anterior limb of the internal capsule (ALIC), right anterior cingulum and left inferior fronto-occipital fasciculus. (3) Correlations between dMRI metrics and clinical assessments, such as low pre-surgical left fornix and right ALIC fractional anisotropy being related to post-DBS improvements in quality-of-life and depressive symptoms, respectively. We identified widely-distributed differences in SCC connectivity in anorexia nervosa patients consistent with heterogenous clinical disruptions, although these results should be considered with caution given the low number of subjects. Future studies should further explore the use of affect-related connectivity and behavioral assessments to assist with DBS target

  6. Functional Connectivity of the Subcallosal Cingulate Cortex And Differential Outcomes to Treatment With Cognitive-Behavioral Therapy or Antidepressant Medication for Major Depressive Disorder.

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    Dunlop, Boadie W; Rajendra, Justin K; Craighead, W Edward; Kelley, Mary E; McGrath, Callie L; Choi, Ki Sueng; Kinkead, Becky; Nemeroff, Charles B; Mayberg, Helen S

    2017-06-01

    The purpose of this article was to inform the first-line treatment choice between cognitive-behavioral therapy (CBT) or an antidepressant medication for treatment-naive adults with major depressive disorder by defining a neuroimaging biomarker that differentially identifies the outcomes of remission and treatment failure to these interventions. Functional MRI resting-state functional connectivity analyses using a bilateral subcallosal cingulate cortex (SCC) seed was applied to 122 patients from the Prediction of Remission to Individual and Combined Treatments (PReDICT) study who completed 12 weeks of randomized treatment with CBT or antidepressant medication. Of the 122 participants, 58 achieved remission (Hamilton Depression Rating Scale [HAM-D] score ≤7 at weeks 10 and 12), and 24 had treatment failure (depression subtypes defined using resting-state functional connectivity differentially identified an individual's probability of remission or treatment failure with first-line treatment options for major depression. This biomarker should be explored in future research through prospective testing and as a component of multivariate treatment prediction models.

  7. Identification of atrophy of the subgenual anterior cingulate cortex, in particular the subcallosal area, as an effective auxiliary means of diagnosis for major depressive disorder

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    Niida A

    2012-08-01

    cingulate cortex (sACC on the z-score map obtained.Results: No significant difference in atrophy was noted between the left and right sACCs. The VSRAD advance used in the present study was more effective than the VSRAD plus for diagnosis of MDD, with a sensitivity of 90.7%, specificity of 86.7%, accuracy of 89.5%, a positive predictive value of 94.4%, and a negative predictive value of 78.8%. In particular, atrophy was observed in the subcallosal area of the sACC.Conclusion: The identification of atrophy in the sACC, in particular of the subcallosal area, with the use of updated voxel-based morphometric software proved to be effective as an auxiliary diagnostic method for MDD.Keywords: major depressive disorder, magnetic resonance imaging, subgenual anterior cingulate cortex, voxel-based morphometry, VSRAD

  8. Analysis of the presence or absence of atrophy of the subgenual and subcallosal cingulate cortices using voxel-based morphometry on MRI is useful to select prescriptions for patients with depressive symptoms

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    Niida A

    2014-12-01

    Full Text Available Akira Niida,1 Richi Niida,2 Hiroshi Matsuda,3 Makoto Motomura,4 Akihiko Uechi5 1Department of Radiology, Nanbu Hospital, Itoman City, Okinawa, Japan; 2Department of Psychiatry, Nanto Clinic, Urasoe City, Okinawa, Japan; 3Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira City, Tokyo, Japan; 4Department of Human Sciences, University of the Ryukyus, Nakagami County, Okinawa, Japan; 5Cognitive Neuroscience Research Project, Kansai Gaidai University, Hirakata City, Osaka, Japan Objective: We objectively evaluated the presence or absence of atrophy of the subgenual anterior cingulate cortex (sgACC and the subcallosal anterior cingulate cortex (scACC, using new voxel-based morphometry (VBM software employing Statistical Parametric Mapping software v8 and diffeomorphic anatomic registration through an exponentiated lie algebra. We prepared a database covering young-mature adulthood and investigated the clinical usefulness of the evaluation. Subjects and methods: One hundred seven patients with major depressive disorder (MDD, 74 patients with bipolar disorder (BD, and 240 healthy control subjects underwent 1.5T magnetic resonance imaging scanning. Using new VBM software and databases covering young-mature adults and the elderly, target volumes of interest were set in the sgACC and scACC, four indicators (severity, extent, ratio, and whole-brain extent were determined, and the presence or absence of atrophy of the sgACC and scACC was evaluated on the basis of the indicators. In addition, the relationships between the presence or absence of atrophy of the sgACC and scACC and performance of diagnosing MDD and BD and therapeutic drugs were investigated. Results: It was clarified that the disease is likely to be MDD when atrophy is detected in the sgACC, and likely to be BD when no atrophy is detected in the sgACC but is detected in the scACC. Regarding the relationship with therapeutic drugs, it was clarified that, when

  9. Reduced cingulate gyrus volume associated with enhanced cortisol awakening response in young healthy adults reporting childhood trauma.

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    Lu, Shaojia; Gao, Weijia; Wei, Zhaoguo; Wu, Weiwei; Liao, Mei; Ding, Yuqiang; Zhang, Zhijun; Li, Lingjiang

    2013-01-01

    Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA) axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures. Twenty four healthy adults with childhood trauma and 24 age- and gender-matched individuals without childhood trauma were recruited. Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of cortisol awakening response (CAR). The 3D T1-weighted magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner. Voxel-based morphometry analyses were conducted to compare the gray matter volume between two groups. Correlations of gray matter volume changes with severity of childhood trauma and CAR data were further analyzed. Adults with self-reported childhood trauma showed an enhanced CAR and decreased gray matter volume in the right middle cingulate gyrus. Moreover, a significant association was observed between salivary cortisol secretions after awaking and the right middle cingulate gyrus volume reduction in subjects with childhood trauma. The present research outcomes suggest that childhood trauma is associated with hyperactivity of the HPA axis and decreased gray matter volume in the right middle cingulate gyrus, which may represent the vulnerability for developing psychosis after childhood trauma experiences. In addition, this study demonstrates that gray matter loss in the cingulate gyrus is related to increased cortisol levels.

  10. Reduced cingulate gyrus volume associated with enhanced cortisol awakening response in young healthy adults reporting childhood trauma.

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    Shaojia Lu

    Full Text Available BACKGROUND: Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures. METHODS: Twenty four healthy adults with childhood trauma and 24 age- and gender-matched individuals without childhood trauma were recruited. Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of cortisol awakening response (CAR. The 3D T1-weighted magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner. Voxel-based morphometry analyses were conducted to compare the gray matter volume between two groups. Correlations of gray matter volume changes with severity of childhood trauma and CAR data were further analyzed. RESULTS: Adults with self-reported childhood trauma showed an enhanced CAR and decreased gray matter volume in the right middle cingulate gyrus. Moreover, a significant association was observed between salivary cortisol secretions after awaking and the right middle cingulate gyrus volume reduction in subjects with childhood trauma. CONCLUSIONS: The present research outcomes suggest that childhood trauma is associated with hyperactivity of the HPA axis and decreased gray matter volume in the right middle cingulate gyrus, which may represent the vulnerability for developing psychosis after childhood trauma experiences. In addition, this study demonstrates that gray matter loss in the cingulate gyrus is related to increased cortisol levels.

  11. Specialization in pyramidal cell structure in the cingulate cortex of the Chacma baboon (Papio ursinus): an intracellular injection study of the posterior and anterior cingulate gyrus with comparative notes on the macaque and vervet monkeys.

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    Elston, Guy N; Benavides-Piccione, Ruth; Elston, Alejandra; DeFelipe, Javier; Manger, Paul

    2005-10-28

    This study forms part of an ongoing investigation of pyramidal cell structure in the cingulate cortex of primates. Recently we have demonstrated that layer III pyramidal cells in the anterior cingulate gyrus are considerably larger, more branched and more spinous than those in the posterior cingulate gyrus (areas 24 and 23, respectively) in the macaque and vervet monkeys. Moreover, the extent of the interareal difference in specialization in pyramidal cell structure differed between the two species. These data suggest that pyramidal cell circuitry may have evolved differently in these closely related species. Presently there are too few data to speculate on what is selecting for this specialization in structure. Here we extend the basis for comparison by studying pyramidal cell structure in cingulate gyrus of the Chacma baboon (Papio ursinus). Methodology used here is the same as that for our previous studies: intracellular injection of Lucifer Yellow in flat-mounted cortical slices. We found that pyramidal cells in anterior cingulate gyrus (area 24) were more branched and more spinous than those in posterior cingulate gyrus (area 23). Moreover, the complexity in pyramidal cell structure in both the anterior and posterior cingulate gyrus of the baboon differed to that in the corresponding regions in either the macaque or vervet monkeys.

  12. Analysis of the presence or absence of atrophy of the subgenual and subcallosal cingulate cortices using voxel-based morphometry on MRI is useful to select prescriptions for patients with depressive symptoms.

    Science.gov (United States)

    Niida, Akira; Niida, Richi; Matsuda, Hiroshi; Motomura, Makoto; Uechi, Akihiko

    2014-01-01

    We objectively evaluated the presence or absence of atrophy of the subgenual anterior cingulate cortex (sgACC) and the subcallosal anterior cingulate cortex (scACC), using new voxel-based morphometry (VBM) software employing Statistical Parametric Mapping software v8 and diffeomorphic anatomic registration through an exponentiated lie algebra. We prepared a database covering young-mature adulthood and investigated the clinical usefulness of the evaluation. One hundred seven patients with major depressive disorder (MDD), 74 patients with bipolar disorder (BD), and 240 healthy control subjects underwent 1.5T magnetic resonance imaging scanning. Using new VBM software and databases covering young-mature adults and the elderly, target volumes of interest were set in the sgACC and scACC, four indicators (severity, extent, ratio, and whole-brain extent) were determined, and the presence or absence of atrophy of the sgACC and scACC was evaluated on the basis of the indicators. In addition, the relationships between the presence or absence of atrophy of the sgACC and scACC and performance of diagnosing MDD and BD and therapeutic drugs were investigated. It was clarified that the disease is likely to be MDD when atrophy is detected in the sgACC, and likely to be BD when no atrophy is detected in the sgACC but is detected in the scACC. Regarding the relationship with therapeutic drugs, it was clarified that, when atrophy is detected in both the sgACC and the scACC, concomitant administration of mood stabilizers and atypical antipsychotics acting as dopamine-system stabilizers is necessary in many cases. VBM on magnetic resonance imaging enabled automatic analysis of atrophy in the sgACC and scACC, and findings obtained by this procedure are useful not only for differentiation of MDD and BD patients but also for selection of prescriptions.

  13. Correlation between extreme fear and focal cortical dysplasia in anterior cingulate gyrus: Evidence from a surgical case of refractory epilepsy.

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    Qiao, Liang; Yu, Tao; Ni, Duanyu; Wang, Xueyuan; Xu, Cuiping; Liu, Chang; Zhang, Guojun; Li, Yongjie

    2017-12-01

    Localizing the semiology of ictal fear and seizure onset in epilepsy patients is commonly challenging due to limited value of routine electroencephalography (EEG) and very few surgical attempts. Here we reported a case of refractory epilepsy characterized by aura of extreme fear and hypermotor seizures, in which the left (dominant hemisphere) anterior cingulate gyrus (ACG) was determined to be the epileptogenic zone (EZ) through multiple modalities of presurgical evaluation including analysis of high frequency oscillation on intracranial EEG. Tailored resection of EZ was thus performed and pathological examination revealed focal cortical dysplasia (FCD) type IIb. The patient has been seizure free during an 18-month follow-up. The report has provided novel anatomical, electrophysiological and surgical evidences suggesting the critical role of ACG in ictal fear and possibility of surgical management of fear-manifesting refractory epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Errors Recruit both Cognitive and Emotional Monitoring Systems: Simultaneous Intracranial Recordings in the Dorsal Anterior Cingulate Gyrus and Amygdala Combined with fMRI

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    Pourtois, Gilles; Vocat, Roland; N'Diaye, Karim; Spinelli, Laurent; Seeck, Margitta; Vuilleumier, Patrik

    2010-01-01

    We studied error monitoring in a human patient with unique implantation of depth electrodes in both the left dorsal cingulate gyrus and medial temporal lobe prior to surgery. The patient performed a speeded go/nogo task and made a substantial number of commission errors (false alarms). As predicted, intracranial Local Field Potentials (iLFPs) in…

  15. Regional specialization in pyramidal cell structure in the limbic cortex of the vervet monkey (Cercopithecus pygerythrus): an intracellular injection study of the anterior and posterior cingulate gyrus.

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    Elston, Guy N; Benavides-Piccione, Ruth; Elston, Alejandra; Manger, Paul; Defelipe, Javier

    2005-12-01

    The pyramidal cell phenotype varies quite dramatically in structure among different cortical areas in the primate brain. Comparative studies in visual cortex, in particular, but also in sensorimotor and prefrontal cortex, reveal systematic trends for pyramidal cell specialization in functionally related cortical areas. Moreover, there are systematic differences in the extent of these trends between different primate species. Recently we demonstrated differences in pyramidal cell structure in the cingulate cortex of the macaque monkey; however, in the absence of other comparative data it remains unknown as to whether the neuronal phenotype differs in cingulate cortex between species. Here we extend the basis for comparison by studying the structure of the basal dendritic trees of layer III pyramidal cells in the posterior and anterior cingulate gyrus of the vervet monkey (Brodmann's areas 23 and 24, respectively). Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors were determined, and somal areas measured. As in the macaque monkey, we found that pyramidal cells in anterior cingulate gyrus (area 24) were more branched and more spinous than those in posterior cingulate gyrus (area 23). In addition, the extent of the difference in pyramidal cell structure between these two cortical regions was less in the vervet monkey than in the macaque monkey.

  16. Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism.

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    Oblak, Adrian L; Rosene, Douglas L; Kemper, Thomas L; Bauman, Margaret L; Blatt, Gene J

    2011-06-01

    Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social-emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin-stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin-and calbindin-immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social-emotional behaviors as well as functioning of interrelated areas. Copyright © 2011, International Society for Autism Research, Wiley Periodicals, Inc.

  17. The anterior cingulate gyrus signals the net value of others' rewards.

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    Apps, Matthew A J; Ramnani, Narender

    2014-04-30

    Evaluating the costs and benefits of our own choices is central to most forms of decision-making and its mechanisms in the brain are becoming increasingly well understood. To interact successfully in social environments, it is also essential to monitor the rewards that others receive. Previous studies in nonhuman primates have found neurons in the anterior cingulate cortex (ACC) that signal the net value (benefit minus cost) of rewards that will be received oneself and also neurons that signal when a reward will be received by someone else. However, little is understood about the way in which the human brain engages in cost-benefit analyses during social interactions. Does the ACC signal the net value (the benefits minus the costs) of rewards that others will receive? Here, using fMRI, we examined activity time locked to cues that signaled the anticipated reward magnitude (benefit) to be gained and the level of effort (cost) to be incurred either by a subject themselves or by a social confederate. We investigated whether activity in the ACC covaries with the net value of rewards that someone else will receive when that person is required to exert effort for the reward. We show that, although activation in the sulcus of the ACC signaled the costs on all trials, gyral ACC (ACC(g)) activity varied parametrically only with the net value of rewards gained by others. These results suggest that the ACC(g) plays an important role in signaling cost-benefit information by signaling the value of others' rewards during social interactions.

  18. Biochemical assessment of precuneus and posterior cingulate gyrus in the context of brain aging and Alzheimer's disease.

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    Chera L Maarouf

    Full Text Available Defining the biochemical alterations that occur in the brain during "normal" aging is an important part of understanding the pathophysiology of neurodegenerative diseases and of distinguishing pathological conditions from aging-associated changes. Three groups were selected based on age and on having no evidence of neurological or significant neurodegenerative disease: 1 young adult individuals, average age 26 years (n = 9; 2 middle-aged subjects, average age 59 years (n = 5; 3 oldest-old individuals, average age 93 years (n = 6. Using ELISA and Western blotting methods, we quantified and compared the levels of several key molecules associated with neurodegenerative disease in the precuneus and posterior cingulate gyrus, two brain regions known to exhibit early imaging alterations during the course of Alzheimer's disease. Our experiments revealed that the bioindicators of emerging brain pathology remained steady or decreased with advancing age. One exception was S100B, which significantly increased with age. Along the process of aging, neurofibrillary tangle deposition increased, even in the absence of amyloid deposition, suggesting the presence of amyloid plaques is not obligatory for their development and that limited tangle density is a part of normal aging. Our study complements a previous assessment of neuropathology in oldest-old subjects, and within the limitations of the small number of individuals involved in the present investigation, it adds valuable information to the molecular and structural heterogeneity observed along the course of aging and dementia. This work underscores the need to examine through direct observation how the processes of amyloid deposition unfold or change prior to the earliest phases of dementia emergence.

  19. Cingulate Epilepsy

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    Alkawadri, Rafeed; So, Norman K.; Van Ness, Paul C.; Alexopoulos, Andreas V.

    2016-01-01

    IMPORTANCE The literature on cingulate gyrus epilepsy in the magnetic resonance imaging era is limited to case reports and small case series. To our knowledge, this is the largest study of surgically confirmed epilepsy arising from the anterior or posterior cingulate region. OBJECTIVE To characterize the clinical and electrophysiological findings of epilepsies arising from the anterior and posterior cingulate gyrus. DESIGN, SETTING, AND PARTICIPANTS We studied consecutive cingulate gyrus epilepsy cases identified retrospectively from the Cleveland Clinic and University of Texas Southwestern Medical Center epilepsy databases from 1992 to 2009. Participants included 14 consecutive cases of cingulate gyrus epilepsies confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. MAIN OUTCOMES AND MEASURES The main outcome measure was improvement in seizure frequency following surgery. The clinical, video electroencephalography, neuroimaging, pathology, and surgical outcome data were reviewed. RESULTS All 14 patients had cingulate epilepsy confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. They were divided into 3 groups based on anatomical location of the lesion and corresponding seizure semiology. In the posterior cingulate group, all 4 patients had electroclinical findings suggestive of temporal origin of the epilepsy. The anterior cingulate cases were divided into a typical (Bancaud) group (6 cases with hypermotor seizures and infrequent generalization with the presence of fear, laughter, or severe interictal personality changes) and an atypical group (4 cases presenting with simple motor seizures and a tendency for more frequent generalization and less-favorable long-term surgical outcome). All atypical cases were associated with an underlying infiltrative astrocytoma. CONCLUSIONS AND RELEVANCE Posterior cingulate gyrus epilepsy may

  20. MR imaging of subcallosal artery infarct causing amnesia after surgery for anterior communicating artery aneurysm.

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    Mugikura, S; Kikuchi, H; Fujii, T; Murata, T; Takase, K; Mori, E; Marinković, S; Takahashi, S

    2014-12-01

    During surgery to treat an aneurysm in the anterior communicating artery, injury to the subcallosal artery, a perforator of the anterior communicating artery, may lead to infarction that produces basal forebrain amnesia after surgery. Our purpose was to examine whether 3D MR imaging can detect subcallosal artery infarction in patients with amnesia after surgery for an anterior communicating artery aneurysm. We evaluated 3D-T2-weighted MR images obtained a median of 4 months after treatment of anterior communicating artery aneurysm for the presence of infarcted foci in 10 consecutive patients with postoperative amnesia. Because the subcallosal artery and its neighboring perforator, the recurrent artery of Heubner, were considered the most easily affected vessels during that surgery, we focused mainly on 8 regions of the subcallosal artery territory per hemisphere and 5 regions of the recurrent artery of Heubner territory per hemisphere. All 10 patients had infarcts in the territory of the subcallosal artery (median, 9 regions per patient), and most were bilateral (9 of 10 patients). Five patients had additional infarcted foci in the territory of the recurrent artery of Heubner (median, 1 region per patient), all unilateral. Among the regions perfused by the subcallosal artery, the column of the fornix was involved in all patients; the anterior commissure, in 9; and the paraterminal gyrus, in 8 patients. 3D MR imaging revealed subcallosal artery infarction, the distribution of which was mostly bilateral, presumably owing to the unpairedness of that artery, in patients with postoperative amnesia after anterior communicating artery aneurysm repair. © 2014 by American Journal of Neuroradiology.

  1. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

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    Mawrin Christian

    2011-08-01

    Full Text Available Abstract Background Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described. Methods Microglial immunoreactivity of the N-methyl-D-aspartate (NMDA glutamate receptor agonist quinolinic acid (QUIN in the subgenual anterior cingulate cortex (sACC, anterior midcingulate cortex (aMCC and pregenual anterior cingulate cortex (pACC of 12 acutely depressed suicidal patients (major depressive disorder/MDD, n = 7; bipolar disorder/BD, n = 5 was analyzed using immunohistochemistry and compared with its expression in 10 healthy control subjects. Results Depressed patients had a significantly increased density of QUIN-positive cells in the sACC (P = 0.003 and the aMCC (P = 0.015 compared to controls. In contrast, counts of QUIN-positive cells in the pACC did not differ between the groups (P = 0.558. Post-hoc tests showed that significant findings were attributed to MDD and were absent in BD. Conclusions These results add a novel link to the immune hypothesis of depression by providing evidence for an upregulation of microglial QUIN in brain regions known to be responsive to infusion of NMDA antagonists such as ketamine. Further work in this area could lead to a greater understanding of the pathophysiology of depressive disorders and pave the way for novel NMDA receptor therapies or immune-modulating strategies.

  2. Subcallosal Striations: the Role of FLAIR MR Imaging in Detecting ...

    African Journals Online (AJOL)

    FLAIR) in detection of subcallosal striations in clinical Multiple sclerosis (MS) patients and determine its role as a good noninvasive tool for the diagnosis of this disease. Material and Method: Forty patients with clinically proved MS were examined ...

  3. White matter alterations related to attention-deficit hyperactivity disorder and COMT val158met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus)

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    Kabukcu Basay, Burge; Buber, Ahmet; Basay, Omer; Alacam, Huseyin; Ozturk, Onder; Suren, Serkan; Izci Ay, Ozlem; Acikel, Cengizhan; Agladıoglu, Kadir; Erdal, Mehmet Emin; Ercan, Eyup Sabri; Herken, Hasan

    2016-01-01

    Introduction In this article, the COMT gene val158met polymorphism and attention-deficit hyperactivity disorder (ADHD)-related differences in diffusion-tensor-imaging-measured white matter (WM) structure in children with ADHD and controls were investigated. Patients and methods A total of 71 children diagnosed with ADHD and 24 controls aged 8–15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA). Results First, an interaction between the COMT val158met polymorphism and ADHD in the right (R) cingulum (cingulate gyrus) (CGC) was found. According to this, valine (val) homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the R-CGC than ADHD-diagnosed methionine (met) carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L)-uncinate fasciculus and lower RD in the L-posterior corona radiata and L-posterior thalamic radiation (include optic radiation) than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism. Conclusion Significant differences reported here may be evidence that the COMT gene val158met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD. PMID:27143897

  4. White matter alterations related to attention-deficit hyperactivity disorder and COMT val158met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus

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    Kabukcu Basay B

    2016-04-01

    Full Text Available Burge Kabukcu Basay,1 Ahmet Buber,1 Omer Basay,1 Huseyin Alacam,2 Onder Ozturk,1 Serkan Suren,3 Ozlem Izci Ay,4 Cengizhan Acikel,5 Kadir Agladioglu,6 Mehmet Emin Erdal,4 Eyup Sabri Ercan,7 Hasan Herken21Child and Adolescent Psychiatry Department, Pamukkale University Medical Faculty, Denizli, 2Psychiatry Department, Pamukkale University Medical Faculty, Denizli, 3Medical Park Samsun Hospital, Samsun, 4Medical Biology and Genetics Department, Mersin University Medical Faculty, Mersin, 5Biostatistics Department, GATA (GMMA, Ankara, 6Radiology Department, Pamukkale University Medical Faculty, Denizli, 7Child and Adolescent Psychiatry Department, Ege University Medical Faculty, Izmir, TurkeyIntroduction: In this article, the COMT gene val158met polymorphism and attention-deficit hyperactivity disorder (ADHD-related differences in diffusion-tensor-imaging-measured white matter (WM structure in children with ADHD and controls were investigated.Patients and methods: A total of 71 children diagnosed with ADHD and 24 controls aged 8–15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA.Results: First, an interaction between the COMT val158met polymorphism and ADHD in the right (R cingulum (cingulate gyrus (CGC was found. According to this, valine (val homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA and higher radial diffusivity (RD in the R-CGC than ADHD-diagnosed methionine (met carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L-uncinate fasciculus and lower RD in the L-posterior corona radiata and L

  5. The anterior cingulate cortex

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    Pavlović D.M.

    2009-01-01

    Full Text Available The anterior cingulate cortex (ACC has a role in attention, analysis of sensory information, error recognition, problem solving, detection of novelty, behavior, emotions, social relations, cognitive control, and regulation of visceral functions. This area is active whenever the individual feels some emotions, solves a problem, or analyzes the pros and cons of an action (if it is a right decision. Analogous areas are also found in higher mammals, especially whales, and they contain spindle neurons that enable complex social interactions. Disturbance of ACC activity is found in dementias, schizophrenia, depression, the obsessive-compulsive syndrome, and other neuropsychiatric diseases.

  6. Isolation and Culture of Adult Neural Stem Cells from the Mouse Subcallosal Zone.

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    Kim, Joo Yeon; Lee, Ju-Hyun; Sun, Woong

    2016-12-15

    Adult neural stem cells (aNSCs) can be used for the regeneration of damaged brain tissue. NSCs have the potential for differentiation and proliferation into three types of cells: neurons, astrocytes, and oligodendrocytes. Identifying aNSC-derived regions and characterizing the aNSC properties are critical for the potential use of aNSCs and for the elucidation of their role in neural regeneration. The subcallosal zone (SCZ), located between white matter and the hippocampus, has recently been reported to contain aNSCs and continuously give rise to neuroblasts. A low percentage of aNSCs from the SCZ is differentiated into neurons; most cells are differentiated into glial cells, such as oligodendrocytes and astrocytes. These cells are suggested to have a therapeutic potential for traumatic cortical injury. This protocol describes in detail the process to generate SCZ-aNSCs from an adult mouse brain. A brain matrix with intervals of 1 mm is used to obtain the SCZ-containing coronal slices and to precisely dissect the SCZ from the whole brain. The SCZ sections are initially subjected to a neurosphere culture. A well-developed culture system allows for the verification of their characteristics and can increase research on NSCs. A neurosphere culture system provides a useful tool for determining proliferation and collecting the genuine NSCs. A monolayer culture is also an in vitro system to assay proliferation and differentiation. Significantly, this culture system provides a more homogenous environment for NSCs than the neurosphere culture system. Thus, using a discrete brain region, these culture systems will be helpful for expanding our knowledge about aNSCs and their applications for therapeutic uses.

  7. Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment

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    Svensson Leif

    2002-09-01

    Full Text Available Abstract Background Mild cognitive impairment (MCI was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD. Regional cerebral blood flow (rCBF as measured by single photon emission computed tomography (SPECT was used to study the heterogeneity of MCI and to look for predictors of future development of AD. Methods rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO. An automated analysis software (BRASS was applied to analyze the relative blood flow (cerebellar ratios of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI and 37 subjects remained stable (SMCI. The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC analysis was applied for the discrimination of the two subgroups at baseline. Results The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%–76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. Conclusion A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD.

  8. Effects of nicotine on hippocampal and cingulate activity during smooth pursuit eye movement in schizophrenia.

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    Tanabe, Jody; Tregellas, Jason R; Martin, Laura F; Freedman, Robert

    2006-04-15

    Abnormal smooth pursuit eye movement (SPEM) in schizophrenic patients is a well known phenomenon, but the neurophysiological mechanisms underlying the deficit are unknown. Nicotine temporarily improves SPEM and has been associated with reduced hippocampal hemodynamic activity in schizophrenics. Nicotine's effect on brain activity in control subjects performing SPEM has not been studied. The purpose of this work was to determine if nicotine differentially affects brain activity in schizophrenic and control subjects during pursuit eye tracking. 16 subjects with schizophrenia and 16 control subjects underwent functional MR imaging during SPEM after receiving placebo or nicotine gum. Four brain regions were analyzed for main effects of group, drug, and interactions: hippocampus, cingulate gyrus, frontal eye fields, and area MT. Nicotine reduced hippocampal activity in both groups, but the effect was greater in control subjects. A group by drug interaction was observed in the anterior cingulate gyrus, where nicotine decreased activity in control subjects and increased activity in schizophrenic subjects. There were no significant effects of group, drug, or interactions in frontal eye fields or area MT. Nicotine may improve SPEM performance in people with schizophrenia through cholinergic stimulation of the hippocampus and cingulate gyrus. Potential mechanisms include improved inhibitory function and attention.

  9. Contributions of anterior cingulate cortex to behaviour.

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    Devinsky, O; Morrell, M J; Vogt, B A

    1995-02-01

    Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior

  10. The cingulate cortex of older adults with excellent memory capacity.

    Science.gov (United States)

    Lin, Feng; Ren, Ping; Mapstone, Mark; Meyers, Steven P; Porsteinsson, Anton; Baran, Timothy M

    2017-01-01

    Memory deterioration is the earliest and most devastating cognitive deficit in normal aging and Alzheimer's disease (AD). Some older adults, known as "Supernormals", maintain excellent memory. This study examined relationships between cerebral amyloid deposition and functional connectivity (FC) within the cingulate cortex (CC) and between CC and other regions involved in memory maintenance between Supernormals, healthy controls (HC), and those at risk for AD (amnestic mild cognitive impairment [MCI]). Supernormals had significantly stronger FC between anterior CC and R-hippocampus, middle CC (MCC) and L-superior temporal gyrus, and posterior CC (PCC) and R-precuneus, while weaker FC between MCC and R-middle frontal gyrus and MCC and R-thalamus than other groups. All of these FC were significantly related to memory and global cognition in all participants. Supernormals had less amyloid deposition than other groups. Relationships between global cognition and FC were stronger among amyloid positive participants. Relationships between memory and FC remained regardless of amyloid level. This revealed how CC-related neural function participates in cognitive maintenance in the presence of amyloid deposition, potentially explaining excellent cognitive function among Supernormals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Demonstration of decreased posterior cingulate perfusion in mild Alzheimer`s disease by means of H{sub 2}{sup 15}O positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Kazunari [Division of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders (HI-ABCD), Himeji (Japan); Sasaki, Masahiro [Division of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders (HI-ABCD), Himeji (Japan); Yamaji, Shigeru [Division of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders (HI-ABCD), Himeji (Japan); Sakamoto, Setsu [Division of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders (HI-ABCD), Himeji (Japan)]|[Department of Radiology, Kobe University School of Medicine, Kobe (Japan); Kitagaki, Hajime [Division of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders (HI-ABCD), Himeji (Japan); Mori, Etsuro [Division of Clinical Neurosciences, Hyogo Institute for Aging Brain and Cognitive Disorders (HI-ABCD), Himeji (Japan)

    1997-06-10

    Although decreased posterior cingulate metabolism in Alzheimer`s disease (AD) has been previously reported, there have been no reports on posterior cingulate perfusion. In this study we evaluated posterior cingulate perfusion as a relative value using statistical parametric maps (SPMs) and as an absolute value using conventional region of interest (ROI) settings. Twenty-eight subjects, including 14 patients with mild AD (mean age: 66.4{+-}12.1 years) and 14 normal controls (65.9{+-}7.3 years) were studied. Regional cerebral blood flow (CBF) was measured with H{sub 2}{sup 15}O and positron emission tomography (PET). In the SPM analysis, the left posterior cingulate and left parietotemporal CBFs were significantly decreased in the patients with mild AD (P<0.001). At a lower statistical threshold (P<0.05), the right posterior cingulate and right parietotemporal CBFs were also significantly decreased in the AD patients. In the ROI studies, the left parietal and posterior cingulate CBFs in the patients with mild AD were significantly lower than those of the normal controls by analysis of variance and post-hoc Scheffe`s test (P<0.001). We conclude that posterior cingulate perfusion is decreased in mild AD, reflecting the pathological changes and metabolic reduction in the posterior cingulate gyrus that have previously been reported to occur in mild AD. (orig.). With 1 fig., 2 tabs.

  12. The dorsal anterior cingulate cortex modulates dialectical self-thinking

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    Fei eWang

    2016-02-01

    Full Text Available Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC plays a crucial role in conflict monitoring as well as self-related processing. Here we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking, in which participants had to make a judgment whether a simultaneously presented pair of contradictory or non-contradictory traits properly described them while brain activity was recording using functional magnetic resonance imaging (fMRI. The data showed that activity in the dACC during the processing of self-relevant conflicting information was positively correlated with participants' dispositional level of naïve dialecticism (measured with the Dialectical Self Scale. Psychophysiological interaction (PPI analyses further revealed increased functional connectivity between the dACC and the caudate, middle temporal gyrus and hippocampus during the processing of self-relevant conflicting information for dialectical thinkers. These results support the hypothesis that the dACC has a key role in dialectical self-thinking.

  13. The Dorsal Anterior Cingulate Cortex Modulates Dialectical Self-Thinking.

    Science.gov (United States)

    Wang, Fei; Peng, Kaiping; Bai, Yang; Li, Rui; Zhu, Ying; Sun, Pei; Guo, Hua; Yuan, Chun; Rotshtein, Pia; Sui, Jie

    2016-01-01

    Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here, we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgment whether a simultaneously presented pair of contradictory or non-contradictory traits properly described them while brain activity was recording using functional magnetic resonance imaging (fMRI). The data showed that activity in the dACC during the processing of self-relevant conflicting information was positively correlated with participants' dispositional level of naïve dialecticism (measured with the Dialectical Self Scale). Psychophysiological interaction (PPI) analyses further revealed increased functional connectivity between the dACC and the caudate, middle temporal gyrus and hippocampus during the processing of self-relevant conflicting information for dialectical thinkers. These results support the hypothesis that the dACC has a key role in dialectical self-thinking.

  14. Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia.

    Science.gov (United States)

    White, Thomas P; Joseph, Verghese; Francis, Susan T; Liddle, Peter F

    2010-11-01

    A salience network, comprising bilateral insula and anterior cingulate cortex (ACC), is thought to play a role in recruiting relevant brain regions for the processing of sensory information. Here, we present a functional network connectivity (FNC) analysis of spatial networks identified during somatosensation, performed to test the hypothesis that salience network connectivity is disturbed during information processing in schizophrenia. 19 medicated individuals with schizophrenia and 19 matched healthy controls participated in a functional magnetic resonance imaging study. 100 Hz vibrotactile stimuli were presented to the right index fingertip while whole-head blood oxygenation level-dependent contrast gradient-echo echo-planar images were acquired. Six spatial components of interest were identified using group independent component analysis: (1) bilateral insula, superior temporal and precentral gyrus (INS); (2) dorsal ACC; (3) left dorsolateral frontal and parietal cortex (left central executive network (LCEN)); (4) right dorsolateral frontal and parietal cortex (RCEN); (5) ventromedial frontal cortex (FDMN); and (6) precuneus, posterior cingulate and angular gyrus (PDMN). Maximal-lagged correlation was examined between all pairwise combinations of components. Significantly reduced FNC was observed in schizophrenia compared to controls between: INS and ACC; INS and FDMN; and LCEN and PDMN. There was no evidence of increased FNC in schizophrenia. Reduced salience network connectivity during information processing in schizophrenia suggests disturbance to the system which effects changes between contextually-relevant functional brain states. This aberrance may provide a mechanistic explanation of several clinical features of the disorder. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Impairments of cingulated cortex in the generalized tonic-clonic seizure epilepsy by combining morphological and functional connectivity magnetic resonance imaging.

    Science.gov (United States)

    Ke, Ming; Jin, Bixia; Liu, Guangyao; Yang, Xiaoping

    2017-01-01

    Previous studies suggested that the patients with generalized tonic-clonic seizure had structural abnormalities in the thalamus, cingulated cortex and some other specific brain regions. Concurrently, the abnormality in thalamocortical network and basal ganglia network has been found in idiopathic generalized epilepsy. The cingulated cortex, a nexus of information processing and regulation in human brain, is implicated in the propagation of generalized spike in IGE and the previous studies have suggested that the structural features and functional connectivity of the cingulated cortex have been changed. The aim of this study was to demonstrate the alterations in the cingulated cortex in generalized tonic-clonic seizure by combining morphological and functional connectivity magnetic resonance imaging. 19 patients with generalized tonic-clonic seizure and 19 age-and gender-matched healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted magnetic resonance imaging data were acquired for voxel-based morphometry analysis, two-sample t-test run on the T1-weighted structural images revealed clusters exhibiting significant decreases in grey-matter volume in the generalized tonic-clonic seizure group, located within the cingulated cortex, thalamus, frontal lobe, temporal lobe, and cerebellum. The decreased gray matter volume in the cingulated cortex indicating that the cingulated cortex has structural impairments in generalized tonic-clonic seizure patients. The bilateral cingulated cortex, as detected with decreased gray matter volume in patients with generalized tonic-clonic seizure through voxel-based morphometry analysis, was selected as seed regions for functional connectivity analysis. Compared with controls, we found decreased functional connectivity to left anterior cingulated cortex (ROI1) in the cuneus, frontal lobe and precentral gyrus. There was no significant result when seeding at the right anterior cingulum gyrus (ROI2

  16. Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions.

    Science.gov (United States)

    Scheck, Simon M; Pannek, Kerstin; Raffelt, David A; Fiori, Simona; Boyd, Roslyn N; Rose, Stephen E

    2015-01-01

    In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions. Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task. The ACC-precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC-superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = -0.5856), suggesting that reduced connectivity correlates with executive dysfunction. Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function.

  17. The Cingulate Cortex and Human Memory Processes

    Directory of Open Access Journals (Sweden)

    Maria M.Pyasik

    2012-01-01

    Full Text Available This study presents data from a magnetic-resonance morphometric (MRMM analysisof the main regions of the cingulate cortex (in both hemispheres and theirrole in memory processes in a group of healthy, females of older age. The resultsdemonstrate a statistically reliable correlation between overall performance andthe type of errors in different neuropsychological memory tests and the relativesize of these regions. The discovered pattern of correlations can be explained byhypothesizing the reciprocal functional influence of the two major areas of thecingulate cortex – its anterior and posterior dorsal parts – on performance in neuropsychologicalmemory tests.

  18. Altered functional connectivity of fusiform gyrus in subjects with amnestic mild cognitive impairment: a resting state fMRI study

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    SuPing eCai

    2015-08-01

    Full Text Available Visual cognition such as face recognition requires a high level of functional interaction between distributed regions of a network. It has been reported that the fusiform gyrus (FG is an important brain area involved in facial cognition; altered connectivity of FG to some other regions may lead to a deficit in visual cognition especially face recognition. However, whether functional connectivity between the FG and other brain regions changes remains unclear during the resting state in amnestic mild cognitive impairment (aMCI subjects. Here, we employed a resting state functional MRI (fMRI to examine changes in functional connectivity of left/right FG comparing aMCI patients with age-matched control subjects. Forty-eight aMCI and thirty-eight control subjects from the Alzheimer’s disease Neuroimaging Initiative (ADNI were analyzed. We focused on the correlation between low frequency fMRI signal fluctuations in the FG and those in all other brain regions. Compared to the control group, we found some discrepant regions in the aMCI group which presented increased or decreased connectivity with the left/right FG including the left precuneus, left lingual gyrus, right thalamus, supramarginal gyrus, left supplementary motor area, left inferior temporal gyrus, and left parahippocampus. More importantly, we also obtained that both left and right FG have increased functional connections with the left middle occipital gyrus (MOG and right anterior cingulate gyrus (ACC in aMCI patients. That was not a coincidence and might imply that the MOG and ACC also play a critical role in visual cognition, especially face recognition. These findings in a large part supported our hypothesis and provided a new insight in understanding the important subtype of MCI.

  19. Changed hub and corresponding functional connectivity of subgenual anterior cingulate cortex in major depressive disorder

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    Huawang Wu

    2016-12-01

    Full Text Available Major depressive disorder (MDD is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS map in each subject in 34 MDD patients and 34 gender-, age-, and education level-matched healthy controls (HC. Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decreased FCS in subgenual anterior cingulate cortex (sgACC in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus, and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD.

  20. Extended Interneuronal Network of the Dentate Gyrus

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    Gergely G. Szabo

    2017-08-01

    Full Text Available Local interneurons control principal cells within individual brain areas, but anecdotal observations indicate that interneuronal axons sometimes extend beyond strict anatomical boundaries. Here, we use the case of the dentate gyrus (DG to show that boundary-crossing interneurons with cell bodies in CA3 and CA1 constitute a numerically significant and diverse population that relays patterns of activity generated within the CA regions back to granule cells. These results reveal the existence of a sophisticated retrograde GABAergic circuit that fundamentally extends the canonical interneuronal network.

  1. 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.

  2. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients

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    Eduardo A. Garza-Villarreal

    2015-07-01

    Full Text Available Music reduces pain in fibromyalgia (FM, a chronic pain disease, but the functional neural correlates of music-induced analgesia are still largely unknown. We recruited FM patients (n = 22 who listened to their preferred relaxing music and an auditory control (pink noise for 5 minutes without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the left angular gyrus showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex, the left caudate, and decreased connectivity with right anterior cingulate cortex, right supplementary motor area, precuneus and right precentral gyrus. Pain intensity analgesia was correlated (r = .61 to the connectivity of the left angular gyrus with the right precentral gyrus. Our results show that music-induced analgesia in FM is related to top-down regulation of the pain modulatory network by the default-mode network.

  3. Decision salience signals in posterior cingulate cortex

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    Sarah eHeilbronner

    2011-04-01

    Full Text Available Despite its phylogenetic antiquity and clinical importance, the posterior cingulate cortex (CGp remains an enigmatic nexus of attention, memory, motivation, and decision making. Here we show that CGp neurons track decision salience—the degree to which an option differs from a standard—but not the subjective value of a decision. To do this, we recorded the spiking activity of CGp neurons in monkeys choosing between options varying in reward-related risk, delay to reward, and social outcomes, each of which varied in level of decision salience. Firing rates were higher when monkeys chose the risky option, consistent with their risk-seeking preferences, but were also higher when monkeys chose the delayed and social options, contradicting their preferences. Thus, across decision contexts, neuronal activity was uncorrelated with how much monkeys valued a given option, as inferred from choice. Instead, neuronal activity signaled the deviation of the chosen option from the standard, independently of how it differed. The observed decision salience signals suggest a role for CGp in the flexible allocation of neural resources to motivationally significant information, akin to the role of attention in selective processing of sensory inputs.

  4. Cognitive Control Signals in Posterior Cingulate Cortex

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    Benjamin eHayden

    2010-12-01

    Full Text Available Efficiently shifting between tasks is a central function of cognitive control. The role of the default network—a constellation of areas with high baseline activity that declines during task performance—in cognitive control remains poorly understood. We hypothesized that task switching demands cognitive control to shift the balance of processing towards the external world, and therefore predicted that switching between the two tasks would require suppression of activity of neurons within the CGp. To test this idea, we recorded the activity of single neurons in posterior cingulate cortex (CGp, a central node in the default network, in monkeys performing two interleaved tasks. As predicted, we found that basal levels of neuronal activity were reduced following a switch from one task to another and gradually returned to pre-switch baseline on subsequent trials. We failed to observe these effects in lateral intraparietal cortex (LIP, part of the dorsal fronto-parietal cortical attention network directly connected to CGp. These findings indicate that suppression of neuronal activity in CGp facilitates cognitive control, and suggest that activity in the default network reflects processes that directly compete with control processes elsewhere in the brain..

  5. Abnormally increased effective connectivity between parahippocampal gyrus and ventromedial prefrontal regions during emotion labeling in bipolar disorder

    Science.gov (United States)

    Almeida, Jorge R. C.; Mechelli, Andrea; Hassel, Stefanie; Versace, Amelia; Kupfer, David J.; Phillips, Mary L.

    2009-01-01

    Emotional liability and mood dysregulation characterize bipolar disorder (BD), yet no study has examined effective connectivity between parahippocampal gyrus and prefrontal cortical regions in ventromedial and dorsal/lateral neural systems subserving mood regulation in BD. Forty-six individuals (age range: 18–56 years); 21 with a DSM-IV diagnosis of BD, type I currently remitted; 25 age- and gender-matched healthy controls (HC). Participants performed an event-related paradigm, viewing mild and intense happy and neutral faces. We employed dynamic causal modeling (DCM) to identify significant alterations in effective connectivity between BD and HC. Bayes model selection was used to determine the best model. The right parahippocampal gyrus (PHG) and right subgenual cingulate gyrus (sgCG) were included as representative regions of the ventromedial neural system. The right dorsolateral prefrontal cortex (DLPFC) region was included as representative of the dorsal/lateral neural system. Right PHG-sgCG effective connectivity was significantly greater in BD than HC, reflecting more rapid, forward PHG-sgCG signaling in BD than HC. There was no between-group difference in sgCG-DLPFC effective connectivity. In BD, abnormally increased right PHG-sgCG effective connectivity and reduced right PHG activity to emotional stimuli suggest a dysfunctional ventromedial neural system implicated in early stimulus appraisal, encoding and automatic regulation of emotion, that may represent a pathophysiological functional neural mechanism for mood dysregulation in BD. PMID:19910166

  6. Impaired cognitive control and reduced cingulate activity during mental fatigue

    NARCIS (Netherlands)

    Lorist, MM; Boksem, MAS; Ridderinkhof, KR

    Neurocognitive mechanisms underlying the effects of mental fatigue are poorly understood. Here, we examined whether error-related brain activity, indexing performance monitoring by the anterior cingulate cortex (ACC), and strategic behavioural adjustments were modulated by mental fatigue, as induced

  7. Impaired cognitive control and reduced cingulate activity during mental fatigue

    NARCIS (Netherlands)

    Lorist, M.M.; Boksem, M.A.S.; Ridderinkhof, K.R.

    2005-01-01

    Neurocognitive mechanisms underlying the effects of mental fatigue are poorly understood. Here, we examined whether error-related brain activity, indexing performance monitoring by the anterior cingulate cortex (ACC), and strategic behavioural adjustments were modulated by mental fatigue, as induced

  8. Orbitofrontal sulcal and gyrus pattern in human: an anatomical study

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    Thiago Pereira Rodrigues

    2015-05-01

    Full Text Available The anatomical characterization of the orbitofrontal cortex in human is limited in literature instead of many functional and clinical studies involving it. Objective Anatomically define the orbitofrontal region aiming to possible neurosurgical treatments and unify the scientific nomenclature as well. Method We analyze eighty four human hemispheres using a surgical microscope. Then we chose four hemispheres and dissect them according to Klinger’ technique. Results We found five main sulcus: olfatory sulcus, orbital medial sulcus, orbital lateral sulcus, orbital transverse sulcus and orbital intermediate sulcus. These sulcus, excluding the intermediate sulcus, delimit five gyrus: rectus gurys, orbital medial gyrus, orbital anterior gyrus, orbital lateral gyrus and orbital posterior gyrus. The main sulcal configuration can be divided on four more frequently patterns. Conclusion Orbitofrontal cortex is associated with many psychiatric disorders. Better anatomical and functional characterization of the orbitofrontal cortex and its connections will improve our knowledge about these diseases.

  9. The Role of Cingulate Cortex in Vicarious Pain

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    Esther H. Yesudas

    2015-01-01

    Full Text Available Vicarious pain is defined as the observation of individuals in pain. There is growing neuroimaging evidence suggesting that the cingulate cortex plays a significant role in self-experienced pain processing. Yet, very few studies have directly tested the distinct functions of the cingulate cortex for vicarious pain. In this review, one EEG and eighteen neuroimaging studies reporting cingulate cortex activity during pain observation were discussed. The data indicate that there is overlapping neural activity in the cingulate cortex during self- and vicarious pain. Such activity may contribute to shared neural pain representations that permit inference of the affective state of individuals in pain, facilitating empathy. However, the exact location of neuronal populations in which activity overlaps or differs for self- and observed pain processing requires further confirmation. This review also discusses evidence suggesting differential functions of the cingulate cortex in cognitive, affective, and motor processing during empathy induction. While affective processing in the cingulate cortex during pain observation has been explored relatively more often, its attention and motor roles remain underresearched. Shedding light on the neural correlates of vicarious pain and corresponding empathy in healthy populations can provide neurobiological markers and intervention targets for empathic deficits found in various clinical disorders.

  10. Connectivity-based parcellation increases network detection sensitivity in resting state fMRI: An investigation into the cingulate cortex in autism

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    Joshua H. Balsters

    2016-01-01

    Full Text Available Although resting state fMRI (RS-fMRI is increasingly used to generate biomarkers of psychiatric illnesses, analytical choices such as seed size and placement can lead to variable findings. Seed placement especially impacts on RS-fMRI studies of Autism Spectrum Disorder (ASD, because individuals with ASD are known to possess more variable network topographies. Here, we present a novel pipeline for analysing RS-fMRI in ASD using the cingulate cortex as an exemplar anatomical region of interest. Rather than using seeds based on previous literature, or gross morphology, we used a combination of structural information, task-independent (RS-fMRI and task-dependent functional connectivity (Meta-Analytic Connectivity Modeling to partition the cingulate cortex into six subregions with unique connectivity fingerprints and diverse behavioural profiles. This parcellation was consistent between groups and highly replicable across individuals (up to 93% detection suggesting that the organisation of cortico-cingulo connections is highly similar between groups. However, our results showed an age-related increase in connectivity between the anterior middle cingulate cortex and right lateral prefrontal cortex in ASD, whilst this connectivity decreased in controls. There was also a Group × Grey Matter (GM interaction, showing increased connectivity between the anterior cingulate cortex and the rectal gyrus in concert with increasing rectal gyrus GM in controls. By comparing our approach to previously established methods we revealed that our approach improves network detection in both groups, and that the ability to detect group differences using 4 mm radius spheres varies greatly with seed placement. Using our multi-modal approach we find disrupted cortico-cingulo circuits that, based on task-dependent information, may contribute to ASD deficits in attention and social interaction. Moreover, we highlight how more sensitive approaches to RS-fMRI are crucial for

  11. Stimulating the Brain's Language Network: Syntactic Ambiguity Resolution after TMS to the Inferior Frontal Gyrus and Middle Temporal Gyrus

    NARCIS (Netherlands)

    Acheson, D.J.; Hagoort, P.

    2013-01-01

    The posterior middle temporal gyrus (MTG) and inferior frontal gyrus (IFG) are two critical nodes of the brain's language network. Previous neuroimaging evidence has supported a dissociation in language comprehension in which parts of the MTG are involved in the retrieval of lexical syntactic

  12. Inflexible Functional Connectivity of the Dorsal Anterior Cingulate Cortex in Adolescent Major Depressive Disorder.

    Science.gov (United States)

    Ho, Tiffany C; Sacchet, Matthew D; Connolly, Colm G; Margulies, Daniel S; Tymofiyeva, Olga; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T

    2017-11-01

    Recent evidence suggests that anterior cingulate cortex (ACC) maturation during adolescence contributes to or underlies the development of major depressive disorder (MDD) during this sensitive period. The ACC is a structure that sits at the intersection of several task-positive networks (eg, central executive network, CEN), which are still developing during adolescence. While recent work using seed-based approaches indicate that depressed adolescents show limited task-evoked vs resting-state connectivity (termed 'inflexibility') between the ACC and task-negative networks, no study has used network-based approaches to investigate inflexibility of the ACC in task-positive networks to understand adolescent MDD. Here, we used graph theory to compare flexibility of network-level topology in eight subregions of the ACC (spanning three task-positive networks) in 42 unmedicated adolescents with MDD and 53 well-matched healthy controls. All participants underwent fMRI scanning during resting state and a response inhibition task that robustly engages task-positive networks. Relative to controls, depressed adolescents were characterized by inflexibility in local efficiency of a key ACC node in the CEN: right dorsal anterior cingulate cortex/medial frontal gyrus (R dACC/MFG). Furthermore, individual differences in flexibility of local efficiency of R dACC/MFG significantly predicted inhibition performance, consistent with current literature demonstrating that flexible network organization affords successful cognitive control. Finally, reduced local efficiency of dACC/MFG during the task was significantly associated with an earlier age of depression onset, consistent with prior work suggesting that MDD may alter functional network development. Our results support a neurodevelopmental hypothesis of MDD wherein dysfunctional self-regulation is potentially reflected by altered ACC maturation.

  13. Attention for speaking: domain-general control from the anterior cingulate cortex in spoken word production

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    Vitoria ePiai

    2013-12-01

    Full Text Available Accumulating evidence suggests that some degree of attentional control is required to regulate and monitor processes underlying speaking. Although progress has been made in delineating the neural substrates of the core language processes involved in speaking, substrates associated with regulatory and monitoring processes have remained relatively underspecified. We report the results of an fMRI study examining the neural substrates related to performance in three attention-demanding tasks varying in the amount of linguistic processing: vocal picture naming while ignoring distractors (picture-word interference, PWI; vocal colour naming while ignoring distractors (Stroop; and manual object discrimination while ignoring spatial position (Simon task. All three tasks had congruent and incongruent stimuli, while PWI and Stroop also had neutral stimuli. Analyses focusing on common activation across tasks identified a portion of the dorsal anterior cingulate cortex that was active in incongruent trials for all three tasks, suggesting that this region subserves a domain-general attentional control function. In the language tasks, this area showed increased activity for incongruent relative to congruent stimuli, consistent with the involvement of domain-general mechanisms of attentional control in word production. The two language tasks also showed activity in anterior-superior temporal gyrus. Activity increased for neutral PWI stimuli (picture and word did not share the same semantic category relative to incongruent (categorically related and congruent stimuli. This finding is consistent with the involvement of language-specific areas in word production, possibly related to retrieval of lexical-semantic information from memory. The current results thus suggest that in addition to engaging language-specific areas for core linguistic processes, speaking also engages the anterior cingulate cortex, a region that is likely implementing domain

  14. Altered SPECT 123I iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa

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    Shinichiro eNagamitsu

    2016-02-01

    Full Text Available Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN in children. The purpose of this study was to examine cortical GABA(A-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single photon emission computed tomography (SPECT measurements using 123I iomazenil, which binds to GABA(A-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26 and the short form of the Profile of Mood States (POMS. Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil binding activity in cortical regions of interest (ROIs and psychometric profiles, and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil binding activity in the anterior posterior cingulate cortex (ACC. Higher POMS subscale scores were significantly associated with lower iomazenil binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC. Depression-Dejection, and Confusion POMS subscale scores, and total POMS score, showed interaction effects with brain regions in iomazenil binding activity. Decreased binding in the ACC and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered in children

  15. Superior temporal gyrus, language function, and autism.

    Science.gov (United States)

    Bigler, Erin D; Mortensen, Sherstin; Neeley, E Shannon; Ozonoff, Sally; Krasny, Lori; Johnson, Michael; Lu, Jeffrey; Provencal, Sherri L; McMahon, William; Lainhart, Janet E

    2007-01-01

    Deficits in language are a core feature of autism. The superior temporal gyrus (STG) is involved in auditory processing, including language, but also has been implicated as a critical structure in social cognition. It was hypothesized that subjects with autism would display different size-function relationships between the STG and intellectual-language-based abilities when compared to controls. Intellectual ability was assessed by either the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) or Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), where three intellectual quotients (IQ) were computed: verbal (VIQ), performance (PIQ), and full-scale (FSIQ). Language ability was assessed by the Clinical Evaluation of Language Fundamentals-Third Edition (CELF-3), also divided into three index scores: receptive, expressive, and total. Seven to 19-year-old rigorously diagnosed subjects with autism (n = 30) were compared to controls (n = 39; 13 of whom had a deficit in reading) of similar age who were matched on education, PIQ, and head circumference. STG volumes were computed based on 1.5 Tesla magnetic resonance imaging (MRI). IQ and CELF-3 performance were highly interrelated regardless of whether subjects had autism or were controls. Both IQ and CELF-3 ability were positively correlated with STG in controls, but a different pattern was observed in subjects with autism. In controls, left STG gray matter was significantly (r = .42, p receptive language on the CELF-3; in contrast, a zero order correlation was found with autism. When plotted by age, potential differences in growth trajectories related to language development associated with STG were observed between controls and those subjects with autism. Taken together, these findings suggest a possible failure in left hemisphere lateralization of language function involving the STG in autism.

  16. Evolution of the mammalian dentate gyrus.

    Science.gov (United States)

    Hevner, Robert F

    2016-02-15

    The dentate gyrus (DG), a part of the hippocampal formation, has important functions in learning, memory, and adult neurogenesis. Compared with homologous areas in sauropsids (birds and reptiles), the mammalian DG is larger and exhibits qualitatively different phenotypes: 1) folded (C- or V-shaped) granule neuron layer, concave toward the hilus and delimited by a hippocampal fissure; 2) nonperiventricular adult neurogenesis; and 3) prolonged ontogeny, involving extensive abventricular (basal) migration and proliferation of neural stem and progenitor cells (NSPCs). Although gaps remain, available data indicate that these DG traits are present in all orders of mammals, including monotremes and marsupials. The exception is Cetacea (whales, dolphins, and porpoises), in which DG size, convolution, and adult neurogenesis have undergone evolutionary regression. Parsimony suggests that increased growth and convolution of the DG arose in stem mammals concurrently with nonperiventricular adult hippocampal neurogenesis and basal migration of NSPCs during development. These traits could all result from an evolutionary change that enhanced radial migration of NSPCs out of the periventricular zones, possibly by epithelial-mesenchymal transition, to colonize and maintain nonperiventricular proliferative niches. In turn, increased NSPC migration and clonal expansion might be a consequence of growth in the cortical hem (medial patterning center), which produces morphogens such as Wnt3a, generates Cajal-Retzius neurons, and is regulated by Lhx2. Finally, correlations between DG convolution and neocortical gyrification (or capacity for gyrification) suggest that enhanced abventricular migration and proliferation of NSPCs played a transformative role in growth and folding of neocortex as well as archicortex. © 2015 Wiley Periodicals, Inc.

  17. The role of medial frontal gyrus in action anticipation in professional badminton players

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    Huan Xu

    2016-11-01

    Full Text Available Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent (BOLD activation was assessed by means of functional magnetic resonance imaging (fMRI. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex. Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate

  18. Spontaneous Activity Associated with Delusions of Schizophrenia in the Left Medial Superior Frontal Gyrus: A Resting-State fMRI Study.

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    Bin Gao

    Full Text Available Delusions of schizophrenia have been found to be associated with alterations of some brain regions in structure and task-induced activation. However, the relationship between spontaneously occurring symptoms and spontaneous brain activity remains unclear. In the current study, 14 schizophrenic patients with delusions and 14 healthy controls underwent a resting-state functional magnetic resonance imaging (RS-fMRI scan. Patients with delusions of schizophrenia patients were rated with Positive and Negative Syndrome Scale (PANSS and Characteristics of Delusional Rating Scale (CDRS. Regional homogeneity (ReHo was calculated to measure the local synchronization of the spontaneous activity in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior cingulate gyrus and left medial superior frontal gyrus were higher in patients, and ReHo of the left superior occipital gyrus was lower, compared to healthy controls. Further, among patients, correlation analysis showed a significant difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the left medial superior frontal gyrus was negatively correlated with patients' CDRS scores but not with delusional PANSS scores. These results suggested that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of delusion in schizophrenia.

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  6. Reduced anterior cingulate gray matter volume in treatment-naïve clinically depressed adolescents

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    Justine Nienke Pannekoek

    2014-01-01

    Full Text Available Adolescent depression is associated with increased risk for suicidality, social and educational impairment, smoking, substance use, obesity, and depression in adulthood. It is of relevance to further our insight in the neurobiological mechanisms underlying this disorder in the developing brain, as this may be essential to optimize treatment and prevention of adolescent depression and its negative clinical trajectories. The equivocal findings of the limited number of studies on neural abnormalities in depressed youth stress the need for further neurobiological investigation of adolescent depression. We therefore performed a voxel-based morphometry study of the hippocampus, amygdala, superior temporal gyrus, and anterior cingulate cortex (ACC in 26 treatment-naïve, clinically depressed adolescents and 26 pair-wise matched healthy controls. Additionally, an exploratory whole-brain analysis was performed. Clinically depressed adolescents showed a volume reduction of the bilateral dorsal ACC compared to healthy controls. However, no association was found between gray matter volume of the ACC and clinical severity scores for depression or anxiety. Our finding of a smaller ACC in clinically depressed adolescents is consistent with literature on depressed adults. Future research is needed to investigate if gray matter abnormalities precede or follow clinical depression in adolescents.

  7. Reduced anterior cingulate gray matter volume in treatment-naïve clinically depressed adolescents☆

    Science.gov (United States)

    Pannekoek, Justine Nienke; van der Werff, Steven J.A.; van den Bulk, Bianca G.; van Lang, Natasja D.J.; Rombouts, Serge A.R.B.; van Buchem, Mark A.; Vermeiren, Robert R.J.M.; van der Wee, Nic J.A.

    2014-01-01

    Adolescent depression is associated with increased risk for suicidality, social and educational impairment, smoking, substance use, obesity, and depression in adulthood. It is of relevance to further our insight in the neurobiological mechanisms underlying this disorder in the developing brain, as this may be essential to optimize treatment and prevention of adolescent depression and its negative clinical trajectories. The equivocal findings of the limited number of studies on neural abnormalities in depressed youth stress the need for further neurobiological investigation of adolescent depression. We therefore performed a voxel-based morphometry study of the hippocampus, amygdala, superior temporal gyrus, and anterior cingulate cortex (ACC) in 26 treatment-naïve, clinically depressed adolescents and 26 pair-wise matched healthy controls. Additionally, an exploratory whole-brain analysis was performed. Clinically depressed adolescents showed a volume reduction of the bilateral dorsal ACC compared to healthy controls. However, no association was found between gray matter volume of the ACC and clinical severity scores for depression or anxiety. Our finding of a smaller ACC in clinically depressed adolescents is consistent with literature on depressed adults. Future research is needed to investigate if gray matter abnormalities precede or follow clinical depression in adolescents. PMID:24501702

  8. Aberrant functional connectivity differentiates retrosplenial cortex from posterior cingulate cortex in prodromal Alzheimer's disease.

    Science.gov (United States)

    Dillen, Kim N H; Jacobs, Heidi I L; Kukolja, Juraj; von Reutern, Boris; Richter, Nils; Onur, Özgür A; Dronse, Julian; Langen, Karl-Josef; Fink, Gereon R

    2016-08-01

    The posterior cingulate cortex (PCC) is a key hub of the default mode network, a resting-state network involved in episodic memory, showing functional connectivity (FC) changes in Alzheimer's disease (AD). However, PCC is a cytoarchitectonically heterogeneous region. Specifically, the retrosplenial cortex (RSC), often subsumed under the PCC, is an area functionally and microanatomically distinct from PCC. To investigate FC patterns of RSC and PCC separately, we used resting-state functional magnetic resonance imaging in healthy aging participants, patients with subjective cognitive impairment, and prodromal AD. Compared to the other 2 groups, we found higher FC from RSC to frontal cortex in subjective cognitive impairment but higher FC to occipital cortex in prodromal AD. Conversely, FC from PCC to the lingual gyrus was higher in prodromal AD. Furthermore, data indicate that RSC and PCC are characterized by differential FC patterns represented by hub-specific interactions with memory and attentions scores in prodromal AD compared to cognitively normal individuals, possibly reflecting compensatory mechanisms for RSC and neurodegenerative processes for PCC. Data thus confirm and extend previous studies suggesting that the RSC is functionally distinct from PCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. From Thirst to Satiety: The Anterior Mid-Cingulate Cortex and Right Posterior Insula Indicate Dynamic Changes in Incentive Value

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    Christoph A. Becker

    2017-05-01

    Full Text Available The cingulate cortex and insula are among the neural structures whose activations have been modulated in functional imaging studies examining discrete states of thirst and drinking to satiation. Building upon these findings, the present study aimed to identify neural structures that change their pattern of activation elicited by water held in the mouth in relation to the internal body state, i.e., proportional to continuous water consumption. Accordingly, participants in a thirsty state were scanned while receiving increments of water until satiety was reached. As expected, fluid ingestion led to a clear decrease in self-reported thirst and the pleasantness ratings of the water ingested. Furthermore, linear decreases in the blood oxygenation level dependent (BOLD response to water ingestion were observed in the anterior mid-cingulate cortex (aMCC and right posterior insula as participants shifted towards the non-thirsty state. In addition, regions in the superior temporal gyrus (STG, supplementary motor area (SMA, superior parietal lobule (SPL, precuneus and calcarine sulcus also showed a linear decrease with increasing fluid consumption. Further analyses related single trial BOLD responses of associated regions to trial-by-trial ratings of thirst and pleasantness. Overall, the aMCC and posterior insula may be key sites of a neural network representing the motivation for drinking based on the dynamic integration of internal state and external stimuli.

  10. Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit—a mechanism of relevance to resistant depression?

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    Jing J. Wong

    2016-02-01

    Full Text Available Background. Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC with other brain regions. Methods. Thirteen right-handed healthy male subjects underwent a 15 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml starting at 5 min. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results. Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC activity became negatively correlated with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion. Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.

  11. Anterior Cingulate Cortex in Schema Assimilation and Expression

    Science.gov (United States)

    Wang, Szu-Han; Tse, Dorothy; Morris, Richard G. M.

    2012-01-01

    In humans and in animals, mental schemas can store information within an associative framework that enables rapid and efficient assimilation of new information. Using a hippocampal-dependent paired-associate task, we now report that the anterior cingulate cortex is part of a neocortical network of schema storage with NMDA receptor-mediated…

  12. Mining the posterior cingulate: Segregation between memory and pain components

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Balslev, Daniela; Hansen, Lars Kai

    2005-01-01

    We present a general method for automatic meta-analyses in neuroscience and apply it on text data from published functional imaging studies to extract main functions associated with a brain area --- the posterior cingulate cortex. Abstracts from PubMed are downloaded, words extracted and converted...

  13. Spiders, ladybugs and bees: A case of unusual sensations in a child with cingulate epilepsy

    Directory of Open Access Journals (Sweden)

    Robyn Whitney

    2017-01-01

    Full Text Available Cingulate epilepsy is a rare form of epilepsy. Seizures from the anterior cingulate may present with mood change, fear, hypermotor activity, and autonomic signs, while posterior cingulate seizures resemble temporal lobe seizures. We describe a child with cingulate epilepsy who experienced unpleasant/painful sensory phenomenon. The sensations were described as spiders crawling on his forehead/right leg, ladybugs causing right ear pain and bees stinging his head/right extremities. Unpleasant sensory phenomenon/pain are rarely reported in cingulate epilepsy. Recognizing the role of the cingulate in producing pain/unusual sensory phenomenon is important, and may have localizing value when evaluating children for epilepsy surgery.

  14. Spiders, ladybugs and bees: A case of unusual sensations in a child with cingulate epilepsy.

    Science.gov (United States)

    Whitney, Robyn; AlMehmadi, Sameer; Go, Cristina; Ochi, Ayako; Otsubo, Hiroshi; Bradbury, Laura; Jones, Kevin; Christian, Eisha; Rutka, James; McCoy, Bláthnaid

    2017-01-01

    Cingulate epilepsy is a rare form of epilepsy. Seizures from the anterior cingulate may present with mood change, fear, hypermotor activity, and autonomic signs, while posterior cingulate seizures resemble temporal lobe seizures. We describe a child with cingulate epilepsy who experienced unpleasant/painful sensory phenomenon. The sensations were described as spiders crawling on his forehead/right leg, ladybugs causing right ear pain and bees stinging his head/right extremities. Unpleasant sensory phenomenon/pain are rarely reported in cingulate epilepsy. Recognizing the role of the cingulate in producing pain/unusual sensory phenomenon is important, and may have localizing value when evaluating children for epilepsy surgery.

  15. Spiders, ladybugs and bees: A case of unusual sensations in a child with cingulate epilepsy

    OpenAIRE

    Robyn Whitney; Sameer AlMehmadi; Cristina Go; Ayako Ochi; Hiroshi Otsubo; Laura Bradbury; Kevin Jones; Eisha Christian; James Rutka; Bláthnaid McCoy

    2017-01-01

    Cingulate epilepsy is a rare form of epilepsy. Seizures from the anterior cingulate may present with mood change, fear, hypermotor activity, and autonomic signs, while posterior cingulate seizures resemble temporal lobe seizures. We describe a child with cingulate epilepsy who experienced unpleasant/painful sensory phenomenon. The sensations were described as spiders crawling on his forehead/right leg, ladybugs causing right ear pain and bees stinging his head/right extremities. Unpleasant se...

  16. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  17. The dorsal prefrontal and dorsal anterior cingulate cortices exert complementary network signatures during encoding and retrieval in associative memory.

    Science.gov (United States)

    Woodcock, Eric A; White, Richard; Diwadkar, Vaibhav A

    2015-09-01

    Cognitive control includes processes that facilitate execution of effortful cognitive tasks, including associative memory. Regions implicated in cognitive control during associative memory include the dorsal prefrontal (dPFC) and dorsal anterior cingulate cortex (dACC). Here we investigated the relative degrees of network-related interactions originating in the dPFC and dACC during oscillating phases of associative memory: encoding and cued retrieval. Volunteers completed an established object-location associative memory paradigm during fMRI. Psychophysiological interactions modeled modulatory network interactions from the dPFC and dACC during memory encoding and retrieval. Results were evaluated in second level analyses of variance with seed region and memory process as factors. Each seed exerted differentiable modulatory effects during encoding and retrieval. The dACC exhibited greater modulation (than the dPFC) on the fusiform and parahippocampal gyrus during encoding, while the dPFC exhibited greater modulation (than the dACC) on the fusiform, hippocampus, dPFC and basal ganglia. During retrieval, the dPFC exhibited greater modulation (than the dACC) on the parahippocampal gyrus, hippocampus, superior parietal lobule, and dPFC. The most notable finding was a seed by process interaction indicating that the dACC and the dPFC exerted complementary modulatory control on the hippocampus during each of the associative memory processes. These results provide evidence for differentiable, yet complementary, control-related modulation by the dACC and dPFC, while establishing the primacy of dPFC in exerting network control during both associative memory phases. Our approach and findings are relevant for understanding basic processes in human memory and psychiatric disorders that impact associative memory-related networks. Copyright © 2015. Published by Elsevier B.V.

  18. The Subgenual Anterior Cingulate Cortex in Mood Disorders

    Science.gov (United States)

    Drevets, Wayne C.; Savitz, Jonathan; Trimble, Michael

    2009-01-01

    INTRODUCTION In the latest edition of our series of neuroanatomical areas of importance for neuropsychiatry, Wayne Drevets, MD, and Jonathan Savitz, PhD, have outlined the clinical importance of the ventral anterior cingulate structures for the regulation of mood. This area was an early target for interventional neurosurgery for depression some half a century ago, and today has become one of the key sites of deep brain stimulation for affective disorders. The anterior cingulate cortex was a part of the initial circuit of Papez thought to be related to the regulation of emotion. However, since then, much experimental work has outlined different cingulate regions with differing anatomical connectivity and functions. Drevets and Savitz draw attention to the subgenual area and describe the local and distant anatomical connectivities that emphasize its relevance for several neuropsychiatric disorders. ABSTRACT The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this “subgenual” ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other

  19. The dorsal anterior cingulate cortex modulates dialectical self-thinking

    OpenAIRE

    Fei eWang; Kaiping ePeng; Yang eBai; Rui eLi; Ying eZhu; Pei eSun; Hua eGuo; Chun eYuan; Pia eRotshtein; Jie eSui

    2016-01-01

    Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here, we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgme...

  20. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation

    Directory of Open Access Journals (Sweden)

    Alessandro eGrecucci

    2013-09-01

    Full Text Available Previous studies have reported the effect of emotion regulation strategies on both individual and social decision making, however the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer’s intentions as more negative, down-regulation (reappraising the proposer’s intentions as less negative, as well as a baseline ‘look’ condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, regulating regions were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, regulated regions were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners’ behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal emotion regulation strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others’ intentions may affect the way we emotionally react.

  1. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation.

    Science.gov (United States)

    Grecucci, Alessandro; Giorgetta, Cinzia; Bonini, Nicolao; Sanfey, Alan G

    2013-01-01

    Previous studies have reported the effect of emotion regulation (ER) strategies on both individual and social decision-making, however, the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game (DG) in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer's intentions as more negative), down-regulation (reappraising the proposer's intentions as less negative), as well as a baseline "look" condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, "regulating regions") were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, "regulated regions") were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners' behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal ER strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others' intentions may affect the way we emotionally react.

  2. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation

    Science.gov (United States)

    Grecucci, Alessandro; Giorgetta, Cinzia; Bonini, Nicolao; Sanfey, Alan G.

    2013-01-01

    Previous studies have reported the effect of emotion regulation (ER) strategies on both individual and social decision-making, however, the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game (DG) in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer's intentions as more negative), down-regulation (reappraising the proposer's intentions as less negative), as well as a baseline “look” condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, “regulating regions”) were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, “regulated regions”) were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners' behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal ER strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others' intentions may affect the way we emotionally react. PMID:24027512

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  15. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients

    DEFF Research Database (Denmark)

    Garza-Villarreal, Eduardo A; Jiang, Zhiguo; Vuust, Peter

    2015-01-01

    , correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (r......Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without...... external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn...

  16. Segregated and integrated coding of reward and punishment in the cingulate cortex.

    Science.gov (United States)

    Fujiwara, Juri; Tobler, Philippe N; Taira, Masato; Iijima, Toshio; Tsutsui, Ken-Ichiro

    2009-06-01

    Reward and punishment have opposite affective value but are both processed by the cingulate cortex. However, it is unclear whether the positive and negative affective values of monetary reward and punishment are processed by separate or common subregions of the cingulate cortex. We performed a functional magnetic resonance imaging study using a free-choice task and compared cingulate activations for different levels of monetary gain and loss. Gain-specific activation (increasing activation for increasing gain, but no activation change in relation to loss) occurred mainly in the anterior part of the anterior cingulate and in the posterior cingulate cortex. Conversely, loss-specific activation (increasing activation for increasing loss, but no activation change in relation to gain) occurred between these areas, in the middle and posterior part of the anterior cingulate. Integrated coding of gain and loss (increasing activation throughout the full range, from biggest loss to biggest gain) occurred in the dorsal part of the anterior cingulate, at the border with the medial prefrontal cortex. Finally, unspecific activation increases to both gains and losses (increasing activation to increasing gains and increasing losses, possibly reflecting attention) occurred in dorsal and middle regions of the cingulate cortex. Together, these results suggest separate and common coding of monetary reward and punishment in distinct subregions of the cingulate cortex. Further meta-analysis suggested that the presently found reward- and punishment-specific areas overlapped with those processing positive and negative emotions, respectively.

  17. Inferior Frontal Gyrus Activation Underlies the Perception of Emotions, While Precuneus Activation Underlies the Feeling of Emotions during Music Listening.

    Science.gov (United States)

    Tabei, Ken-ichi

    2015-01-01

    While music triggers many physiological and psychological reactions, the underlying neural basis of perceived and experienced emotions during music listening remains poorly understood. Therefore, using functional magnetic resonance imaging (fMRI), I conducted a comparative study of the different brain areas involved in perceiving and feeling emotions during music listening. I measured fMRI signals while participants assessed the emotional expression of music (perceived emotion) and their emotional responses to music (felt emotion). I found that cortical areas including the prefrontal, auditory, cingulate, and posterior parietal cortices were consistently activated by the perceived and felt emotional tasks. Moreover, activity in the inferior frontal gyrus increased more during the perceived emotion task than during a passive listening task. In addition, the precuneus showed greater activity during the felt emotion task than during a passive listening task. The findings reveal that the bilateral inferior frontal gyri and the precuneus are important areas for the perception of the emotional content of music as well as for the emotional response evoked in the listener. Furthermore, I propose that the precuneus, a brain region associated with self-representation, might be involved in assessing emotional responses.

  18. Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2009-05-01

    Full Text Available Abstract Functional human brain imaging studies have indicated the essential role of cortical regions, such as the anterior cingulate cortex (ACC, in romantic love and sex. However, the neurobiological basis of how the ACC neurons are activated and engaged in sexual attraction remains unknown. Using transgenic mice in which the expression of green fluorescent protein (GFP is controlled by the promoter of the activity-dependent gene c-fos, we found that ACC pyramidal neurons are activated by sexual attraction. The presynaptic glutamate release to the activated neurons is increased and pharmacological inhibition of neuronal activities in the ACC reduced the interest of male mice to female mice. Our results present direct evidence of the critical role of the ACC in sexual attraction, and long-term increases in glutamate mediated excitatory transmission may contribute to sexual attraction between male and female mice.

  19. Posterior Cingulate Neurons Dynamically Signal Decisions to Disengage during Foraging.

    Science.gov (United States)

    Barack, David L; Chang, Steve W C; Platt, Michael L

    2017-10-11

    Foraging for resources is a fundamental behavior balancing systematic search and strategic disengagement. The foraging behavior of primates is especially complex and requires long-term memory, value comparison, strategic planning, and decision-making. Here we provide evidence from two different foraging tasks that neurons in primate posterior cingulate cortex (PCC) signal decision salience during foraging to motivate disengagement from the current strategy. In our foraging tasks, salience refers to the difference between decision thresholds and the net harvested reward. Salience signals were stronger in poor foraging contexts than rich ones, suggesting low harvest rates recruit mechanisms in PCC that regulate strategic disengagement and exploration during foraging. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Motivation of extended behaviors by anterior cingulate cortex.

    Science.gov (United States)

    Holroyd, Clay B; Yeung, Nick

    2012-02-01

    Intense research interest over the past decade has yielded diverse and often discrepant theories about the function of anterior cingulate cortex (ACC). In particular, a dichotomy has emerged between neuropsychological theories suggesting a primary role for ACC in motivating or 'energizing' behavior, and neuroimaging-inspired theories emphasizing its contribution to cognitive control and reinforcement learning. To reconcile these views, we propose that ACC supports the selection and maintenance of 'options' - extended, context-specific sequences of behavior directed toward particular goals - that are learned through a process of hierarchical reinforcement learning. This theory accounts for ACC activity in relation to learning and control while simultaneously explaining the effects of ACC damage as disrupting the motivational context supporting the production of goal-directed action sequences. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Immature Dentate Gyrus: An Endophenotype of Neuropsychiatric Disorders

    Science.gov (United States)

    Walton, Noah M.; Matsumoto, Mitsuyuki; Miyakawa, Tsuyoshi

    2013-01-01

    Adequate maturation of neurons and their integration into the hippocampal circuit is crucial for normal cognitive function and emotional behavior, and disruption of this process could cause disturbances in mental health. Previous reports have shown that mice heterozygous for a null mutation in α-CaMKII, which encodes a key synaptic plasticity molecule, display abnormal behaviors related to schizophrenia and other psychiatric disorders. In these mutants, almost all neurons in the dentate gyrus are arrested at a pseudoimmature state at the molecular and electrophysiological levels, a phenomenon defined as “immature dentate gyrus (iDG).” To date, the iDG phenotype and shared behavioral abnormalities (including working memory deficit and hyperlocomotor activity) have been discovered in Schnurri-2 knockout, mutant SNAP-25 knock-in, and forebrain-specific calcineurin knockout mice. In addition, both chronic fluoxetine treatment and pilocarpine-induced seizures reverse the neuronal maturation, resulting in the iDG phenotype in wild-type mice. Importantly, an iDG-like phenomenon was observed in post-mortem analysis of brains from patients with schizophrenia/bipolar disorder. Based on these observations, we proposed that the iDG is a potential endophenotype shared by certain types of neuropsychiatric disorders. This review summarizes recent data describing this phenotype and discusses the data's potential implication in elucidating the pathophysiology of neuropsychiatric disorders. PMID:23840971

  2. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients.

    Science.gov (United States)

    Garza-Villarreal, Eduardo A; Jiang, Zhiguo; Vuust, Peter; Alcauter, Sarael; Vase, Lene; Pasaye, Erick H; Cavazos-Rodriguez, Roberto; Brattico, Elvira; Jensen, Troels S; Barrios, Fernando A

    2015-01-01

    Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (rACC), right supplementary motor area (rSMA), precuneus and right precentral gyrus (rPreG). Pain intensity (PI) analgesia was correlated (r = 0.61) to the connectivity of the lAnG with the rPreG. Our results show that MIA in FM is related to top-down regulation of the pain modulatory network by the default mode network (DMN).

  3. Dissociation between the activity of the right middle frontal gyrus and the middle temporal gyrus in processing semantic priming.

    Directory of Open Access Journals (Sweden)

    Ilan Laufer

    Full Text Available The aim of this event-related functional magnetic resonance imaging (fMRI study was to test whether the right middle frontal gyrus (MFG and middle temporal gyrus (MTG would show differential sensitivity to the effect of prime-target association strength on repetition priming. In the experimental condition (RP, the target occurred after repetitive presentation of the prime within an oddball design. In the control condition (CTR, the target followed a single presentation of the prime with equal probability of the target as in RP. To manipulate semantic overlap between the prime and the target both conditions (RP and CTR employed either the onomatopoeia "oink" as the prime and the referent "pig" as the target (OP or vice-versa (PO since semantic overlap was previously shown to be greater in OP. The results showed that the left MTG was sensitive to release of adaptation while both the right MTG and MFG were sensitive to sequence regularity extraction and its verification. However, dissociated activity between OP and PO was revealed in RP only in the right MFG. Specifically, target "pig" (OP and the physically equivalent target in CTR elicited comparable deactivations whereas target "oink" (PO elicited less inhibited response in RP than in CTR. This interaction in the right MFG was explained by integrating these effects into a competition model between perceptual and conceptual effects in priming processing.

  4. Dorsal anterior cingulate cortex and the value of control.

    Science.gov (United States)

    Shenhav, Amitai; Cohen, Jonathan D; Botvinick, Matthew M

    2016-09-27

    Debates over the function(s) of dorsal anterior cingulate cortex (dACC) have persisted for decades. So too have demonstrations of the region's association with cognitive control. Researchers have struggled to account for this association and, simultaneously, dACC's involvement in phenomena related to evaluation and motivation. We describe a recent integrative theory that achieves this goal. It proposes that dACC serves to specify the currently optimal allocation of control by determining the overall expected value of control (EVC), thereby licensing the associated cognitive effort. The EVC theory accounts for dACC's sensitivity to a wide array of experimental variables, and their relationship to subsequent control adjustments. Finally, we contrast our theory with a recent theory proposing a primary role for dACC in foraging-like decisions. We describe why the EVC theory offers a more comprehensive and coherent account of dACC function, including dACC's particular involvement in decisions regarding foraging or otherwise altering one's behavior.

  5. Reward-based contextual learning supported by anterior cingulate cortex.

    Science.gov (United States)

    Umemoto, Akina; HajiHosseini, Azadeh; Yates, Michael E; Holroyd, Clay B

    2017-06-01

    The anterior cingulate cortex (ACC) is commonly associated with cognitive control and decision making, but its specific function is highly debated. To explore a recent theory that the ACC learns the reward values of task contexts (Holroyd & McClure in Psychological Review, 122, 54-83, 2015; Holroyd & Yeung in Trends in Cognitive Sciences, 16, 122-128, 2012), we recorded the event-related brain potentials (ERPs) from participants as they played a novel gambling task. The participants were first required to select from among three games in one "virtual casino," and subsequently they were required to select from among three different games in a different virtual casino; unbeknownst to them, the payoffs for the games were higher in one casino than in the other. Analysis of the reward positivity, an ERP component believed to reflect reward-related signals carried to the ACC by the midbrain dopamine system, revealed that the ACC is sensitive to differences in the reward values associated with both the casinos and the games inside the casinos, indicating that participants learned the values of the contexts in which rewards were delivered. These results highlight the importance of the ACC in learning the reward values of task contexts in order to guide action selection.

  6. The structural involvement of the cingulate cortex in premanifest and early Huntington's disease.

    Science.gov (United States)

    Hobbs, Nicola Z; Pedrick, Amy V; Say, Miranda J; Frost, Chris; Dar Santos, Rachelle; Coleman, Allison; Sturrock, Aaron; Craufurd, David; Stout, Julie C; Leavitt, Blair R; Barnes, Josephine; Tabrizi, Sarah J; Scahill, Rachael I

    2011-08-01

    The impact of Huntington's disease neuropathology on the structure of the cingulate is uncertain, with evidence of both cortical enlargement and atrophy in this structure in early clinical disease. We sought to determine differences in cingulate volume between premanifest Huntington's disease and early Huntington's disease groups compared with controls using detailed manual measurements. Thirty controls, 30 subjects with premanifest Huntington's disease, and 30 subjects with early Huntington's disease were selected from the Vancouver site of the TRACK-HD study. Subjects underwent 3 Tesla magnetic resonance imaging and motor, cognitive, and neuropsychiatric assessment. The cingulate was manually delineated and subdivided into rostral, caudal, and posterior segments. Group differences in volume and associations with performance on 4 tasks thought to utilize cingulate function were examined, with adjustment for appropriate covariates. Cingulate volumes were, on average, 1.7 mL smaller in early Huntington's disease (P=.001) and 0.9 mL smaller in premanifest Huntington's disease (P=.1) compared with controls. Smaller volumes in subsections of the cingulate were associated with impaired recognition of negative emotions (P=.04), heightened depression (P=.009), and worse visual working memory performance (P=.01). There was no evidence of associations between volume and ability on a performance-monitoring task. This study disputes previous findings of enlargement of the cingulate cortex in Huntington's disease and instead suggests that the cingulate undergoes structural degeneration during early Huntington's disease with directionally consistent, nonsignificant differences seen in premanifest Huntington's disease. Cingulate atrophy may contribute to deficits in mood, emotional processing, and visual working memory in Huntington's disease. Copyright © 2011 Movement Disorder Society.

  7. Enhanced rostral anterior cingulate cortex activation during cognitive control is related to orbitofrontal volume reduction in unipolar depression.

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    Wagner, Gerd; Koch, Kathrin; Schachtzabel, Claudia; Reichenbach, Jürgen R; Sauer, Heinrich; Schlösser Md, Ralf G M

    2008-05-01

    In patients with major depressive disorder (MDD), enhanced activation of the rostral anterior cingulate cortex (rACC) during conflict resolution has been demonstrated with the use of functional magnetic resonance imaging (fMRI), which suggests dysregulation of the affective compartment of the ACC associated with error monitoring and cognitive control. Moreover, several previous studies have reported disrupted structural integrity in limbic brain areas and the orbitofrontal cortex in MDD. However, the relation between structural and functional alterations remains unclear. Therefore, the present study sought to investigate whether structural brain aberrations in terms of grey matter decreases directly in the medial frontal regions or in anatomically closely connected areas might be related to our previously reported functional alterations. A sample of 16 female, drug-free patients with an acute episode of MDD and 16 healthy control subjects matched for age, sex and education were examined with structural high-resolution T(1)-weighted MRI; fMRI images were obtained in the same session. Voxel-based morphometry (VBM) revealed grey matter decreases in the orbitofrontal and subgenual cortex, in the hippocampus-amygdala complex and in the middle frontal gyrus. The relative hyperactivation of the rACC in terms of inability to deactivate this region during the Stroop Color-Word Test showed an inverse correlation with grey matter reduction in the orbitofrontal cortex. The present study provides strong evidence for an association between structural alterations in the orbitofrontal cortex and disturbed functional activation in the emotional compartment of the ACC in patients with MDD during cognitive control.

  8. Effect of dentate gyrus disruption on remembering what happened where

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    Min W Jung

    2015-06-01

    Full Text Available Our previous studies using Bax knockout (Bax-KO mice, in which newly generated granule cells continue to accumulate, disrupting neural circuitry specifically in the dentate gyrus (DG, suggest the involvement of the DG in binding the internally-generated spatial map with sensory information on external landmarks (spatial map-object association in forming a distinct spatial context for each environment. In order to test whether the DG is also involved in binding the internal spatial map with sensory information on external events (spatial map-event association, we tested the behavior of Bax-KO mice in a delayed-non-match-to-place task. Performance of Bax-KO mice was indistinguishable from that of wild-type mice as long as there was no interruption during the delay period (tested up to 5 min, suggesting that on-line maintenance of working memory is intact in Bax-KO mice. However, Bax-KO mice showed profound performance deficits when they were removed from the maze during the delay period (interruption condition with a sufficiently long (65 s delay, suggesting that episodic memory was impaired in Bax-KO mice. Together with previous findings, these results suggest the role of the DG in binding spatial information derived from dead reckoning and nonspatial information, such as external objects and events, in the process of encoding episodic memory.

  9. The angular gyrus: multiple functions and multiple subdivisions.

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    Seghier, Mohamed L

    2013-02-01

    There is considerable interest in the structural and functional properties of the angular gyrus (AG). Located in the posterior part of the inferior parietal lobule, the AG has been shown in numerous meta-analysis reviews to be consistently activated in a variety of tasks. This review discusses the involvement of the AG in semantic processing, word reading and comprehension, number processing, default mode network, memory retrieval, attention and spatial cognition, reasoning, and social cognition. This large functional neuroimaging literature depicts a major role for the AG in processing concepts rather than percepts when interfacing perception-to-recognition-to-action. More specifically, the AG emerges as a cross-modal hub where converging multisensory information is combined and integrated to comprehend and give sense to events, manipulate mental representations, solve familiar problems, and reorient attention to relevant information. In addition, this review discusses recent findings that point to the existence of multiple subdivisions in the AG. This spatial parcellation can serve as a framework for reporting AG activations with greater definition. This review also acknowledges that the role of the AG cannot comprehensibly be identified in isolation but needs to be understood in parallel with the influence from other regions. Several interesting questions that warrant further investigations are finally emphasized.

  10. Cholinergic mechanism involved in the nociceptive modulation of dentate gyrus.

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    Jiao, Runsheng; Yang, Chunxiao; Zhang, Ying; Xu, Manying; Yang, Xiaofang

    2009-02-20

    Acetylcholine (ACh) causes a wide variety of anti-nociceptive effects. The dentate gyrus (DG) region of the hippocampal formation (HF) has been demonstrated to be involved in nociceptive perception. However, the mechanisms underlying this anti-nociceptive role have not yet been elucidated in the cholinergic pain-related neurons of DG. The electrical activities of pain-related neurons of DG were recorded by a glass microelectrode. Two kinds of pain-related neurons were found: pain-excited neurons (PEN) and pain-inhibited neurons (PIN). The experimental protocol involved intra-DG administration of muscarinic cholinergic receptor (mAChR) agonist or antagonist. Intra-DG microinjection of 1 microl of ACh (0.2 microg/microl) or 1 microl of pilocarpine (0.4 microg/microl) decreased the discharge frequency of PEN and prolonged firing latency, but increased the discharge frequency of PIN and shortened PIN inhibitory duration (ID). Intra-DG administration of 1 microl of atropine (1.0 microg/microl) showed exactly the opposite effects. According to the above experimental results, we can presume that cholinergic pain-related neurons in DG are involved in the modulation of the nociceptive response by affecting the discharge of PEN and PIN.

  11. Participation of the left inferior frontal gyrus in human originality.

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    Kleinmintz, Oded M; Abecasis, Donna; Tauber, Amitay; Geva, Amit; Chistyakov, Andrei V; Kreinin, Isabella; Klein, Ehud; Shamay-Tsoory, Simone G

    2018-01-01

    Human creative cognition is commonly described as a twofold cyclic process that involves an idea generation phase and an idea evaluation phase. Although the evaluation phase makes a crucial contribution to originality, its underlying mechanisms have not received sufficient research attention. Here, we suggest that the left inferior frontal gyrus (lIFG) plays a major role in the interplay between the evaluation and generation networks and that inhibiting this region's activity may have an effect on "releasing" the generation neural network, resulting in greater originality. To examine the neural networks that mediate the generation and evaluation of ideas, we conducted an fMRI experiment on a group of healthy human participants (Study 1), in which we compared an idea generation task to an idea evaluation task. We found that evaluating the originality of ideas is indeed associated with a relative increase in lIFG activation, as opposed to generating original ideas. We further showed that temporarily inhibiting the lIFG using continuous theta-burst stimulation (Study 2) results in less strict evaluation on the one hand and increased originality scores on the other. Our findings provide converging evidence from multiple methods to show that the lIFG participates in evaluating the originality of ideas.

  12. Morphologic and electrophysiologic maturation in developing dentate gyrus granule cells.

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    Liu, X; Tilwalli, S; Ye, G; Lio, P A; Pasternak, J F; Trommer, B L

    2000-02-21

    Dentate gyrus granule cells from immature (7-28 days) Sprague-Dawley rats were examined with whole cell patch clamp recordings and biocytin filling in in vitro hippocampal slice preparations. Although recordings were confined to the middle third of the suprapyramidal limb of the dentate, the granule cells exhibited marked variability in their physiologic properties: input resistance (IR) ranged from 250 MOmega to 3 GOmega, and resting membrane potential (RMP) from -82 to -41 mV. Both IR and RMP were inversely correlated with dendritic length, a morphometric indicator of cell maturity. Thus the highest IR cells were the youngest, and maturation was characterized by a progressive decrease in IR, hyperpolarization of RMP, and elongation of the dendritic arbor. When cells were grouped by IR, significant intergroup differences were found in RMP, dendritic length, and number of dendritic terminal branches. Although cells of all IR categories were examined throughout the age spectrum under study, none of the inter-IR group differences was age-dependent. These data suggest that IR provides a reasonable estimate of granule cell maturity and that maturation entails predictable changes in cell properties and morphology. These aspects of maturation correlate with each other, are independent of animal age, and most likely proceed according to a program related to cell birth.

  13. Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease

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    Laura J. de Schipper

    2017-01-01

    Conclusions: We identified loss of integrity and atrophy in the anterior and posterior cingulate networks in PD patients. Abnormalities of both networks were associated with predominantly non-dopaminergic features, specifically cognition and excessive daytime sleepiness. Our findings suggest that (components of the cingulate networks display a specific vulnerability to the pathobiology of PD and may operate as interfaces between networks involved in cognition and alertness.

  14. DETACHING FROM THE NEGATIVE BY REAPPRAISAL: THE ROLE OF RIGHT SUPERIOR FRONTAL GYRUS (BA9/32

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    Rosalux eFalquez

    2014-05-01

    Full Text Available The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself, i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and grey matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM analysis to identify deficit related areas (ROI. Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM analysis was run, in which healthy participant’s REAPPself ability scores were correlated with grey matter intensities. Results showed that 1 regions in the right superior frontal gyrus (SFG, comprising the right dorsolateral prefrontal cortex (BA9 and the right dorsal anterior cingulate cortex (BA32, were associated with patient’s impaired down-regulation of arousal, 2 a lesion in the depicted ROI occasioned significant REAPPself impairments, 3 REAPPself ability of controls was linked with increased grey matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32 might be indispensable for REAPPself. Implications for neurofeedback research

  15. Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type

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    Ravi Rajmohan

    2017-05-01

    Full Text Available Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT through the use of the sex determination test (SDT. In the current study, four (1 female, 3 males CDDAT and nine (4 females, 5 males age-matched neurotypicals (NT completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA and anterior cingulate cortex (ACC. DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC, but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability.

  16. Separate face and body selectivity on the fusiform gyrus.

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    Schwarzlose, Rebecca F; Baker, Chris I; Kanwisher, Nancy

    2005-11-23

    Recent reports of a high response to bodies in the fusiform face area (FFA) challenge the idea that the FFA is exclusively selective for face stimuli. We examined this claim by conducting a functional magnetic resonance imaging experiment at both standard (3.125 x 3.125 x 4.0 mm) and high resolution (1.4 x 1.4 x 2.0 mm). In both experiments, regions of interest (ROIs) were defined using data from blocked localizer runs. Within each ROI, we measured the mean peak response to a variety of stimulus types in independent data from a subsequent event-related experiment. Our localizer scans identified a fusiform body area (FBA), a body-selective region reported recently by Peelen and Downing (2005) that is anatomically distinct from the extrastriate body area. The FBA overlapped with and was adjacent to the FFA in all but two participants. Selectivity of the FFA to faces and FBA to bodies was stronger for the high-resolution scans, as expected from the reduction in partial volume effects. When new ROIs were constructed for the high-resolution experiment by omitting the voxels showing overlapping selectivity for both bodies and faces in the localizer scans, the resulting FFA* ROI showed no response above control objects for body stimuli, and the FBA* ROI showed no response above control objects for face stimuli. These results demonstrate strong selectivities in distinct but adjacent regions in the fusiform gyrus for only faces in one region (the FFA*) and only bodies in the other (the FBA*).

  17. Adiponectin modulates synaptic plasticity in hippocampal dentate gyrus.

    Science.gov (United States)

    Pousti, Farideh; Ahmadi, Ramesh; Mirahmadi, Fatemeh; Hosseinmardi, Narges; Rohampour, Kambiz

    2018-01-01

    Recent studies have suggested the involvement of some metabolic hormones in memory formation and synaptic plasticity. Insulin dysfunction is known as an essential process in the pathogenesis of sporadic Alzheimer's disease (AD). In this study we examined whether adiponectin (ADN), as an insulin-sensitizing adipokine, could affect hippocampal synaptic plasticity. Field potential recordings were performed on intracerebroventricular (icv) cannulated urethane anesthetized rats. After baseline recording from dentate gyrus (DG) and 10min prior to high/low frequency stimulation (HFS/LFS), 10μl icv ADN (600nm) were injected. The slope of field excitatory postsynaptic potentials (fEPSP) and the amplitude of population spikes (PS) were recorded in response to perforanth path (PP) stimulation. Paired pulse stimuli and ADN injection without any stimulation protocols were also evaluated. Application of ADN before HFS increased PS amplitude recorded in DG significantly (P≤0.05) in comparison to HFS only group. ADN suppressed the potency of LFS to induce long-term depression (LTD), causing a significant difference between fEPSP slope (P≤0.05) and PS amplitude (P≤0.01) between ADN+LFS and ADN group. Paired pulse stimuli applied at 20ms intervals showed more paired pulse facilitation (PPF), when applied after ADN (P≤0.05). ADN induced a chemical long-term potentiation (LTP) in which fEPSP slope and PS amplitude increased significantly (P≤0.01 and P≤0.05, respectively). It is concluded that ADN is able to potentiate the HFS-induced LTP and suppress LFS-induced LTD. ADN caused a chemical LTP, when applied without any tetanic protocol. ADN may enhance the presynaptic release probability. Copyright © 2017. Published by Elsevier B.V.

  18. Human primary auditory cortex follows the shape of Heschl's gyrus.

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    Da Costa, Sandra; van der Zwaag, Wietske; Marques, Jose P; Frackowiak, Richard S J; Clarke, Stephanie; Saenz, Melissa

    2011-10-05

    The primary auditory cortex (PAC) is central to human auditory abilities, yet its location in the brain remains unclear. We measured the two largest tonotopic subfields of PAC (hA1 and hR) using high-resolution functional MRI at 7 T relative to the underlying anatomy of Heschl's gyrus (HG) in 10 individual human subjects. The data reveals a clear anatomical-functional relationship that, for the first time, indicates the location of PAC across the range of common morphological variants of HG (single gyri, partial duplications, and complete duplications). In 20/20 individual hemispheres, two primary mirror-symmetric tonotopic maps were clearly observed with gradients perpendicular to HG. PAC spanned both divisions of HG in cases of partial and complete duplications (11/20 hemispheres), not only the anterior division as commonly assumed. Specifically, the central union of the two primary maps (the hA1-R border) was consistently centered on the full Heschl's structure: on the gyral crown of single HGs and within the sulcal divide of duplicated HGs. The anatomical-functional variants of PAC appear to be part of a continuum, rather than distinct subtypes. These findings significantly revise HG as a marker for human PAC and suggest that tonotopic maps may have shaped HG during human evolution. Tonotopic mappings were based on only 16 min of fMRI data acquisition, so these methods can be used as an initial mapping step in future experiments designed to probe the function of specific auditory fields.

  19. Early and sustained supramarginal gyrus contributions to phonological processing

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    Magdalena Wiktoria Wiktoria Sliwinska

    2012-05-01

    Full Text Available Reading is a surprisingly difficult task that, at a minimum, requires recognizing a visual stimulus and linking it with its corresponding sound and meaning. Neurologically, this involves an anatomically distributed set of brain regions cooperating to solve the problem. It has been hypothesized that the supramarginal gyrus (SMG contributes preferentially to phonological aspects of word processing and thus plays an important role in visual word recognition. Here, we used chronometric transcranial magnetic stimulation (TMS to investigate the functional specificity and timing of SMG involvement in reading visually presented words. Participants performed tasks designed to focus on either the phonological, semantic, or visual aspects of written words while double pulses of TMS (delivered 40 msec apart were used to temporarily interfere with neural information processing in the left SMG at five different time windows. Stimulation at 80/120, 120/160 and 160/200 msec post-stimulus onset significantly slowed subjects’ reaction times in the phonological task. This inhibitory effect was specific to the phonological condition, with no effect of TMS in the semantic or visual tasks, consistent with claims that SMG contributes preferentially to phonological aspects of word processing. The fact that the effect began within 80–120 msec of the onset of the stimulus and continued for approximately 100 msec, indicates that phonological processing initiates early and is sustained over time. These findings are consistent with accounts of visual word recognition that posit parallel activation of orthographic, phonological and semantic information that interact over time to settle into a distributed, but stable, representation of a word.

  20. Early and sustained supramarginal gyrus contributions to phonological processing.

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    Sliwinska, Magdalena W; Khadilkar, Manali; Campbell-Ratcliffe, Jonathon; Quevenco, Frances; Devlin, Joseph T

    2012-01-01

    Reading is a difficult task that, at a minimum, requires recognizing a visual stimulus and linking it with its corresponding sound and meaning. Neurologically, this involves an anatomically distributed set of brain regions cooperating to solve the problem. It has been hypothesized that the supramarginal gyrus (SMG) contributes preferentially to phonological aspects of word processing and thus plays an important role in visual word recognition. Here, we used chronometric transcranial magnetic stimulation (TMS) to investigate the functional specificity and timing of SMG involvement in reading visually presented words. Participants performed tasks designed to focus on either the phonological, semantic, or visual aspects of written words while double pulses of TMS (delivered 40 ms apart) were used to temporarily interfere with neural information processing in the left SMG at five different time windows. Stimulation at 80/120, 120/160, and 160/200 ms post-stimulus onset significantly slowed subjects' reaction times in the phonological task. This inhibitory effect was specific to the phonological condition, with no effect of TMS in the semantic or visual tasks, consistent with claims that SMG contributes preferentially to phonological aspects of word processing. The fact that the effect began within 80-120 ms of the onset of the stimulus and continued for approximately 100 ms, indicates that phonological processing initiates early and is sustained over time. These findings are consistent with accounts of visual word recognition that posit parallel activation of orthographic, phonological, and semantic information that interact over time to settle into a distributed, but stable, representation of a word.

  1. Dentate gyrus volume and memory performance in major depressive disorder.

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    Travis, Scott; Coupland, Nicholas J; Silversone, Peter H; Huang, Yushan; Fujiwara, Esther; Carter, Rawle; Seres, Peter; Malykhin, Nikolai V

    2015-02-01

    Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Patients with MDD have consistently demonstrated worse performance than healthy controls a number of memory tests. Memory functions within the hippocampus in healthy younger subjects appear to be linked to cornu ammonis (CA1-3) and dentate gyrus (DG) subfields. Therefore, the main goal of the present study was to investigate whether memory deficits in MDD patients are related to reduction in hippocampal subfields volumes, particularly DG and CA 1-3. 15 MDD patients meeting DSM-IV criteria for MDD with moderate or severe episodes were recruited, together with 15 healthy controls. We used T2-weighted 2D Fast Spin Echo (FSE) and T1-weighted 3D MPRAGE sequences at 4.7 T to compare hippocampal subfield volumes at 0.09 μl voxel volume. Participants were administered the Wechsler Memory Scale. MDD patients underperformed in several episodic visual memory tasks, as well as in visual working memory, compared to healthy controls. Global hippocampal volumes were similar between groups; however, MDD patients showed significantly reduced DG volumes within the hippocampal body. Duration of depression correlated with MDD patients׳ total volumes in the hippocampal body and CA1-3 and DG subfields within it. Our study sample was relatively small and the majority of patients were on antidepressant treatment. Our findings suggest that DG volumes in particular may be worthy of further study to further elucidate their precise role in MDD, both by itself as well as in relation to memory. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Adult neurogenesis modifies excitability of the dentate gyrus

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    Taruna eIkrar

    2013-12-01

    Full Text Available Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern

  3. Prevalence and function of Heschl's gyrus morphotypes in musicians.

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    Benner, Jan; Wengenroth, Martina; Reinhardt, Julia; Stippich, Christoph; Schneider, Peter; Blatow, Maria

    2017-11-01

    Morphological variations of the first transverse Heschl's gyrus (HG) in the human auditory cortex (AC) are common, yet little is known about their functional implication. We investigated individual morphology and function of HG variations in the AC of 41 musicians, using structural and functional magnetic resonance imaging (fMRI) as well as magnetoencephalography (MEG). Four main morphotypes of HG were (i) single HG, (ii) common stem duplication (CSD), (iii) complete posterior duplication (CPD), and (iv) multiple duplications (MD). The vast majority of musicians (90%) exhibited HG multiplications (type ii-iv) in either one (39%) or both (51%) hemispheres. In 27% of musicians, MD with up to four gyri were found. To probe the functional contribution of HG multiplications to auditory processing we performed fMRI and MEG with auditory stimulation using analogous instrumental tone paradigms. Both methods pointed to the recruitment of all parts of HG during auditory stimulation, including multiplications if present. FMRI activations extended with the degree of HG gyrification. MEG source waveform patterns were distinct for the different types of HG: (i) hemispheres with single HG and (ii) CSD exhibited dominant N1 responses, whereas hemispheres with (iii) CPD and (iv) MD exhibited dominant P1 responses. N1 dipole amplitudes correlated with the localization of the first complete Heschl's sulcus (cHS), designating the most posterior anatomical border of HG. P2 amplitudes were significantly higher in professional as compared to amateur musicians. The results suggest that HG multiplications occur much more frequently in musicians than in the general population and constitute a functional unit with HG.

  4. Effect of parental morphine addiction on extracellular glutamate concentration of dentate gyrus in rat offsprings

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    rahele Assaee

    2004-01-01

    Findings: In male offsprings of sham control1, sham control2, test1 and test2 basal and electrical stimulated of extracellular glutamate concentration of dentate gyrus were: 0.67±0.04, 1.11±0.1, and in female offsprings were 0.47±0.06, 0.88±0.05 (n=5. The basal and stimulated extra cellular glutamate concentration of dentate gyrus was decreased in both test1 and test2 offsprings. It was less in test1 than test2 offsprings. The glutamate concentration of dentate gyrus in female offsprings of test1 group was less than that of the male offsprings. conclusion: The results suggest that parental morphine addiction may cause learning deficiency through reduction of extracellular glutamate concentration in dentate gyrus so the side effects of parental morphine addiction in offsprings must be considered.

  5. Temporal changes in prosaposin expression in the rat dentate gyrus after birth.

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    Midori Morishita

    Full Text Available Neurogenesis in the hippocampal dentate gyrus occurs constitutively throughout postnatal life. Adult neurogenesis includes a multistep process that ends with the formation of a postmitotic and functionally integrated new neuron. During adult neurogenesis, various markers are expressed, including GFAP, nestin, Pax6, polysialic acid-neural cell adhesion molecule (PSA-NCAM, neuronal nuclei (NeuN, doublecortin, TUC-4, Tuj-1, and calretinin. Prosaposin is the precursor of saposins A-D; it is found in various organs and can be excreted. Strong prosaposin expression has been demonstrated in the developing brain including the hippocampus, and its neurotrophic activity has been proposed. This study investigated changes in prosaposin in the dentate gyrus of young and adult rats using double immunohistochemistry with antibodies to prosaposin, PSA-NCAM, and NeuN. Prosaposin immunoreactivity was intense in the dentate gyrus at postnatal day 3 (P3 and P7, but decreased gradually after P14. In the dentate gyrus at P28, immature PSA-NCAM-positive neurons localized exclusively in the subgranular zone were prosaposin-negative, whereas mature Neu-N-positive neurons were positive for prosaposin. Furthermore, these prosaposin-negative immature neurons were saposin B-positive, suggesting that the neurons take up and degrade prosaposin. In situ hybridization assays showed that prosaposin in the adult dentate gyrus is dominantly the Pro+9 type, a secreted type of prosaposin. These results imply that prosaposin secreted from mature neurons stimulates proliferation and maturation of immature neurons in the dentate gyrus.

  6. Passive music listening spontaneously engages limbic and paralimbic systems.

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    Brown, Steven; Martinez, Michael J; Parsons, Lawrence M

    2004-09-15

    In this PET study, non-musicians passively listened to unfamiliar instrumental music revealed afterward to elicit strongly pleasant feelings. Activations were observed in the subcallosal cingulate gyrus, prefrontal anterior cingulate, retrosplenial cortex, hippocampus, anterior insula, and nucleus accumbens. This is the first observation of spontaneous responses in such limbic and paralimbic areas during passive listening to unfamiliar although liked music. Activations were also seen in primary auditory, secondary auditory, and temporal polar areas known to respond to music. Our findings complement neuroimaging studies of aesthetic responses to music that have used stimuli selected by subjects or designed by experimenters. The observed pattern of activity is discussed in terms of a model synthesizing emotional and cognitive responses to music.

  7. A direct anterior cingulate pathway to the primate primary olfactory cortex may control attention to olfaction

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    García-Cabezas, Miguel Á.; Barbas, Helen

    2016-01-01

    Behavioral and functional studies in humans suggest that attention plays a key role in activating the primary olfactory cortex through an unknown circuit mechanism. We report that a novel pathway from the anterior cingulate cortex, an area which has a key role in attention, projects directly to the primary olfactory cortex in rhesus monkeys, innervating mostly the anterior olfactory nucleus. Axons from the anterior cingulate cortex formed synapses mostly with spines of putative excitatory pyramidal neurons and with a small proportion of a neurochemical class of inhibitory neurons that are thought to have disinhibitory effect on excitatory neurons. This novel pathway from the anterior cingulate is poised to exert a powerful excitatory effect on the anterior olfactory nucleus, which is a critical hub for odorant processing via extensive bilateral connections with primary olfactory cortices and the olfactory bulb. Acting on the anterior olfactory nucleus, the anterior cingulate may activate the entire primary olfactory cortex to mediate the process of rapid attention to olfactory stimuli. PMID:23797208

  8. Cognitive Functioning after Medial Frontal Lobe Damage Including the Anterior Cingulate Cortex: A Preliminary Investigation

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    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa

    2006-01-01

    Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was…

  9. Anterior Cingulate Volumetric Alterations in Treatment-Naive Adults with ADHD: A Pilot Study

    Science.gov (United States)

    Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.

    2010-01-01

    Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…

  10. Divergent influences of anterior cingulate cortex GABA concentrations on the emotion circuitry

    NARCIS (Netherlands)

    Levar, Nina; van Leeuwen, Judith M C; Denys, Damiaan; Van Wingen, G.

    2017-01-01

    Neuroimaging research has revealed that emotion processing recruits a widespread neural network including the dorsal anterior cingulate cortex (dACC), hippocampus, and amygdala. Recent studies have started to investigate the role of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA)

  11. Generation of theta activity (RSA) in the cingulate cortex of the rat

    NARCIS (Netherlands)

    Holsheimer, J.

    1982-01-01

    Unit activity recorded from the cingulate cortex during theta rhythm shows periodic trains of spikes which are phase-locked to the local theta field potential waves. These cortical theta units were also shown to be correlated with hippocampal theta units. These findings, along with the fact that

  12. Converging evidence for the neuroanatomic basis of combinatorial semantics in the angular gyrus.

    Science.gov (United States)

    Price, Amy R; Bonner, Michael F; Peelle, Jonathan E; Grossman, Murray

    2015-02-18

    Human thought and language rely on the brain's ability to combine conceptual information. This fundamental process supports the construction of complex concepts from basic constituents. For example, both "jacket" and "plaid" can be represented as individual concepts, but they can also be integrated to form the more complex representation "plaid jacket." Although this process is central to the expression and comprehension of language, little is known about its neural basis. Here we present evidence for a neuroanatomic model of conceptual combination from three experiments. We predicted that the highly integrative region of heteromodal association cortex in the angular gyrus would be critical for conceptual combination, given its anatomic connectivity and its strong association with semantic memory in functional neuroimaging studies. Consistent with this hypothesis, we found that the process of combining concepts to form meaningful representations specifically modulates neural activity in the angular gyrus of healthy adults, independent of the modality of the semantic content integrated. We also found that individual differences in the structure of the angular gyrus in healthy adults are related to variability in behavioral performance on the conceptual combination task. Finally, in a group of patients with neurodegenerative disease, we found that the degree of atrophy in the angular gyrus is specifically related to impaired performance on combinatorial processing. These converging anatomic findings are consistent with a critical role for the angular gyrus in conceptual combination. Copyright © 2015 the authors 0270-6474/15/353276-09$15.00/0.

  13. Anodal transcranial direct current stimulation over the supramarginal gyrus facilitates pitch memory.

    Science.gov (United States)

    Schaal, Nora K; Williamson, Victoria J; Banissy, Michael J

    2013-11-01

    Functional neuroimaging studies have shown activation of the supramarginal gyrus during pitch memory tasks. A previous transcranial direct current stimulation study using cathodal stimulation over the left supramarginal gyrus reported a detrimental effect on short-term pitch memory performance, indicating an important role of the supramarginal gyrus in pitch memory. The current study aimed to determine whether pitch memory could be improved following anodal stimulation of the left supramarginal gyrus. The performances of non-musicians on two pitch memory tasks (pitch recognition and recall) and a visual memory control task following anodal or sham transcranial direct current stimulation were compared. The results show that, post-stimulation, the anodal group but not the control group performed significantly better on both pitch memory tasks; performance did not differ on the face memory task. These findings provide strong support for the causal involvement of the left supramarginal gyrus in the pitch memory process, and highlight the potential efficacy of transcranial direct current stimulation as a tool to improve pitch memory. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Pivotal role of anterior cingulate cortex in working memory after traumatic brain injury in youth

    Directory of Open Access Journals (Sweden)

    Fabienne eCazalis

    2011-01-01

    Full Text Available In this fMRI study, the functions of the Anterior Cingulate Cortex were studied in a group of adolescents who had sustained a moderate to severe Traumatic Brain Injury. A spatial working memory task with varying working memory loads, representing experimental conditions of increasing difficulty, was administered.In a cross-sectional comparison between the patients and a matched control group, patients performed worse than Controls, showing longer reaction times and lower response accuracy on the spatial working memory task. Brain imaging findings suggest a possible double-dissociation: activity of the Anterior Cingulate Cortex in the Traumatic Brain Injury group, but not in the Control group, was associated with task difficulty; conversely, activity of the left Sensorimotor Cortex in the Control group, but not in the TBI group, was correlated with task difficulty.In addition to the main cross-sectional study, a longitudinal study of a group of adolescent patients with moderate to severe Traumatic Brain Injury was done using fMRI and the same spatial working memory task. The patient group was studied at two time points: one time point during the post-acute phase and one time point 12 months later, during the chronic phase. Results indicated that patients' behavioral performance improved over time, suggesting cognitive recovery. Brain imaging findings suggest that, over this 12 month period, patients recruited less of the Anterior Cingulate Cortex and more of the left Sensorimotor Cortex in response to increasing task difficulty.The role of Anterior Cingulate Cortex in executive functions following a moderate to severe brain injury in adolescence is discussed within the context of conflicting models of the Anterior Cingulate Cortex functions in the existing literature.

  15. Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex.

    Directory of Open Access Journals (Sweden)

    Susanna A Walter

    Full Text Available Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD responses in functional magnetic resonance imaging (fMRI is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.

  16. Origin of human motor readiness field linked to left middle frontal gyrus by MEG and PET

    DEFF Research Database (Denmark)

    Pedersen, Jane Rygaard; Johannsen, P; Bak, Christen Kjeldahl

    1998-01-01

    Combined magnetoencephalography and positron emission tomography identified a prior source of activity in the left middle frontal gyrus duping uncued movements of the right index finger Voluntary movements gave rise to a change in the cortical electrical potential known as the Bereitschaftspotent......Combined magnetoencephalography and positron emission tomography identified a prior source of activity in the left middle frontal gyrus duping uncued movements of the right index finger Voluntary movements gave rise to a change in the cortical electrical potential known...... in the period from 900 ms before, to 100 ms after; the onset of the movement. The first source to be active was registered between 900 and 200 ms prior to the onset of the movement. This source of initial activity was mapped by positron emission tomography to the middle frontal gyrus, Brodmann area 9. The three...

  17. [Incomplete Gerstmann syndrome with a cerebral infarct in the left middle frontal gyrus].

    Science.gov (United States)

    Ando, Yoshihito; Sawada, Mikio; Morita, Mitsuya; Kawamura, Mitsuru; Nakano, Imaharu

    2009-09-01

    A 65-year-old right-handed man noted a sudden onset of numbness and weakness of the right hand. On the initial visit to our hospital, he showed severe acalculia, and transient agraphia (so called incomplete Gerstmann syndrome) and transcortical sensory aphasia. Brain MRI revealed a fresh infarct in the left middle frontal gyrus. The paragraphia and aphasia improved within 14 days after onset, but the acalculia persisted even at seven months after onset In an 123I-IMP SPECT study, the cerebral blood flow (CBF) was found to be decreased in the infarction lesion and its adjacent wide area, the ipsilateral angular and supramarginal gyri, and contralateral cerebellar hemisphere. We speculate that inactivation in the infarction lesion caused the CBF decrease in the non-infarcted areas due to diaschisis. This case indicates that Gerstmann syndrome can be caused by not only dysfunction of the angular gyrus but also of the left middle frontal gyrus in the dominant hemisphere.

  18. Gray Matter Volume of the Lingual Gyrus Mediates the Relationship between Inhibition Function and Divergent Thinking

    Directory of Open Access Journals (Sweden)

    Lijie Zhang

    2016-10-01

    Full Text Available Abstract: Although previous research provides converging evidence for the role of posterior regions of the brain (including temporal, occipital, and parietal regions involved in inhibition on creative thinking, it remains unclear as to how these regions influence individual differences in creative thinking. Thus, we explored the relationship between posterior regions (i.e., hippocampal, parahippocampal, lingual gyrus, precuneus, and cuneus , inhibition function, and divergent thinking in 128 healthy college students. The results revealed that lower inhibition was associated with larger gray matter volume (GMV in the lingual gyrus, which in turn was associated with higher divergent thinking. In addition, GMV in the lingual gyrus mediated the association between inhibition and divergent thinking. These results provide new evidence for the role of inhibition in creative thinking. Inhibition may affect the amount of information stored in long-term memory, which, in turn influences divergent thinking.

  19. Recruitment of the left precentral gyrus in reading epilepsy: A multimodal neuroimaging study

    Directory of Open Access Journals (Sweden)

    Dima Safi

    2016-01-01

    Conclusion: This study is the first to investigate ictogenesis in reading epilepsy during both lexical and phonological reading while using three different multimodal neuroimaging techniques. The somatosensory and motor control functions of the left precentral gyrus that are congruently involved in lexical as well as phonological reading can explain the identical spike localization in both reading pathways. The concurrence between our findings in this study and those from our previous one supports the role of the left precentral gyrus in phonological output computation as well as seizure activity in a case of reading epilepsy.

  20. Exaggerated Activation of Dorsal Anterior Cingulate Cortex During Cognitive Interference: A Monozygotic Twin Study of Posttraumatic Stress Disorder

    Science.gov (United States)

    Shin, Lisa M.; Bush, George; Milad, Mohammed R.; Lasko, Natasha B.; Brohawn, Kathryn Handwerger; Hughes, Katherine C.; Macklin, Michael L.; Gold, Andrea L.; Karpf, Rachel D.; Orr, Scott P.; Rauch, Scott L.; Pitman, Roger K.

    2013-01-01

    Objective Neuroimaging studies have revealed functional abnormalities in the anterior cingulate cortex in posttraumatic stress disorder (PTSD). The goal of the current research was to determine whether hyperresponsivity of the dorsal anterior cingulate in PTSD is an acquired characteristic or familial risk factor. Method Using a case-control twin design, we studied combat-exposed veterans with PTSD (n=12) and their identical combat-unexposed co-twins (n=12), as well as combat-exposed veterans without PTSD (n=14) and their identical combat-unexposed co-twins (n=14). Participants underwent functional magnetic resonance imaging during completion of the Multi-Source Interference Task, which reliably activates the dorsal anterior cingulate. Results Combat veterans with PTSD and their co-twins had significantly greater activation in the dorsal anterior cingulate and tended to have larger response time difference scores, as compared to non-PTSD veterans and their co-twins. Dorsal anterior cingulate activation in the exposed twins was positively correlated with their PTSD symptom severity. Dorsal anterior cingulate activation in the unexposed twins was positively correlated with their combat-exposed co-twins’ PTSD symptom severity, but not with depression or alcohol use severity in the combat-exposed co-twins. Conclusions Hyperresponsivity in the dorsal anterior cingulate appears to be a familial risk factor for the development of PTSD following psychological trauma. PMID:21724666

  1. PARCELLATION OF THE CINGULATE CORTEX AT REST AND DURING TASKS: A META-ANALYTIC CLUSTERING AND EXPERIMENTAL STUDY

    Directory of Open Access Journals (Sweden)

    Diana M.E. Torta

    2013-06-01

    Full Text Available Anatomical, morphological and histological data have consistently shown that the cingulate cortex can be divided into four main regions. However, less is known about parcellations of the cingulate cortex when involved in active tasks. Here, we aimed at comparing how the pattern of clusterization of the cingulate cortex changes across different levels of task complexity. We parcellated the cingulate cortex using the results of a meta-analytic study and of three experimental studies. The experimental studies, which included two active tasks and a resting state protocol, were used to control the results obtained with the meta-analytic parcellation. We explored the meta-analytic parcellation by applying a meta-analytic clustering (MaC to papers retrieved from the BrainMap database. The MaC is a meta-analytic connectivity driven parcellation technique recently developed by our group which allowed us to parcellate the cingulate cortex on the basis of its pattern of co-activations during active tasks. The MaC results indicated that the cingulate cortex can be parcellated into three clusters. These clusters covered different percentages of the cingulate parenchyma and had a different density of foci, with the first cluster being more densely connected. The control experiments showed different clusterization results, suggesting that the co-activations of the cingulate cortex are highly dependent on the task that is tested. Our results highlight the importance of the cingulate cortex as a hub, which modifies its pattern of co-activations depending on the task requests and on the level of task complexity. The neurobiological meaning of these results is discussed.

  2. a-Band Oscillations in Intracellular Membrane Potentials of Dentate Gyrus Neurons in Awake Rodents

    Science.gov (United States)

    Anderson, Ross W.; Strowbridge, Ben W.

    2014-01-01

    The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a…

  3. Role of Dentate Gyrus in Aligning Internal Spatial Map to External Landmark

    Science.gov (United States)

    Lee, Jong Won; Kim, Woon Ryoung; Sun, Woong; Jung, Min Whan

    2009-01-01

    Humans and animals form internal representations of external space based on their own body movement (dead reckoning) as well as external landmarks. It is poorly understood, however, how different types of information are integrated to form a unified representation of external space. To examine the role of dentate gyrus (DG) in this process, we…

  4. Atrophy in the parahippocampal gyrus as an early biomarker of Alzheimer's disease

    NARCIS (Netherlands)

    Echavarri, C.; Aalten, P.; Uylings, H.B.M.; Jacobs, H.I.L.; Visser, P.J.; Gronenschild, E.H.B.M.; Verhey, F.R.J.; Burgmans, S.

    2011-01-01

    The main aim of the present study was to compare volume differences in the hippocampus and parahippocampal gyrus as biomarkers of Alzheimer's disease (AD). Based on the previous findings, we hypothesized that there would be significant volume differences between cases of healthy aging, amnestic mild

  5. Inferior Frontal Gyrus Activity Triggers Anterior Insula Response to Emotional Facial Expressions

    NARCIS (Netherlands)

    Jabbi, Mbemba; Keysers, Christian

    2008-01-01

    The observation of movies of facial expressions of others has been shown to recruit similar areas involved in experiencing one's own emotions: the inferior frontal gyrus (IFG). the anterior insula and adjacent frontal operculum (IFO). The Causal link bet between activity in these 2 regions,

  6. Apraxia of speech associated with an infarct in the precentral gyrus of the insula

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, M.; Komori, T.; Isozaki, E.; Hirai, S. [Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo (Japan); Takeda, K. [Department of Neuropsychology, Tokyo Metropolitan Institute for Neuroscience, Tokyo (Japan)

    1999-05-01

    It has been postulated that the precentral gyrus in the left insula is responsible for co-ordination of speech. We report a paitent with this disturbance who showed an acute infarct limited to this region. (orig.) With 1 fig., 3 refs.

  7. Dentate Gyrus Local Circuit is Implicated in Learning Under Stress--a Role for Neurofascin.

    Science.gov (United States)

    Zitman, Femke M P; Lucas, Morgan; Trinks, Sabine; Grosse-Ophoff, Laura; Kriebel, Martin; Volkmer, Hansjürgen; Richter-Levin, Gal

    2016-03-01

    The inhibitory synapses at the axon initial segment (AIS) of dentate gyrus granular cells are almost exclusively innervated by the axo-axonic chandelier interneurons. However, the role of chandelier neurons in local circuitry is poorly understood and controversially discussed. The cell adhesion molecule neurofascin is specifically expressed at the AIS. It is crucially required for the stabilization of axo-axonic synapses. Knockdown of neurofascin is therefore a convenient tool to interfere with chandelier input at the AIS of granular neurons of the dentate gyrus. In the current study, feedback and feedforward inhibition of granule cells was measured in the dentate gyrus after knockdown of neurofascin and concomitant reduction of axo-axonic input. Results show increased feedback inhibition as a result of neurofascin knockdown, while feedforward inhibition remained unaffected. This suggests that chandelier neurons are predominantly involved in feedback inhibition. Neurofascin knockdown rats also exhibited impaired learning under stress in the two-way shuttle avoidance task. Remarkably, this learning impairment was not accompanied by differences in electrophysiological measurements of dentate gyrus LTP. This indicates that the local circuit may be involved in (certain types) of learning.

  8. Age-Related Increase in Inferior Frontal Gyrus Activity and Social Functioning in Autism Spectrum Disorder

    NARCIS (Netherlands)

    Bastiaansen, Jojanneke A.; Thioux, Marc; Nanetti, Luca; van der Gaag, Christiaan; Ketelaars, Cees; Minderaa, Ruud; Keysers, Christian

    2011-01-01

    Background: Hypoactivation of the inferior frontal gyrus during the perception of facial expressions has been interpreted as evidence for a deficit of the mirror neuron system in children with autism. We examined whether this dysfunction persists in adulthood, and how brain activity in the mirror

  9. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.

    Science.gov (United States)

    Planche, Vincent; Koubiyr, Ismail; Romero, José E; Manjon, José V; Coupé, Pierrick; Deloire, Mathilde; Dousset, Vincent; Brochet, Bruno; Ruet, Aurélie; Tourdias, Thomas

    2018-01-13

    Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05). The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance. © 2018 Wiley Periodicals, Inc.

  10. TMS over the Left Angular Gyrus Impairs the Ability to Discriminate Left from Right

    Science.gov (United States)

    Hirnstein, Marco; Bayer, Ulrike; Ellison, Amanda; Hausmann, Markus

    2011-01-01

    The underlying cognitive and neural mechanisms of the ability to discriminate left from right are hardly explored. Clinical studies from patients with impairments of left-right discrimination (LRD) and neuroimaging data suggest that the left angular gyrus is particularly involved in LRD. Moreover, it is argued that the often reported sex…

  11. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium

    NARCIS (Netherlands)

    Walton, E.; Hibar, D. P.; van Erp, T. G M; Potkin, S. G.; Roiz-Santiañez, R.; Crespo-Facorro, B.; Suarez-Pinilla, P.; Van Haren, N. E M|info:eu-repo/dai/nl/271562161; de Zwarte, S. M C; Kahn, R. S.|info:eu-repo/dai/nl/073778532; Cahn, W.|info:eu-repo/dai/nl/250566370; Doan, N. T.; Jørgensen, K. N.; Gurholt, T. P.; Agartz, I.; Andreassen, O. A.; Westlye, L. T.; Melle, I.; Berg, A. O.; Mørch-Johnsen, L.; Færden, A.; Flyckt, L.; Fatouros-Bergman, H.; Jönsson, E. G.; Hashimoto, R.; Yamamori, H.; Fukunaga, M.; Preda, A.; De Rossi, P.; Piras, F.; Banaj, N.; Ciullo, V.; Spalletta, G.; Gur, R. E.; Gur, R. C.; Wolf, D. H.; Satterthwaite, T. D.; Beard, L. M.; Sommer, I. E.|info:eu-repo/dai/nl/258791519; Koops, S.; Gruber, O.; Richter, A.; Krämer, B.; Kelly, S.; Donohoe, G.; McDonald, C.; Cannon, D. M.; Corvin, A.; Gill, M.; Di Giorgio, A.; Bertolino, A.; Lawrie, S.; Nickson, T.; Whalley, H. C.; Neilson, E.; Calhoun, V. D.; Thompson, P. M.; Turner, J. A.; Ehrlich, S.; Farde, L.; Engberg, G.; Erhardt, S.; Fatouros-Bergman, H.; Cervenka, S.; Schwieler, L.; Piehl, F.; Ikonen, P.; Collste, K.; Orhan, F.; Malmqvist, A.; Hedberg, M.

    2017-01-01

    Objective: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. Method: This prospective meta-analysis

  12. Neurotoxic Doses of Chronic Methamphetamine Trigger Retrotransposition of the Identifier Element in Rat Dorsal Dentate Gyrus

    Science.gov (United States)

    Moszczynska, Anna; Burghardt, Kyle J.; Yu, Dongyue

    2017-01-01

    Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present investigation was to determine whether neurotoxic doses of binge or chronic methamphetamine (METH) trigger retrotransposition of the identifier (ID) element, a member of the rat SINE family, in the dentate gyrus genomic DNA. Adult male Sprague-Dawley rats were treated with saline or high doses of binge or chronic METH and sacrificed at three different time points thereafter. DNA methylation analysis, immunohistochemistry and next-generation sequencing (NGS) were performed on the dorsal dentate gyrus samples. Binge METH triggered hypomethylation, while chronic METH triggered hypermethylation of the CpG-2 site. Both METH regimens were associated with increased intensities in poly(A)-binding protein 1 (PABP1, a SINE regulatory protein)-like immunohistochemical staining in the dentate gyrus. The amplification of several ID element sequences was significantly higher in the chronic METH group than in the control group a week after METH, and they mapped to genes coding for proteins regulating cell growth and proliferation, transcription, protein function as well as for a variety of transporters. The results suggest that chronic METH induces ID element retrotransposition in the dorsal dentate gyrus and may affect hippocampal neurogenesis. PMID:28272323

  13. Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test

    NARCIS (Netherlands)

    Korte, S.M.; de Kloet, E.R.; Buwalda, B; Bouman, S.D.; Bohus, B

    1996-01-01

    Immobility time of rats in the forced swim test was reduced after bilateral infusion of an 18-mer antisense phosphorothioate oligodeoxynucleotide targeted to the glucocorticoid receptor mRNA into the dentate gyrus of the hippocampus. Vehicle-, sense- and scrambled sequence-treated animals spent

  14. Anterior cingulate volume predicts response to cognitive behavioral therapy in major depressive disorder.

    Science.gov (United States)

    Fujino, Junya; Yamasaki, Nobuyuki; Miyata, Jun; Sasaki, Hitoshi; Matsukawa, Noriko; Takemura, Ariyoshi; Tei, Shisei; Sugihara, Genichi; Aso, Toshihiko; Fukuyama, Hidenao; Takahashi, Hidehiko; Inoue, Kazuomi; Murai, Toshiya

    2015-03-15

    Cognitive behavioral therapy (CBT) is widely used to treat major depressive disorder (MDD). Although improved response prediction could facilitate the development of individualized treatment plans, few studies have investigated whether underlying brain structure is related to CBT response in MDD. Ten MDD patients who received individual CBT were studied in this study. We investigated the relationship between the regional gray matter (GM) volume and subsequent responses to CBT using voxel-based morphometry. The degree of improvement in depressive symptoms was positively correlated with GM volume in the caudal portion of the anterior cingulate cortex. The sample size was small, and the effects of medication on the results could not be excluded. Our results, although preliminary, suggest that the anterior cingulate cortex is a key structure whose volume can be used to predict responses to CBT and is thus a potential prognostic marker in MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. A Role for the Left Angular Gyrus in Episodic Simulation and Memory.

    Science.gov (United States)

    Thakral, Preston P; Madore, Kevin P; Schacter, Daniel L

    2017-08-23

    Functional magnetic resonance imaging (fMRI) studies indicate that episodic simulation (i.e., imagining specific future experiences) and episodic memory (i.e., remembering specific past experiences) are associated with enhanced activity in a common set of neural regions referred to as the core network. This network comprises the hippocampus, medial prefrontal cortex, and left angular gyrus, among other regions. Because fMRI data are correlational, it is unknown whether activity increases in core network regions are critical for episodic simulation and episodic memory. In the current study, we used MRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of the left angular gyrus would impair both episodic simulation and memory (16 participants, 10 females). Relative to TMS to a control site (vertex), disruption of the left angular gyrus significantly reduced the number of internal (i.e., episodic) details produced during the simulation and memory tasks, with a concomitant increase in external detail production (i.e., semantic, repetitive, or off-topic information), reflected by a significant detail by TMS site interaction. Difficulty in the simulation and memory tasks also increased after TMS to the left angular gyrus relative to the vertex. In contrast, performance in a nonepisodic control task did not differ statistically as a function of TMS site (i.e., number of free associates produced or difficulty in performing the free associate task). Together, these results are the first to demonstrate that the left angular gyrus is critical for both episodic simulation and episodic memory. SIGNIFICANCE STATEMENT Humans have the ability to imagine future episodes (i.e., episodic simulation) and remember episodes from the past (i.e., episodic memory). A wealth of neuroimaging studies have revealed that these abilities are associated with enhanced activity in a core network of neural regions, including the hippocampus, medial prefrontal

  16. Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder.

    Science.gov (United States)

    Comasco, Erika; Hahn, Andreas; Ganger, Sebastian; Gingnell, Malin; Bannbers, Elin; Oreland, Lars; Wikström, Johan; Epperson, C Neill; Lanzenberger, Rupert; Sundström-Poromaa, Inger

    2014-09-01

    Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  17. Early natural stimulation through environmental enrichment accelerates neuronal development in the mouse dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Na Liu

    Full Text Available The dentate gyrus is the primary afferent into the hippocampal formation, with important functions in learning and memory. Granule cells, the principle neuronal type in the dentate gyrus, are mostly formed postnatally, in a process that continues into adulthood. External stimuli, including environmental enrichment, voluntary exercise and learning, have been shown to significantly accelerate the generation and maturation of dentate granule cells in adult rodents. Whether, and to what extent, such environmental stimuli regulate the development and maturation of dentate granule cells during early postnatal development is largely unknown. Furthermore, whether natural stimuli affect the synaptic properties of granule cells had been investigated neither in newborn neurons of the adult nor during early development. To examine the effect of natural sensory stimulation on the dentate gyrus, we reared newborn mice in an enriched environment (EE. Using immunohistochemistry, we showed that dentate granule cells from EE-reared mice exhibited earlier morphological maturation, manifested as faster peaking of doublecortin expression and elevated expression of mature neuronal markers (including NeuN, calbindin and MAP2 at the end of the second postnatal week. Also at the end of the second postnatal week, we found increased density of dendritic spines across the entire dentate gyrus, together with elevated levels of postsynaptic scaffold (post-synaptic density 95 and receptor proteins (GluR2 and GABA(ARγ2 of excitatory and inhibitory synapses. Furthermore, dentate granule cells of P14 EE-reared mice had lower input resistances and increased glutamatergic and GABAergic synaptic inputs. Together, our results demonstrate that EE-rearing promotes morphological and electrophysiological maturation of dentate granule cells, underscoring the importance of natural environmental stimulation on development of the dentate gyrus.

  18. Volumetric differences in the anterior cingulate cortex prospectively predict alcohol-related problems in adolescence.

    Science.gov (United States)

    Cheetham, Ali; Allen, Nicholas B; Whittle, Sarah; Simmons, Julian; Yücel, Murat; Lubman, Dan I

    2014-04-01

    Individual differences in brain structure and function are suggested to exist prior to the onset of alcohol abuse. Cross-sectional studies have demonstrated abnormalities in brain regions underlying affective processes that may form a pathway to the emergence of later alcohol abuse and dependence in vulnerable individuals. However, no prospective studies have examined whether these abnormalities predict later problems with alcohol. This study aims to examine whether individual differences in affect and brain volume prospectively predict alcohol-related problems in adolescence. Adolescent drinkers (n = 98) were recruited from an ongoing prospective, longitudinal study examining adolescent emotional development. At age 12, participants underwent structural magnetic resonance imaging to obtain volumetric data on the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex (ACC), and completed a self-report measure of affective temperament. At age 16, participants completed a questionnaire measuring alcohol use, with 39 % reporting alcohol-related problems in the past year. Pre-existing differences in the left ACC predicted problem drinking. Alcohol-related problems were associated with higher levels of temperamental negative affectivity; however, these were not correlated with anterior cingulate volumes. These findings indicate that individual differences in the structural morphology of the anterior cingulate, a region implicated in affective processes, self-control, and drug addiction, predict later alcohol-related problems. Although this finding remained significant after controlling for other substance use and psychopathology, future research is required to test its specificity for alcohol use disorders.

  19. Greater anterior cingulate activation and connectivity in response to visual and auditory high-calorie food cues in binge eating: Preliminary findings.

    Science.gov (United States)

    Geliebter, Allan; Benson, Leora; Pantazatos, Spiro P; Hirsch, Joy; Carnell, Susan

    2016-01-01

    Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or orbitofrontal cortex [OFC]. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Gray Matter and Functional Connectivity in Anterior Cingulate Cortex are Associated with the State of Mental Silence During Sahaja Yoga Meditation.

    Science.gov (United States)

    Hernández, Sergio Elías; Barros-Loscertales, Alfonso; Xiao, Yaqiong; González-Mora, José Luis; Rubia, Katya

    2017-12-22

    Some meditation techniques teach the practitioner to achieve the state of mental silence. The aim of this study was to investigate brain regions that are associated with their volume and functional connectivity (FC) with the depth of mental silence in long-term practitioners of Sahaja Yoga Meditation. Twenty-three long-term practitioners of this meditation were scanned using Magnetic Resonance Imaging. In order to identify the neural correlates of the depth of mental silence, we tested which gray matter volumes (GMV) were correlated with the depth of mental silence and which regions these areas were functionally connected to under a meditation condition. GMV in medial prefrontal cortex including rostral anterior cingulate cortex were positively correlated with the subjective perception of the depth of mental silence inside the scanner. Furthermore, there was significantly increased FC between this area and bilateral anterior insula/putamen during a meditation-state specifically, while decreased connectivity with the right thalamus/parahippocampal gyrus was present during the meditation-state and the resting-state. The capacity of long-term meditators to establish a durable state of mental silence inside an MRI scanner was associated with larger gray matter volume in a medial frontal region that is crucial for top-down cognitive, emotion and attention control. This is furthermore corroborated by increased FC of this region during the meditation-state with bilateral anterior insula/putamen, which are important for interoception, emotion, and attention regulation. The findings hence suggest that the depth of mental silence is associated with medial fronto-insular-striatal networks that are crucial for top-down attention and emotional control. Copyright © 2017 IBRO. All rights reserved.

  1. Preserved self-awareness following extensive bilateral brain damage to the insula, anterior cingulate, and medial prefrontal cortices

    National Research Council Canada - National Science Library

    Philippi, Carissa L; Feinstein, Justin S; Khalsa, Sahib S; Damasio, Antonio; Tranel, Daniel; Landini, Gregory; Williford, Kenneth; Rudrauf, David

    2012-01-01

    It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC...

  2. Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices: e38413

    National Research Council Canada - National Science Library

    Carissa L Philippi; Justin S Feinstein; Sahib S Khalsa; Antonio Damasio; Daniel Tranel; Gregory Landini; Kenneth Williford; David Rudrauf

    2012-01-01

      It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC...

  3. Cingulate Alpha-2A Adrenoceptors Mediate the Effects of Clonidine on Spontaneous Pain Induced by Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Yong-Jie Wang

    2017-09-01

    Full Text Available The anterior cingulate cortex (ACC is an important brain area for the regulation of neuropathic pain. The α2A adrenoceptor is a good target for pain management. However, the role of cingulate α2A adrenoceptors in the regulation of neuropathic pain has been less studied. In this study, we investigated the involvement of cingulate α2A adrenoceptors in the regulation of neuropathic pain at different time points after peripheral nerve injury in mice. The application of clonidine, either systemically (0.5 mg/kg intraperitoneally or specifically to the ACC, increased paw withdrawal thresholds (PWTs and induced conditioned place preference (CPP at day 7 after nerve injury, suggesting that cingulate α2 adrenoceptors are involved in the regulation of pain-like behaviors. Quantitative real-time PCR data showed that α2A adrenoceptors are the dominant α2 adrenoceptors in the ACC. Furthermore, the expression of cingulate α2A adrenoceptors was increased at day 3 and day 7 after nerve injury, but decreased at day 14, while no change was detected in the concentration of adrenaline or noradrenaline. BRL-44408 maleate, a selective antagonist of α2A adrenoceptors, was microinfused into the ACC. This blocking of cingulate α2A adrenoceptors activity abolished the CPP induced by clonidine (0.5 mg/kg intraperitoneally but not the effects on PWTs at day 7. However, clonidine applied systemically or specifically to the ACC at day 14 increased the PWTs but failed to induce CPP; this negative effect was reversed by the overexpression of cingulate α2A adrenoceptors. These results suggest that cingulate α2A adrenoceptors are necessary for the analgesic effects of clonidine on spontaneous pain.

  4. Effects of infrasound on cell proliferation in the dentate gyrus of adult rats.

    Science.gov (United States)

    Liu, Juanfang; Lin, Tian; Yan, Xiaodong; Jiang, Wen; Shi, Ming; Ye, Ruidong; Rao, Zhiren; Zhao, Gang

    2010-06-02

    Adult rats were used to identify the effects of infrasound on neurogenesis in the hippocampal dentate gyrus. After 7 consecutive days' exposure to infrasound of 16 Hz at 130 dB, immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) was preformed. Compared with those in normal groups, the numbers of BrdU+ and DCX+/BrdU+ cells in the subgranular zone in infrasound groups were significantly decreased at 3, 6, 10 and 14 days and returned to normal at 18 days. The percentage of BrdU+ cells that were co-labeled with DCX showed no significant differences between the infrasound and normal groups. These data suggest that infrasound inhibits the cell proliferation in adult rat dentate gyrus but has no effects on early migration and differentiation of these newborn cells.

  5. Prenatal alcohol exposure affects progenitor cell numbers in olfactory bulbs and dentate gyrus of vervet monkeys

    DEFF Research Database (Denmark)

    Burke, Mark W; Inyatkin, Alexey; Ptito, Maurice

    2016-01-01

    Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed...... cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts...... vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years...

  6. Response inhibition of face stimuli linked to inferior frontal gyrus microstructure in adolescents

    DEFF Research Database (Denmark)

    Holm-Skjold, Jonathan; Baaré, William Frans Christiaan; Jernigan, Terry Lynne

    . Inhibition of negative faces has been shown to be more difficult than that of positive faces1,3. The brain network underlying response inhibition includes the right inferior frontal gyrus (IFG), right presupplementary motor area (preSMA), and superior longitudinal fasciculus (SLF) bilaterally 4–6. The white...... that better response inhibition (i.e. lower false alarm rate) of negative faces would be associated with higher FA in right IFG, right preSMA, and bilateral SLF in adolescents....

  7. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus

    OpenAIRE

    Harish eBabu; Jan-Hendrik eClaasen; Jan-Hendrik eClaasen; Jan-Hendrik eClaasen; Suresh eKannan; Annette E. Rünker; Theo ePalmer; Gerd eKempermann; Gerd eKempermann

    2011-01-01

    In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons, PLoS One 2007, 2:e388) to isolate neural precursor cells from the hippocampus of adult mice and maintain and pro...

  8. Differential Involvement of the Dentate Gyrus in Adaptive Forgetting in the Rat.

    Directory of Open Access Journals (Sweden)

    Mickaël Antoine Joseph

    Full Text Available How does the brain discriminate essential information aimed to be stored permanently from information required only temporarily, and that needs to be cleared away for not saturating our precious memory space? Reference Memory (RM refers to the long-term storage of invariable information whereas Working Memory (WM depends on the short-term storage of trial-unique information. Previous work has revealed that WM tasks are very sensitive to proactive interference. In order to prevent such interference, irrelevant old memories must be forgotten to give new ones the opportunity to be stabilized. However, unlike memory, physiological processes underlying this adaptive form of forgetting are still poorly understood. Here, we precisely ask what specific brain structure(s could be responsible for such process to occur. To answer this question, we trained rats in a radial maze using three paradigms, a RM task and two WM tasks involving or not the processing of interference but strictly identical in terms of locomotion or motivation. We showed that an inhibition of the expression of Zif268 and c-Fos, two indirect markers of neuronal activity and synaptic plasticity, was observed in the dentate gyrus of the dorsal hippocampus when processing such interfering previously stored information. Conversely, we showed that inactivating the dentate gyrus impairs both RM and WM, but improves the processing of interference. Altogether, these results strongly suggest for the first time that the dentate gyrus could be a key structure involved in adaptive forgetting.

  9. Modeling the nonlinear dynamic interactions of afferent pathways in the dentate gyrus of the hippocampus.

    Science.gov (United States)

    Dimoka, Angelika; Courellis, Spiros H; Marmarelis, Vasilis Z; Berger, Theodore W

    2008-05-01

    The dentate gyrus is the first region of the hippocampus that receives and integrates sensory information (e.g., visual, auditory, and olfactory) via the perforant path, which is composed of two distinct neuronal pathways: the Lateral Perforant Path (LPP) and the Medial Perforant Path (MPP). This paper examines the nonlinear dynamic interactions among arbitrary stimulation patterns at these two afferent pathways and their combined effect on the resulting response of the granule cells at the dentate gyrus. We employ non-parametric Poisson-Volterra models that serve as canonical quantitative descriptors of the nonlinear dynamic transformations of the neuronal signals propagating through these two neuronal pathways. These Poisson-Volterra models are estimated in the so-called "reduced form" with experimental data from in vitro hippocampal slices and provide excellent predictions of the electrophysiological activity of the granule cells in response to arbitrary stimulation patterns. The data are acquired through a custom-made multi-electrode-array system, which stimulated simultaneously the two pathways with random impulse trains and recorded the neuronal postsynaptic activity at the granule cell layer. The results of this study show that significant nonlinear interactions exist between the LPP and the MPP that may be critical for the integration of sensory information performed by the dentate gyrus of the hippocampus.

  10. Electrophysiological characterization of granule cells in the dentate gyrus immediately after birth

    Directory of Open Access Journals (Sweden)

    Andrea ePedroni

    2014-02-01

    Full Text Available Granule cells (GCs in the dentate gyrus are generated mainly postnatally. Between embryonic day 10 and 14, neural precursors migrate from the primary dentate matrix to the dentate gyrus where they differentiate into neurons. Neurogenesis reaches a peak at the end of the first postnatal week and it is completed at the end of the first postnatal month. This process continues at a reduced rate throughout life. Interestingly, immediately after birth, GCs exhibit a clear GABAergic phenotype. Only later they integrate the classical glutamatergic trisynaptic hippocampal circuit. Here, whole patch clamp recordings, in current clamp mode, were performed from immature GCs, intracellularly loaded with biocytin (in hippocampal slices from P0-P3 old rats in order to compare their morphological characteristics with their electrophysiological properties. The vast majority of GCs were very immature with small somata, few dendritic branches terminating with small varicosities and growth cones. In spite of their immaturity their axons reached often the CA3 area. Immature GCs generated, upon membrane depolarization, either rudimentary sodium spikes or more clear overshooting action potentials that fired repetitively. They exhibited also low threshold calcium spikes. In addition, most spiking neurons showed spontaneous synchronized network activity, reminiscent of giant depolarizing potentials (GDPs generated in the hippocampus by the synergistic action of glutamate and GABA, both depolarizing and excitatory. This early synchronized activity, absent during adult neurogenesis, may play a crucial role in the refinement of local neuronal circuits within the developing dentate gyrus.

  11. Enhanced Synaptic Connectivity in the Dentate Gyrus during Epileptiform Activity: Network Simulation

    Directory of Open Access Journals (Sweden)

    Keite Lira de Almeida França

    2013-01-01

    Full Text Available Structural rearrangement of the dentate gyrus has been described as the underlying cause of many types of epilepsies, particularly temporal lobe epilepsy. It is said to occur when aberrant connections are established in the damaged hippocampus, as described in human epilepsy and experimental models. Computer modelling of the dentate gyrus circuitry and the corresponding structural changes has been used to understand how abnormal mossy fibre sprouting can subserve seizure generation observed in experimental models when epileptogenesis is induced by status epilepticus. The model follows the McCulloch-Pitts formalism including the representation of the nonsynaptic mechanisms. The neuronal network comprised granule cells, mossy cells, and interneurons. The compensation theory and the Hebbian and anti-Hebbian rules were used to describe the structural rearrangement including the effects of the nonsynaptic mechanisms on the neuronal activity. The simulations were based on neuroanatomic data and on the connectivity pattern between the cells represented. The results suggest that there is a joint action of the compensation theory and Hebbian rules during the inflammatory process that accompanies the status epilepticus. The structural rearrangement simulated for the dentate gyrus circuitry promotes speculation about the formation of the abnormal mossy fiber sprouting and its role in epileptic seizures.

  12. Prenatal Alcohol Exposure Affects Progenitor Cell Numbers in Olfactory Bulbs and Dentate Gyrus of Vervet Monkeys

    Directory of Open Access Journals (Sweden)

    Mark W. Burke

    2016-10-01

    Full Text Available Fetal alcohol exposure (FAE alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts vervet monkey (Chlorocebus sabeus to (1 investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2 determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years. Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group. These data are unique with respect to fetal ethanol effects on progenitor proliferation in the primate brain and suggest that the olfactory bulb may be a useful structure for studies of cellular proliferation.

  13. Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals.

    Science.gov (United States)

    Zakiniaeiz, Yasmin; Scheinost, Dustin; Seo, Dongju; Sinha, Rajita; Constable, R Todd

    2017-01-01

    Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC), mid (MCC) and posterior cingulate cortex (PCC), voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome). Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC) participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.

  14. Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma.

    Science.gov (United States)

    Stevens, Jennifer S; Kim, Ye Ji; Galatzer-Levy, Isaac R; Reddy, Renuka; Ely, Timothy D; Nemeroff, Charles B; Hudak, Lauren A; Jovanovic, Tanja; Rothbaum, Barbara O; Ressler, Kerry J

    2017-06-15

    Studies suggest that exaggerated amygdala reactivity is a vulnerability factor for posttraumatic stress disorder (PTSD); however, our understanding is limited by a paucity of prospective, longitudinal studies. Recent studies in healthy samples indicate that, relative to reactivity, habituation is a more reliable biomarker of individual differences in amygdala function. We investigated reactivity of the amygdala and cortical areas to repeated threat presentations in a prospective study of PTSD. Participants were recruited from the emergency department of a large level I trauma center within 24 hours of trauma. PTSD symptoms were assessed at baseline and approximately 1, 3, 6, and 12 months after trauma. Growth curve modeling was used to estimate symptom recovery trajectories. Thirty-one individuals participated in functional magnetic resonance imaging around the 1-month assessment, passively viewing fearful and neutral face stimuli. Reactivity (fearful > neutral) and habituation to fearful faces was examined. Amygdala reactivity, but not habituation, 5 to 12 weeks after trauma was positively associated with the PTSD symptom intercept and predicted symptoms at 12 months after trauma. Habituation in the ventral anterior cingulate cortex was positively associated with the slope of PTSD symptoms, such that decreases in ventral anterior cingulate cortex activation over repeated presentations of fearful stimuli predicted increasing symptoms. Findings point to neural signatures of risk for maintaining PTSD symptoms after trauma exposure. Specifically, chronic symptoms were predicted by amygdala hyperreactivity, and poor recovery was predicted by a failure to maintain ventral anterior cingulate cortex activation in response to fearful stimuli. The importance of identifying patients at risk after trauma exposure is discussed. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease.

    Science.gov (United States)

    de Schipper, Laura J; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

    2017-01-01

    In Parkinson's disease (PD), the relation between cortical brain atrophy on MRI and clinical progression is not straightforward. Determination of changes in structural covariance networks - patterns of covariance in grey matter density - has shown to be a valuable technique to detect subtle grey matter variations. We evaluated how structural network integrity in PD is related to clinical data. 3 Tesla MRI was performed in 159 PD patients. We used nine standardized structural covariance networks identified in 370 healthy subjects as a template in the analysis of the PD data. Clinical assessment comprised motor features (Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MDS-UPDRS motor scale) and predominantly non-dopaminergic features (SEverity of Non-dopaminergic Symptoms in Parkinson's Disease; SENS-PD scale: postural instability and gait difficulty, psychotic symptoms, excessive daytime sleepiness, autonomic dysfunction, cognitive impairment and depressive symptoms). Voxel-based analyses were performed within networks significantly associated with PD. The anterior and posterior cingulate network showed decreased integrity, associated with the SENS-PD score, p = 0.001 (β = - 0.265, ηp2 = 0.070) and p = 0.001 (β = - 0.264, ηp2 = 0.074), respectively. Of the components of the SENS-PD score, cognitive impairment and excessive daytime sleepiness were associated with atrophy within both networks. We identified loss of integrity and atrophy in the anterior and posterior cingulate networks in PD patients. Abnormalities of both networks were associated with predominantly non-dopaminergic features, specifically cognition and excessive daytime sleepiness. Our findings suggest that (components of) the cingulate networks display a specific vulnerability to the pathobiology of PD and may operate as interfaces between networks involved in cognition and alertness.

  16. Prefrontal Thinning Affects Functional Connectivity and Regional Homogeneity of the Anterior Cingulate Cortex in Depression

    Science.gov (United States)

    Späti, Jakub; Hänggi, Jürgen; Doerig, Nadja; Ernst, Jutta; Sambataro, Fabio; Brakowski, Janis; Jäncke, Lutz; grosse Holtforth, Martin; Seifritz, Erich; Spinelli, Simona

    2015-01-01

    Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment. PMID:25598428

  17. Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals

    Directory of Open Access Journals (Sweden)

    Yasmin Zakiniaeiz

    2017-01-01

    Full Text Available Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC, mid (MCC and posterior cingulate cortex (PCC, voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome. Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.

  18. Modulation of Subgenual Anterior Cingulate Cortex Activity With Real-Time Neurofeedback

    OpenAIRE

    Hamilton, J. Paul; Gary H Glover; Hsu, Jung-Jiin; Johnson, Rebecca F.; Gotlib, Ian H.

    2011-01-01

    The advent of real-time neurofeedback techniques has allowed us to begin to map the controllability of sensory and cognitive and, more recently, affective centers in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in generation of affective states and has been implicated in psychopathology. In this study, we examined whether individuals could use realtime fMRI neurofeedback to modulate sACC activity. Following a localizer task used to identify an sACC regio...

  19. Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway.

    Science.gov (United States)

    Shyu, Bai-Chuang; Vogt, Brent A

    2009-09-04

    Although the mechanisms of short- and long-term potentiation of nociceptive-evoked responses are well known in the spinal cord, including central sensitization, there has been a growing body of information on such events in the cerebral cortex. In view of the importance of anterior cingulate cortex (ACC) in chronic pain conditions, this review considers neuronal plasticities in the thalamocingulate pathway that may be the earliest changes associated with such syndromes. A single nociceptive electrical stimulus to the sciatic nerve induced a prominent sink current in the layer II/III of the ACC in vivo, while high frequency stimulation potentiated the response of this current. Paired-pulse facilitation by electrical stimulation of midline, mediodorsal and intralaminar thalamic nuclei (MITN) suggesting that the MITN projection to ACC mediates the nociceptive short-term plasticity. The short-term synaptic plasticities were evaluated for different inputs in vitro where the medial thalamic and contralateral corpus callosum afferents were compared. Stimulation of the mediodorsal afferent evoked a stronger short-term synaptic plasticity and effectively transferred the bursting thalamic activity to cingulate cortex that was not true for contralateral stimulation. This short-term enhancement of synaptic transmission was mediated by polysynaptic pathways and NMDA receptors. Layer II/III neurons of the ACC express a short-term plasticity that involves glutamate and presynaptic calcium influx and is an important mechanism of the short-term plasticity. The potentiation of ACC neuronal activity induced by thalamic bursting suggest that short-term synaptic plasticities enable the processing of nociceptive information from the medial thalamus and this temporal response variability is particularly important in pain because temporal maintenance of the response supports cortical integration and memory formation related to noxious events. Moreover, these modifications of cingulate

  20. Functional connectivity of the human rostral and caudal cingulate motor areas in the brain resting state at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Habas, Christophe [CHNO des Quinze-Vingts, UPMC Paris 6, Service de NeuroImagerie, Paris (France)

    2010-01-15

    Three cingulate motor areas have been described in monkeys, the rostral, dorsal, and ventral cingulate motor areas, and would control limbic-related motor activity. However, little anatomical data are available in human about the functional networks these cingulate areas underlie. Therefore, networks anchored in the rostral and caudal cingulate motor areas (rCMA and cCMA, respectively) were studied in human using functional connectivity during the brain resting state. Since the rCMA and cCMA are located just under the pre-supplementary and supplementary motor areas (pre-SMA and SMA), the pre-SMA- and SMA-centered networks were also studied to ensure that these four circuits were correctly dissociated. Data from 14 right-handed healthy volunteers were acquired at rest and analyzed by region of interest (ROI)-based functional connectivity. The blood oxygenation level-dependent (BOLD) signal fluctuations of separate ROIs located in rCMA, cCMA, pre-SMA, and SMA were successively used to identify significant temporal correlations with BOLD signal fluctuations of other brain regions. Low-frequency BOLD signal of the CMA was correlated with signal fluctuations in the prefrontal, cingulate, insular, premotor, motor, medial and inferior parietal cortices, putamen and thalamus, and anticorrelated with the default-mode network. rCMA was more in relation with prefrontal, orbitofrontal, and language-associated cortices than cCMA more related to sensory cortex. These cingulate networks were very similar to the pre-SMA- and SMA-centered networks, although pre-SMA and SMA showed stronger correlation with the prefrontal and inferior parietal cortices and with the cerebellum and the superior parietal cortex, respectively. The human cingulate motor areas constitute an interface between sensorimotor, limbic and executive systems, sharing common cortical, striatal, and thalamic relays with the overlying premotor medial areas. (orig.)

  1. Anterior cingulate serotonin 1B receptor binding is associated with emotional response inhibition.

    Science.gov (United States)

    da Cunha-Bang, Sofi; Hjordt, Liv Vadskjær; Dam, Vibeke Høyrup; Stenbæk, Dea Siggaard; Sestoft, Dorte; Knudsen, Gitte M

    2017-09-01

    Serotonin has a well-established role in emotional processing and is a key neurotransmitter in impulsive aggression, presumably by facilitating response inhibition and regulating subcortical reactivity to aversive stimuli. In this study 44 men, of whom 19 were violent offenders and 25 were non-offender controls, completed an emotional Go/NoGo task requiring inhibition of prepotent motor responses to emotional facial expressions. We also measured cerebral serotonin 1B receptor (5-HT1BR) binding with [11C]AZ10419369 positron emission tomography within regions of the frontal cortex. We hypothesized that 5-HT1BR would be positively associated with false alarms (failures to inhibit nogo responses) in the context of aversive (angry and fearful) facial expressions. Across groups, we found that frontal cortex 5-HT1BR binding was positively correlated with false alarms when angry faces were go stimuli and neutral faces were nogo stimuli (p = 0.05, corrected alpha = 0.0125), but not with false alarms for non-emotional stimuli (failures to inhibit geometric figures). A posthoc analysis revealed the strongest association in anterior cingulate cortex (p = 0.006). In summary, 5-HT1BRs in the anterior cingulate are involved in withholding a prepotent response in the context of angry faces. Our findings suggest that serotonin modulates response inhibition in the context of certain emotional stimuli. Copyright © 2017. Published by Elsevier Ltd.

  2. Task-related deactivation and functional connectivity of the subgenual cingulate cortex in major depressive disorder

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    Christopher G Davey

    2012-02-01

    Full Text Available Background: Major depressive disorder is associated with functional alterations in activity and resting-state connectivity of the extended medial frontal network. In this study we aimed to examine how task-related medial network activity and connectivity were affected by depression.Methods: Eighteen patients with major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy control participants. We characterised task-related activations and deactivations while participants engaged with an executive-control task (the multi-source interference task; MSIT. We used a psycho-physiological interactions (PPI approach to examine functional connectivity changes with subgenual ACC. Voxelwise statistical maps for each analysis were compared between the patient and control groups.Results: There were no differences between groups in their behavioral performances on the MSIT task, and nor in patterns of activation and deactivation. Assessment of functional connectivity with the subgenual cingulate showed that depressed patients did not demonstrate the same reduction in functional connectivity with the ventral striatum during task performance, but that they showed greater reduction in functional connectivity with adjacent ventromedial frontal cortex. The magnitude of this latter connectivity change predicted the relative activation of task-relevant executive control regions in depressed patients.Conclusions: The study reinforces the importance of the subgenual cingulate cortex for depression, and demonstrates how dysfunctional connectivity with ventral brain regions might influence executive–attentional processes.

  3. Visual motion responses in the posterior cingulate sulcus: a comparison to V5/MT and MST.

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    Fischer, Elvira; Bülthoff, Heinrich H; Logothetis, Nikos K; Bartels, Andreas

    2012-04-01

    Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements.

  4. To retrieve or to calculate? Left angular gyrus mediates the retrieval of arithmetic facts during problem solving.

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    Grabner, Roland H; Ansari, Daniel; Koschutnig, Karl; Reishofer, Gernot; Ebner, Franz; Neuper, Christa

    2009-01-01

    While there is consistent evidence from neuropsychological and brain imaging studies for an association between the left angular gyrus and mental arithmetic, its specific role in calculation has remained poorly understood. It has been speculated that the angular gyrus mediates the retrieval of arithmetic facts during problem solving, but this hypothesis has not been directly tested. In the present functional Magnetic Resonance Imaging study comprising 28 adults, we used trial-by-trial strategy self-reports to identify brain regions underpinning different strategies in arithmetic problem solving. Analyses revealed stronger activation of the left angular gyrus while solving arithmetic problems for which participants reported fact retrieval whereas the application of procedural strategies was accompanied by widespread activation in a fronto-parietal network. These data directly link the left angular gyrus with arithmetic fact retrieval and show that strategy self-reports can be used to predict differential patterns of brain activation.

  5. Characteristics of Cerebral Blood Flow in Vascular Dementia using SPM Analysis Compared to Normal Control and Alzheimer's Dementia

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    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo [College of Medicine, Univ. of Donga, Busan (Korea, Republic of)

    2003-07-01

    Cerebral perfusion pattern of vascular dementia (VD) was not well established and overlap of cerebral perfusion pattern was reported between VD and Alzheimer's dementia (AD). The aim of this study is to assess the specific patterns of SPECT finding in VD compared with normal control subjects and to disclose differences of cerebral blood flow between subjects with VD and AD were investigated using statistic parametric mapping analysis. Thirty-two VD (mean age ; 67.86.4 years, mean CDR ; 0.980.27), 51 AD (mean age ; 71.47.2 years, CDR ; 1.160.47), which were matched for age and severity of dementia, and 30 normal control subjects (mean age ; 60.17.7 years) participated in this study. The Tc-99m HMPAO brain perfusion SPECT data were analyzed by SPM99. The SPECT data of the patients with VD were compared to those of the control subjects and then compared to the patients with AD. SPM analysis of the SPECT image showed significant perfusion deficits in the both frontal (both cingulate gyrus, both inferior frontal gyrus, B no.47, right frontal rectal gyrus, left frontal subcallosal gyrus, B no.25), both temporal (right insula, B no.13, left superior temporal gyrus, left parahippocampal gyrus, B no.35), occipital (occipital lingual gyrus), right corpus callosum and right cerebellar tonsil regions in subjects with VD compared with normal control subjects (uncorrected p<0.01). Comparison of the two dementia groups (uncorrected p<0.01) revealed significant hypoperfusion in both parietal posterior central gyrus, right inferior frontal gyrus (B no.47), left insula, right thalamus (ventral lateral nucleus), right claustrum and right occipital cuneus regions in VD group compared with AD. There were no typical confined regional hypoperfusion areas but scattered multiple perfusion deficits in VD compared AD. These findings may be helpful to reflect the pathophysiological mechanisms of VD and to disclose differences of cerebral blood flow between subjects with VD and AD.

  6. Proton MR Spectroscopy: Higher Right Anterior Cingulate N-Acetylaspartate/Choline Ratio in Asperger Syndrome Compared with Healthy Controls

    Science.gov (United States)

    Oner, O.; Devrimci-Ozguven, H.; Oktem, F.; Yagmurlu, B.; Baskak, B.; Munir, K.M.

    2011-01-01

    BACKGROUND AND PURPOSE One former study reported higher prefrontal N-acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by 1H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17–38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = –2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = –1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = –1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale-Brown Obsessive Compulsive Scale total scores. PMID:17846198

  7. Effects of chronic buproprion and nicotine administration on cell genesis and DNA fragmentation in adult rat dentate gyrus

    OpenAIRE

    Scerri, Charles;

    2006-01-01

    Previous experiments have shown that chronic subcutaneous administration of nicotine dose-dependently inhibits the acquisition and retention of a spatial task in the Morris water maze and reduces cell genesis in the dentate gyrus (DG) of adult rats.1 In the present study, the effects of nicotine and buproprion, an atypical antidepressant used in smoking cessation, on dentate gyrus cell genesis and DNA fragmentation were investigated. The results show that nicotine, chronically infused for 21 ...

  8. Frontal and anterior cingulate activation during overt verbal fluency in patients with first episode psychosis Ativação frontal e do cíngulo anterior durante tarefa de fluência verbal em pacientes em primeiro episódio psicótico

    Directory of Open Access Journals (Sweden)

    Maristela Schaufelberger

    2005-09-01

    Full Text Available OBJECTIVE: Functional neuroimaging studies using phonological verbal fluency tasks allow the assessment of neural circuits relevant to the neuropsychology of psychosis. There is evidence that the prefrontal cortex and anterior cingulate gyrus present different activation patterns in subjects with chronic schizophrenia relative to healthy controls. We assessed the functioning in these brain regions during phonological verbal fluency in subjects with recent-onset functional psychoses, using functional magnetic resonance imaging (FMRI. METHODS: Seven patients with functional psychoses (3 schizophreniform, 4 affective and 9 healthy controls were studied. We compared functional magnetic resonance images acquired during articulation of words beginning with letters classified as easy for word production in Portuguese. Statistical comparisons were performed using non-parametric tests. RESULTS: There were no differences between patients and controls in task performance. Controls showed greater activation than patients in the left rostral anterior cingulate gyrus and right inferior prefrontal cortex, whereas patients showed stronger activation than controls in a more dorsal part of the anterior cingulate gyrus bilaterally and in a more superior portion of the right prefrontal cortex. CONCLUSION: Our preliminary findings of attenuated engagement of inferior prefrontal cortex and anterior cingulate gyrus in patients with recent onset psychosis during phonological verbal fluency are consistent with those of previous studies. The greater activation found in other parts of the anterior cingulate gyrus and prefrontal cortex in patients may be related to a compensatory response that is required to maintain normal task performance, and suggests a pattern of disorganized activity of different functional anterior cingulate gyrus units in association with psychotic conditions.OBJETIVO: Estudos de neuroimagem funcional empregando tarefa de fluência verbal fonol

  9. Differential activation of the anterior cingulate cortex and caudate nucleus during a gambling simulation in persons with a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project.

    Science.gov (United States)

    Acheson, Ashley; Robinson, Jennifer L; Glahn, David C; Lovallo, William R; Fox, Peter T

    2009-02-01

    Individuals with a family history of alcoholism (FH+) are at enhanced risk of developing an alcohol or other substance use disorder relative to those without this history (FH-). Recent studies comparing FH+ and FH- individuals have revealed differences in cognition, emotion processing, sociability, and decision-making. These differences suggest possible altered brain functioning in FH+ individuals that may play a crucial role in vulnerability to substance use disorders. In the present study, 15 FH+ and 19 FH- individuals performed the Iowa Gambling Task (IGT), a simulated card game requiring integration of payoff-to-penalty ratios, while undergoing functional magnetic resonance imaging. All participants performed the task more conservatively as the session progressed, and the FH groups achieved similar payoffs by the end of the game. Imaging revealed a distributed network of brain regions that was engaged when subjects performed this task, including the right inferior frontal and postcentral gyri, left parahippocampal gyrus, insula and precuneous cortices, left inferior and superior parietal lobules, left lentiform nucleus and bilateral culmen, claustrum, lingual gyri and cerebellar tonsils. Despite a lack of behavioral differences between groups, the FH+ participants showed significantly more activation in the left dorsal anterior cingulate cortex and left caudate nucleus. These findings correspond to models of risk in FH+ persons that postulate biases in brain decision-making systems as underlying elevated risk for alcoholism.

  10. The Effects of Obstructive Sleep Apnea Syndrome on the Dentate Gyrus and Learning and Memory in Children.

    Science.gov (United States)

    Cha, Jiook; Zea-Hernandez, Johanna A; Sin, Sanghun; Graw-Panzer, Katharina; Shifteh, Keivan; Isasi, Carmen R; Wagshul, Mark E; Moran, Eileen E; Posner, Jonathan; Zimmerman, Molly E; Arens, Raanan

    2017-04-19

    Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS (n = 11) and control subjects (n = 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus (p = 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial η(2) = 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's r = -0.50, p = 0.008) and a greater arousal index (r = -0.44, p = 0.017). OSAS did not significantly affect neuropsychological measures (p values >0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity (r = 0.54, p = 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS.SIGNIFICANCE STATEMENT In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children

  11. Anterior Cingulate Volumetric Alterations in Treatment-Naïve Adults With ADHD

    Science.gov (United States)

    Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.

    2013-01-01

    Objective We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naïve adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and inattention, which are cardinal behavioral manifestations of ADHD. Method Segmentation and parcellation of the ACC was performed on controls (n = 22), treated (n = 13) and treatment-naïve adults with ADHD (n = 13). Results There was a 21% volume reduction in the left ACC of the treatment-naïve group relative to the control group. Also, there was a 23% volume reduction in the right ACC of the treated group relative to the control group. Conclusion These results raise the possibility that in ADHD there are volumetric deficits persistent into adulthood, that are independent of medical treatment. PMID:20008822

  12. Disconnectivity between Dorsal Raphe Nucleus and Posterior Cingulate Cortex in Later Life Depression

    Directory of Open Access Journals (Sweden)

    Toshikazu Ikuta

    2017-08-01

    Full Text Available The dorsal raphe nucleus (DRN has been repeatedly implicated as having a significant relationship with depression, along with its serotoninergic innervation. However, functional connectivity of the DRN in depression is not well understood. The current study aimed to isolate functional connectivity of the DRN distinct in later life depression (LLD compared to a healthy age-matched population. Resting state functional magnetic resonance imaging (rsfMRI data from 95 participants (33 LLD and 62 healthy were collected to examine functional connectivity from the DRN to the whole brain in voxel-wise fashion. The posterior cingulate cortex (PCC bilaterally showed significantly smaller connectivity in the LLD group than the control group. The DRN to PCC connectivity did not show any association with the depressive status. The findings implicate that the LLD involves disruption of serotoninergic input to the PCC, which has been suggested to be a part of the reduced default mode network in depression.

  13. The expected value of control: an integrative theory of anterior cingulate cortex function.

    Science.gov (United States)

    Shenhav, Amitai; Botvinick, Matthew M; Cohen, Jonathan D

    2013-07-24

    The dorsal anterior cingulate cortex (dACC) has a near-ubiquitous presence in the neuroscience of cognitive control. It has been implicated in a diversity of functions, from reward processing and performance monitoring to the execution of control and action selection. Here, we propose that this diversity can be understood in terms of a single underlying function: allocation of control based on an evaluation of the expected value of control (EVC). We present a normative model of EVC that integrates three critical factors: the expected payoff from a controlled process, the amount of control that must be invested to achieve that payoff, and the cost in terms of cognitive effort. We propose that dACC integrates this information, using it to determine whether, where and how much control to allocate. We then consider how the EVC model can explain the diverse array of findings concerning dACC function. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Diffusion tensor imaging reveals thalamus and posterior cingulate cortex abnormalities in internet gaming addicts.

    Science.gov (United States)

    Dong, Guangheng; DeVito, Elise; Huang, Jie; Du, Xiaoxia

    2012-09-01

    Internet gaming addiction (IGA) is increasingly recognized as a widespread disorder with serious psychological and health consequences. Diminished white matter integrity has been demonstrated in a wide range of other addictive disorders which share clinical characteristics with IGA. Abnormal white matter integrity in addictive populations has been associated with addiction severity, treatment response and cognitive impairments. This study assessed white matter integrity in individuals with internet gaming addiction (IGA) using diffusion tensor imaging (DTI). IGA subjects (N = 16) showed higher fractional anisotropy (FA), indicating greater white matter integrity, in the thalamus and left posterior cingulate cortex (PCC) relative to healthy controls (N = 15). Higher FA in the thalamus was associated with greater severity of internet addiction. Increased regional FA in individuals with internet gaming addiction may be a pre-existing vulnerability factor for IGA, or may arise secondary to IGA, perhaps as a direct result of excessive internet game playing. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Learning to cope with stress modulates anterior cingulate cortex stargazin expression in monkeys and mice.

    Science.gov (United States)

    Lee, Alex G; Capanzana, Roxanne; Brockhurst, Jacqueline; Cheng, Michelle Y; Buckmaster, Christine L; Absher, Devin; Schatzberg, Alan F; Lyons, David M

    2016-05-01

    Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping with gains in subsequent emotion regulation. Here we investigate the effects of learning to cope with stress on anterior cingulate cortex gene expression in monkeys and mice. Anterior cingulate cortex is involved in learning, memory, cognitive control, and emotion regulation. Monkeys and mice were randomized to either stress coping or no-stress treatment conditions. Profiles of gene expression were acquired with HumanHT-12v4.0 Expression BeadChip arrays adapted for monkeys. Three genes identified in monkeys by arrays were then assessed in mice by quantitative real-time polymerase chain reaction. Expression of a key gene (PEMT) involved in acetylcholine biosynthesis was increased in monkeys by coping but this result was not verified in mice. Another gene (SPRY2) that encodes a negative regulator of neurotrophic factor signaling was decreased in monkeys by coping but this result was only partly verified in mice. The CACNG2 gene that encodes stargazin (also called TARP gamma-2) was increased by coping in monkeys as well as mice randomized to coping with or without subsequent behavioral tests of emotionality. As evidence of coping effects distinct from repeated stress exposures per se, increased stargazin expression induced by coping correlated with diminished emotionality in mice. Stargazin modulates glutamate receptor signaling and plays a role in synaptic plasticity. Molecular mechanisms of synaptic plasticity that mediate learning and memory in the context of coping with stress may provide novel targets for new treatments of disorders in human mental health. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Biochemistry of the cingulate cortex in autism: An MR spectroscopy study.

    Science.gov (United States)

    Libero, Lauren E; Reid, Meredith A; White, David M; Salibi, Nouha; Lahti, Adrienne C; Kana, Rajesh K

    2016-06-01

    Neuroimaging studies have uncovered structural and functional alterations in the cingulate cortex in individuals with autism spectrum disorders (ASD). Such abnormalities may underlie neurochemical imbalance. In order to characterize the neurochemical profile, the current study examined the concentration of brain metabolites in dorsal ACC (dACC) and posterior cingulate cortex (PCC) in high-functioning adults with ASD. Twenty high-functioning adults with ASD and 20 age-and-IQ-matched typically developing (TD) peers participated in this Proton magnetic resonance spectroscopy (1H-MRS) study. LCModel was used in analyzing the spectra to measure the levels of N-Acetyl aspartate (NAA), choline (Cho), creatine (Cr), and glutamate/glutamine (Glx) in dACC and PCC. Groups were compared using means for the ratio of each metabolite to their respective Cr levels as well as on absolute internal-water-referenced measures of each metabolite. There was a significant increase in Cho in PCC for ASD adults, with a marginal increase in dACC. A reduction in NAA/Cr in dACC was found in ASD participants, compared to their TD peers. No significant differences in Glx/Cr or Cho/Cr were found in dACC. There were no statistically significant group differences in the absolute concentration of NAA, Cr, Glx, or NAA/Cr, Cho/Cr, and Glx/Cr in the PCC. Differences in the metabolic properties of dACC compared to PCC were also found. Results of this study provide evidence for possible cellular and metabolic differences in the dACC and PCC in adults with ASD. This may suggest neuronal dysfunction in these regions and may contribute to the neuropathology of ASD. Autism Res 2016, 9: 643-657. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  17. Cholinergic enhancement increases regional cerebral blood flow to the posterior cingulate cortex in mild Alzheimer's disease.

    Science.gov (United States)

    Iizuka, Tomomichi; Kameyama, Masashi

    2017-06-01

    The brain region that shows reductions in regional cerebral blood flow (rCBF) earliest is the posterior cingulate cortex (PCC), which is thought to have a relationship with cognitive function. We made a hypothesis that the PCC hypoperfusion is a result of cholinergic dysfunction and can be restored by cholinergic enhancement. This present longitudinal study aimed to detect the restoration of PCC rCBF in response to donepezil, an acetylcholine esterase inhibitor. We evaluated rCBF changes in the PCC, precuneus and anterior cingulate cortex using perfusion single-photon emission computed tomography (SPECT), statistical analysis and region of interest analysis, prospectively. We allocated 36 patients with mild AD to either the responder or non-responder groups based on changes in Mini-Mental State Examination scores. The patients were followed up for 18 months. The PCC rCBF significantly increased in responders after 6 months of donepezil therapy. Statistical maps at baseline showed a typical decreased pattern of mild AD and obvious rCBF restoration in the bilateral PCC at 6 months in responders. Changes in Mini-Mental State Examination scores and the AD assessment scale cognitive scores significantly correlated with rCBF changes in the PCC of responders. Cholinergic enhancement restored PCC rCBF under the three conditions of mild AD, responders and short follow-up interval, and that increase correlated with improved cognitive function. These findings support our hypothesis that PCC rCBF reflects cholinergic function in AD patients. Geriatr Gerontol Int 2017; 17: 951-958. © 2016 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

  18. Involvement of the left anterior insula and frontopolar gyrus in odor discrimination.

    Science.gov (United States)

    Plailly, Jane; Radnovich, Alexander J; Sabri, Merav; Royet, Jean-Pierre; Kareken, David A

    2007-05-01

    Discriminating between successively presented odors requires brief storage of the first odor's perceptual trace, which then needs to be subsequently compared to the second odor in the pair. This study explores the cortical areas involved in odor discrimination and compares them with findings from studies of working-memory, traditionally investigated with n-back paradigms. Sixteen right-handed subjects underwent H(2) (15)O positron emission tomography during counterbalanced conditions of odorless sniffing, repeated single odor detection, multiple odor detection, and conscious successive discrimination between odor pairs. Eight odorants were delivered using a computer-controlled olfactometer through a birhinal nasal cannula. Conscious successive odor discrimination evoked significantly greater activity in the left anterior insula and frontopolar gyrus when compared to reported sensory detection of the identical odors. Additional activation was found in the left lateral orbital/inferior frontal and middle frontal gyri when discrimination was compared to the odorless condition. The left anterior insula is likely involved in the evaluation of odor properties. Consistent with other studies, frontopolar and middle frontal gyrus activation is more likely related to working memory during odor discrimination.

  19. How music alters a kiss: superior temporal gyrus controls fusiform–amygdalar effective connectivity

    Science.gov (United States)

    Deserno, Lorenz; Bakels, Jan-Hendrik; Schlochtermeier, Lorna H.; Kappelhoff, Hermann; Jacobs, Arthur M.; Fritz, Thomas Hans; Koelsch, Stefan; Kuchinke, Lars

    2014-01-01

    While watching movies, the brain integrates the visual information and the musical soundtrack into a coherent percept. Multisensory integration can lead to emotion elicitation on which soundtrack valences may have a modulatory impact. Here, dynamic kissing scenes from romantic comedies were presented to 22 participants (13 females) during functional magnetic resonance imaging scanning. The kissing scenes were either accompanied by happy music, sad music or no music. Evidence from cross-modal studies motivated a predefined three-region network for multisensory integration of emotion, consisting of fusiform gyrus (FG), amygdala (AMY) and anterior superior temporal gyrus (aSTG). The interactions in this network were investigated using dynamic causal models of effective connectivity. This revealed bilinear modulations by happy and sad music with suppression effects on the connectivity from FG and AMY to aSTG. Non-linear dynamic causal modeling showed a suppressive gating effect of aSTG on fusiform–amygdalar connectivity. In conclusion, fusiform to amygdala coupling strength is modulated via feedback through aSTG as region for multisensory integration of emotional material. This mechanism was emotion-specific and more pronounced for sad music. Therefore, soundtrack valences may modulate emotion elicitation in movies by differentially changing preprocessed visual information to the amygdala. PMID:24298171

  20. Suspension of Mitotic Activity in Dentate Gyrus of the Hibernating Ground Squirrel

    Directory of Open Access Journals (Sweden)

    Victor I. Popov

    2011-01-01

    Full Text Available Neurogenesis occurs in the adult mammalian hippocampus, a region of the brain important for learning and memory. Hibernation in Siberian ground squirrels provides a natural model to study mitosis as the rapid fall in body temperature in 24 h (from 35-36°C to +4–6°C permits accumulation of mitotic cells at different stages of the cell cycle. Histological methods used to study adult neurogenesis are limited largely to fixed tissue, and the mitotic state elucidated depends on the specific phase of mitosis at the time of day. However, using an immunohistochemical study of doublecortin (DCX and BrdU-labelled neurons, we demonstrate that the dentate gyrus of the ground squirrel hippocampus contains a population of immature cells which appear to possess mitotic activity. Our data suggest that doublecortin-labelled immature cells exist in a mitotic state and may represent a renewable pool for generation of new neurons within the dentate gyrus.

  1. How music alters a kiss: superior temporal gyrus controls fusiform-amygdalar effective connectivity.

    Science.gov (United States)

    Pehrs, Corinna; Deserno, Lorenz; Bakels, Jan-Hendrik; Schlochtermeier, Lorna H; Kappelhoff, Hermann; Jacobs, Arthur M; Fritz, Thomas Hans; Koelsch, Stefan; Kuchinke, Lars

    2014-11-01

    While watching movies, the brain integrates the visual information and the musical soundtrack into a coherent percept. Multisensory integration can lead to emotion elicitation on which soundtrack valences may have a modulatory impact. Here, dynamic kissing scenes from romantic comedies were presented to 22 participants (13 females) during functional magnetic resonance imaging scanning. The kissing scenes were either accompanied by happy music, sad music or no music. Evidence from cross-modal studies motivated a predefined three-region network for multisensory integration of emotion, consisting of fusiform gyrus (FG), amygdala (AMY) and anterior superior temporal gyrus (aSTG). The interactions in this network were investigated using dynamic causal models of effective connectivity. This revealed bilinear modulations by happy and sad music with suppression effects on the connectivity from FG and AMY to aSTG. Non-linear dynamic causal modeling showed a suppressive gating effect of aSTG on fusiform-amygdalar connectivity. In conclusion, fusiform to amygdala coupling strength is modulated via feedback through aSTG as region for multisensory integration of emotional material. This mechanism was emotion-specific and more pronounced for sad music. Therefore, soundtrack valences may modulate emotion elicitation in movies by differentially changing preprocessed visual information to the amygdala. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Non-invasive brain stimulation targeting the right fusiform gyrus selectively increases working memory for faces.

    Science.gov (United States)

    Brunyé, Tad T; Moran, Joseph M; Holmes, Amanda; Mahoney, Caroline R; Taylor, Holly A

    2017-04-01

    The human extrastriate cortex contains a region critically involved in face detection and memory, the right fusiform gyrus. The present study evaluated whether transcranial direct current stimulation (tDCS) targeting this anatomical region would selectively influence memory for faces versus non-face objects (houses). Anodal tDCS targeted the right fusiform gyrus (Brodmann's Area 37), with the anode at electrode site PO10, and cathode at FP2. Two stimulation conditions were compared in a repeated-measures design: 0.5mA versus 1.5mA intensity; a separate control group received no stimulation. Participants completed a working memory task for face and house stimuli, varying in memory load from 1 to 4 items. Individual differences measures assessed trait-based differences in facial recognition skills. Results showed 1.5mA intensity stimulation (versus 0.5mA and control) increased performance at high memory loads, but only with faces. Lower overall working memory capacity predicted a positive impact of tDCS. Results provide support for the notion of functional specialization of the right fusiform regions for maintaining face (but not non-face object) stimuli in working memory, and further suggest that low intensity electrical stimulation of this region may enhance demanding face working memory performance particularly in those with relatively poor baseline working memory skills. Published by Elsevier Inc.

  3. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Harish eBabu

    2011-07-01

    Full Text Available In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons, PLoS One 2007, 2:e388 to isolate neural precursor cells from the hippocampus of adult mice and maintain and propagate them as adherent monolayer cultures. The strategy is based on the use of Percoll density gradient centrifugation to enrich precursor cells from the micro-dissected dentate gyrus. Based on the expression of Nestin and Sox2, a culture-purity of more than 98% can be achieved. The cultures are expanded under serum-free conditions in Neurobasal A medium with addition of the mitogens EGF and FGF2 as well as the supplements Glutamax-1 and B27. Under differentiation conditions, the precursor cells reliably generate approximately 30% neurons with appropriate morphological, molecular and electrophysiological characteristics that might reflect granule cell properties as their in vivo counterpart. We also highlight potential modifications to the protocol.

  4. The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors.

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    Linya You

    2015-03-01

    Full Text Available Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1 is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regulator for patterning the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.

  5. Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats

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    Jiro Kasahara

    2016-01-01

    Full Text Available Poststroke depression is one of the major symptoms observed in the chronic stage of brain stroke such as cerebral ischemia. Its pathophysiological mechanisms, however, are not well understood. Using the transient right middle cerebral artery occlusion- (MCAO-, 90 min operated rats as an ischemia model in this study, we first observed that aggravation of anhedonia spontaneously occurred especially after 20 weeks of MCAO, and it was prevented by chronic antidepressants treatment (imipramine or fluvoxamine. The anhedonia specifically associated with loss of the granular neurons in the ipsilateral side of hippocampal dentate gyrus and was also prevented by an antidepressant imipramine. Immunohistochemical analysis showed increased apoptosis inside the granular cell layer prior to and associated with the neuronal loss, and imipramine seemed to recover the survival signal rather than suppressing the death signal to prevent neurons from apoptosis. Proliferation and development of the neural stem cells were increased transiently in the subgranular zone of both ipsi- and contralateral hippocampus within one week after MCAO and then decreased and almost ceased after 6 weeks of MCAO, while chronic imipramine treatment prevented them partially. Overall, our study suggests new insights for the mechanistic correlation between poststroke depression and the delayed neurodegenerative changes in the hippocampal dentate gyrus with effective use of antidepressants on them.

  6. Spatial Reference Memory is Associated with Modulation of Theta-Gamma Coupling in the Dentate Gyrus.

    Science.gov (United States)

    Bott, Jean-Bastien; Muller, Marc-Antoine; Jackson, Jesse; Aubert, Julien; Cassel, Jean-Christophe; Mathis, Chantal; Goutagny, Romain

    2016-09-01

    Spatial reference memory in rodents represents a unique opportunity to study brain mechanisms responsible for encoding, storage and retrieval of a memory. Even though its reliance on hippocampal networks has long been established, the precise computations performed by different hippocampal subfields during spatial learning are still not clear. To study the evolution of electrophysiological activity in the CA1-dentate gyrus axis of the dorsal hippocampus over an iterative spatial learning paradigm, we recorded local field potentials in behaving mice using a newly designed appetitive version of the Barnes maze. We first showed that theta and gamma oscillations as well as theta-gamma coupling are differentially modulated in particular hippocampal subfields during the task. In addition, we show that dentate gyrus networks, but not CA1 networks, exhibit a transient learning-dependent increase in theta-gamma coupling specifically at the vicinity of the target area in the maze. In contrast to previous immediate early-gene studies, our results point to a long-lasting involvement of dentate networks in navigational memory in the Barnes maze. Based on these findings, we propose that theta-gamma coupling might represent a mechanism by which hippocampal areas compute relevant information. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Resting state functional connectivity of the anterior cingulate cortex in veterans with and without post-traumatic stress disorder

    NARCIS (Netherlands)

    Kennis, Mitzy; Rademaker, Arthur R.; van Rooij, Sanne J H; Kahn, René S.; Geuze, Elbert

    2015-01-01

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated with structural and functional alterations in several brain areas, including the anterior cingulate cortex (ACC). Here, we examine resting state functional connectivity of ACC subdivisions in PTSD, using a seed-based

  8. Anterior Cingulate Cortex and Cognitive Control: Neuropsychological and Electrophysiological Findings in Two Patients with Lesions to Dorsomedial Prefrontal Cortex

    Science.gov (United States)

    Lovstad, M.; Funderud, I.; Meling, T.; Kramer, U. M.; Voytek, B.; Due-Tonnessen, P.; Endestad, T.; Lindgren, M.; Knight, R. T.; Solbakk, A. K.

    2012-01-01

    Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial…

  9. Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus.

    Science.gov (United States)

    Wang, Shaobo; Brunne, Bianka; Zhao, Shanting; Chai, Xuejun; Li, Jiawei; Lau, Jeremie; Failla, Antonio Virgilio; Zobiak, Bernd; Sibbe, Mirjam; Westbrook, Gary L; Lutz, David; Frotscher, Michael

    2018-01-03

    Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the

  10. Effortless awareness: using real time neurofeedback to investigate correlates of posterior cingulate cortex activity in meditators’ self-report.

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    Kathleen eGarrison

    2013-08-01

    Full Text Available Neurophenomenological studies seek to utilize first-person self-report to elucidate cognitive processes related to physiological data. Grounded theory offers an approach to the qualitative analysis of self-report, whereby theoretical constructs are derived from empirical data. Here we used grounded theory methodology to assess how the first-person experience of meditation relates to neural activity in a core region of the default mode network –the posterior cingulate cortex. We analyzed first-person data consisting of meditators’ accounts of their subjective experience during runs of a real-time fMRI neurofeedback study of meditation, and third-person data consisting of corresponding feedback graphs of posterior cingulate cortex activity during the same runs. We found that for meditators, the subjective experiences of ‘undistracted awareness’ such as ‘concentration’ and ‘observing sensory experience’, and ‘effortless doing’ such as ‘observing sensory experience’, ‘not efforting’, and ‘contentment’, correspond with posterior cingulate cortex deactivation. Further, the subjective experiences of ‘distracted awareness’ such as ‘distraction’ and ‘interpreting’, and ‘controlling’ such as ‘efforting’ and ‘discontentment’, correspond with posterior cingulate cortex activation. Moreover, we derived several novel hypotheses about how specific qualities of cognitive processes during meditation relate to posterior cingulate cortex activity, such as the difference between meditation and ‘trying to meditate’. These findings offer novel insights into the relationship between meditation and self-related thinking and neural activity in the default mode network, driven by the first-person experience.

  11. Memory of music: roles of right hippocampus and left inferior frontal gyrus.

    Science.gov (United States)

    Watanabe, Takamitsu; Yagishita, Sho; Kikyo, Hideyuki

    2008-01-01

    We investigated neural correlates of retrieval success for music memory using event-related functional magnetic resonance imaging. To minimize the interference from MRI scan noise, we used sparse temporal sampling technique. Newly composed music materials were employed as stimuli, which enabled us to detect regions in absence of effects of experience with the music stimuli in this study. Whole brain analyses demonstrated significant retrieval success activities in the right hippocampus, bilateral lateral temporal regions, left inferior frontal gyrus and left precuneus. Anatomically defined region-of-interests analyses showed that the activity of the right hippocampus was stronger than that of the left, while the activities of the inferior frontal gyri showed the reverse pattern. Furthermore, performance-based analyses demonstrated that the retrieval success activity of the right hippocampus was positively correlated with the corrected recognition rate, suggesting that the right hippocampus contributes to the accuracy of music retrieval outcome.

  12. BOLD response to motion verbs in left posterior middle temporal gyrus during story comprehension

    DEFF Research Database (Denmark)

    Wallentin, Mikkel; Nielsen, Andreas Højlund; Vuust, Peter

    2011-01-01

    A primary focus within neuroimaging research on language comprehension is on the distribution of semantic knowledge in the brain. Studies have shown that the left posterior middle temporal gyrus (LPMT), a region just anterior to area MT/V5, is important for the processing of complex action......MRI participants listened to a recording of the story ‘‘The Ugly Duckling’’. We incorporated a nuisance elimination regression approach for factoring out known nuisance variables both in terms of physiological noise, sound intensity, linguistic variables and emotional content. Compared to the remaining text......, clauses containing motion verbs were accompanied by a robust activation of LPMT with no other significant effects, consistent with the hypothesis that this brain region is important for processing motion knowledge, even during naturalistic language comprehension conditions....

  13. Separation or binding? Role of the dentate gyrus in hippocampal mnemonic processing.

    Science.gov (United States)

    Lee, Jong Won; Jung, Min Whan

    2017-04-01

    As a major component of the hippocampal trisynaptic circuit, the dentate gyrus (DG) relays inputs from the entorhinal cortex to the CA3 subregion. Although the anatomy of the DG is well characterized, its contribution to hippocampal mnemonic processing is still unclear. A currently popular theory proposes that the primary function of the DG is to orthogonalize incoming input patterns into non-overlapping patterns (pattern separation). We critically review the available data and conclude that the theoretical support and empirical evidence for this theory are not strong. We then review an alternative theory that posits a role for the DG in binding together different types of incoming sensory information. We conclude that 'binding' better captures the contribution of the DG to memory encoding than 'pattern separation'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Joint Contribution of Left Dorsal Premotor Cortex and Supramarginal Gyrus to Rapid Action Reprogramming

    DEFF Research Database (Denmark)

    Hartwigsen, Gesa; Siebner, Hartwig R

    2015-01-01

    . Moreover, the disruptive effect of rTMS over left PMd on response speed became stronger after SMG had been conditioned with offline rTMS. CONCLUSIONS: These results corroborate the notion that left PMd and SMG jointly contribute to rapid action reprogramming. Moreover, the strong virtual lesion effect......BACKGROUND: The rapid adaptation of actions to changes in the environment is crucial for survival. We previously demonstrated a joint contribution of left dorsal premotor cortex (PMd) and left supramarginal gyrus (SMG) to action reprogramming. However, we did not probe the contribution of PMd...... human subjects performed a spatially-precued reaction time task. RESULTS: Relative to sham rTMS, effective online perturbation of left PMd significantly impaired both the response speed and accuracy in trials that were invalidly pre-cued and required the subject to reprogram the prepared action...

  15. Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation.

    Science.gov (United States)

    Rangarajan, Vinitha; Parvizi, Josef

    2016-03-01

    The ventral temporal cortex (VTC) contains several areas with selective responses to words, numbers, faces, and objects as demonstrated by numerous human and primate imaging and electrophysiological studies. Our recent work using electrocorticography (ECoG) confirmed the presence of face-selective neuronal populations in the human fusiform gyrus (FG) in patients implanted with intracranial electrodes in either the left or right hemisphere. Electrical brain stimulation (EBS) disrupted the conscious perception of faces only when it was delivered in the right, but not left, FG. In contrast to our previous findings, here we report both negative and positive EBS effects in right and left FG, respectively. The presence of right hemisphere language dominance in the first, and strong left-handedness and poor language processing performance in the second case, provide indirect clues about the functional architecture of the human VTC in relation to hemispheric asymmetries in language processing and handedness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A case of tactile agnosia with a lesion restricted to the post-central gyrus.

    Science.gov (United States)

    Estañol, Bruno; Baizabal-Carvallo, José Fidel; Sentíes-Madrid, Horacio

    2008-01-01

    Tactile agnosia has been described after lesions of the primary sensory cortex but the exact location and extension of those lesions is not clear. We report the clinical features and imaging findings in a patient with an acute ischemic stroke restricted to the primary sensory area (S1). A 73-year-old man had a sudden onset of a left alien hand, without left hemiparesis. Neurological examination showed intact primary sensory functions, but impaired recognition of shape, size (macrogeometrical) and texture (microgeometrical) of objects; damage confined to the post-central gyrus, sparing the posterior parietal cortex was demonstrated on MRI. An embolic occlusion of the anterior parietal artery was suspected as mechanism of stroke. Tactile agnosia with impaired microgeometrical and macrogeometrical features' recognition can result from a single lesion in the primary sensory cortex (S1) in the right parietal hemisphere, sparing other regions of the cerebral cortex which presumably participate in tactile object recognition.

  17. Damage to the Left Precentral Gyrus Is Associated With Apraxia of Speech in Acute Stroke.

    Science.gov (United States)

    Itabashi, Ryo; Nishio, Yoshiyuki; Kataoka, Yuka; Yazawa, Yukako; Furui, Eisuke; Matsuda, Minoru; Mori, Etsuro

    2016-01-01

    Apraxia of speech (AOS) is a motor speech disorder, which is clinically characterized by the combination of phonemic segmental changes and articulatory distortions. AOS has been believed to arise from impairment in motor speech planning/programming and differentiated from both aphasia and dysarthria. The brain regions associated with AOS are still a matter of debate. The aim of this study was to address this issue in a large number of consecutive acute ischemic stroke patients. We retrospectively studied 136 patients with isolated nonlacunar infarcts in the left middle cerebral artery territory (70.5±12.9 years old, 79 males). In accordance with speech and language assessments, the patients were classified into the following groups: pure form of AOS (pure AOS), AOS with aphasia (AOS-aphasia), and without AOS (non-AOS). Voxel-based lesion-symptom mapping analysis was performed on T2-weighted images or fluid-attenuated inversion recovery images. Using the Liebermeister method, group-wise comparisons were made between the all AOS (pure AOS plus AOS-aphasia) and non-AOS, pure AOS and non-AOS, AOS-aphasia and non-AOS, and pure AOS and AOS-aphasia groups. Of the 136 patients, 22 patients were diagnosed with AOS (7 patients with pure AOS and 15 patients with AOS-aphasia). The voxel-based lesion-symptom mapping analysis demonstrated that the brain regions associated with AOS were centered on the left precentral gyrus. Damage to the left precentral gyrus is associated with AOS in acute to subacute stroke patients, suggesting a role of this brain region in motor speech production. © 2015 American Heart Association, Inc.

  18. Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders

    Science.gov (United States)

    Boldrini, Maura; Butt, Tanya H.; Santiago, Adrienne N.; Tamir, Hadassah; Dwork, Andrew J.; Rosoklija, Gorazd B.; Arango, Victoria; Hen, René; Mann, J. John

    2015-01-01

    Modest antidepressant response rates of mood disorders (MD) encourage benzodiazepine (BZD) co-medication with debatable benefit. Adult hippocampal neurogenesis may underlie antidepressant responses, but diazepam co-administration impairs murine neuron maturation and survival in response to fluoxetine. We counted neural progenitor cells (NPCs), mitotic cells, and mature granule neurons postmortem in dentate gyrus (DG) from subjects with: untreated DSM-IV MD (n=17); antidepressant-treated MD (MD*ADT, n=10); benzodiazepine-antidepressant-treated MD (MD*ADT*BZD, n=7); no psychopathology or treatment (controls, n=18). MD*ADT*BZD had fewer granule neurons vs. MD*ADT in anterior DG and vs. controls in mid DG, and did not differ from untreated-MD in any DG subregion. MD*ADT had more granule neurons than untreated-MD in anterior and mid DG and comparable granule neuron number to controls in all dentate subregions. Untreated-MD had fewer granule neurons than controls in anterior and mid DG, and did not differ from any other group in posterior DG. MD*ADT*BZD had fewer NPCs vs. MD*ADT in mid DG. MD*ADT had more NPCs vs. untreated-MD and controls in anterior and mid DG. MD*ADT*BZD and MD*ADT had more mitotic cells in anterior DG vs. controls and untreated-MD. There were no between-group differences in mid DG in mitotic cells or in posterior DG for any cell type. Our results in mid-dentate, and to some degree anterior dentate, gyrus are consistent with murine findings that benzodiazepines counteract antidepressant-induced increases in neurogenesis by interfering with progenitor proliferation. We also confirmed, in this expanded sample, our previous finding of granule neuron deficit in untreated MD. PMID:24969726

  19. Asymmetry and sexual dimorphism of the medial frontal gyrus visible surface in humans

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    Spasojević Goran

    2010-01-01

    Full Text Available Background/Aim. Studies of visible (extrasulcal surface of the brain hemispheres are not feasible for measurements of the brain size, but are valuable for analysis and quantification of sexual dimorphism and/or asymmetries of the human brain. Morphological and morphometric investigations of the brain may contribute in genetic studies of the human nervous system. The aim of this study was to determine and to quantify sexual dimorphism and the right/left morphological asymmetry of the visible surface of medial frontal gyrus (gyrus frontalis medialis - GFM. Methods. Measurements and analysis of the visible surface of GFM were done on 84 hemispheres (42 brains from the persons of both sexes: 26 males and 16 females, 20-65 years of age. After fixation in 10% formalin and dissection, digital morphometric measurements were performed. We studied these in relation to the side of the hemisphere and the person's sex. Standardized digital AutoCAD planimetry of the visible surface of GFM was enabled by the use of coordinate system of intercommissural line. Results. In the whole sample, the visible surface of the right GFM (21.39 cm2 was statistically significantly greater (p < 0.05 than the left GFM (18.35 cm2 indicating the right/left asymmetry of the visible surface of GFM. Also, the visible surface of the right GFM in the males (22.66 cm2 was significantly greater (p < 0.05 than in the females (19.35 cm2, while the difference in size of the left GFM between the males and the females was not significant (p > 0.05. Conclusion. Morphological analysis of visible surface of GFM performed by digital planimetry showed sexual dimorphism of the visible surface and the presence of right/left asymmetry of GFM.

  20. The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans.

    Science.gov (United States)

    Allman, John M; Tetreault, Nicole A; Hakeem, Atiya Y; Manaye, Kebreten F; Semendeferi, Katerina; Erwin, Joseph M; Park, Soyoung; Goubert, Virginie; Hof, Patrick R

    2010-06-01

    The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation

  1. Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex.

    Science.gov (United States)

    Medalla, Maria; Gilman, Joshua P; Wang, Jing-Yi; Luebke, Jennifer I

    2017-05-03

    The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) of the primate play distinctive roles in the mediation of complex cognitive tasks. Compared with the LPFC, integration of information by the ACC can span longer timescales and requires stronger engagement of inhibitory processes. Here, we reveal the synaptic mechanism likely to underlie these differences using in vitro patch-clamp recordings of synaptic events and multiscale imaging of synaptic markers in rhesus monkeys. Although excitatory synaptic signaling does not differ, the level of synaptic inhibition is much higher in ACC than LPFC layer 3 pyramidal neurons, with a significantly higher frequency (∼6×) and longer duration of inhibitory synaptic currents. The number of inhibitory synapses and the ratio of cholecystokinin to parvalbumin-positive inhibitory inputs are also significantly higher in ACC compared with LPFC neurons. Therefore, inhibition is functionally and structurally more robust and diverse in ACC than in LPFC, resulting in a lower excitatory: inhibitory ratio and a greater dynamic range for signal integration and network oscillation by the ACC. These differences in inhibitory circuitry likely underlie the distinctive network dynamics in ACC and LPC during normal and pathological brain states. SIGNIFICANCE STATEMENT The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) play temporally distinct roles during the execution of cognitive tasks (rapid working memory during ongoing tasks and long-term memory to guide future action, respectively). Compared with LPFC-mediated tasks, ACC-mediated tasks can span longer timescales and require stronger engagement of inhibition. This study shows that inhibitory signaling is much more robust and diverse in the ACC than in the LPFC. Therefore, there is a lower excitatory: inhibitory synaptic ratio and a greater dynamic range for signal integration and oscillatory behavior in the ACC. These significant differences in

  2. Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions

    Directory of Open Access Journals (Sweden)

    Simon M. Scheck

    2015-01-01

    Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function.

  3. Increased anterior cingulate cortex response precedes behavioural adaptation in anorexia nervosa

    Science.gov (United States)

    Geisler, Daniel; Ritschel, Franziska; King, Joseph A.; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N.; Ehrlich, Stefan

    2017-01-01

    Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN. PMID:28198813

  4. Comparison of the spatial-cognitive functions of dorsomedial striatum and anterior cingulate cortex in mice.

    Directory of Open Access Journals (Sweden)

    Tine Pooters

    Full Text Available Neurons in anterior cingulate cortex (aCC project to dorsomedial striatum (DMS as part of a corticostriatal circuit with putative roles in learning and other cognitive functions. In the present study, the spatial-cognitive importance of aCC and DMS was assessed in the hidden-platform version of the Morris water maze (MWM. Brain lesion experiments that focused on areas of connectivity between these regions indicated their involvement in spatial cognition. MWM learning curves were markedly delayed in DMS-lesioned mice in the absence of other major functional impairments, whereas there was a more subtle, but still significant influence of aCC lesions. Lesioned mice displayed impaired abilities to use spatial search strategies, increased thigmotaxic swimming, and decreased searching in the proximity of the escape platform. Additionally, aCC and DMS activity was compared in mice between the early acquisition phase (2 and 3 days of training and the over-trained high-proficiency phase (after 30 days of training. Neuroplasticity-related expression of the immediate early gene Arc implicated both regions during the goal-directed, early phases of spatial learning. These results suggest the functional involvement of aCC and DMS in processes of spatial cognition that model associative cortex-dependent, human episodic memory abilities.

  5. Spatiotemporal Spike Coding of Behavioral Adaptation in the Dorsal Anterior Cingulate Cortex.

    Directory of Open Access Journals (Sweden)

    Laureline Logiaco

    2015-08-01

    Full Text Available The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70-200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys' behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators.

  6. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

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    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, d.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-09-21

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  7. The anterior insular and anterior cingulate cortices in emotional processing for self-face recognition.

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    Morita, Tomoyo; Tanabe, Hiroki C; Sasaki, Akihiro T; Shimada, Koji; Kakigi, Ryusuke; Sadato, Norihiro

    2014-05-01

    Individuals can experience embarrassment when exposed to self-feedback images, depending on the extent of the divergence from the internal representation of the standard self. Our previous work implicated the anterior insular cortex (AI) and the anterior cingulate cortex (ACC) in the processing of embarrassment; however, their exact functional contributions have remained uncertain. Here, we explored the effects of being observed by others while viewing self-face images on the extent of embarrassment, and the activation and connectivity patterns in the AI and ACC. We conducted functional magnetic resonance imaging hyperscanning in pairs of healthy participants using an interaction system that allowed an individual to be observed by a partner in real time. Being observed increased the extent of embarrassment reported when viewing self-face images; a corresponding increase in self-related activity in the right AI suggested that this region played a direct role in the subjective experience. Being observed also increased the functional connectivity between the caudal ACC and prefrontal regions, which are involved in processing the reflective self. The ACC might therefore serve as a hub, integrating information about the reflective self that is used in evaluating perceptual self-face images.

  8. Involvement of posterior cingulate cortex in ketamine-induced psychosis relevant behaviors in rats.

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    Ma, Jingyi; Leung, L Stan

    2018-02-15

    The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABA A receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s.c.) induced an increase in power of electrographic activity in the gamma band (30-100Hz) in both the PCC and the hippocampus; peak theta (4-10Hz) power was not significantly altered, but peak theta frequency was increased by ketamine. In order to exclude volume conduction from the hippocampus to PCC, inactivation of the hippocampus was made by local infusion of muscimol into the hippocampus prior to ketamine administration. Muscimol in the hippocampus effectively blocked ketamine-induced increase of gamma power in the hippocampus but not in the PCC, suggesting independent generation of gamma waves in PCC and hippocampus. It is suggested that the PCC is part of the brain network mediating ketamine-induced psychosis related behaviors. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control.

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    White, Michael G; Panicker, Matthew; Mu, Chaoqi; Carter, Ashley M; Roberts, Bradley M; Dharmasri, Poorna A; Mathur, Brian N

    2018-01-02

    Cognitive abilities, such as volitional attention, operate under top-down, executive frontal cortical control of hierarchically lower structures. The circuit mechanisms underlying this process are unresolved. The claustrum possesses interconnectivity with many cortical areas and, thus, is hypothesized to orchestrate the cortical mantle for top-down control. Whether the claustrum receives top-down input and how this input may be processed by the claustrum have yet to be formally tested, however. We reveal that a rich anterior cingulate cortex (ACC) input to the claustrum encodes a preparatory top-down information signal on a five-choice response assay that is necessary for optimal task performance. We further show that ACC input monosynaptically targets claustrum inhibitory interneurons and spiny glutamatergic projection neurons, the latter of which amplify ACC input in a manner that is powerfully constrained by claustrum inhibitory microcircuitry. These results demonstrate ACC input to the claustrum is critical for top-down control guiding action. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. A Novel Neural Prediction Error Found in Anterior Cingulate Cortex Ensembles.

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    Hyman, James Michael; Holroyd, Clay Brian; Seamans, Jeremy Keith

    2017-07-19

    The function of the anterior cingulate cortex (ACC) remains controversial, yet many theories suggest a role in behavioral adaptation, partly because a robust event-related potential, the feedback-related negativity (FN), is evoked over the ACC whenever expectations are violated. We recorded from the ACC as rats performed a task identical to one that reliably evokes an FN in humans. A subset of neurons was found that encoded expected outcomes as abstract outcome representations. The degree to which a reward/non-reward outcome representation emerged during a trial depended on the history of outcomes that preceded it. A prediction error was generated on incongruent trials as the ensembles shifted from representing the expected to the actual outcome, at the same time point we have previously reported an FN in the local field potential. The results describe a novel mode of prediction error signaling by ACC neurons that is associated with the generation of an FN. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. What about the self is processed in the posterior cingulate cortex?

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    Judson eBrewer

    2013-10-01

    Full Text Available In the past decade, neuroimaging research has begun to identify key brain regions involved in self-referential processing, most consistently midline structures such as the posterior cingulate cortex (PCC. The majority of studies have employed cognitive tasks such as judgment about trait adjectives or mind-wandering, that have been associated with increased PCC activity. Conversely, tasks that share an element of present centered attention (being on task, ranging from working memory to meditation, have been associated with decreased PCC activity. Given the complexity of cognitive processes that likely contribute to these tasks, the specific contribution of the PCC to self-related processes still remains unknown. Building on this prior literature, recent studies have employed sampling methods that more precisely link subjective experience to brain activity, such as real-time fMRI neurofeedback. This recent work suggests that PCC activity may represent a sub-component cognitive process of self-reference – getting caught up in one’s experience. For example, getting caught up in a drug craving or a particular viewpoint. In this paper, we will review evidence across a number of different domains of cognitive neuroscience that converges in activation and deactivation of the PCC including recent neurophenomenological studies of PCC activity using real-time fMRI neurofeedback.

  12. A role for primate subgenual cingulate cortex in sustaining autonomic arousal.

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    Rudebeck, Peter H; Putnam, Philip T; Daniels, Teresa E; Yang, Tianming; Mitz, Andrew R; Rhodes, Sarah E V; Murray, Elisabeth A

    2014-04-08

    The subgenual anterior cingulate cortex (subgenual ACC) plays an important role in regulating emotion, and degeneration in this area correlates with depressed mood and anhedonia. Despite this understanding, it remains unknown how this part of the prefrontal cortex causally contributes to emotion, especially positive emotions. Using Pavlovian conditioning procedures in macaque monkeys, we examined the contribution of the subgenual ACC to autonomic arousal associated with positive emotional events. After such conditioning, autonomic arousal increases in response to cues that predict rewards, and monkeys maintain this heightened state of arousal during an interval before reward delivery. Here we show that although monkeys with lesions of the subgenual ACC show the initial, cue-evoked arousal, they fail to sustain a high level of arousal until the anticipated reward is delivered. Control procedures showed that this impairment did not result from differences in autonomic responses to reward delivery alone, an inability to learn the association between cues and rewards, or to alterations in the light reflex. Our data indicate that the subgenual ACC may contribute to positive affect by sustaining arousal in anticipation of positive emotional events. A failure to maintain positive affect for expected pleasurable events could provide insight into the pathophysiology of psychological disorders in which negative emotions dominate a patient's affective experience.

  13. Nociception coma scale-revised scores correlate with metabolism in the anterior cingulate cortex.

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    Chatelle, Camille; Thibaut, Aurore; Bruno, Marie-Aurélie; Boly, Mélanie; Bernard, Claire; Hustinx, Roland; Schnakers, Caroline; Laureys, Steven

    2014-02-01

    The Nociception Coma Scale-Revised (NCS-R) was recently validated to assess possible pain perception in patients with disorders of consciousness. To identify correlations between cerebral glucose metabolism and NCS-R total scores. [18F]-fluorodeoxyglucose positron emission tomography, NCS-R, and Coma Recovery Scale-Revised assessments were performed in 49 patients with disorders of consciousness. We identified a significant positive correlation between NCS-R total scores and metabolism in the posterior part of the anterior cingulate cortex, known to be involved in pain processing. No other cluster reached significance. No significant effect of clinical diagnosis (vegetative/unresponsive vs minimally conscious states), etiology or interval since insult was observed. Our data support the hypothesis that the NCS-R total scores are related to cortical processing of nociception and may constitute an appropriate behavioral tool to assess, monitor, and treat possible pain in brain-damaged noncommunicative patients with disorders of consciousness. Future studies using event-related functional magnetic resonance imaging should investigate the correlation between NCS-R scores and brain activation in response to noxious stimulation at the single-subject level.

  14. Anterior cingulate cortex involved in social food-foraging decision-making strategies of rats.

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    Zhong, Xiaolin; Deng, Sihao; Ma, Wenbo; Yang, Yuchen; Lu, Dahua; Cheng, Na; Chen, Dan; Wang, Hui; Zhang, Jianyi; Li, Fang; Li, Changqi; Huang, Hua-Lin; Li, Zhiyuan

    2017-10-01

    Decision making as a complex cognitive process involves assessing risk, reward, and costs. Typically, it has been studied in nonsocial contexts. We have developed a novel laboratory model used with rodents to detect food-foraging decision-making strategies in different social settings. However, the brain regions that mediate these behaviors are not well identified. Substantial evidence shows that the anterior cingulate cortex (ACC) participates in evaluation of social information and in decision making. In this study, we investigated the effect of bilateral lesions in the ACC on established behaviors. Kainic acid (KA) was administered bilaterally to induce ACC lesions, and saline microinjection into the ACC was used in the sham group. In contrast to the sham-lesioned animals, when faced with the choice of foraging under a social context, rats with ACC lesions preferred foraging for the less desirable food. Moreover, in these situations, the total amount of food foraged by the ACC-lesioned group was less than the amount foraged by the sham group. Notably, neither social interactions nor social agonistic behaviors were affected by ACC lesions. These data suggest that the ACC is a key region underlying neural processing of social decision-making, specifically tending to compete for foraging high predictive reward food.

  15. Antinociception induced by galanin in anterior cingulate cortex in rats with acute inflammation.

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    Zhang, Meng-Lin; Fu, Feng-Hua; Yu, Long-Chuan

    2017-01-18

    The present study was performed to explore the role of galanin in nociceptive modulation in anterior cingulate cortex (ACC) of rats with acute inflammation, and the changes in galanin and galanin receptor 2 (Gal R2) expressions in rats with acute inflammation. Intra-ACC injection of galanin induced antinociception in rats with acute inflammation, the antinociceptive effects induced by galanin were attenuated significantly by intra-ACC injection of the Gal R2 antagonist M871, indicating an involvement of Gal R2 in nociceptive modulation in ACC in rats with acute inflammation. Furthermore, we found that both the galanin mRNA expression and galanin content increased significantly in ACC in rats with acute inflammation than that in normal rats. Moreover, both the mRNA levels of Gal R2 and the content of Gal R2 in ACC increased significantly in rats with acute inflammation than that in normal rats. These results demonstrated that galanin induced antinociception in ACC in rats with acute inflammation. And there were changes in the expression of galanin and Gal R2 in rats with acute inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. The role of dorsal anterior cingulate cortex in the regulation of craving by reappraisal in smokers.

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    Zhao, Li-Yan; Tian, Jie; Wang, Wei; Qin, Wei; Shi, Jie; Li, Qiang; Yuan, Kai; Dong, Ming-Hao; Yang, Wei-Chuang; Wang, Ya-Rong; Sun, Li-Li; Lu, Lin

    2012-01-01

    Drug cues can induce craving for drugs of abuse. Dysfunctional regulation of emotion and motivation regarding rewarding objects appears to be an integral part of addiction. It has been found that cognitive strategies decreased the intensity of craving in addicts. Reappraisal strategy is a type of cognitive strategy that requires participants to reinterpret the meaning of an emotional situation. In addition, studies have found that activation of the dorsal anterior cingulate cortex (dACC) is associated with the selection and application of cognitive reappraisal. In present study, we sought to determine whether such cognitive regulation engages the dACC and improves inhibition of craving in smokers. Sixteen smokers underwent functional magnetic resonance imaging (fMRI) during performance of a cigarette reward-conditioning procedure with cognitive reappraisal. We focused our analyses on the dACC as a key structure of cognitive control of craving. Cue induced craving under different conditions was obtained. Correlational analysis between the functional response in the dACC and the subjective craving was performed. We found that using a cognitive reappraisal was successful in decreasing the conditioned craving. Right dACC (BA 24/32) engaged in the cognitive reappraisal. In addition, the individual's subjective craving was negatively correlated with the right dACC activation. These findings suggest that the dACC are important substrates of Inhibition of cue induced craving in smokers. Cognitive regulation by cognitive reappraisal may help addicted individuals avoid the anticipated situations where they are exposed to conditioned cues.

  17. Hierarchical Error Representation: A Computational Model of Anterior Cingulate and Dorsolateral Prefrontal Cortex.

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    Alexander, William H; Brown, Joshua W

    2015-11-01

    Anterior cingulate and dorsolateral prefrontal cortex (ACC and dlPFC, respectively) are core components of the cognitive control network. Activation of these regions is routinely observed in tasks that involve monitoring the external environment and maintaining information in order to generate appropriate responses. Despite the ubiquity of studies reporting coactivation of these two regions, a consensus on how they interact to support cognitive control has yet to emerge. In this letter, we present a new hypothesis and computational model of ACC and dlPFC. The error representation hypothesis states that multidimensional error signals generated by ACC in response to surprising outcomes are used to train representations of expected error in dlPFC, which are then associated with relevant task stimuli. Error representations maintained in dlPFC are in turn used to modulate predictive activity in ACC in order to generate better estimates of the likely outcomes of actions. We formalize the error representation hypothesis in a new computational model based on our previous model of ACC. The hierarchical error representation (HER) model of ACC/dlPFC suggests a mechanism by which hierarchically organized layers within ACC and dlPFC interact in order to solve sophisticated cognitive tasks. In a series of simulations, we demonstrate the ability of the HER model to autonomously learn to perform structured tasks in a manner comparable to human performance, and we show that the HER model outperforms current deep learning networks by an order of magnitude.

  18. The role of the anterior cingulate cortex in women's sexual decision making.

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    Rupp, Heather A; James, Thomas W; Ketterson, Ellen D; Sengelaub, Dale R; Janssen, Erick; Heiman, Julia R

    2009-01-02

    Women's sexual decision making is a complex process balancing the potential rewards of conception and pleasure against the risks of possible low paternal care or sexually transmitted infection. Although neural processes underlying social decision making are suggested to overlap with those involved in economic decision making, the neural systems associated with women's sexual decision making are unknown. Using fMRI, we measured the brain activation of 12 women while they viewed photos of men's faces. Face stimuli were accompanied by information regarding each man's potential risk as a sexual partner, indicated by a written description of the man's number of previous sexual partners and frequency of condom use. Participants were asked to evaluate how likely they would be to have sex with the man depicted. Women reported that they would be more likely to have sex with low compared to high risk men. Stimuli depicting low risk men also elicited stronger activation in the anterior cingulate cortex (ACC), midbrain, and intraparietal sulcus, possibly reflecting an influence of sexual risk on women's attraction, arousal, and attention during their sexual decision making. Activation in the ACC was positively correlated with women's subjective evaluations of sex likelihood and response times during their evaluations of high, but not low risk men. These findings provide evidence that neural systems involved in sexual decision making in women overlap with those described previously to underlie nonsexual decision making.

  19. Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism

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    Suda Shiro

    2011-08-01

    Full Text Available Abstract Background Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins. Results The mRNA and protein expression of axon-guidance proteins, including ephrin (EFNA4, eEFNB3, plexin (PLXNA4, roundabout 2 (ROBO2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively and control brains (n = 13 and n = 8, respectively using real-time reverse-transcriptase PCR (RT-PCR and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains. Conclusions In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism.

  20. The beneficial effects of meditation: contribution of the anterior cingulate and locus coeruleus

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    Nancy Alker Craigmyle

    2013-10-01

    Full Text Available Abstract During fMRI studies of meditation the cortical salience detecting and executive networks become active during awareness of mind wandering, shifting and sustained attention. The anterior cingulate (AC is activated during awareness of mind wandering.The AC modulates both the peripheral sympathetic nervous system (SNS and the central locus coeruleus (LC norepinephrine systems, which form the principal neuromodulatory system, regulating in multiple ways both neuronal and non-neuronal cells to maximize adaptation in changing environments. The LC is the primary source of central norepinephrine (C-NE and nearly the exclusive source of cortical norepinephrine. Normally activated by novel or salient stimuli, the AC initially inhibits the SNS reflexively, lowering peripheral norepinephrine (P-NE and activates the LC, increasing C-NE.Moderate levels of C-NE enhance working memory through alpha 2 adrenergic receptors, while higher levels of C-NE, acting on alpha 1 and beta receptors, enhance other executive network functions such as the stopping of ongoing behavior, attentional set shifting and sustained attention. The actions of the AC on both the central and peripheral noradrenergic systems are implicated in the beneficial effects of meditation. This paper will explore some of the known functions and interrelationships of the AC, SNS and LC with respect to their possible relevance to meditation.

  1. Anterior cingulate engagement in a foraging context reflects choice difficulty, not foraging value.

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    Shenhav, Amitai; Straccia, Mark A; Cohen, Jonathan D; Botvinick, Matthew M

    2014-09-01

    Previous theories predict that human dorsal anterior cingulate (dACC) should respond to decision difficulty. An alternative theory has been recently advanced that proposes that dACC evolved to represent the value of 'non-default', foraging behavior, calling into question its role in choice difficulty. However, this new theory does not take into account that choosing whether or not to pursue foraging-like behavior can also be more difficult than simply resorting to a default. The results of two neuroimaging experiments show that dACC is only associated with foraging value when foraging value is confounded with choice difficulty; when the two are dissociated, dACC engagement is only explained by choice difficulty, and not the value of foraging. In addition to refuting this new theory, our studies help to formalize a fundamental connection between choice difficulty and foraging-like decisions, while also prescribing a solution for a common pitfall in studies of reward-based decision making.

  2. Mild blast events alter anxiety, memory, and neural activity patterns in the anterior cingulate cortex.

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    Kun Xie

    Full Text Available There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder.

  3. Subgenual anterior cingulate responses to peer rejection: A marker of adolescents’ risk for depression

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    MASTEN, CARRIE L.; EISENBERGER, NAOMI I.; BOROFSKY, LARISSA A.; MCNEALY, KRISTIN; PFEIFER, JENNIFER H.; DAPRETTO, MIRELLA

    2011-01-01

    Extensive developmental research has linked peer rejection during adolescence with a host of psychopathological outcomes, including depression. Moreover, recent neuroimaging research has suggested that increased activity in the subgenual region of the anterior cingulate cortex (subACC), which has been consistently linked with depression, is related to heightened sensitivity to peer rejection among adolescents. The goal of the current study was to directly test the hypothesis that adolescents’ subACC responses are predictive of their risk for future depression, by examining the relationship between subACC activity during peer rejection and increases in depressive symptoms during the following year. During a functional magnetic resonance imaging scan, 20 13-year-olds were ostensibly excluded by peers during an online social interaction. Participants’ depressive symptoms were assessed via parental reports at the time of the scan and 1 year later. Region of interest and whole-brain analyses indicated that greater subACC activity during exclusion was associated with increases in parent-reported depressive symptoms during the following year. These findings suggest that subACC responsivity to social exclusion may serve as a neural marker of adolescents’ risk for future depression and have implications for understanding the relationship between sensitivity to peer rejection and the increased risk of depression that occurs during adolescence. PMID:21262054

  4. Subgenual anterior cingulate responses to peer rejection: a marker of adolescents' risk for depression.

    Science.gov (United States)

    Masten, Carrie L; Eisenberger, Naomi I; Borofsky, Larissa A; McNealy, Kristin; Pfeifer, Jennifer H; Dapretto, Mirella

    2011-02-01

    Extensive developmental research has linked peer rejection during adolescence with a host of psychopathological outcomes, including depression. Moreover, recent neuroimaging research has suggested that increased activity in the subgenual region of the anterior cingulate cortex (subACC), which has been consistently linked with depression, is related to heightened sensitivity to peer rejection among adolescents. The goal of the current study was to directly test the hypothesis that adolescents' subACC responses are predictive of their risk for future depression, by examining the relationship between subACC activity during peer rejection and increases in depressive symptoms during the following year. During a functional magnetic resonance imaging scan, 20 13-year-olds were ostensibly excluded by peers during an online social interaction. Participants' depressive symptoms were assessed via parental reports at the time of the scan and 1 year later. Region of interest and whole-brain analyses indicated that greater subACC activity during exclusion was associated with increases in parent-reported depressive symptoms during the following year. These findings suggest that subACC responsivity to social exclusion may serve as a neural marker of adolescents' risk for future depression and have implications for understanding the relationship between sensitivity to peer rejection and the increased risk of depression that occurs during adolescence.

  5. Posterior cingulate atrophy and metabolic decline in early stage Alzheimer's disease.

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    Shima, Keisuke; Matsunari, Ichiro; Samuraki, Miharu; Chen, Wei-Ping; Yanase, Daisuke; Noguchi-Shinohara, Moeko; Takeda, Nozomi; Ono, Kenjiro; Yoshita, Mitsuhiro; Miyazaki, Yoshiharu; Matsuda, Hiroshi; Yamada, Masahito

    2012-09-01

    To test the hypothesis that Alzheimer's disease (AD) patients with posterior cingulate/precuneus (PCP) atrophy would be a distinct disease form in view of metabolic decline. Eighty-one AD patients underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and structural magnetic resonance imaging (MRI). Positron emission tomography and voxel-based morphometry (VBM) Z-score maps were generated for the individual patients using age-specific normal databases. The patients were classified into 3 groups based on atrophic patterns (no-Hipp-PCP, atrophy in neither hippocampus nor PCP; Hipp, hippocampal atrophy; PCP, PCP atrophy). There were 16 patients classified as no-Hipp-PCP, 55 as Hipp, and 10 as PCP. The Mini Mental State Examination (MMSE) score was similar among the groups. The greater FDG decline than atrophy was observed in all groups, including the no-Hipp-PCP. The PCP group was younger, and was associated with a greater degree of FDG decline in PCP than the others. There are diverse atrophic patterns in a spectrum of AD. In particular, a subset of patients show PCP atrophy, which is associated with greater metabolic burden. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder.

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    Ernst, J; Hock, A; Henning, A; Seifritz, E; Boeker, H; Grimm, S

    2017-01-01

    There is ample evidence that glucose metabolism in the pregenual anterior cingulate cortex (PACC) is increased in major depressive disorder (MDD), whereas it is still unknown whether glucose levels per se are also elevated. Elevated cerebrospinal fluid (CSF) lactate concentrations in MDD patients might indicate that increased glycolytical metabolization of glucose to lactate in astrocytes either alone or in conjunction with mitochondrial dysfunction results in an accumulation of lactate and contributes to pathophysiological mechanisms of MDD. However, until now, no study investigated in vivo PACC glucose and lactate levels in MDD. Proton magnetic resonance spectroscopy was therefore used to test the hypothesis that patients with MDD have increased PACC glucose and lactate levels. In 40 healthy and depressed participants, spectra were acquired from the PACC using a maximum echo J-resolved spectroscopy protocol. Results show significant increases of glucose and lactate in patients, which are also associated with depression severity. These findings indicate impaired brain energy metabolism in MDD with increased fraction of energy utilization via glycolysis and reduced mitochondrial oxidative clearance of lactate. Targeting these metabolic disturbances might affect the balance of metabolic pathways regulating neuronal energetics and result in an attenuation of the elevated basal activity of brain regions within the neural circuitry of depression.

  7. Smoking reduces conflict-related anterior cingulate activity in abstinent cigarette smokers performing a Stroop task.

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    Azizian, Allen; Nestor, Liam J; Payer, Doris; Monterosso, John R; Brody, Arthur L; London, Edythe D

    2010-02-01

    Prior research suggests that abrupt initiation of abstinence from cigarette smoking reduces neural cognitive efficiency. When cognitive efficiency is high, processing speed and accuracy are maximized with minimal allocation of cognitive resources. The study presented here tested the effects of resumption of smoking on cognitive response conflict after overnight abstinence from smoking, hypothesizing that smoking would enhance cognitive efficiency. Twenty paid research volunteers who were chronic cigarette smokers abstained from smoking overnight (>12 h) before undergoing fMRI while performing a color-word Stroop task during two separate test sessions: one that did not include smoking before testing and another one that did. Statistical analyses were performed by modeling the Stroop effect (incongruent >congruent) BOLD response within a collection of a priori regions of interest that have consistently been associated with cognitive control. Behavioral assessment alone did not reveal any significant differences in the Stroop effect between the two sessions. BOLD activations, however, indicated that in the right anterior cingulate cortex (ACC), smokers had significantly less task-related activity following smoking (pconflict activity together with improvement in conflict resolution involving the dorsolateral prefrontal cortex.

  8. Dorsal Anterior Cingulate Thickness Is Related to Alexithymia in Childhood Trauma-Related PTSD.

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    Lauren A Demers

    Full Text Available Alexithymia, or "no words for feelings", is highly prevalent in samples with childhood maltreatment and posttraumatic stress disorder (PTSD. The dorsal anterior cingulate cortex (dACC has been identified as a key region involved in alexithymia, early life trauma, and PTSD. Functional alterations in the dACC also have been associated with alexithymia in PTSD. This study examined whether dACC morphology is a neural correlate of alexithymia in child maltreatment-related PTSD. Sixteen adults with PTSD and a history of childhood sexual abuse, physical abuse, or exposure to domestic violence, and 24 healthy controls (HC completed the Toronto Alexithymia Scale 20 (TAS-20 and underwent magnetic resonance imaging. Cortical thickness of the dACC was measured using FreeSurfer, and values were correlated with TAS-20 scores, controlling for sex and age, in both groups. Average TAS-20 score was significantly higher in the PTSD than the HC group. TAS-20 scores were significantly positively associated with dACC thickness only in the PTSD group. This association was strongest in the left hemisphere and for TAS-20 subscales that assess difficulty identifying and describing feelings. We found that increasing dACC gray matter thickness is a neural correlate of greater alexithymia in the context of PTSD with childhood maltreatment. While findings are correlational, they motivate further inquiry into the relationships between childhood adversity, emotional awareness and expression, and dACC morphologic development in trauma-related psychopathology.

  9. Posterior Cingulate Lactate as a Metabolic Biomarker in Amnestic Mild Cognitive Impairment

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    Kurt E. Weaver

    2015-01-01

    Full Text Available Mitochondrial dysfunction represents a central factor within the pathogenesis of the Alzheimer’s disease (AD spectrum. We hypothesized that in vivo measurements of lactate (lac, a by-product of glycolysis, would correlate with functional impairment and measures of brain health in a cohort of 15 amnestic mild cognitive impairment (aMCI individuals. Lac was quantified from the precuneus/posterior cingulate (PPC using 2-dimensional J-resolved magnetic resonance spectroscopy (MRS. Additionally, standard behavioral and imaging markers of aMCI disease progression were acquired. PPC lac was negatively correlated with performance on the Wechsler logical memory tests and on the minimental state examination even after accounting for gray matter, cerebral spinal fluid volume, and age. No such relationships were observed between lac and performance on nonmemory tests. Significant negative relationships were also noted between PPC lac and hippocampal volume and PPC functional connectivity. Together, these results reveal that aMCI individuals with a greater disease progression have increased concentrations of PPC lac. Because lac is upregulated as a compensatory response to mitochondrial impairment, we propose that J-resolved MRS of lac is a noninvasive, surrogate biomarker of impaired metabolic function and would provide a useful means of tracking mitochondrial function during therapeutic trials targeting brain metabolism.

  10. GABA concentration in posterior cingulate cortex predicts putamen response during resting state fMRI.

    Directory of Open Access Journals (Sweden)

    Jorge Arrubla

    Full Text Available The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS being one of the key techniques. MRS permits the measurement of γ-aminobutyric acid (GABA and glutamate levels, the central biochemical constituents of the excitation-inhibition balance in vivo. The inhibitory effects of GABA in the brain have been largely investigated in relation to the activity of resting state networks in functional magnetic resonance imaging (fMRI. In this study GABA concentration in the posterior cingulate cortex (PCC was measured using single voxel spectra acquired with standard point resolved spectroscopy (PRESS from 20 healthy male volunteers at 3 T. Resting state fMRI was consecutively measured and the values of GABA/Creatine+Phosphocreatine ratio (GABA ratio were included in a general linear model matrix as a step of dual regression analysis in order to identify voxels whose neuroimaging metrics during rest were related to individual levels of the GABA ratio. Our data show that the connection strength of putamen to the default-mode network during resting state has a negative linear relationship with the GABA ratio measured in the PCC. These findings highlight the role of PCC and GABA in segregation of the motor input, which is an inherent condition that characterises resting state.

  11. Fear avoidance beliefs in back pain-free subjects are reflected by amygdala-cingulate responses.

    Science.gov (United States)

    Meier, Michael L; Stämpfli, Phillipp; Vrana, Andrea; Humphreys, Barry K; Seifritz, Erich; Hotz-Boendermaker, Sabina

    2015-01-01

    In most individuals suffering from chronic low back pain, psychosocial factors, specifically fear avoidance beliefs (FABs), play central roles in the absence of identifiable organic pathology. On a neurobiological level, encouraging research has shown brain system correlates of somatic and psychological factors during the transition from (sub) acute to chronic low back pain. The characterization of brain imaging signatures in pain-free individuals before any injury will be of high importance regarding the identification of relevant networks for low back pain (LBP) vulnerability. Fear-avoidance beliefs serve as strong predictors of disability and chronification in LBP and current research indicates that back pain related FABs already exist in the general and pain-free population. Therefore, we aimed at investigating possible differential neural functioning between high- and low fear-avoidant individuals in the general population using functional magnetic resonance imaging. Results revealed that pain-free individuals without a history of chronic pain episodes could be differentiated in amygdala activity and connectivity to the pregenual anterior cingulate cortex by their level of back pain related FABs. These results shed new light on brain networks underlying psychological factors that may become relevant for enhanced disability in a future LBP episode.

  12. Anterior cingulate synapses in prefrontal areas 10 and 46 suggest differential influence in cognitive control.

    Science.gov (United States)

    Medalla, Maria; Barbas, Helen

    2010-12-01

    Dorsolateral prefrontal areas 46 and 10 are involved in distinct aspects of cognition. Area 46 has a key role in working memory tasks, and frontopolar area 10 is recruited in complex multitask operations. Both areas are innervated by the anterior cingulate cortex (ACC), a region associated with emotions and memory but is also important for attentional control through unknown synaptic mechanisms. Here, we found that in rhesus monkeys (Macaca mulatta) most axon terminals labeled from tracers injected into ACC area 32 innervated spines of presumed excitatory neurons, but ∼20-30% formed mostly large synapses with dendritic shafts of presumed inhibitory neurons in the upper layers (I-IIIa) of dorsolateral areas 10, 46, and 9. Moreover, area 32 terminals targeted preferentially calbindin and, to a lesser extent, calretinin neurons, which are thought to be inhibitory neurons that modulate the gain of task-relevant activity during working memory tasks. Area 46 was distinguished as a recipient of more (by ∼40%) area 32 synapses on putative inhibitory neurons. Area 10 stood apart as recipient of significantly larger (by ∼40% in volume) area 32 terminals on spines of putative excitatory neurons. These synaptic specializations suggest that area 32 has complementary roles, potentially enhancing inhibition in area 46 and strengthening excitation in area 10, which may help direct attention to new tasks while temporarily holding in memory another task.

  13. Longitudinal stability of the folding pattern of the anterior cingulate cortex during development

    Directory of Open Access Journals (Sweden)

    A. Cachia

    2016-06-01

    Full Text Available Prenatal processes are likely critical for the differences in cognitive ability and disease risk that unfold in postnatal life. Prenatally established cortical folding patterns are increasingly studied as an adult proxy for earlier development events – under the as yet untested assumption that an individual's folding pattern is developmentally fixed. Here, we provide the first empirical test of this stability assumption using 263 longitudinally-acquired structural MRI brain scans from 75 typically developing individuals spanning ages 7 to 32 years. We focus on the anterior cingulate cortex (ACC – an intensely studied cortical region that presents two qualitatively distinct and reliably classifiable sulcal patterns with links to postnatal behavior. We show – without exception–that individual ACC sulcal patterns are fixed from childhood to adulthood, at the same time that quantitative anatomical ACC metrics are undergoing profound developmental change. Our findings buttress use of folding typology as a postnatally-stable marker for linking variations in early brain development to later neurocognitive outcomes in ex utero life.

  14. Folding of the anterior cingulate cortex partially explains inhibitory control during childhood: A longitudinal study

    Directory of Open Access Journals (Sweden)

    G. Borst

    2014-07-01

    Full Text Available Difficulties in cognitive control including inhibitory control (IC are related to the pathophysiology of several psychiatric conditions. In healthy subjects, IC efficiency in childhood is a strong predictor of academic and professional successes later in life. The dorsal anterior cingulate cortex (ACC is one of the core structures responsible for IC. Although quantitative structural characteristics of the ACC contribute to IC efficiency, the qualitative structural brain characteristics contributing to IC development are less-understood. Using anatomical magnetic resonance imaging, we investigated whether the ACC sulcal pattern at age 5, a stable qualitative characteristic of the brain determined in utero, explains IC at age 9. 18 children performed Stroop tasks at age 5 and age 9. Children with asymmetrical ACC sulcal patterns (n = 7 had better IC efficiency at age 5 and age 9 than children with symmetrical ACC sulcal patterns (n = 11. The ACC sulcal patterns appear to affect specifically IC efficiency given that the ACC sulcal patterns had no effect on verbal working memory. Our study provides the first evidence that the ACC sulcal pattern – a qualitative structural characteristic of the brain not affected by maturation and learning after birth – partially explains IC efficiency during childhood.

  15. Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment.

    Science.gov (United States)

    Boespflug, E L; McNamara, R K; Eliassen, J C; Schidler, M D; Krikorian, R

    2016-02-01

    To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. Randomized, double-blind, placebo-controlled study. Academic medical center. Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p ≤ 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. Dietary fish oil supplementation increases red blood cell omega-3 content

  16. Perturbation of the left inferior frontal gyrus triggers adaptive plasticity in the right homologous area during speech production

    DEFF Research Database (Denmark)

    Hartwigsen, Gesa; Saur, Dorothee; Price, Cathy J

    2013-01-01

    functions. Alternatively, the right hemisphere may actively contribute to language functions by supporting disrupted processing in the left hemisphere via interhemispheric connections. To test this hypothesis, we applied off-line continuous theta burst stimulation (cTBS) over the left inferior frontal gyrus...

  17. Dentate Gyrus-Specific Knockdown of Adult Neurogenesis Impairs Spatial and Object Recognition Memory in Adult Rats

    Science.gov (United States)

    Jessberger, Sebastian; Clark, Robert E.; Broadbent, Nicola J.; Clemenson, Gregory D., Jr.; Consiglio, Antonella; Lie, D. Chichung; Squire, Larry R.; Gage, Fred H.

    2009-01-01

    New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons…

  18. Involuntary switching into the native language induced by electrocortical stimulation of the superior temporal gyrus: a multimodal mapping study.

    Science.gov (United States)

    Tomasino, Barbara; Marin, Dario; Canderan, Cinzia; Maieron, Marta; Budai, Riccardo; Fabbro, Franco; Skrap, Miran

    2014-09-01

    We describe involuntary language switching from L2 to L1 evoked by electro-stimulation in the superior temporal gyrus in a 30-year-old right-handed Serbian (L1) speaker who was also a late Italian learner (L2). The patient underwent awake brain surgery. Stimulation of other portions of the exposed cortex did not cause language switching as did not stimulation of the left inferior frontal gyrus, where we evoked a speech arrest. Stimulation effects on language switching were selective, namely, interfered with counting behaviour but not with object naming. The coordinates of the positive site were combined with functional and fibre tracking (DTI) data. Results showed that the language switching site belonged to a significant fMRI cluster in the left superior temporal gyrus/supramarginal gyrus found activated for both L1 and L2, and for both the patient and controls, and did not overlap with the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF). This area, also known as Stp, has a role in phonological processing. Language switching phenomenon we observed can be partly explained by transient dysfunction of the feed-forward control mechanism hypothesized by the DIVA (Directions Into Velocities of Articulators) model (Golfinopoulos, E., Tourville, J. A., & Guenther, F. H. (2010). The integration of large-scale neural network modeling and functional brain imaging in speech motor control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Non-symbolic and symbolic notations in simple arithmetic differentially involve intraparietal sulcus and angular gyrus activity

    NARCIS (Netherlands)

    Ven, F. van der; Takashima, A.; Segers, E.; Fernandez, G.S.E.; Verhoeven, L.

    2016-01-01

    Addition problems can be solved by mentally manipulating quantities for which the bilateral intraparietal sulcus (IPS) is likely recruited, or by retrieving the answer directly from fact memory in which the left angular gyrus (AG) and perisylvian areas may play a role. Mental addition is usually

  20. D1/D5 Receptors and Histone Deacetylation Mediate the Gateway Effect of LTP in Hippocampal Dentate Gyrus

    Science.gov (United States)

    Huang, Yan-You; Lavine, Amir; Kandel, Denise B.; Yin, Deqi; Colnaghi, Luca; Drisaldi, Bettina; Kandel, Eric R.

    2014-01-01

    The dentate gyrus (DG) of the hippocampus is critical for spatial memory and is also thought to be involved in the formation of drug-related associative memory. Here, we attempt to test an aspect of the Gateway Hypothesis, by studying the effect of consecutive exposure to nicotine and cocaine on long-term synaptic potentiation (LTP) in the DG. We…

  1. Ethanol extract of Oenanthe javanica increases cell proliferation and neuroblast differentiation in the adolescent rat dentate gyrus

    Directory of Open Access Journals (Sweden)

    Bai Hui Chen

    2015-01-01

    Full Text Available Oenanthe javanica is an aquatic perennial herb that belongs to the Oenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glutamate-induced neurotoxicity. However, few studies regarding effects of Oenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract of Oenanthe javanica on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 (an endogenous marker for cell proliferation and doublecortin (a marker for neuroblast. Our results showed that Oenanthe javanica extract significantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was significantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not find that vascular endothelial growth factor expression was increased in the Oenanthe javanica extract-treated group compared with the control group. These results indicate that Oenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-derived neurotrophic factor immunoreactivity in the rat dentate gyrus.

  2. Regrowing the Adult Brain: NF-κB Controls Functional Circuit Formation and Tissue Homeostasis in the Dentate Gyrus

    Science.gov (United States)

    Imielski, Yvonne; Schwamborn, Jens C.; Lüningschrör, Patrick; Heimann, Peter; Holzberg, Magdalena; Werner, Hendrikje; Leske, Oliver; Püschel, Andreas W.; Memet, Sylvie; Heumann, Rolf; Israel, Alain; Kaltschmidt, Christian; Kaltschmidt, Barbara

    2012-01-01

    Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus) of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders. PMID:22312433

  3. Transient Beneficial Effects of Excitatory Theta Burst Stimulation in a Patient with Phonological Agraphia after Left Supramarginal Gyrus Infarction

    Science.gov (United States)

    Nardone, Raffaele; De Blasi, Pierpaolo; Zuccoli, Giulio; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

    2012-01-01

    We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient…

  4. Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

    Science.gov (United States)

    Lee, Vallent; MacKenzie, Georgina; Hooper, Andrew; Maguire, Jamie

    2016-10-01

    It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition

  5. Is dorsal anterior cingulate cortex activation in response to social exclusion due to expectancy violation?: An fMRI study

    OpenAIRE

    Taishi eKawamoto; Keiichi eOnoda; Ken'ichiro eNakashima; Hiroshi eNittono; Shuhei eYamaguchi; Mitsuhiro eUra

    2012-01-01

    People are typically quite sensitive about being accepted or excluded by others. Previous studies have suggested that the dorsal anterior cingulate cortex (dACC) is a key brain region involved in the detection of social exclusion. However, this region has also been shown to be sensitive to non-social expectancy violations. We often expect other people to follow an unwritten rule in which they include us as they would expect to be included, such that social exclusion likely involves some degre...

  6. Neural Correlates of Vocal Production and Motor Control in Human Heschl's Gyrus.

    Science.gov (United States)

    Behroozmand, Roozbeh; Oya, Hiroyuki; Nourski, Kirill V; Kawasaki, Hiroto; Larson, Charles R; Brugge, John F; Howard, Matthew A; Greenlee, Jeremy D W

    2016-02-17

    The present study investigated how pitch frequency, a perceptually relevant aspect of periodicity in natural human vocalizations, is encoded in Heschl's gyrus (HG), and how this information may be used to influence vocal pitch motor control. We recorded local field potentials from multicontact depth electrodes implanted in HG of 14 neurosurgical epilepsy patients as they vocalized vowel sounds and received brief (200 ms) pitch perturbations at 100 Cents in their auditory feedback. Event-related band power responses to vocalizations showed sustained frequency following responses that tracked voice fundamental frequency (F0) and were significantly enhanced in posteromedial HG during speaking compared with when subjects listened to the playback of their own voice. In addition to frequency following responses, a transient response component within the high gamma frequency band (75-150 Hz) was identified. When this response followed the onset of vocalization, the magnitude of the response was the same for the speaking and playback conditions. In contrast, when this response followed a pitch shift, its magnitude was significantly enhanced during speaking compared with playback. We also observed that, in anterolateral HG, the power of high gamma responses to pitch shifts correlated with the magnitude of compensatory vocal responses. These findings demonstrate a functional parcellation of HG with neural activity that encodes pitch in natural human voice, distinguishes between self-generated and passively heard vocalizations, detects discrepancies between the intended and heard vocalization, and contains information about the resulting behavioral vocal compensations in response to auditory feedback pitch perturbations. The present study is a significant contribution to our understanding of sensor-motor mechanisms of vocal production and motor control. The findings demonstrate distinct functional parcellation of core and noncore areas within human auditory cortex on Heschl

  7. Dissociative contributions of the anterior cingulate cortex to apathy and depression: Topological evidence from resting-state functional MRI.

    Science.gov (United States)

    Onoda, Keiichi; Yamaguchi, Shuhei

    2015-10-01

    Apathy is defined as a mental state characterized by a lack of goal-directed behavior. However, the underlying mechanisms of apathy remain to be fully understood. Apathy shares certain symptoms with depression and both these affective disorders are known to be associated with dysfunctions of the frontal cortex-basal ganglia circuits. It is expected that clarifying differences in neural mechanisms between the two conditions would lead to an improved understanding of apathy. The present study was designed to investigate whether apathy and depression depend on different network properties of the frontal cortex-basal ganglia circuits, by using resting state fMRI. Resting-state fMRI measurement and neuropsychological testing were conducted on middle-aged and older adults (N=392). Based on graph theory, we estimated nodal efficiency (functional integration), local efficiency (functional segregation), and betweenness centrality. We conducted multiple regression analyses for the network parameters using age, sex, apathy, and depression as predictors. Interestingly, results indicated that the anterior cingulate cortex showed lower nodal efficiency, local efficiency, and betweenness centrality in apathy, whereas in depression, it showed higher nodal efficiency and betweenness centrality. The anterior cingulate cortex constitutes the so-called "salience network", which detects salient experiences. Our results indicate that apathy is characterized by decreased salience-related processing in the anterior cingulate cortex, whereas depression is characterized by increased salience-related processing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Causal Interactions Within a Frontal-Cingulate-Parietal Network During Cognitive Control: Convergent Evidence from a Multisite-Multitask Investigation.

    Science.gov (United States)

    Cai, Weidong; Chen, Tianwen; Ryali, Srikanth; Kochalka, John; Li, Chiang-Shan R; Menon, Vinod

    2016-05-01

    Cognitive control plays an important role in goal-directed behavior, but dynamic brain mechanisms underlying it are poorly understood. Here, using multisite fMRI data from over 100 participants, we investigate causal interactions in three cognitive control tasks within a core Frontal-Cingulate-Parietal network. We found significant causal influences from anterior insula (AI) to dorsal anterior cingulate cortex (dACC) in all three tasks. The AI exhibited greater net causal outflow than any other node in the network. Importantly, a similar pattern of causal interactions was uncovered by two different computational methods for causal analysis. Furthermore, the strength of causal interaction from AI to dACC was greater on high, compared with low, cognitive control trials and was significantly correlated with individual differences in cognitive control abilities. These results emphasize the importance of the AI in cognitive control and highlight its role as a causal hub in the Frontal-Cingulate-Parietal network. Our results further suggest that causal signaling between the AI and dACC plays a fundamental role in implementing cognitive control and are consistent with a two-stage cognitive control model in which the AI first detects events requiring greater access to cognitive control resources and then signals the dACC to execute load-specific cognitive control processes. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Transient inactivation of the anterior cingulate cortex in rats disrupts avoidance of a dynamic object.

    Science.gov (United States)

    Svoboda, Jan; Lobellová, Veronika; Popelíková, Anna; Ahuja, Nikhil; Kelemen, Eduard; Stuchlík, Aleš

    2017-03-01

    Although animals often learn and monitor the spatial properties of relevant moving objects such as conspecifics and predators to properly organize their own spatial behavior, the underlying brain substrate has received little attention and hence remains elusive. Because the anterior cingulate cortex (ACC) participates in conflict monitoring and effort-based decision making, and ACC neurons respond to objects in the environment, it may also play a role in the monitoring of moving cues and exerting the appropriate spatial response. We used a robot avoidance task in which a rat had to maintain at least a 25cm distance from a small programmable robot to avoid a foot shock. In successive sessions, we trained ten Long Evans male rats to avoid a fast-moving robot (4cm/s), a stationary robot, and a slow-moving robot (1cm/s). In each condition, the ACC was transiently inactivated by bilateral injections of muscimol in the penultimate session and a control saline injection was given in the last session. Compared to the corresponding saline session, ACC-inactivated rats received more shocks when tested in the fast-moving condition, but not in the stationary or slow robot conditions. Furthermore, ACC-inactivated rats less frequently responded to an approaching robot with appropriate escape responses although their response to shock stimuli remained preserved. Since we observed no effect on slow or stationary robot avoidance, we conclude that the ACC may exert cognitive efforts for monitoring dynamic updating of the position of an object, a role complementary to the dorsal hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Children who stutter show reduced action-related activity in the rostral cingulate zone.

    Science.gov (United States)

    Harrewijn, A; Schel, M A; Boelens, H; Nater, C M; Haggard, P; Crone, E A

    2017-02-01

    Previous studies have indicated that children who stutter show not only speech-related problems, but also wider difficulties in self-control. In this study we test the novel hypothesis that children who stutter may experience difficulties with inhibitory control over voluntary actions. We used functional MRI to compare brain activity between children who stutter and children who do not stutter in a task that captures key cognitive aspects of voluntary action control. Participants performed a rolling marble task, in which they were instructed to press a key to stop a rolling marble from crashing on some of the trials (instructed action condition). They were also asked to choose voluntarily whether to execute or inhibit this prepotent response in other trials (volition condition). Children who stutter reported less motor and cognitive impulsivity and had shorter stop-signal reaction times when controlled for IQ, consistent with greater inhibition, compared to children who do not stutter. At the neural level, children who stutter showed decreased activation in the rostral cingulate zone during voluntary action selection compared to children who do not stutter. This effect was more pronounced for children who were rated as showing more stuttered syllables in the stutter screening, and was furthermore correlated with stop-signal reaction times and impulsivity ratings. These findings suggest that stuttering in childhood could reflect wider difficulties in self-control, also in the non-verbal domain. Understanding these neural mechanisms could potentially lead to more focused treatments of stuttering. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic.

    Science.gov (United States)

    Ruland, Tillmann; Domschke, Katharina; Schütte, Valerie; Zavorotnyy, Maxim; Kugel, Harald; Notzon, Swantje; Vennewald, Nadja; Ohrmann, Patricia; Arolt, Volker; Pfleiderer, Bettina; Zwanzger, Peter

    2015-10-01

    An excitatory-inhibitory neurotransmitter dysbalance has been suggested in pathogenesis of panic disorder. The neuropeptide S (NPS) system has been implicated in modulating GABA and glutamate neurotransmission in animal models and to genetically drive altered fear circuit function and an increased risk of panic disorder in humans. Probing a multi-level imaging genetic risk model of panic, in the present magnetic resonance spectroscopy (MRS) study brain glutamate+glutamine (Glx) levels in the bilateral anterior cingulate cortex (ACC) during a pharmacological cholecystokinin tetrapeptide (CCK-4) panic challenge were assessed depending on the functional neuropeptide S receptor gene (NPSR1) rs324981 A/T variant in a final sample of 35 healthy male subjects. The subjective panic response (Panic Symptom Scale; PSS) as well as cortisol and ACTH levels were ascertained throughout the experiment. CCK-4 injection was followed by a strong panic response. A significant time×genotype interaction was detected (p=.008), with significantly lower ACC Glx/Cr levels in T allele carriers as compared to AA homozygotes 5min after injection (p=.003). CCK-4 induced significant HPA axis stimulation, but no effect of genotype was discerned. The present pilot data suggests NPSR1 gene variation to modulate Glx levels in the ACC during acute states of stress and anxiety, with blunted, i.e. possibly maladaptive ACC glutamatergic reactivity in T risk allele carriers. Our results underline the notion of a genetically driven rapid and dynamic response mechanism in the neural regulation of human anxiety and further strengthen the emerging role of the NPS system in anxiety. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  12. Muscarinic receptor binding increases in anterior thalamus and cingulate cortex during discriminative avoidance learning

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, B.A.; Gabriel, M.; Vogt, L.J.; Poremba, A.; Jensen, E.L.; Kubota, Y.; Kang, E. (Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina (USA))

    1991-06-01

    Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OxO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OxO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early in training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OxO-M/PZ binding progressively increased throughout training, reached a peak at the criterion stage of performance, and returned to control values during extinction sessions. Peak OxO-M/PZ binding in AVp was significantly elevated over that for cases yoked to criterion performance. In the magnocellular division of the anteroventral nucleus (AVm), OxO-M/PZ binding was elevated only during criterion performance of the task, and it was unaltered in any other limbic thalamic nuclei. Specific OxO-M/PZ binding was also elevated in most layers in rostral area 29c when subjects first performed a significant behavioral discrimination. Training-induced alterations in OxO-M/PZ binding in AVp and layer Ia of area 29c were similar and highly correlated.

  13. The role of the anterior cingulate cortex in emotional response inhibition.

    Science.gov (United States)

    Albert, Jacobo; López-Martín, Sara; Tapia, Manuel; Montoya, Daniel; Carretié, Luis

    2012-09-01

    Although the involvement of the anterior cingulate cortex (ACC) in emotional response inhibition is well established, there are several outstanding issues about the nature of this involvement that are not well understood. The present study aimed to examine the precise contribution of the ACC to emotion-modulated response inhibition by capitalizing on fine temporal resolution of the event-related potentials (ERPs) and the recent advances in source localization. To this end, participants (N = 30) performed an indirect affective Go/Nogo task (i.e., unrelated to the emotional content of stimulation) that required the inhibition of a motor response to three types of visual stimuli: arousing negative (A-), neutral (N), and arousing positive (A+). Behavioral data revealed that participants made more commission errors to A+ than to N and A-. Electrophysiological data showed that a specific region of the ACC at the intersection of its dorsal and rostral subdivisions was significantly involved in the interaction between emotional processing and motor inhibition. Specifically, activity reflecting this interaction was observed in the P3 (but not in the N2) time range, and was greater during the inhibition of responses to A+ than to N and A-. Additionally, regression analyses showed that inhibition-related activity within this ACC region was associated with the emotional content of the stimuli (its activity increased as stimulus valence was more positive), and also with behavioral performance (both with reaction times and commission errors). The present results provide additional data for understanding how, when, and where emotion interacts with response inhibition within the ACC. Copyright © 2011 Wiley Periodicals, Inc.

  14. Rapid synaptic potentiation within the anterior cingulate cortex mediates trace fear learning

    Directory of Open Access Journals (Sweden)

    Descalzi Giannina

    2012-02-01

    Full Text Available Abstract Although the cortex has been extensively studied in long-term memory storage, less emphasis has been placed on immediate cortical contributions to fear memory formation. AMPA receptor plasticity is strongly implicated in learning and memory, and studies have identified calcium permeable AMPA receptors (CP-AMPARs as mediators of synaptic strengthening. Trace fear learning engages the anterior cingulate cortex (ACC, but whether plastic events occur within the ACC in response to trace fear learning, and whether GluN2B subunits are required remains unknown. Here we show that the ACC is necessary for trace fear learning, and shows a rapid 20% upregulation of membrane AMPA receptor GluA1 subunits that is evident immediately after conditioning. Inhibition of NMDA receptor GluN2B subunits during training prevented the upregulation, and disrupted trace fear memory retrieval 48 h later. Furthermore, intra-ACC injections of the CP-AMPAR channel antagonist, 1-naphthylacetyl spermine (NASPM immediately following trace fear conditioning blocked 24 h fear memory retrieval. Accordingly, whole cell patch clamp recordings from c-fos positive and c-fos negative neurons within the ACC in response to trace fear learning revealed an increased sensitivity to NASPM in recently activated neurons that was reversed by reconsolidation update extinction. Our results suggest that trace fear learning is mediated through rapid GluN2B dependent trafficking of CP-AMPARs, and present in vivo evidence that CP-AMPAR activity within the ACC immediately after conditioning is necessary for subsequent memory consolidation processes.

  15. Pregnancy and maternal behavior induce changes in glia, glutamate and its metabolism within the cingulate cortex.

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    Natalina Salmaso

    Full Text Available An upregulation of the astrocytic proteins GFAP and bFGF within area 2 of the cingulate cortex (Cg2 occurs within 3 hours of parturition in rats. These changes are the result of an interaction between hormonal state and maternal experience and are associated with increased dendritic spine density in this area. Here, we examined whether this upregulation of astrocytic proteins generalized to other glial markers and, in particular those associated with glutamate metabolism. We chose glial markers commonly used to reflect different aspects of glial function: vimentin, like GFAP, is a marker of intermediate filaments; glutamine synthetase (GS, and S-100beta, are used as markers for mature astrocytes and GS has also been used as a specific marker for glutamatergic enzymatic activity. In addition, we examined levels of proteins associated with glutamine synthetase, glutamate, glutamine and two excitatory amino acid transporters found in astrocytes, glt-1 and glast. S100beta immunoreactivity did not vary with reproductive state in either Cg2 or MPOA suggesting no change in the number of mature astrocytes across these conditions. Vimentin-ir did not differ across groups in Cg2, but expression of this protein decreased from Day 1 postpartum onwards in the MPOA. By contrast, GS-ir was increased within 24 h postpartum in Cg2 but not MPOA and similarly to GFAP and bFGF this upregulation of GS resulted from an interaction between hormonal state and maternal experience. Within Cg2, upregulation of GS was not accompanied by changes in the astrocytic glutamatergic transporters, glt-1 and glast, however, an increase in both glutamate and glutamine proteins were observed within the Cg2 of postpartum animals. Together, these changes suggest postpartum upregulation of glutamatergic activity and metabolism within Cg2 that is stimulated by pregnancy hormones and maternal experience.

  16. LOWER POSTERIOR CINGULATE CORTEX GLUTATHIONE LEVELS IN OBSESSIVE-COMPULSIVE DISORDER

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    Brennan, Brian P.; Jensen, J. Eric; Perriello, Christine; Pope, Harrison G.; Jenike, Michael A.; Hudson, James I.; Rauch, Scott L.; Kaufman, Marc J.

    2015-01-01

    Background Several lines of evidence support the hypothesis that lower cerebral levels of glutathione (GSH), associated with increased oxidative stress, may contribute to obsessive-compulsive disorder (OCD). However, no studies to date have investigated brain GSH levels in individuals with OCD. Methods Twenty-nine individuals with OCD and 25 age-, sex-, and race-matched comparison individuals without OCD underwent single voxel 2D J-resolved proton magnetic resonance spectroscopy (MRS) to examine GSH levels in the posterior cingulate cortex (PCC). MRS data were analyzed using LCModel and a simulated basis set. Group metabolite differences referenced to total creatine (Cr), as well as relationships between metabolite ratios and symptom severity as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), were analyzed using linear regression with adjustment for age, sex, and race. Results One OCD participant failed to produce usable PCC MRS data. We found significantly lower PCC GSH/Cr in OCD participants compared with non-OCD participants (β = −0.027 [95% CI: −0.049 to −5.9 × 10−3]; P = 0.014). PCC GSH/Cr was not significantly associated with total Y-BOCS score in the OCD group (β = 5.7 × 10−4 [95% CI: −4.8 × 10−3 to 5.9 × 10−3]; P = 0.83). Conclusions Lower PCC GSH/Cr may be indicative of increased oxidative stress secondary to hypermetabolism in this brain region in OCD. Future MRS studies are warranted to investigate GSH levels in other brain regions that comprise the cortico-striato-thalamo-cortical circuit thought to be abnormal in OCD. PMID:26949749

  17. Dissociable recruitment of rostral anterior cingulate and inferior frontal cortex in emotional response inhibition.

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    Chiu, Pearl H; Holmes, Avram J; Pizzagalli, Diego A

    2008-08-15

    The integrity of decision-making under emotionally evocative circumstances is critical to navigating complex environments, and dysfunctions in these processes may play an important role in the emergence and maintenance of various psychopathologies. The goal of the present study was to examine the spatial and temporal dynamics of neural responses to emotional stimuli and emotion-modulated response inhibition. High-density event-related brain potentials (ERPs) were measured as participants (N=25) performed an emotional Go/NoGo task that required button presses to words of a "target" emotional valence (i.e., positive, negative, neutral) and response inhibition to words of a different "distractor" valence. Using scalp ERP analyses in conjunction with source-localization techniques, we identified distinct neural responses associated with affective salience and affect-modulated response inhibition, respectively. Both earlier (approximately 300 ms) and later (approximately 700 ms) ERP components were enhanced with successful response inhibition to emotional distractors. Only ERPs to target stimuli differentiated affective from neutral cues. Moreover, source localization analyses revealed right ventral lateral prefrontal cortex (VLPFC) activation in affective response inhibition regardless of emotional valence, whereas rostral anterior cingulate activation (rACC) was potentiated by emotional valence but was not modulated by response inhibition. This dissociation was supported by a significant Region x Trial Type x Emotion interaction, confirming that distinct regional dynamics characterize neural responses to affective valence and affective response-inhibition. The results are discussed in the context of an emerging affective neuroscience literature and implications for understanding psychiatric pathologies characterized by a detrimental susceptibility to emotional cues, with an emphasis on major depressive disorder.

  18. Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

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    Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M

    2015-10-01

    Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Enhanced subgenual cingulate response to altruistic decisions in remitted major depressive disorder.

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    Pulcu, Erdem; Zahn, Roland; Moll, Jorge; Trotter, Paula D; Thomas, Emma J; Juhasz, Gabriella; Deakin, J F William; Anderson, Ian M; Sahakian, Barbara J; Elliott, Rebecca

    2014-01-01

    Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown. Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD. Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture. We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called "warm glow" of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.

  20. The role of dorsal anterior cingulate cortex in the regulation of craving by reappraisal in smokers.

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    Li-Yan Zhao

    Full Text Available RATIONALE AND OBJECTIVE: Drug cues can induce craving for drugs of abuse. Dysfunctional regulation of emotion and motivation regarding rewarding objects appears to be an integral part of addiction. It has been found that cognitive strategies decreased the intensity of craving in addicts. Reappraisal strategy is a type of cognitive strategy that requires participants to reinterpret the meaning of an emotional situation. In addition, studies have found that activation of the dorsal anterior cingulate cortex (dACC is associated with the selection and application of cognitive reappraisal. In present study, we sought to determine whether such cognitive regulation engages the dACC and improves inhibition of craving in smokers. METHODS: Sixteen smokers underwent functional magnetic resonance imaging (fMRI during performance of a cigarette reward-conditioning procedure with cognitive reappraisal. We focused our analyses on the dACC as a key structure of cognitive control of craving. Cue induced craving under different conditions was obtained. Correlational analysis between the functional response in the dACC and the subjective craving was performed. RESULTS: We found that using a cognitive reappraisal was successful in decreasing the conditioned craving. Right dACC (BA 24/32 engaged in the cognitive reappraisal. In addition, the individual's subjective craving was negatively correlated with the right dACC activation. CONCLUSIONS: These findings suggest that the dACC are important substrates of Inhibition of cue induced craving in smokers. Cognitive regulation by cognitive reappraisal may help addicted individuals avoid the anticipated situations where they are exposed to conditioned cues.

  1. Increased BOLD signal in the fusiform gyrus during implicit emotion processing in anorexia nervosa.

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    Fonville, Leon; Giampietro, Vincent; Surguladze, Simon; Williams, Steven; Tchanturia, Kate

    2014-01-01

    The behavioural literature in anorexia nervosa (AN) has suggested impairments in psychosocial functioning and studies using facial expression processing tasks (FEPT) have reported poorer recognition and slower identification of emotions. Functional magnetic resonance imaging (fMRI) was used alongside a FEPT, depicting neutral, mildly happy and happy faces, to examine the neural correlates of implicit emotion processing in AN. Participants were instructed to specify the gender of the faces. Levels of depression, anxiety, obsessive-compulsive symptoms and eating disorder behaviour were obtained and principal component analysis (PCA) was performed to acquire uncorrelated variables. fMRI analysis revealed a greater blood-oxygenation level dependent (BOLD) response in AN in the right fusiform gyrus to all facial expressions. This response showed a linear increase with the happiness of the facial expression and was found to be stronger in those not taking medication. PCA analysis revealed a single component indicating a greater level of general clinical symptoms. Neuroimaging findings would suggest that alterations in implicit emotion processing in AN occur during early perceptual processing of social signals and illustrate greater engagement on the FEPT. The lack of separate components using PCA suggests that the questionnaires used might not be suited as predictive measures.

  2. Anorexia Nervosa during Adolescence Is Associated with Decreased Gray Matter Volume in the Inferior Frontal Gyrus.

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    Fujisawa, Takashi X; Yatsuga, Chiho; Mabe, Hiroyo; Yamada, Eiji; Masuda, Masato; Tomoda, Akemi

    2015-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by the relentless pursuit to lose weight, mostly through self-starvation, and a distorted body image. AN tends to begin during adolescence among women. However, the underlying neural mechanisms related to AN remain unclear. Using voxel-based morphometry based on magnetic resonance imaging scans, we investigated whether the presence of AN was associated with discernible changes in brain morphology. Participants were 20 un-medicated, right-handed patients with early-onset AN and 14 healthy control subjects. Group differences in gray matter volume (GMV) were assessed using high-resolution, T1-weighted, volumetric magnetic resonance imaging datasets (3T Trio scanner; Siemens AG) and analyzed after controlling for age and total GMV, which was decreased in the bilateral inferior frontal gyrus (IFG) (left IFG: FWE corrected, p < 0.05; right IFG: uncorrected, p < 0.05) of patients with AN. The GMV in the bilateral IFG correlated significantly with current age (left IFG: r = -.481, p < .05; right IFG: r = -.601, p < .01) and was limited to the AN group. We speculate that decreased IFG volume might lead to deficits in executive functioning or inhibitory control within neural reward systems. Precocious or unbalanced neurological trimming within this particular region might be an important factor for the pathogenesis of AN onset.

  3. Anorexia Nervosa during Adolescence Is Associated with Decreased Gray Matter Volume in the Inferior Frontal Gyrus.

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    Takashi X Fujisawa

    Full Text Available Anorexia nervosa (AN is an eating disorder characterized by the relentless pursuit to lose weight, mostly through self-starvation, and a distorted body image. AN tends to begin during adolescence among women. However, the underlying neural mechanisms related to AN remain unclear. Using voxel-based morphometry based on magnetic resonance imaging scans, we investigated whether the presence of AN was associated with discernible changes in brain morphology. Participants were 20 un-medicated, right-handed patients with early-onset AN and 14 healthy control subjects. Group differences in gray matter volume (GMV were assessed using high-resolution, T1-weighted, volumetric magnetic resonance imaging datasets (3T Trio scanner; Siemens AG and analyzed after controlling for age and total GMV, which was decreased in the bilateral inferior frontal gyrus (IFG (left IFG: FWE corrected, p < 0.05; right IFG: uncorrected, p < 0.05 of patients with AN. The GMV in the bilateral IFG correlated significantly with current age (left IFG: r = -.481, p < .05; right IFG: r = -.601, p < .01 and was limited to the AN group. We speculate that decreased IFG volume might lead to deficits in executive functioning or inhibitory control within neural reward systems. Precocious or unbalanced neurological trimming within this particular region might be an important factor for the pathogenesis of AN onset.

  4. Anosognosia for Hemiplegia: The Contributory Role of Right Inferior Frontal Gyrus

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    Kortte, Kathleen B.; McWhorter, Jessica Wolfman; Pawlak, Mikolaj A.; Slentz, Jamie; Sur, Sandeepa; Hillis, Argye E.

    2014-01-01

    Objective Awareness of motor functioning is most likely a complex process that requires integration of sensory-motor feedback in order to constantly update the system on the functioning of the limb during motor behavior. Using lesion mapping procedures and behavioral measures, the current study aimed to evaluate neural correlates of anosognosia for hemiplegia (AHP) in the acute stage (first 48 hours) of right hemisphere stroke. Method Thirty-five individuals with right hemisphere stroke who presented to an urban medical center within 24 hours of symptom onset were included in the study. All thirty-five individuals had hemiplegia, and eight of these individuals exhibited AHP. Results Fisher exact test statistical map of lesion-deficit association (range is between-log(p) 4 to 11) found maximal value of 10.9 located in pars orbitalis (Brodmann’s Area 47; BA). In this selected location, six out of eight patients with AHP had tissue abnormality, whereas none of the unaffected subjects had tissue abnormality in BA 47. Right BA 44/45 was also found to be lesioned more frequently in individuals with AHP (75%) than without AHP (11%). Conclusions The current study findings provide preliminary support for unique involvement of the right inferior frontal gyrus (IFG), pars orbitalis (BA 47) in AHP. The current data suggest that frontal operculum may play a key role in awareness of limb functioning. PMID:25133319

  5. Effect of head orientation on gaze processing in fusiform gyrus and superior temporal sulcus.

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    Pageler, Natalie M; Menon, Vinod; Merin, Noah M; Eliez, Stephan; Brown, Wendy E; Reiss, Allan L

    2003-09-01

    We used functional MRI with an event-related design to dissociate the brain activation in the fusiform gyrus (FG) and posterior superior temporal sulcus (STS) for multiple face and gaze orientations. The event-related design allowed for concurrent behavioral analysis, which revealed a significant effect of both head and gaze orientation on the speed of gaze processing, with the face and gaze forward condition showing the fastest reaction times. In conjunction with this behavioral finding, the FG responded with the greatest activation to face and gaze forward, perhaps reflecting the unambiguous social salience of congruent face and gaze directed toward the viewer. Random effects analysis showed greater activation in both the FG and posterior STS when the subjects viewed a direct face compared to an angled face, regardless of gaze direction. Additionally, the FG showed greater activation for forward gaze compared to angled gaze, but only when the face was forward. Together, these findings suggest that head orientation has a significant effect on gaze processing and these effects are manifest not only in the STS, but also the FG.

  6. Impaired neurogenesis of the dentate gyrus is associated with pattern separation deficits: A computational study.

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    Faghihi, Faramarz; Moustafa, Ahmed A

    2016-09-01

    The separation of input patterns received from the entorhinal cortex (EC) by the dentate gyrus (DG) is a well-known critical step of information processing in the hippocampus. Although the role of interneurons in separation pattern efficiency of the DG has been theoretically known, the balance of neurogenesis of excitatory neurons and interneurons as well as its potential role in information processing in the DG is not fully understood. In this work, we study separation efficiency of the DG for different rates of neurogenesis of interneurons and excitatory neurons using a novel computational model in which we assume an increase in the synaptic efficacy between excitatory neurons and interneurons and then its decay over time. Information processing in the EC and DG was simulated as information flow in a two layer feed-forward neural network. The neurogenesis rate was modeled as the percentage of new born neurons added to the neuronal population in each time bin. The results show an important role of an optimal neurogenesis rate of interneurons and excitatory neurons in the DG in efficient separation of inputs from the EC in pattern separation tasks. The model predicts that any deviation of the optimal values of neurogenesis rates leads to different decreased levels of the separation deficits of the DG which influences its function to encode memory.

  7. Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus.

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    Kim, D H; Lee, H E; Kwon, K J; Park, S J; Heo, H; Lee, Y; Choi, J W; Shin, C Y; Ryu, J H

    2015-01-22

    Throughout adulthood, neurons are continuously replaced by new cells in the dentate gyrus (DG) of the hippocampus, and this neurogenesis is increased by various neuronal injuries including ischemic stroke and seizure. While several mechanisms of this injury-induced neurogenesis have been elucidated, the initiation factor remains unclear. Here, we investigated which signal(s) trigger(s) ischemia-induced cell proliferation and neurogenesis in the hippocampal DG region. We found that early apoptotic cell death of the immature neurons occurred in the DG region following transient forebrain ischemia/reperfusion in mice. Moreover, early immature neuronal death in the DG initiated transient forebrain ischemia/reperfusion-induced neurogenesis through glycogen synthase kinase-3β/β-catenin signaling, which was mediated by microglia-derived insulin-like growth factor-1 (IGF-1). Additionally, we observed that the blockade of immature neuronal cell death, early microglial activation, or IGF-1 signaling attenuated ischemia-induced neurogenesis. These results suggest that early immature neuronal cell death initiates ischemia-induced neurogenesis through microglial IGF-1 in mice. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. A causal involvement of the left supramarginal gyrus during the retention of musical pitches.

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    Schaal, Nora K; Williamson, Victoria J; Kelly, Maria; Muggleton, Neil G; Pollok, Bettina; Krause, Vanessa; Banissy, Michael J

    2015-03-01

    Brain stimulation studies have previously demonstrated a causal link between general pitch memory processes and activity within the left supramarginal gyrus (SMG). Building on this evidence, the present study tested the impact of left SMG stimulation on two distinct pitch memory phases, retention and encoding. Repetitive transcranial magnetic stimulation (rTMS) was employed during the retention stage (Experiment 1) and the encoding phase (Experiment 2) of a pitch recognition task. Stimulation was applied on a trial-by-trial basis over the left SMG (target site) or the vertex (control site). A block without TMS was also completed. In Experiment 1, rTMS over the left SMG during pitch retention led to significantly increased reaction times compared to control conditions. In Experiment 2 no rTMS modulation effects were found during encoding. Experiment 3 was conducted as a control for non-specific stimulation effects; no effects were found when rTMS was applied over the left SMG at the two different time points during a perceptual task. Taken together, these findings highlight a phase-specific involvement of the left SMG in the retention phase of pitch memory, thereby indicating that the left SMG is involved in the maintenance of pitch information. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. An interplay of fusiform gyrus and hippocampus enables prototype- and exemplar-based category learning.

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    Lech, Robert K; Güntürkün, Onur; Suchan, Boris

    2016-09-15

    The aim of the present study was to examine the contributions of different brain structures to prototype- and exemplar-based category learning using functional magnetic resonance imaging (fMRI). Twenty-eight subjects performed a categorization task in which they had to assign prototypes and exceptions to two different families. This test procedure usually produces different learning curves for prototype and exception stimuli. Our behavioral data replicated these previous findings by showing an initially superior performance for prototypes and typical stimuli and a switch from a prototype-based to an exemplar-based categorization for exceptions in the later learning phases. Since performance varied, we divided participants into learners and non-learners. Analysis of the functional imaging data revealed that the interaction of group (learners vs. non-learners) and block (Block 5 vs. Block 1) yielded an activation of the left fusiform gyrus for the processing of prototypes, and an activation of the right hippocampus for exceptions after learning the categories. Thus, successful prototype- and exemplar-based category learning is associated with activations of complementary neural substrates that constitute object-based processes of the ventral visual stream and their interaction with unique-cue representations, possibly based on sparse coding within the hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults

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    Brickman, Adam M; Khan, Usman A; Provenzano, Frank A; Yeung, Lok-Kin; Suzuki, Wendy; Schroeter, Hagen; Wall, Melanie; Sloan, Richard P; Small, Scott A

    2016-01-01

    The dentate gyrus (DG) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline. Causal evidence is needed, however, to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function. We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging (fMRI) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site. Then, in a controlled randomized trial, we applied these tools to study healthy 50–69-year-old subjects who consumed either a high or low cocoa–containing diet for 3 months. A high-flavanol intervention was found to enhance DG function, as measured by fMRI and by cognitive testing. Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration. PMID:25344629

  11. Increases in Doublecortin Immunoreactivity in the Dentate Gyrus following Extinction of Heroin-Seeking Behavior

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    Megan P. Hicks

    2012-01-01

    Full Text Available Adult-generated neurons in the dentate gyrus (DG of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV. We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.

  12. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium.

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    Walton, E; Hibar, D P; van Erp, T G M; Potkin, S G; Roiz-Santiañez, R; Crespo-Facorro, B; Suarez-Pinilla, P; Van Haren, N E M; de Zwarte, S M C; Kahn, R S; Cahn, W; Doan, N T; Jørgensen, K N; Gurholt, T P; Agartz, I; Andreassen, O A; Westlye, L T; Melle, I; Berg, A O; Mørch-Johnsen, L; Faerden, A; Flyckt, L; Fatouros-Bergman, H; Jönsson, E G; Hashimoto, R; Yamamori, H; Fukunaga, M; Preda, A; De Rossi, P; Piras, F; Banaj, N; Ciullo, V; Spalletta, G; Gur, R E; Gur, R C; Wolf, D H; Satterthwaite, T D; Beard, L M; Sommer, I E; Koops, S; Gruber, O; Richter, A; Krämer, B; Kelly, S; Donohoe, G; McDonald, C; Cannon, D M; Corvin, A; Gill, M; Di Giorgio, A; Bertolino, A; Lawrie, S; Nickson, T; Whalley, H C; Neilson, E; Calhoun, V D; Thompson, P M; Turner, J A; Ehrlich, S

    2017-05-01

    Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. Positive symptom severity was negatively related to STG thickness in both hemispheres (left: β std = -0.052; P = 0.021; right: β std = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Fluoxetine and the dentate gyrus: memory, recovery of function, and electrophysiology.

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    Keith, Julian R; Wu, Ying; Epp, Jonathon R; Sutherland, Robert J

    2007-09-01

    Chronic fluoxetine increases neurogenesis in the dentate gyrus (DG). In view of the widespread clinical use of fluoxetine and the well-established role of the DG in memory, surprisingly few studies have examined the effects of fluoxetine on memory and hippocampal electrophysiology. Additionally, few studies have evaluated the potential for fluoxetine to promote recovery of function after DG damage. Therefore, we studied the effects of long-term administration of fluoxetine on both spatial-reference memory and working memory, recovery of function after intrahippocampal colchicine infusions, which can destroy 50-70% of DG granule cells, and electrophysiological responses in the DG to perforant path stimulation in freely moving rats. Chronic fluoxetine did not affect matching-to-place or reference-memory performance in intact rats in the Morris water-maze task. Surprisingly, in rats with DG damage, recovery of function on both tasks was adversely affected by chronic fluoxetine. Finally, unlike an earlier study that reported fluoxetine-induced increases in hippocampal population spike amplitudes and excitatory postsynaptic potential slopes in urethane-anesthetized rats, electrophysiological measures in DG of freely moving rats were not affected by chronic fluoxetine treatment.

  14. Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy.

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    Adachi, Megumi; Barrot, Michel; Autry, Anita E; Theobald, David; Monteggia, Lisa M

    2008-04-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neural plasticity in the adult nervous system and has been suggested as a target gene for antidepressant treatment. The neurotrophic hypothesis of depression suggests that loss of BDNF from the hippocampus contributes to an increased vulnerability for depression, whereas upregulation of BDNF in the hippocampus is suggested to mediate antidepressant efficacy. We have used a viral-mediated gene transfer approach to assess the role of BDNF in subregions of the hippocampus in a broad array of behavioral paradigms, including depression-like behavior and antidepressant responses. We have combined the adeno-associated virus (AAV) with the Cre/loxP site-specific recombination system to induce the knockout of BDNF selectively in either the CA1 or dentate gyrus (DG) subregions of the hippocampus. We show that the loss of BDNF in either the CA1 or the DG of the hippocampus does not alter locomotor activity, anxiety-like behavior, fear conditioning, or depression-related behaviors. However, the selective loss of BDNF in the DG but not the CA1 region attenuates the actions of desipramine and citalopram in the forced swim test. These data suggest that the loss of hippocampal BDNF per se is not sufficient to mediate depression-like behavior. However, these results support the view that BDNF in the DG might be essential in mediating the therapeutic effect of antidepressants.

  15. Anorexia Nervosa during Adolescence Is Associated with Decreased Gray Matter Volume in the Inferior Frontal Gyrus

    Science.gov (United States)

    Mabe, Hiroyo; Yamada, Eiji; Masuda, Masato; Tomoda, Akemi

    2015-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by the relentless pursuit to lose weight, mostly through self-starvation, and a distorted body image. AN tends to begin during adolescence among women. However, the underlying neural mechanisms related to AN remain unclear. Using voxel-based morphometry based on magnetic resonance imaging scans, we investigated whether the presence of AN was associated with discernible changes in brain morphology. Participants were 20 un-medicated, right-handed patients with early-onset AN and 14 healthy control subjects. Group differences in gray matter volume (GMV) were assessed using high-resolution, T1-weighted, volumetric magnetic resonance imaging datasets (3T Trio scanner; Siemens AG) and analyzed after controlling for age and total GMV, which was decreased in the bilateral inferior frontal gyrus (IFG) (left IFG: FWE corrected, p < 0.05; right IFG: uncorrected, p < 0.05) of patients with AN. The GMV in the bilateral IFG correlated significantly with current age (left IFG: r = -.481, p < .05; right IFG: r = -.601, p < .01) and was limited to the AN group. We speculate that decreased IFG volume might lead to deficits in executive functioning or inhibitory control within neural reward systems. Precocious or unbalanced neurological trimming within this particular region might be an important factor for the pathogenesis of AN onset. PMID:26067825

  16. BACE1 Deficiency Causes Abnormal Neuronal Clustering in the Dentate Gyrus

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    Hailong Hou

    2017-07-01

    Full Text Available BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ. Such clusters were rarely observed in wild-type SPZ and not reported in other mouse models. To understand their origins and fates, we examined how neuroblasts in BACE1-null SPZ mature and migrate during early postnatal development. We show that such neuroblasts are destined to form Prox1-positive granule cells in the dentate granule cell layer, and mainly mature to form excitatory neurons, but not inhibitory neurons. Mechanistically, higher levels of reelin potentially contribute to abnormal neurogenesis and timely migration in BACE1-null SPZ. Altogether, we demonstrate that BACE1 is a critical regulator in forming the dentate granule cell layer through timely maturation and migration of SPZ neuroblasts.

  17. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus.

    Science.gov (United States)

    Babu, Harish; Claasen, Jan-Hendrik; Kannan, Suresh; Rünker, Annette E; Palmer, Theo; Kempermann, Gerd

    2011-01-01

    In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., 2007) to isolate neural precursor cells from the hippocampus of adult mice and maintain and propagate them as adherent monolayer cultures. The strategy is based on the use of Percoll density gradient centrifugation to enrich precursor cells from the micro-dissected dentate gyrus. Based on the expression of Nestin and Sox2, a culture-purity of more than 98% can be achieved. The cultures are expanded under serum-free conditions in Neurobasal A medium with addition of the mitogens Epidermal growth factor and Fibroblast growth factor 2 as well as the supplements Glutamax-1 and B27. Under differentiation conditions, the precursor cells reliably generate approximately 30% neurons with appropriate morphological, molecular, and electrophysiological characteristics that might reflect granule cell properties as their in vivo counterpart. We also highlight potential modifications to the protocol.

  18. Differential Processing of Consonance and Dissonance within the Human Superior Temporal Gyrus

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    Francine eFoo

    2016-04-01

    Full Text Available The auditory cortex is well known to be critical for music perception, including the perception of consonance and dissonance. Studies on the neural correlates of consonance and dissonance perception have largely employed non-invasive electrophysiological and functional imaging techniques in humans as well as neurophysiological recordings in animals, but the fine-grained spatiotemporal dynamics within the human auditory cortex remain unknown. We recorded electrocorticographic (ECoG signals directly from the lateral surface of either the left or right temporal lobe of 8 patients undergoing neurosurgical treatment as they passively listened to highly consonant and highly dissonant musical chords. We assessed ECoG activity in the high gamma (γhigh, 70-150 Hz frequency range within the superior temporal gyrus (STG and observed two types of cortical sites of interest in both hemispheres: one type showed no significant difference in γhigh activity between consonant and dissonant chords, and another type showed increased γhigh responses to dissonant chords between 75-200ms post-stimulus onset. Furthermore, a subset of these sites exhibited additional sensitivity towards different types of dissonant chords. We also observed a distinct spatial organization of cortical sites in the right STG, with dissonant-sensitive sites located anterior to non-sensitive sites. In sum, these findings demonstrate differential processing of consonance and dissonance in bilateral STG with the right hemisphere exhibiting robust and spatially organized sensitivity towards dissonance.

  19. Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells.

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    Boku, Shuken; Nakagawa, Shin; Masuda, Takahiro; Nishikawa, Hiroyuki; Kato, Akiko; Toda, Hiroyuki; Song, Ning; Kitaichi, Yuji; Inoue, Takeshi; Koyama, Tsukasa

    2011-01-15

    Neurogenesis in the adult dentate gyrus (DG) is considered to be partly involved in the action of mood stabilizers. However, it remains unclear how mood stabilizers affect neural precursor cells in adult DG. We have established a culture system of adult rat DG-derived neural precursor cells (ADP) and have shown that lithium, a mood stabilizer, and dexamethasone, an agonist of glucocorticoid receptor, reciprocally regulate ADP proliferation. Neurogenesis constitutes not only proliferation of neural precursor cells but also apoptosis and differentiation. To develop further understanding of mood stabilizer effects on neural precursor cells in adult DG, we investigated and compared the effects of four common mood stabilizers-lithium, valproate, carbamazepine, and lamotrigine-on ADP proliferation, apoptosis, and differentiation. ADP proliferation, decreased by dexamethasone, was examined using Alamar Blue assay. Using TUNEL assay, ADP apoptosis induced by staurosporine was examined. The differentiated ADP induced by retinoic acid was characterized by immunostaining with anti-GFAP or anti-Tuj1 antibody. Lithium and valproate, but not carbamazepine and lamotrigine, recovered ADP proliferation decreased by dexamethasone. All four mood stabilizers decreased ADP apoptosis. Retinoic acid differentiated ADP into both neurons and astrocytes. Lithium and carbamazepine increased the ratio of neurons and decreased that of astrocytes. However, valproate and lamotrigine increased the ratio of astrocytes and decreased that of neurons. Therefore, these four stabilizers exhibited both common and differential effects on ADP proliferation, apoptosis, and differentiation. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Dexterity with numbers: rTMS over left angular gyrus disrupts finger gnosis and number processing.

    Science.gov (United States)

    Rusconi, Elena; Walsh, Vincent; Butterworth, Brian

    2005-01-01

    Since the original description of Gerstmann's syndrome with its four cardinal symptoms, among which are finger agnosia and acalculia, the neuro-cognitive relationship between fingers and calculation has been debated. We asked our participants to perform four different tasks, two of which involved fingers and the other two involving numbers, during repetitive transcranial magnetic stimulation (rTMS) over the posterior parietal lobe of either hemisphere. In the finger tasks, they were required to transform a tactile stimulus randomly delivered on one of their fingers into a speeded key-press response either with the same or with the homologous finger on the opposite hand. In the numerical tasks, they were asked to perform a magnitude or a parity matching on pairs of single digits, in the context of arithmetically related or unrelated numerical primes. In accordance with the original anatomical hypothesis put forward by Gerstmann [Gerstmann, J. (1924). Fingeragnosie: eine umschriebene Stoerung der Orienterung am eigenen Koerper. Wiener clinische Wochenschrift, 37, 1010-12], we found that rTMS over the left angular gyrus disrupted tasks requiring access to the finger schema and number magnitude processing in the same group of participants. In addition to the numerous studies which have employed special populations such as neurological patients and children, our data confirm the presence of a relationship between numbers and body knowledge in skilled adults who no longer use their fingers for solving simple arithmetical tasks.

  1. Maturation of the limbic system revealed by MR FLAIR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Jacques F.; Vergesslich, Klara [University Children' s Hospital UKBB, Department of Paediatric Radiology, Basel (Switzerland)

    2007-04-15

    Cortical signal intensity (SI) of the limbic system in adults is known to be higher than in neocortical structures, but time-related changes in SI during childhood have not been described. To detect maturation-related SI changes within the limbic system using a fluid-attenuated inversion recovery (FLAIR) MR sequence. Twenty children (10 boys, 10 girls; age 3.5-18 years, mean 11.2 years) with no neurological abnormality and normal MR imaging examination were retrospectively selected. On two coronal FLAIR slices, ten regions of interest (ROI) with a constant area of 10 mm{sup 2} were manually placed in the archeocortex (hippocampus), periarcheocortex (parahippocampal gyrus, subcallosal area, cingulate gyrus) and in the neocortex at the level of the superior frontal gyrus on both sides. Significant SI gradients were observed with a higher intensity in the archeocortex, intermediate intensity in the periarcheocortex and low intensity in the neocortex. Significant higher SI values in hippocampal and parahippocampal structures were detected in children up to 10 years of age. These differences mainly reflected differences in cortical structure and myelination state. Archeocortical structures especially showed significant age-related intensity progression suggesting ongoing organization and/or myelination until early adolescence. (orig.)

  2. Homayoun as a Persian Music Scale on Non-Musician’s Brain: an fMRI Study

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    Farzaneh Pouladi

    2011-10-01

    Full Text Available The aim of this study was to get to a neurological evaluation of one of the Persian music scales, Homayoun, on brain activation of non-musician subjects. We selected this scale because Homayoun is one of the main scales in Persian classical music which is similar to minor mode in western scales. This study was performed on 19 right handed subjects, Aging 22-31. Here some pices from Homayoun Dastgah are used in both rhythmic and non- rhythmic. The results of this study revealed the brain activities for each of rhythmic and non-rhythmic versions of Homayoun Dastgah. The activated regions for non-rhythmic Homayoun contained: right and left Subcallosal Cortex, left Medial Frontal cortex, left anterior Cingulate Gyrus, left Frontal Pole and for rhythmic Homayoun contained: left Precentral Gyrus, left Precuneous Cortex, left anterior Supramarginal, left Superior Parietal Lobule, left Postcentral Gyrus. Also, we acquired amygdala area in both pieces of music. Based on arousal effects of rhythm and Damasio's somatic marker hypothesis, non-rhythmic Homayoun activates regions related to emotion and thinking while activity of rhythmic Homayoun is related to areas of movement and motion.

  3. Psychotherapy as assisted homeostasis: activation of emotional processing mediated by the anterior cingulate cortex.

    Science.gov (United States)

    Corrigan, F M

    2004-01-01

    Although psychotherapy is successful in altering emotional distress, the biological mechanism by which it achieves this has not been the subject of intensive neurobiological investigation. Mindful processing of emotion has been proposed [Mindfulness-Based Cognitive Therapy for Depression, The Guilford Press, New York, 2002] to be a key factor in prevention of relapse in depressive illness and here that hypothesis is developed and extended to include other conditions in which emotion processing may be obstructed or dysregulated. Cognitive therapy, interpersonal psychotherapy, psycho-dynamic psychotherapy and dialectical behaviour therapy, each in a different way and with a distinct emphasis, encourage awareness of emotions and their associated cognitions and biographies, and their varying success may depend on the degree to which they achieve activation of internal healing processes. In eye movement desensitisation and reprocessing (EMDR), the selected target is formatted for endogenous processing which is facilitated and accelerated by eye movements or alternating bilateral auditory or tactile stimulation. The ability to sustain focussed attention on the affect and its visceral, cognitive and biographical components is postulated to activate a homeostatic process of distress resolution, seen most clearly in treatment of post-traumatic stress disorder (PTSD) with EMDR, in which resolution of distress can be intense and rapid while therapist input is non-directive, although supportive, empathic, and non-judgemental. Once the therapist has helped to frame the questions, the patient's brain will find the answers needed for the resolution of the distress and all the components of the traumatic event, whether visceral, cognitive, affective or interpersonal. The anterior cingulate cortex, especially the dorsal and rostral components, is suggested to be the key neurobiological substrate for the efficacious psychotherapeutic relief of distress, and relevant functional

  4. Axo-somatic synapses in the normal and X-irradiated dendate gyrus; factors affecting the density of afferent innervation

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    Lee, K.S. (Max-Planck-Institut fuer Psychiatrie, Muenchen (Germany, F.R.)); Gerbrandt, L. (Neuroscience Research Program, Boston, MA (USA)); Lynch, G. (California Univ., Irvine (USA))

    1982-10-07

    The density of synaptic input to the somata of dentate gyrus granule cells was examined utilizing quantitative electron microscopic techniques. In control (non-irradiated) material, greater numbers of axo-somatic synapses were observed in the superficial, earlier-generated cells as compared to the deep, later-generated cells. We further studied the X-irradiated dentate gyrus, in which the majority of granule cells were destroyed during postnatal genesis. The surviving cells displayed a density of innervation on their somata which exceeded that observed in either layer of the control material. These data are discussed in terms of the possible contribution of afferent-target cell interactions to the regulation of the density of synaptic innervation.

  5. The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo

    DEFF Research Database (Denmark)

    Dallérac, Glenn; Zerwas, Meike; Novikova, Tatiana

    2011-01-01

    The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have...... and maintenance of synaptic plasticity in the dentate gyrus (DG) in vivo. For this, we first assessed the effect of the FGL peptide on synaptic functions at perforant path-dentate gyrus synapses in the anesthetized rat. FGL, or its control inactive peptide, was injected locally 60 min before applying high......-frequency stimulation (HFS) to the medial perforant path. The results suggest that although FGL did not alter basal synaptic transmission, it facilitated both the induction and maintenance of LTP. Interestingly, FGL also modified the heterosynaptic plasticity observed at the neighboring lateral perforant path synapses...

  6. A Computational Model of Pattern Separation Efficiency in the Dentate Gyrus with Implications in Schizophrenia

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    Faramarz eFaghihi

    2015-03-01

    Full Text Available Information processing in the hippocampus begins by transferring spiking activity of the Entorhinal Cortex (EC into the Dentate Gyrus (DG. Activity pattern in the EC is separated by the DG such that it plays an important role in hippocampal functions including memory. The structural and physiological parameters of these neural networks enable the hippocampus to be efficient in encoding a large number of inputs that animals receive and process in their life time. The neural encoding capacity of the DG depends on its single neurons encoding and pattern separation efficiency. In this study, encoding by the DG is modelled such that single neurons and pattern separation efficiency are measured using simulations of different parameter values. For this purpose, a probabilistic model of single neurons efficiency is presented to study the role of structural and physiological parameters. Known neurons number of the EC and the DG is used to construct a neural network by electrophysiological features of neuron in the DG. Separated inputs as activated neurons in the EC with different firing probabilities are presented into the DG. For different connectivity rates between the EC and DG, pattern separation efficiency of the DG is measured. The results show that in the absence of feedback inhibition on the DG neurons, the DG demonstrates low separation efficiency and high firing frequency. Feedback inhibition can increase separation efficiency while resulting in very low single neuron’s encoding efficiency in the DG and very low firing frequency of neurons in the DG (sparse spiking. This work presents a mechanistic explanation for experimental observations in the hippocampus, in combination with theoretical measures. Moreover, the model predicts a critical role for impaired inhibitory neurons in schizophrenia where deficiency in pattern separation of the DG has been observed.

  7. DREADD in parvalbumin interneurons of the dentate gyrus modulates anxiety, social interaction and memory extinction.

    Science.gov (United States)

    Zou, D; Chen, L; Deng, D; Jiang, D; Dong, F; McSweeney, C; Zhou, Y; Liu, L; Chen, G; Wu, Y; Mao, Y

    2016-01-01

    Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.

  8. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

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    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  9. Inferior frontal gyrus preserves working memory and emotional learning under conditions of impaired noradrenergic signaling

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    Benjamin eBecker

    2013-12-01

    Full Text Available Compensation has been widely applied to explain neuroimaging findings in neuropsychiatric patients. Functional compensation is often invoked when patients display equal performance and increased neural activity in comparison to healthy controls. According to the compensatory hypothesis increased activity allows the brain to maintain cognitive performance despite underlying neuropathological changes. Due to methodological and pathology-related issues, however, the functional relevance of the increased activity and the specific brain regions involved in the compensatory response remain unclear. An experimental approach that allows a transient induction of compensatory responses in the healthy brain could help to overcome these issues. To this end we used the nonselective beta-blocker propranolol to pharmacologically induce sub-optimal noradrenergic signaling in healthy participants. In two independent fMRI experiments participants received either placebo or propranolol before they underwent a cognitive challenge (experiment 1: working memory; experiment 2: emotional learning: Pavlovian fear conditioning. In experiment 1 propranolol had no effects on working memory performance, but evoked stronger activity in the left inferior frontal gyrus (IFG. In experiment 2 propranolol produced no effects on emotional memory formation, but evoked stronger activity in the right IFG. The present finding that sub-optimal beta-adrenergic signaling did not disrupt performance and concomitantly increased IFG activity is consistent with, and extends, current perspectives on functional compensation. Together, our findings suggest that under conditions of impaired noradrenergic signaling, heightened activity in brain regions located within the cognitive control network, particularly the IFG, may reflect compensatory operations subserving the maintenance of behavioral performance.

  10. Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures

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    Oana eToader

    2013-08-01

    Full Text Available Neuronal circuit disturbances that lead to hyperexcitability in the cortico-hippocampal network are one of the landmarks of temporal lobe epilepsy. The dentate gyrus (DG network plays an important role in regulating the excitability of the entire hippocampus by filtering and integrating information received via the perforant path. Here, we investigated possible epileptogenic abnormalities in the function of the DG neuronal network in the Synapsin II (Syn II knockout mouse (Syn II-/-, a genetic mouse model of epilepsy. Syn II is a presynaptic protein whose deletion in mice reproducibly leads to generalized seizures starting at the age of two months. We made use of a high-resolution microelectrode array (4096 electrodes and patch-clamp recordings, and found that in acute hippocampal slices of young pre-symptomatic (3-6 weeks-old Syn II-/- mice excitatory synaptic output of the mossy fibers is reduced. Moreover, we showed that the main excitatory neurons present in the polymorphic layer of the DG, hilar mossy cells, display a reduced excitability. We also provide evidence of a predominantly inhibitory regulatory output from mossy cells to granule cells, through feed-forward inhibition, and show that the excitatory-inhibitory ratio is increased in both pre-symptomatic and symptomatic Syn II-/- mice. These results support the key role of the hilar mossy neurons in maintaining the normal excitability of the hippocampal network and show that the late epileptic phenotype of the Syn II-/- mice is preceded by neuronal circuitry dysfunctions. Our data provide new insights into the mechanisms of epileptogenesis in the Syn II-/- mice and open the possibility for early diagnosis and therapeutic interventions.

  11. Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats.

    Science.gov (United States)

    Huang, He; Liu, Cun-Ming; Sun, Jie; Hao, Ting; Xu, Chun-Mei; Wang, Dan; Wu, Yu-Qing

    2016-08-01

    Ketamine has been reported to cause neonatal neurotoxicity via a neuronal apoptosis mechanism; however, no in vivo research has reported whether ketamine could affect postnatal neurogenesis in the hippocampal dentate gyrus (DG). A growing number of experiments suggest that postnatal hippocampal neurogenesis is the foundation of maintaining normal hippocampus function into adulthood. Therefore, this study investigated the effect of ketamine on hippocampal neurogenesis. Male Sprague-Dawley rats were divided into two groups: the control group (equal volume of normal saline), and the ketamine-anesthesia group (40 mg/kg ketamine in four injections at 1 h intervals). The S-phase marker 5-bromodeoxyuridine (BrdU) was administered after ketamine exposure to postnatal day 7 (PND-7) rats, and the neurogenesis in the hippocampal DG was assessed using single- or double-immunofluorescence staining. The expression of GFAP in the hippocampal DG was measured by western blot analysis. Spatial reference memory was tested by Morris water maze at 2 months after PND-7 rats exposed to ketamine treatment. The present results showed that neonatal ketamine exposure significantly inhibited neural stem cell (NSC) proliferation, decreased astrocytic differentiation, and markedly enhanced neuronal differentiation. The disruptive effect of ketamine on the proliferation and differentiation of NSCs lasted at least 1 week and disappeared by 2 weeks after ketamine exposure. Moreover, the migration of newborn neurons in the granule cell layer and the growth of astrocytes in the hippocampal DG were inhibited by ketamine on PND-37 and PND-44. Finally, ketamine caused a deficit in hippocampal-dependent spatial reference memory tasks at 2 months old. Our results suggested that ketamine may interfere with hippocampal neurogenesis and long-term neurocognitive function in PND-7 rats. These findings may provide a new perspective to explain the adult neurocognitive dysfunction induced by neonatal

  12. Developmental hypothyroidism abolishes bilateral differences in sonic hedgehog gene control in the rat hippocampal dentate gyrus.

    Science.gov (United States)

    Tanaka, Takeshi; Wang, Liyun; Kimura, Masayuki; Abe, Hajime; Mizukami, Sayaka; Yoshida, Toshinori; Shibutani, Makoto

    2015-03-01

    Both developmental and adult-stage hypothyroidism disrupt rat hippocampal neurogenesis. We previously showed that exposing mouse offspring to manganese permanently disrupts hippocampal neurogenesis and abolishes the asymmetric distribution of cells expressing Mid1, a molecule regulated by sonic hedgehog (Shh) signaling. The present study examined the involvement of Shh signaling on the disruption of hippocampal neurogenesis in rats with hypothyroidism. Pregnant rats were treated with methimazole (MMI) at 0 or 200 ppm in the drinking water from gestation day 10-21 days after delivery (developmental hypothyroidism). Adult male rats were treated with MMI in the same manner from postnatal day (PND) 46 to PND 77 (adult-stage hypothyroidism). Developmental hypothyroidism reduced the number of Mid1(+) cells within the subgranular zone of the dentate gyrus of offspring on PND 21, and consequently abolished the normal asymmetric predominance of Mid1(+) cells on the right side through the adult stage. In control animals, Shh was expressed in a subpopulation of hilar neurons, showing asymmetric distribution with left side predominance on PND 21; however, this asymmetry did not continue through the adult stage. Developmental hypothyroidism increased Shh(+) neurons bilaterally and abolished the asymmetric distribution pattern on PND 21. Adult hypothyroidism also disrupted the asymmetric distribution of Mid1(+) cells but did not affect the distribution of Shh(+) hilar neurons. The results suggest that the hippocampal neurogenesis disruption seen in hypothyroidism involves changes in asymmetric Shh(+) neuron distribution in developmental hypothyroidism and altered Mid1 expression in both developmental and adult-stage hypothyroidism. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. The role of the ventral dentate gyrus in olfactory pattern separation.

    Science.gov (United States)

    Weeden, Christy S S; Hu, Nathan J; Ho, Liana U N; Kesner, Raymond P

    2014-05-01

    Dorsoventral lesion studies of the hippocampus have indicated that the dorsal axis of the hippocampus is important for spatial processing and the ventral axis of the hippocampus is important for olfactory learning and memory and anxiety. There is some evidence to suggest that the ventral CA3 and ventral CA1 conduct parallel processes for pattern completion and temporal processing, respectively. Studies have indicated that the dorsal dentate gyrus (DG) is importantly involved in processes reflecting underlying pattern separation activity for spatial information. However, the ventral DG is less understood. The current study investigated the less-understood role of the ventral DG in olfactory pattern separation. A series of odor stimuli that varied on only one level, number of carbon chains (methyl groups), was used in a matching-to-sample paradigm in order to investigate ventral DG involvement in working memory for similar and less similar odors. Rats with ventral DG lesions were impaired at delays of 60 sec, but not at delays of 15 sec. A memory-based pattern separation effect was observed performance was poorest with only one carbon chain separation between trial odors and was highest for trials with four separations. The present study indicates that the ventral DG plays an important role in olfactory learning and memory processes for highly similar odors. The results also indicate a role for the ventral DG in pattern separation for odor information, which may have further implications for parallel processing across the dorsoventral axis for the DG in spatial (dorsal) and olfactory (ventral) pattern separation. Copyright © 2014 Wiley Periodicals, Inc.

  14. A role of right middle frontal gyrus in reorienting of attention: a case study

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    Shruti eJapee

    2015-03-01

    Full Text Available The right middle fontal gyrus (MFG has been proposed to be a site of convergence of the dorsal and ventral attention networks, by serving as a circuit-breaker, to interrupt ongoing endogenous processes in the dorsal network, and reorienting a person’s attention to an exogenous stimulus. Here, we probed the contribution of the right MFG to both endogenous and exogenous attention by comparing performance on an orientation discrimination task of a patient with a right MFG resection and a group of healthy controls. On endogenously cued trials, participants were shown a central cue that predicted with 90% accuracy the location of a subsequent peri-threshold Gabor patch stimulus. On exogenously cued trials, a cue appeared briefly at one of two peripheral locations, followed by a variable inter-stimulus interval (ISI; range 0 to 700 ms and a Gabor patch in the same or opposite location as the cue. Behavioral data showed that for endogenous, and short ISI exogenous trials, valid cues facilitated faster responses compared to invalid cues, for both the patient and controls. However, at long ISIs, the patient exhibited difficulty in reverting back to top-down attentional control, once the facilitatory effect of the exogenous cue had dissipated. When explicitly cued during long ISIs to attend to both stimulus locations, the patient was able to re-engage successfully in top-down control. This result indicates that the right MFG may play an important role in reorienting attention from exogenous to endogenous control. Resting state fMRI data revealed that the right superior parietal lobule and right orbitofrontal cortex, showed significantly higher correlations with a left MFG seed region (a region tightly coupled with the resected region in controls in the patient relative to controls. We hypothesize that this paradoxical increase in cortical coupling represents a compensatory mechanism to offset the loss of function of the resected tissue in right

  15. Nitric oxide facilitates active avoidance learning via enhancement of glutamate levels in the hippocampal dentate gyrus.

    Science.gov (United States)

    Wang, Shi; Pan, De-Xi; Wang, Dan; Wan, Peng; Qiu, De-Lai; Jin, Qing-Hua

    2014-09-01

    The hippocampus is a key structure for learning and memory in mammals, and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. Despite a number of studies indicating that nitric oxide (NO) is involved in the formation and maintenance of LTP as a retrograde messenger, few studies have used neurotransmitter release as a visual indicator in awake animals to explore the role of NO in learning-dependent long-term enhancement of synaptic efficiency. Therefore, in the present study, the effects of l-NMMA (a NO synthase inhibitor) and SNP (a NO donor) on extracellular glutamate (Glu) concentrations and amplitudes of field excitatory postsynaptic potential (fEPSP) were measured in the hippocampal dentate gyrus (DG) region during the acquisition and extinction of active-avoidance behavior in freely-moving conscious rats. In the control group, the extracellular concentration of Glu in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to baseline levels following extinction training. In the experimental group, the change in Glu concentration was significantly reduced by local microinjection of l-NMMA, as was the acquisition of the active-avoidance behavior. In contrast, the change in Glu concentration was significantly enhanced by SNP, and the acquisition of the active-avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in extracellular Glu were accompanied by corresponding changes in fEPSP amplitude and active-avoidance behavior. Our results suggest that NO in the hippocampal DG facilitates active avoidance learning via enhancements of glutamate levels and synaptic efficiency in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Postsynaptic GABAB receptors enhance extrasynaptic GABAA receptor function in dentate gyrus granule cells.

    Science.gov (United States)

    Tao, Wucheng; Higgs, Matthew H; Spain, William J; Ransom, Christopher B

    2013-02-27

    Ambient GABA in the brain tonically activates extrasynaptic GABA(A) receptors, and activity-dependent changes in ambient GABA concentration can also activate GABA(B) receptors. To investigate an interaction between postsynaptic GABA(B) and GABA(A) receptors, we recorded GABA(A) currents elicited by exogenous GABA (10 μm) from dentate gyrus granule cells (DGGCs) in adult rat hippocampal slices. The GABA(B) receptor agonist baclofen (20 μm) enhanced GABA(A) currents. This enhancement was blocked by the GABA(B) receptor antagonist CGP 55845 and intracellular solutions containing the GTP analog GDP-β-s, indicating that baclofen was acting on postsynaptic GABA(B) receptors. Modulation of GABA(A) currents by postsynaptic GABA(B) receptors was not observed in CA1 pyramidal cells or layer 2/3 cortical pyramidal neurons. Baclofen reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but did not alter sIPSC amplitude or kinetics. Thus, GABA(A) receptors activated at synapses were not modulated by postsynaptic GABA(B) receptors. In contrast, tonic GABA currents and currents activated by the GABA(A) receptor δ subunit-selective agonist THIP (10 μm) were potentiated by baclofen. Our data indicate that postsynaptic GABA(B) receptors enhance the function of extrasynaptic GABA(A) receptors, including δ subunit-containing receptors that mediate tonic inhibition in DGGCs. The modulation of GABA(A) receptor function by postsynaptic GABA(B) receptors is a newly identified mechanism that will influence the inhibitory tone of DGGCs when GABA(B) and GABA(A) receptors are both activated.

  17. Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders

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    Yamasaki Nobuyuki

    2008-09-01

    Full Text Available Abstract Elucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here we report that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/- have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG. The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were significantly changed. Strikingly, among the 20 most downregulated genes, 5 had highly selective expression in the DG. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neurons in the DG was dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after electric footshock was almost completely and selectively abolished in the mutants. Statistical clustering of human post-mortem brains using 10 genes differentially-expressed in the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an "immature DG" in adulthood might induce alterations in behavior and

  18. Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

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    Sofia Baptista

    2014-09-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG. Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10 nM decreased DG stem cell self-renewal, while 1 nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase, which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10 nM did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10 nM decreased Sox2+/Sox2+ while increased Sox2−/Sox2− pairs of daughter cells. This effect relied on N-methyl-d-aspartate (NMDA signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10 μM. Moreover, METH (10 nM increased doublecortin (DCX protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers.

  19. Forced mastication increases survival of adult neural stem cells in the hippocampal dentate gyrus.

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    Akazawa, Yuki; Kitamura, Takamasa; Fujihara, Yuri; Yoshimura, Yoshitaka; Mitome, Masato; Hasegawa, Tomokazu

    2013-02-01

    In this study, we examined the effect of forced mastication on neurogenesis in the hippocampal dentate gyrus (DG) of adult mice. Six-week-old mice were subjected to either a hard or normal diet for 13 weeks. They received a daily injection of bromodeoxyuridine (BrdU) for 12 consecutive days beginning at 14 weeks of age. The number of BrdU-positive cells in the DG was counted 1 day after and 5 weeks after the final BrdU injection. The number of BrdU-positive cells 1 day after injection did not differ between the 2 diet groups. However, the number of BrdU-positive cells in the group fed the hard diet was significantly increased 5 weeks after BrdU injection compared to the group fed the normal diet. The results of the Morris water maze test showed that mice fed a hard diet required significantly less time to reach the platform than the control mice when tested at 10 days. Moreover, mice in the group fed the hard diet spent significantly more time in the former platform area than the group fed the normal diet, indicating that hard diet feeding improved spatial memory compared to normal diet feeding. Real-time PCR analysis showed that the expression of glutamate receptor 1 mRNA was significantly increased in the group fed the hard diet compared with the group fed the normal diet. These results suggest that mastication increases the survival of adult neural stem cells in the hippocampal DG.

  20. A role of right middle frontal gyrus in reorienting of attention: a case study.

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    Japee, Shruti; Holiday, Kelsey; Satyshur, Maureen D; Mukai, Ikuko; Ungerleider, Leslie G

    2015-01-01

    The right middle fontal gyrus (MFG) has been proposed to be a site of convergence of the dorsal and ventral attention networks, by serving as a circuit-breaker to interrupt ongoing endogenous attentional processes in the dorsal network and reorient attention to an exogenous stimulus. Here, we probed the contribution of the right MFG to both endogenous and exogenous attention by comparing performance on an orientation discrimination task of a patient with a right MFG resection and a group of healthy controls. On endogenously cued trials, participants were shown a central cue that predicted with 90% accuracy the location of a subsequent peri-threshold Gabor patch stimulus. On exogenously cued trials, a cue appeared briefly at one of two peripheral locations, followed by a variable inter-stimulus interval (ISI; range 0-700 ms) and a Gabor patch in the same or opposite location as the cue. Behavioral data showed that for endogenous, and short ISI exogenous trials, valid cues facilitated responses compared to invalid cues, for both the patient and controls. However, at long ISIs, the patient exhibited difficulty in reverting to top-down attentional control, once the facilitatory effect of the exogenous cue had dissipated. When explicitly cued during long ISIs to attend to both stimulus locations, the patient was able to engage successfully in top-down control. This result indicates that the right MFG may play an important role in reorienting attention from exogenous to endogenous attentional control. Resting state fMRI data revealed that the right superior parietal lobule and right orbitofrontal cortex, showed significantly higher correlations with a left MFG seed region (a region tightly coupled with the right MFG in controls) in the patient relative to controls. We hypothesize that this paradoxical increase in cortical coupling represents a compensatory mechanism in the patient to offset the loss of function of the resected tissue in right prefrontal cortex.

  1. R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity.

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    Bharanidharan Shanmugasundaram

    Full Text Available Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP. Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT, and its phosphorylated form (ph-DAT in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes.

  2. A case of foreign accent syndrome without aphasia caused by a lesion of the left precentral gyrus.

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    Takayama, Y; Sugishita, M; Kido, T; Ogawa, M; Akiguchi, I

    1993-07-01

    We report a case of foreign accent syndrome (FAS) without aphasia. The patient was a right-handed, 44-year-old woman, a native Japanese. Disposition and inversion of pitch accents and appearance of unnecessary stress accents made her speech sound foreign, like that of a Korean. MRI demonstrated an infarction in the middle fifth of the posterior lateral aspect of the left precentral gyrus. Limited motor cortex damage causes FAS without dysarthria, apraxia of speech, or aphasia.

  3. Inhibition of PI3K-Akt Signaling Blocks Exercise-Mediated Enhancement of Adult Neurogenesis and Synaptic Plasticity in the Dentate Gyrus

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    Bruel-Jungerman, Elodie; Veyrac, Alexandra; Dufour, Franck; Horwood, Jennifer; Laroche, Serge; Davis, Sabrina

    2009-01-01

    Background Physical exercise has been shown to increase adult neurogenesis in the dentate gyrus and enhances synaptic plasticity. The antiapoptotic kinase, Akt has also been shown to be phosphorylated following voluntary exercise; however, it remains unknown whether the PI3K-Akt signaling pathway is involved in exercise-induced neurogenesis and the associated facilitation of synaptic plasticity in the dentate gyrus. Methodology/Principal Findings To gain insight into the potential role of this signaling pathway in exercise-induced neurogenesis and LTP in the dentate gyrus rats were infused with the PI3K inhibitor, LY294002 or vehicle control solution (icv) via osmotic minipumps and exercised in a running wheel for 10 days. Newborn cells in the dentate gyrus were date-labelled with BrdU on the last 3 days of exercise. Then, they were either returned to the home cage for 2 weeks to assess exercise-induced LTP and neurogenesis in the dentate gyrus, or were killed on the last day of exercise to assess proliferation and activation of the PI3K-Akt cascade using western blotting. Conclusions/Significance Exercise increases cell proliferation and promotes survival of adult-born neurons in the dentate gyrus. Immediately after exercise, we found that Akt and three downstream targets, BAD, GSK3β and FOXO1 were activated. LY294002 blocked exercise-induced phosphorylation of Akt and downstream target proteins. This had no effect on exercise-induced cell proliferation, but it abolished most of the beneficial effect of exercise on the survival of newly generated dentate gyrus neurons and prevented exercise-induced increase in dentate gyrus LTP. These results suggest that activation of the PI3 kinase-Akt signaling pathway plays a significant role via an antiapoptotic function in promoting survival of newly formed granule cells generated during exercise and the associated increase in synaptic plasticity in the dentate gyrus. PMID:19936256

  4. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

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    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  5. Decrease in temporal gyrus gray matter volume in first-episode, early onset schizophrenia: an MRI study.

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    Jinsong Tang

    Full Text Available BACKGROUND: Loss of gray matter has been previously found in early-onset schizophrenic patients. However, there are no consistent findings between studies due to different methods used to measure grey matter volume/density and influences of confounding factors. METHODS: The volume of gray matter (GM was measured in 29 first episode early-onset schizophrenia (EOS and 34 well-matched healthy controls by using voxel-based morphometry (VBM. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS. The correlations between the GM volume and PANSS scores, age of psychosis onset, duration of psychosis, and chlorpromazine (CPZ equivalent value were investigated. RESULTS: Relative to healthy subjects, the patients with first episode EOS showed significantly lower GM volume in the left middle and superior temporal gyrus. The loss of GM volume negatively correlated with PANSS-positive symptoms (p = 0.002, but not with PANSS-negative symptoms, PANSS-general psychopathology, and PANSS-total score. No significant correlation was found between GM volume and age of psychosis onset, duration of psychosis, and CPZ equivalent value. CONCLUSION: Patients with first episode EOS have evidence of reduced GM in the left middle and superior temporal gyrus. Structural abnormalities in the left middle and superior temporal gyrus may contribute to the pathophysiology of schizophrenia.

  6. Fiction feelings in Harry Potter: haemodynamic response in the mid-cingulate cortex correlates with immersive reading experience.

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    Hsu, Chun-Ting; Conrad, Markus; Jacobs, Arthur M

    2014-12-03

    Immersion in reading, described as a feeling of 'getting lost in a book', is a ubiquitous phenomenon widely appreciated by readers. However, it has been largely ignored in cognitive neuroscience. According to the fiction feeling hypothesis, narratives with emotional contents invite readers more to be empathic with the protagonists and thus engage the affective empathy network of the brain, the anterior insula and mid-cingulate cortex, than do stories with neutral contents. To test the hypothesis, we presented participants with text passages from the Harry Potter series in a functional MRI experiment and collected post-hoc immersion ratings, comparing the neural correlates of passage mean immersion ratings when reading fear-inducing versus neutral contents. Results for the conjunction contrast of baseline brain activity of reading irrespective of emotional content against baseline were in line with previous studies on text comprehension. In line with the fiction feeling hypothesis, immersion ratings were significantly higher for fear-inducing than for neutral passages, and activity in the mid-cingulate cortex correlated more strongly with immersion ratings of fear-inducing than of neutral passages. Descriptions of protagonists' pain or personal distress featured in the fear-inducing passages apparently caused increasing involvement of the core structure of pain and affective empathy the more readers immersed in the text. The predominant locus of effects in the mid-cingulate cortex seems to reflect that the immersive experience was particularly facilitated by the motor component of affective empathy for our stimuli from the Harry Potter series featuring particularly vivid descriptions of the behavioural aspects of emotion.

  7. The regional neuronal activity in left posterior middle temporal gyrus is correlated with the severity of chronic aphasia

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    Li J

    2017-07-01

    Full Text Available Jianlin Li,1,* Dunren Du,2,* Wei Gao,1 Xichun Sun,3 Haizhu Xie,1 Gang Zhang,1 Jian Li,1 Honglun Li,1 Kefeng Li4 1Department of Radiology, Yantai Yuhuangding Hospital, 2Department of Radiology, Yantai Laishan Branch Hospital of Yuhuangding Hospital, Medical College of Qingdao University, 3Department of Radiology, Yantai Hospital of Traditional Chinese Medicine, Yantai, China; 4School of Medicine, University of California, San Diego, CA, USA *These authors contributed equally to this work Background: Aphasia is one of the most disabling cognitive deficits affecting >2 million people in the USA. The neuroimaging characteristics of chronic aphasic patients (>6 months post onset remain largely unknown.Objective: The objective of this study was to investigate the regional signal changes of spontaneous neuronal activity of brain and the inter-regional connectivity in chronic aphasia. Materials and methods: Resting-state blood oxygenation level-dependent functional magnetic resonance imaging (fMRI was used to obtain fMRI data from 17 chronic aphasic patients and 20 healthy control subjects in a Siemens Verio 3.0T MR Scanner. The amplitude of low-frequency fluctuation (ALFF was determined, which directly reflects the regional neuronal activity. The functional connectivity (FC of fMRI was assessed using a seed voxel linear correlation approach. The severity of aphasia was evaluated by aphasia quotient (AQ scores obtained from Western Aphasia Battery test.Results: Compared with normal subjects, aphasic patients showed decreased ALFF values in the regions of left posterior middle temporal gyrus (PMTG, left medial prefrontal gyrus, and right cerebellum. The ALFF values in left PMTG showed strong positive correlation with the AQ score (coefficient r=0.79, P<0.05. There was a positive FC in chronic aphasia between left PMTG and left inferior temporal gyrus (BA20, fusiform gyrus (BA37, and inferior frontal gyrus (BA47\\45\\44. Conclusion: Left PMTG might play

  8. Cingulate neglect in humans: disruption of contralesional reward learning in right brain damage.

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    Lecce, Francesca; Rotondaro, Francesca; Bonnì, Sonia; Carlesimo, Augusto; Thiebaut de Schotten, Michel; Tomaiuolo, Francesco; Doricchi, Fabrizio

    2015-01-01

    Motivational valence plays a key role in orienting spatial attention. Nonetheless, clinical documentation and understanding of motivationally based deficits of spatial orienting in the human is limited. Here in a series of one group-study and two single-case studies, we have examined right brain damaged patients (RBD) with and without left spatial neglect in a spatial reward-learning task, in which the motivational valence of the left contralesional and the right ipsilesional space was contrasted. In each trial two visual boxes were presented, one to the left and one to the right of central fixation. In one session monetary rewards were released more frequently in the box on the left side (75% of trials) whereas in another session they were released more frequently on the right side. In each trial patients were required to: 1) point to each one of the two boxes; 2) choose one of the boxes for obtaining monetary reward; 3) report explicitly the position of reward and whether this position matched or not the original choice. Despite defective spontaneous allocation of attention toward the contralesional space, RBD patients with left spatial neglect showed preserved contralesional reward learning, i.e., comparable to ipsilesional learning and to reward learning displayed by patients without neglect. A notable exception in the group of neglect patients was L.R., who showed no sign of contralesional reward learning in a series of 120 consecutive trials despite being able of reaching learning criterion in only 20 trials in the ipsilesional space. L.R. suffered a cortical-subcortical brain damage affecting the anterior components of the parietal-frontal attentional network and, compared with all other neglect and non-neglect patients, had additional lesion involvement of the medial anterior cingulate cortex (ACC) and of the adjacent sectors of the corpus callosum. In contrast to his lateralized motivational learning deficit, L.R. had no lateral bias in the early phases of

  9. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease.

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    José J Rodríguez

    Full Text Available It has become generally accepted that new neurones are added and integrated mainly in two areas of the mammalian CNS, the subventricular zone and the subgranular zone (SGZ of the dentate gyrus (DG of the hippocampus, which is of central importance in learning and memory. The newly generated cells display neuronal morphology, are able to generate action potentials and receive functional synaptic inputs, i.e. their properties are similar to those found in mature neurones. Alzheimer's disease (AD is the primary and widespread cause of dementia and is an age-related, progressive and irreversible neurodegenerative disease that deteriorates cognitive functions. Here, we have used male and female triple transgenic mice (3xTg-AD harbouring three mutant genes (beta-amyloid precursor protein, presenilin-1 and tau and their respective non-transgenic (non-Tg controls at 2, 3, 4, 6, 9 and 12 months of age to establish the link between AD and neurogenesis. Using immunohistochemistry we determined the area density of proliferating cells within the SGZ of the DG, measured by the presence of phosphorylated Histone H3 (HH3, and their possible co-localisation with GFAP to exclude a glial phenotype. Less than 1% of the HH3 labeled cells co-localised with GFAP. Both non-Tg and 3xTg-AD showed an age-dependent decrease in neurogenesis. However, male 3xTg-AD mice demonstrated a further reduction in the production of new neurones from 9 months of age (73% decrease and a complete depletion at 12 months, when compared to controls. In addition, female 3xTg-AD mice showed an earlier but equivalent decrease in neurogenesis at 4 months (reduction of 63% with an almost inexistent rate at 12 months (88% decrease compared to controls. This reduction in neurogenesis was directly associated with the presence of beta-amyloid plaques and an increase in the number of beta-amyloid containing neurones in the hippocampus; which in the case of 3xgTg females was directly correlated. These

  10. Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome.

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    Morgan, V; Pickens, D; Gautam, S; Kessler, R; Mertz, H

    2005-05-01

    Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

  11. Improved social interaction and increased anterior cingulate metabolism after group reminiscence with reality orientation approach for vascular dementia.

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    Akanuma, Kyoko; Meguro, Kenichi; Meguro, Mitsue; Sasaki, Eriko; Chiba, Kentaro; Ishii, Hiroshi; Tanaka, Naofumi

    2011-06-30

    A group reminiscence approach (GRA) with reality orientation (RO) is widely used as a psychosocial intervention for dementia. Since clinical effectiveness was reported for the intervention, interest has been directed toward areas of the neuronal network that might be being stimulated. We hypothesized that the frontal lobe associated with social interaction was being stimulated. To test this hypothesis, we studied 24 patients with vascular dementia. In addition to conventional care, a 1-h session of GRA with RO was provided once a week for 3 months in the GRA-RO arm (n=12). Only supportive care was provided in the control arm (n=12). Before and after the interventions, cognitive function, depressive state, and social activities were assessed. Since glucose metabolism is associated with brain function, cerebral glucose metabolism was measured by positron emission tomography (PET). Regarding behavioral improvement, 10 patients in the GRA-RO arm showed improvement compared with only two patients in the control arm, a significant difference. PET demonstrated that metabolism in the anterior cingulate was increased in the GRA-RO arm, whereas no significant changes were observed in the control arm. These results suggest that GRA-RO stimulates the anterior cingulate and has a positive effect on social interaction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.

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    Soeiro-de-Souza, Márcio Gerhardt; Pastorello, Bruno F; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A; Garcia Otaduy, Maria Concepción

    2016-08-01

    Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm(3)) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  13. Anterior cingulate cortico-hippocampal dysconnectivity in unaffected relatives of schizophrenia patients: a stochastic dynamic causal modeling study

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    Yi-Bin Xi

    2016-07-01

    Full Text Available Familial risk plays a significant role in the etiology of schizophrenia (SZ. Many studies using neuroimaging have demonstrated structural and functional alterations in relatives of SZ patients, with significant results found in diverse brain regions involving the anterior cingulate cortex (ACC, caudate, dorsolateral prefrontal cortex (DLPFC, and hippocampus. This study investigated whether unaffected relatives of first episode SZ differ from healthy controls (HCs in effective connectivity measures among these regions. Forty-six unaffected first-degree relatives of first episode SZ patients — according to the DSM-IV — were studied. Fifty HCs were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI. We used stochastic dynamic causal modeling (sDCM to estimate the directed connections between the left ACC, right ACC, left caudate, right caudate, left DLPFC, left hippocampus, and right hippocampus. We used Bayesian parameter averaging (BPA to characterize the differences. The BPA results showed hyperconnectivity from the left ACC to right hippocampus and hypoconnectivity from the right ACC to right hippocampus in SZ relatives compared to HCs. The pattern of anterior cingulate cortico-hippocampal connectivity in SZ relatives may be a familial feature of SZ risk, appearing to reflect familial susceptibility for SZ.

  14. Higher language ability is related to angular gyrus activation increase during semantic processing, independent of sentence incongruency

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    Helene eVan Ettinger-Veenstra

    2016-03-01

    Full Text Available This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task - which tapped language comprehension and inference, and modulated sentence congruency - employing functional magnetic resonance imaging. We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, a significant increase of activation in the inferior frontal gyrus bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing is opposed to what the neural efficiency hypothesis would predict. We can conclude that there is no evidence found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

  15. Lithium Promotes Neuronal Repair and Ameliorates Depression-Like Behavior following Trimethyltin-Induced Neuronal Loss in the Dentate Gyrus

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    Yoneyama, Masanori; Shiba, Tatsuo; Hasebe, Shigeru; Umeda, Kasumi; Yamaguchi, Taro; Ogita, Kiyokazu

    2014-01-01

    Lithium, a mood stabilizer, is known to ameliorate the stress-induced decrease in hippocampal neurogenesis seen in animal models of stress-related disorders. However, it is unclear whether lithium has beneficial effect on neuronal repair following neuronal damage in neuronal degenerative diseases. Here, we evaluated the effect of in vivo treatment with lithium on the hippocampal neuronal repair in a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampal dentate gyrus (such mice referred to as “impaired animals”) [Ogita et al. (2005) J Neurosci Res 82: 609–621]. The impaired animals had a dramatically increased number of 5-bromo-2′-deoxyuridine (BrdU)-incorporating cells in their dentate gyrus at the initial time window (days 3 to 5 post-TMT treatment) of the self-repair stage. A single treatment with lithium produced no significant change in the number of BrdU-incorporating cells in the dentate granule cell layer and subgranular zone on day 3 post-TMT treatment. On day 5 post-TMT treatment, however, BrdU-incorporating cells were significantly increased in number by lithium treatment for 3 days. Most interestingly, chronic treatment (15 days) with lithium increased the number of BrdU-incorporating cells positive for NeuN or doublecortin in the dentate granule cell layer of the impaired animals, but not in that of naïve animals. The results of a forced swimming test revealed that the chronic treatment with lithium improved the depression-like behavior seen in the impaired animals. Taken together, our data suggest that lithium had a beneficial effect on neuronal repair following neuronal loss in the dentate gyrus through promoted proliferation and survival/neuronal differentiation of neural stem/progenitor cells in the subgranular zone. PMID:24504050

  16. Specialization of the left supramarginal gyrus for hand-independent praxis representation is not related to hand dominance

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    Króliczak, Gregory; Piper, Brian J.; Frey, Scott H.

    2016-01-01

    Data from focal brain injury and functional neuroimaging studies implicate a distributed network of parieto-fronto-temporal areas in the human left cerebral hemisphere as playing distinct roles in the representation of meaningful actions (praxis). Because these data come primarily from right-handed individuals, the relationship between left cerebral specialization for praxis representation and hand dominance remains unclear. We used functional magnetic resonance imaging (fMRI) to evaluate the hypothesis that strongly left-handed (right hemisphere motor dominant) adults also exhibit this left cerebral specialization. Participants planned familiar actions for subsequent performance with the left or right hand in response to transitive (e.g., “pounding”) or intransitive (e.g. “waving”) action words. In linguistic control trials, cues denoted non-physical actions (e.g., “believing”). Action planning was associated with significant, exclusively left-lateralized and extensive increases of activity in the supramarginal gyrus (SMg), and more focal modulations in the left caudal middle temporal gyrus (cMTg). This activity was hand- and gesture-independent, i.e., unaffected by the hand involved in subsequent action performance, and the type of gesture (i.e., transitive or intransitive). Compared directly with right-handers, left-handers exhibited greater involvement of the right angular gyrus (ANg) and dorsal premotor cortex (dPMC), which is indicative of a less asymmetric functional architecture for praxis representation. We therefore conclude that the organization of mechanisms involved in planning familiar actions is influenced by one’s motor dominance. However, independent of hand dominance, the left SMg and cMTg are specialized for ideomotor transformations—the integration of conceptual knowledge and motor representations into meaningful actions. These findings support the view that higher-order praxis representation and lower-level motor dominance rely

  17. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus.

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    Andrew Collins

    Full Text Available We have shown previously that exercise benefits stress resistance and stress coping capabilities. Furthermore, we reported recently that epigenetic changes related to gene transcription are involved in memory formation of stressful events. In view of the enhanced coping capabilities in exercised subjects we investigated epigenetic, gene expression and behavioral changes in 4-weeks voluntarily exercised rats.Exercised and control rats coped differently when exposed to a novel environment. Whereas the control rats explored the new cage for the complete 30-min period, exercised animals only did so during the first 15 min after which they returned to sleeping or resting behavior. Both groups of animals showed similar behavioral responses in the initial forced swim session. When re-tested 24 h later however the exercised rats showed significantly more immobility behavior and less struggling and swimming. If rats were killed at 2 h after novelty or the initial swim test, i.e. at the peak of histone H3 phospho-acetylation and c-Fos induction, then the exercised rats showed a significantly higher number of dentate granule neurons expressing the histone modifications and immediate-early gene induction.Thus, irrespective of the behavioral response in the novel cage or initial forced swim session, the impact of the event at the dentate gyrus level was greater in exercised rats than in control animals. Furthermore, in view of our concept that the neuronal response in the dentate gyrus after forced swimming is involved in memory formation of the stressful event, the observations in exercised rats of enhanced neuronal responses as well as higher immobility responses in the re-test are consistent with the reportedly improved cognitive performance in these animals. Thus, improved stress coping in exercised subjects seems to involve enhanced cognitive capabilities possibly resulting from distinct epigenetic mechanisms in dentate gyrus neurons.

  18. Lesions of entorhinal cortex produce a calpain-mediated degradation of brain spectrin in dentate gyrus. I. Biochemical studies.

    Science.gov (United States)

    Seubert, P; Ivy, G; Larson, J; Lee, J; Shahi, K; Baudry, M; Lynch, G

    1988-09-06

    Lesions of the rat entorhinal cortex cause extensive synaptic restructuring and perturbation of calcium regulation in the dentate gyrus of hippocampus. Calpain is a calcium-activated protease which has been implicated in degenerative phenomena in muscles and in peripheral nerves. In addition, calpain degrades several major structural neuronal proteins and has been proposed to play a critical role in the morphological changes observed following deafferentation. In this report we present evidence that lesions of the entorhinal cortex produce a marked increase in the breakdown of brain spectrin, a substrate for calpain, in the dentate gyrus. Two lines of evidence indicate that this effect is due to calpain activation: (i) the spectrin breakdown products observed following the lesion are indistinguishable from calpain-generated spectrin fragments in vitro; and (ii) their appearance can be reduced by prior intraventricular in fusion of leupeptin, a calpain inhibitor. Levels of spectrin breakdown products are increased as early as 4 h post-lesion, reach maximal values at 2 days, and remain above normal to some degree for at least 27 days. In addition, a small but significant increase in spectrin proteolysis is also observed in the hippocampus contralateral to the lesioned side in the first week postlesion. At 2 days postlesion the total spectrin immunoreactivity (native polypeptide plus breakdown products) increases by 40%, suggesting that denervation of the dentate gyrus produces not only an increased rate of spectrin degradation but also an increased rate of spectrin synthesis. These results indicate that calpain activation and spectrin degradation are early biochemical events following deafferentation and might well participate in the remodelling of postsynaptic structures. Finally, the magnitude of the observed effects as well as the stable nature of the breakdown products provide a sensitive assay for neuronal pathology.

  19. Gene expression profiling of the hippocampal dentate gyrus in an adult toxicity study captures a variety of neurodevelopmental dysfunctions in rat models of hypothyroidism.

    Science.gov (United States)

    Shiraki, Ayako; Saito, Fumiyo; Akane, Hirotoshi; Akahori, Yumi; Imatanaka, Nobuya; Itahashi, Megu; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    We previously found that developmental hypothyroidism changed the expression of genes in the rat hippocampal dentate gyrus, a brain region where adult neurogenesis is known to occur. In the present study, we performed brain region-specific global gene expression profiling in an adult rat hypothyroidism model to see if it reflected the developmental neurotoxicity we saw in the developmental hypothyroidism model. Starting when male rats were 5 weeks old, we administered 6-propyl-2-thiouracil at a doses of 0, 0.1 and 10 mg kg(-1) body weight by gavage for 28 days. We selected four brain regions to represent both cerebral and cerebellar tissues: hippocampal dentate gyrus, cerebral cortex, corpus callosum and cerebellar vermis. We observed significant alterations in the expression of genes related to neural development (Eph family genes and Robo3) in the cerebral cortex and hippocampal dentate gyrus and in the expression of genes related to myelination (Plp1 and Mbp) in the hippocampal dentate gyrus. We observed only minor changes in the expression of these genes in the corpus callosum and cerebellar vermis. We used real-time reverse-transcription polymerase chain reaction to confirm Chrdl1, Hes5, Mbp, Plp1, Slit1, Robo3 and the Eph family transcript expression changes. The most significant changes in gene expression were found in the dentate gyrus. Considering that the gene expression profile of the adult dentate gyrus closely related to neurogenesis, 28-day toxicity studies looking at gene expression changes in adult hippocampal dentate gyrus may also detect possible developmental neurotoxic effects. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Dentate gyrus-cornu ammonis (CA) 4 volume is decreased and associated with depressive episodes and lipid peroxidation in bipolar II disorder: Longitudinal and cross-sectional analyses.

    Science.gov (United States)

    Elvsåshagen, Torbjørn; Zuzarte, Pedro; Westlye, Lars T; Bøen, Erlend; Josefsen, Dag; Boye, Birgitte; Hol, Per K; Malt, Ulrik F; Young, L Trevor; Andreazza, Ana C

    2016-12-01

    Reduced dentate gyrus volume and increased oxidative stress have emerged as potential pathophysiological mechanisms in bipolar disorder. However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus-cornu ammonis (CA) 4 volume longitudinally in patients with bipolar II disorder (BD-II) and healthy controls and investigated whether BD-II is associated with elevated peripheral levels of oxidative stress. We acquired high-resolution structural 3T-magnetic resonance imaging (MRI) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with BD-II (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4 years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4-hydroxy-2-nonenal [4-HNE] and lipid hydroperoxides [LPH]). First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus-CA4 volume. Second, we found a decreased left dentate gyrus-CA4 volume in patients and that a larger number of depressive episodes between T1 and T2 predicted greater volume decline. Finally, we showed that 4-HNE was elevated in BD-II and that 4-HNE was negatively associated with left and right dentate gyrus-CA4 volumes in patients. These results are consistent with a role for the dentate gyrus in the pathophysiology of bipolar disorder and suggest that depressive episodes and elevated oxidative stress might contribute to hippocampal volume decreases. In addition, these findings provide further support for the hypothesis that peripheral lipid peroxidation markers may reflect brain alterations in bipolar disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Sleepwalking episodes are preceded by arousal-related activation in the cingulate motor area: EEG current density imaging.

    Science.gov (United States)

    Januszko, Piotr; Niemcewicz, Szymon; Gajda, Tomasz; Wołyńczyk-Gmaj, Dorota; Piotrowska, Anna Justyna; Gmaj, Bartłomiej; Piotrowski, Tadeusz; Szelenberger, Waldemar

    2016-01-01

    To investigate local arousal fluctuations in adults who received ICSD-2 diagnosis of somnambulism. EEG neuroimaging (eLORETA) was utilized to compare current density distribution for 4s epochs immediately preceding sleepwalking episode (from -4.0 s to 0 s) to the distribution during earlier 4s epochs (from -8.0 s to -4.0 s) in 20 EEG segments from 15 patients. Comparisons between eLORETA images revealed significant (t>4.52; psleepwalking, with greater current density within beta 3 frequency range (24-30 Hz) in Brodmann areas 33 and 24. Sleepwalking motor events are associated with arousal-related activation of cingulate motor area. These results support the notion of blurred boundaries between wakefulness and NREM sleep in sleepwalking. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Goal-directed selective attention and response competition monitoring: evidence from unilateral parietal and anterior cingulate lesions.

    Science.gov (United States)

    Danckert, J; Maruff, P; Ymer, C; Kinsella, G; Yucel, M; de Graaff, S; Currie, J

    2000-01-01

    Competing visual stimuli lead to slower responses to targets. This response competition must be resolved before correct responses are executed. Neuroimaging suggests that response competition monitoring may be subserved by an integrated neural network including the anterior cingulate cortex (ACC). In this study, 1 patient with a parietal lesion (Patient J.S.) and 1 with an ACC lesion (Patient G.M.) were presented with 2 flanker tasks; 1 required verbal identification of color targets, and the other required an opposite response to targets (e.g., see red and say "green"); a control group was also tested. For controls, perceptually incongruent flankers interfered with the ability to inhibit prepotent responses to targets. Patient J.S. performed in a similar manner, even when flankers appeared in the neglected field. Patient G.M. demonstrated reduced interference effects for contralesional flankers. Results are discussed in terms of goal-directed selective attention and response competition monitoring.

  3. Fabrication and characterization of a novel microparticle with gyrus-patterned surface and growth factor delivery for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Liang Tang [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Jin Yan, E-mail: yanjin@fmmu.edu.cn [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)

    2009-05-05

    Microparticles can serve as substrates for cell amplification and deliver the expanded cells to the site of the defect. It was hypothesized that a novel microparticle combined of sustained and localized delivery of proliferative growth factors and gyrus-patterned surface would influence the cell behaviours of adherence and expansion on the microparticle in the present study. To test the hypothesis, gelatin particles with diameter ranging from 280 to 350 {mu}m were fabricated and were modified by cryogenic freeze-drying treatment and basic fibroblast growth factor (bFGF) incorporation. The results of in vitro chondrocyte culture illustrated that cells could proliferate more obviously on the microparticles with bFGF addition, but no correlation between attachment rate and bFGF was observed. On the other hand, microparticles with gyrus-patterned surface demonstrated the highest cell attachment rate and higher rate of cell growth, in particular on bFGF combined ones. It seems to be a promising candidate as a chondrocyte microparticle and could be the potential application in cartilage tissue engineering.

  4. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Directory of Open Access Journals (Sweden)

    Orli Yarom

    2008-01-01

    Full Text Available Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

  5. A Double Dissociation between Anterior and Posterior Superior Temporal Gyrus for Processing Audiovisual Speech Demonstrated by Electrocorticography.

    Science.gov (United States)

    Ozker, Muge; Schepers, Inga M; Magnotti, John F; Yoshor, Daniel; Beauchamp, Michael S

    2017-06-01

    Human speech can be comprehended using only auditory information from the talker's voice. However, comprehension is improved if the talker's face is visible, especially if the auditory information is degraded as occurs in noisy environments or with hearing loss. We explored the neural substrates of audiovisual speech perception using electrocorticography, direct recording of neural activity using electrodes implanted on the cortical surface. We observed a double dissociation in the responses to audiovisual speech with clear and noisy auditory component within the superior temporal gyrus (STG), a region long known to be important for speech perception. Anterior STG showed greater neural activity to audiovisual speech with clear auditory component, whereas posterior STG showed similar or greater neural activity to audiovisual speech in which the speech was replaced with speech-like noise. A distinct border between the two response patterns was observed, demarcated by a landmark corresponding to the posterior margin of Heschl's gyrus. To further investigate the computational roles of both regions, we considered Bayesian models of multisensory integration, which predict that combining the independent sources of information available from different modalities should reduce variability in the neural responses. We tested this prediction by measuring the variability of the neural responses to single audiovisual words. Posterior STG showed smaller variability than anterior STG during presentation of audiovisual speech with noisy auditory component. Taken together, these results suggest that posterior STG but not anterior STG is important for multisensory integration of noisy auditory and visual speech.

  6. The effect of Urtica dioica extract on the number of astrocytes in the dentate gyrus of diabetic rats.

    Science.gov (United States)

    Jahanshahi, M; Golalipour, M J; Afshar, M

    2009-05-01

    Diabetes mellitus is associated with cerebral alterations in both human and animal models of the disease. These alterations include abnormal expression of hypothalamic neuropeptides and hippocampal astrogliosis. Urtica dioica (Nettle) is among several species listed for their use against diabetes in folk medicine. The aim of this study was the evaluation of the astrocyte number in the dentate gyrus of diabetic rats after treatment with nettle. A total of 21 male albino Wistar rats were used in the present study. The animals were divided into three groups: control, nettle-untreated diabetic, and nettle treated diabetic. Hyperglycaemia was induced by streptozotocin (80 mg/kg) in the animals of the diabetic and treatment groups. One week after injection of the streptozotocin, the animals in the treatment group received a hydroalcoholic extract of Urtica dioica (100 mg/kg/day) for 4 weeks intraperitoneally. After a 5-week survival period, all the rats were sacrificed and coronal sections were taken from the dorsal hippocampal formation of the right cerebral hemispheres. The area densities of the astrocytes were measured and compared between the three groups (p dioica extract helped compensate for astrocytes in the treatment rats dentate gyrus in comparison with diabetic rats.

  7. Theta and beta oscillatory dynamics in the dentate gyrus reveal a shift in network processing state during cue encounters

    Directory of Open Access Journals (Sweden)

    Lara Maria Rangel

    2015-07-01

    Full Text Available The hippocampus is an important structure for learning and memory processes, and has strong rhythmic activity. Although a large amount of research has been dedicated towards understanding the rhythmic activity in the hippocampus during exploratory behaviors, specifically in the theta (5-10 Hz frequency range, few studies have examined the temporal interplay of theta and other frequencies during the presentation of meaningful cues. We obtained in vivo electrophysiological recordings of local field potentials (LFP in the dentate gyrus (DG of the hippocampus as rats performed three different associative learning tasks. In each task, cue presentations elicited pronounced decrements in theta amplitude in conjunction with increases in beta (15-30Hz amplitude. These changes were often transient but were sustained from the onset of cue encounters until the occurrence of a reward outcome. This oscillatory profile shifted in time to precede cue encounters over the course of the session, and was not present during similar behavior in the absence of task relevant stimuli. The observed decreases in theta amplitude and increases in beta amplitude in the dentate gyrus may thus reflect a shift in processing state that occurs when encountering meaningful cues.

  8. Gray matter changes in right superior temporal gyrus in criminal psychopaths. Evidence from voxel-based morphometry.

    Science.gov (United States)

    Müller, Jürgen L; Gänssbauer, Susanne; Sommer, Monika; Döhnel, Katrin; Weber, Tatjana; Schmidt-Wilcke, Tobias; Hajak, Göran

    2008-08-30

    "Psychopathy" according to the PCL-R describes a specific subgroup of antisocial personality disorder with a high risk for criminal relapses. Lesion and imaging studies point towards frontal or temporal brain regions connected with disturbed social behavior, antisocial personality disorder (APD) and psychopathy. Morphologically, some studies described a reduced prefrontal brain volume, whereas others reported on temporal lobe atrophy. To further investigate whether participants with psychopathy according to the Psychopathy Checklist-Revised Version (PCL-R) show abnormalities in brain structure, we used voxel-based morphometry (VBM) to investigate region-specific changes in gray matter in 17 forensic male inpatients with high PCL-R scores (PCL-R>28) and 17 male control subjects with low PCL-R scores (PCLright superior temporal gyrus. This is the first study to show that psychopathy is associated with a decrease in gray matter in both frontal and temporal brain regions, in particular in the right superior temporal gyrus, supporting the hypothesis that a disturbed frontotemporal network is critically involved in the pathogenesis of psychopathy.

  9. [Tractography of the uncinate fasciculus and the posterior cingulate fasciculus in patients with mild cognitive impairment and Alzheimer disease].

    Science.gov (United States)

    Larroza, A; Moratal, D; D'ocón Alcañiz, V; Arana, E

    2014-01-01

    Brain tractography is a non-invasive medical imaging technique which enables in vivo visualisation and various types of quantitative studies of white matter fibre tracts connecting different parts of the brain. We completed a quantitative study using brain tractography with diffusion tensor imaging in patients with mild cognitive impairment, patients with Alzheimer disease, and normal controls, in order to analyse the reproducibility and validity of the results. Fractional anisotropy (FA) and mean diffusivity (MD) were measured across the uncinate fasciculus and the posterior cingulate fasciculus in images, obtained from a database and a research centre, representing 52 subjects distributed among the 3 study groups. Two observers took the measurements twice in order to evaluate intra- and inter-observer reproducibility. Measurements of FA and MD of the uncinate fasciculus delivered an intraclass correlation coefficient above 0.9; ICC was above 0.68 for the posterior cingulate fasciculus. Patients with Alzheimer disease showed lower values of FA and higher MD values in the right uncinate fasciculus in images from the research centre. A comparison of the measurements from the 2 centres revealed significant differences. We established a reproducible methodology for performing tractography of the tracts in question. FA and MD indexes may serve as early indicators of Alzheimer disease. The type of equipment and the method used to acquire images must be considered because they may alter results as shown by comparing the 2 data sets in this study. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  10. Adolescent maturation of inhibitory inputs onto cingulate cortex neurons is cell-type specific and TrkB dependent

    Directory of Open Access Journals (Sweden)

    Angela eVandenberg

    2015-02-01

    Full Text Available The maturation of inhibitory circuits during adolescence may be tied to the onset of mental health disorders such as schizophrenia. Neurotrophin signaling likely plays a critical role in supporting inhibitory circuit development and is also implicated in psychiatric disease. Within the neocortex, subcircuits may mature at different times and show differential sensitivity to neurotrophin signaling. We measured miniature inhibitory and excitatory postsynaptic currents (mIPSC and mEPSCs in Layer 5 cell-types in the mouse anterior cingulate across the periadolescent period. We differentiated cell-types mainly by Thy1 YFP transgene expression and also retrobead injection labeling in the contralateral cingulate and ipsilateral pons. We found that YFP- neurons and commissural projecting neurons had lower frequency of mIPSCs than neighboring YFP+ neurons or pons projecting neurons in juvenile mice (P21-25. YFP- neurons and to a lesser extent commissural projecting neurons also showed a significant increase in mIPSC amplitude during the periadolescent period (P21-25 vs. P40-50, which was not seen in YFP+ neurons or pons projecting neurons. Systemic disruption of tyrosine kinase receptor B (TrkB signaling during P23-50 in TrkBF616A mice blocked developmental changes in mIPSC amplitude, without affecting miniature excitatory post synaptic currents (mEPSCs. Our data suggest that the maturation of inhibitory inputs onto layer 5 pyramidal neurons is cell-type specific. These data may inform our understanding of adolescent brain development across species and aid in identifying candidate subcircuits that may show greater vulnerability in mental illness.

  11. Intra- and Interhemispheric Propagation of Electrophysiological Synchronous Activity and Its Modulation by Serotonin in the Cingulate Cortex of Juvenile Mice.

    Directory of Open Access Journals (Sweden)

    Víctor Rovira

    Full Text Available Disinhibition of the cortex (e.g., by GABA -receptor blockade generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14-20 days, the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7 than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05, which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s. We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere, and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges.

  12. Ketamine-dependent neuronal activation in healthy volunteers.

    Science.gov (United States)

    Höflich, Anna; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S; Vanicek, Thomas; Ganger, Sebastian; Spies, Marie; Windischberger, Christian; Kasper, Siegfried; Winkler, Dietmar; Lanzenberger, Rupert

    2017-04-01

    Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S ® ) was administered intravenously to 35 healthy volunteers. Neural activation as indicated by the BOLD signal using the pharmacokinetic curve of ketamine plasma levels as a regressor was computed. Compared with placebo, ketamine-dependent increases of neural activation were observed in the midcingulate cortex, the dorsal part of the anterior cingulate cortex, the insula bilaterally, and the thalamus (t values ranging between 5.95-9.78, p ketamine condition compared to placebo was found in a cluster within the subgenual/subcallosal part of the anterior cingulate cortex, the orbitofrontal cortex and the gyrus rectus (t = 7.81, p ketamine could be revealed.

  13. Developmental changes in membrane properties and postsynaptic currents of granule cells in rat dentate gyrus.

    Science.gov (United States)

    Liu, Y B; Lio, P A; Pasternak, J F; Trommer, B L

    1996-08-01

    1. Whole cell patch-clamp recordings were used to study dentate gyrus granule cells in hippocampal slices from juvenile rats (postnatal days 8-32). Membrane properties were measured with the use of current-clamp recordings and were correlated with the morphology of a subgroup of neurons filled with biocytin. The components of the postsynaptic currents (PSCs) induced by medial perforant path stimulation were characterized with the use of specific receptor antagonists in voltage-clamp recordings. 2. Granule cells located in the middle third of the superior blade of stratum granulosum from the rostral third of hippocampus were divided into three groups according to their input resistance (IR). Neurons with low IR (206 +/- 182 M omega, mean +/- SD) had hyperpolarized resting membrane potentials (-82 +/- 7 mV) and high-amplitude action potentials (108 +/- 23 mV). Neurons were high IR (1,259 +/- 204 M omega) had more depolarized resting membrane potentials (-54 +/- 6 mV) and lower-amplitude action potentials (71 +/- 10 mV). Neurons with intermediate IR (619 +/- 166 M omega) also had intermediate resting membrane potentials (-63 +/- 7 mV) and action potential amplitudes (86 +/- 14 mV). Low-IR neurons became increasingly prevalent with advancing postnatal age, but neurons from each group could be found throughout the entire period under study. 3. Morphological studies of low-IR neurons revealed an extensive dendritic arborization that traversed the entire molecular layer and was characteristic of mature granule cells. High-IR cells had smaller somata and short, simple dendritic arborization that incompletely penetrated the molecular layer and were classified as immature. Intermediate-IR cells had morphological features of intermediate maturity. 4. The initial phase of the PSC evoked at -80 mV was a fast inward current that was comparable with respect to latency to peak, latency to onset, and 10-90% rise time in neurons of all maturities held at -80 mV. This current was 6

  14. Change in platelet endothelial cell adhesion molecule-1 immunoreactivity in the dentate gyrus in gerbils fed a folate-deficient diet.

    Science.gov (United States)

    Yoo, Ki-Yeon; Hwang, In Koo; Kim, Young Sup; Kwon, Dae Young; Won, Moo Ho

    2008-02-01

    Folate deficiency increases stroke risk. We examined whether folate deficiency affects platelet endothelial cell adhesion molecule-1 (PECAM-1), which is an immunoglobulin-associated cell adhesion molecule and mediates the final common pathway of neutrophil transendothelial migration, in blood vessels in the gerbil dentate gyrus after transient forebrain ischemia. Gerbils were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to common carotid artery occlusion for 5 min. In the control diet (CD)- and FAD-treated sham-operated groups, weak PECAM-1 immunoreactivity was detected in the blood vessels located in the dentate gyrus. PECAM-1 immunoreactivity in both groups was increased by 4 days after ischemic insult. PECAM-1 immunoreactivity in the FAD-treated group was twice as high that in the CD-treated-sham-operated group 4 days after ischemic insult. Western blot analyses showed that the change patterns in PECAM-1 protein levels in the dentate gyrus in both groups after ischemic insult were similar to changes in PECAM-1 immunohistochemistry in the ischemic dentate gyrus. Our results suggest that folate deficiency enhances PECAM-1 in the dentate gyrus induced by transient ischemia.

  15. Inactivation of the Anterior Cingulate Cortex Impairs Extinction of Rabbit Jaw Movement Conditioning and Prevents Extinction-Related Inhibition of Hippocampal Activity

    Science.gov (United States)

    Griffin, Amy L.; Berry, Stephen D.

    2004-01-01

    Although past research has highlighted the involvement of limbic structures such as the anterior cingulate cortex (ACC) and hippocampus in learning, few have addressed the nature of their interaction. The current study of rabbit jaw movement conditioning used a combination of reversible lesions and electrophysiology to examine the involvement of…

  16. Impact of family history of alcoholism on glutamine/glutamate ratio in anterior cingulate cortex in substance-naïve adolescents

    OpenAIRE

    Cohen-Gilbert, Julia E.; Sneider, Jennifer T.; Crowley, David J.; Rosso, Isabelle M.; Jensen, J. Eric; Silveri, Marisa M.

    2015-01-01

    Neuroimaging studies of individuals with family histories of alcoholism provide evidence suggesting neurobiological risk factors for alcoholism. Youth family history positive (FH+) for alcoholism exhibit increased impulsivity compared to family history negative (FH−) peers in conjunction with altered functional activation in prefrontal cortex, including anterior cingulate cortex (ACC). This study examined glutamate (Glu) and glutamine (Gln), amino acids vital to protein synthesis, cellular me...

  17. fMRI Neurofeedback Training for Increasing Anterior Cingulate Cortex Activation in Adult Attention Deficit Hyperactivity Disorder. An Exploratory Randomized, Single-Blinded Study

    NARCIS (Netherlands)

    Zilverstand, A.; Sorger, B.; Slaats-Willemse, D.I.E.; Kan, C.C.; Goebel, R.; Buitelaar, J.K.

    2017-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at

  18. Remedial action and feedback processing in a time-estimation task: Evidence for a role of the rostral cingulate zone in behavioral adjustments without learning

    NARCIS (Netherlands)

    Veen, F.M. van der; Röder, C.H.; Mies, G.W.; Lugt, A. van der; Smits, M.

    2011-01-01

    The present study examined the role of the rostral cingulate zone (RCZ) in feedback processing, and especially focused on effects of modality of the feedback stimulus and remedial action. Participants performed a time-estimation task in which they had to estimate a 1-second interval. After the

  19. Posterior cingulate hypoperfusion in Alzheimer's disease, senile dementia of Alzheimer type, and other dementias evaluated by three-dimensional stereotactic surface projections using Tc-99m HMPAO SPECT.

    Science.gov (United States)

    Kaneko, Koichiro; Kuwabara, Yasuo; Sasaki, Masayuki; Ogomori, Koji; Ichimiya, Atsushi; Koga, Hirofumi; Nakagawa, Makoto; Hayashi, Kazutaka; Honda, Hiroshi

    2004-06-01

    Hypoperfusion in the posterior cingulate cortex is thought to be useful for the early diagnosis of dementia of Alzheimer type (DAT). In the present study, we compared the incidence of posterior cingulate hypoperfusion in patients with Alzheimer's disease (AD), patients with senile dementia of Alzheimer type (SDAT), and patients with other types of dementia, as evaluated by three-dimensional stereotactic surface projection (3D-SSP) imaging. The subjects were 20 AD patients, 20 SDAT patients, 13 frontotemporal dementia patients, and 3 other types of dementia patients. A SPECT study was performed 5 minutes after the injection of 740 MBq technetium-99m hexamethylpropylene amine oxime. 3D-SSP images were obtained with global normalization to perform the statistical analysis. The normal database of 3D-SSP consisted of 15 healthy volunteers. Hypoperfusion was considered to be significant when the Z-score was over 2.5. Posterior cingulate hypoperfusion was observed in 13 of 20 AD patients (65%), in 5 of 20 SDAT patients (25%), but in none of other type of dementia patients. Posterior cingulate hypoperfusion was considered to be a finding specific to DAT, and this finding was thought to be useful to diagnose DAT patients, especially for AD patients. However, it was considered to be difficult to diagnose early-stage SDAT patients.

  20. Reduced Activation in Lateral Prefrontal Cortex and Anterior Cingulate during Attention and Cognitive Control Functions in Medication-Naive Adolescents with Depression Compared to Controls

    Science.gov (United States)

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

    2009-01-01

    Background: 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…

  1. Electrophysiological correlates of anterior cingulate function in a go/no-go task: Effects of response conflict and trial type frequency.

    NARCIS (Netherlands)

    Nieuwenhuis, S.; Yeung, N.; van den Wildenberg, W.; Ridderinkhof, K.R.

    2003-01-01

    Neuroimaging and computational modeling studies have led to the suggestion that response conflict monitoring by the anterior cingulate cortex plays a key role in cognitive control. For example, response conflict is high when a response must be withheld (no-go) in contexts in which there is a

  2. A STEREOLOGICAL ANALYSIS OF THE EFFECT OF EARLY POSTNATAL ETHANOL EXPOSURE ON NEURONAL NUMBERS IN RAT DENTATE GYRUS

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    Takanori Miki

    2011-05-01

    Full Text Available Maternal ethanol ingestion during pregnancy can cause fetal alcohol syndrome (FAS in their offspring. Among the symptoms of FAS, damage to the central nervous system has emerged as one of the most serious problems. We have previously shown that a relatively high dose of ethanol exposure during early postnatal life can cause alterations in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rat pups to ethanol during early postnatal life had effects on the total number of the dentate gyrus neurons. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 to 15. Ethanol exposure was achieved by placing rat pups in a chamber containing ethanol vapour for 3 hours a day. The blood ethanol concentration was found to be about 430 mg/dL at the end of the exposure period. Groups of ethanol treated (ET, separation controls (SC and mother reared controls (MRC were anaesthetised and killed at 16-days-of-age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volume of subdivisions of the dentate gyrus, and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There was, on average, about 421,000 granule cells in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This value was significantly smaller than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. It is concluded that neurons in the hilus region of the dentate gyrus may be particularly vulnerable to the effects of a high dose of ethanol exposure during PND 10-15. It is likely that this deficit was due to neuronal death induced by some mechanisms related to

  3. Posterior Cingulate Glucose Metabolism, Hippocampal Glucose Metabolism, and Hippocampal Volume in Cognitively Normal, Late-Middle-Aged Persons at 3 Levels of Genetic Risk for Alzheimer Disease

    Science.gov (United States)

    Protas, Hillary D.; Chen, Kewei; Langbaum, Jessica B. S.; Fleisher, Adam S.; Alexander, Gene E.; Lee, Wendy; Bandy, Daniel; de Leon, Mony J.; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W.; Caselli, Richard J.; Reiman, Eric M.

    2013-01-01

    Objective To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Design Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxy-glucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Setting Academic medical center. Participants A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. Main Outcome Measures The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Results Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P=.60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P=.001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r=0.29, P=.0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P<.05, determined by use of pairwise Fisher z tests). Conclusions Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or

  4. Proton magnetic resonance spectroscopy of the frontal, cingulate and perirolandic cortices and its relationship to skin conductance in patients with schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Sanches, R.F.; Crippa, J.A.S.; Hallak, J.E.C.; Sousa, J.P.M. de; Zuardi, A.W. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP, (Brazil). Faculdade de Medicina. Dept. de Neurociencias e Ciencias do Comportamento]. E-mail: awzuardi@fmrp.usp.br; Araujo, D.; Santos, A.C. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP, (Brazil). Faculdade de Medicina. Div. de Radiologia

    2008-07-01

    The aim of the present study was to determine whether specific subgroups of schizophrenic patients, grouped according to electrodermal characteristics, show differences in the N-acetylaspartate/creatine plus choline (NAA / (Cr + Cho)) ratios in the frontal, cingulate and perirolandic cortices. Skin conductance levels (SCL) and skin conductance responses to auditory stimulation were measured in 38 patients with schizophrenia and in the same number of matched healthy volunteers (control). All subjects were submitted to multivoxel proton magnetic resonance spectroscopic imaging. When compared to the control group, patients presented significantly lower NAA / (Cr + Cho) ratios in the right dorsolateral prefrontal cortex (schizophrenia 0.95 {+-} 0.03; control = 1.12 {+-} 0.04) and in the right (schizophrenia 0.88 {+-} 0.02; control = 0.94 {+-} 0.03) and left (schizophrenia 0.84 {+-} 0.03; control = 0.94 {+-} 0.03) cingulates. These ratios did not differ between electrodermally responsive and non-responsive patients. When patients were divided into two groups: lower SCL (less than the mean SCL of the control group minus two standard deviations) and normal SCL (similar to the control group), the subgroup with a lower level of SCL showed a lower NAA / (Cr + Cho) ratio in the left cingulate (0.78 {+-} 0.05) than the controls (0.95 {+-} 0.02, P < 0.05) and the subgroup with normal SCL (0.88 {+-} 0.03, P < 0.05). There was a negative correlation between the NAA / (Cr + Cho) ratio in the left cingulate of patients with schizophrenia and the duration of the disease and years under medication. These data suggest the existence of a schizophrenic subgroup characterized by low SCL that could be a consequence of the lower neuronal viability observed in the left cingulate of these patients. (author)

  5. Opposite effective connectivity in the posterior cingulate and medial prefrontal cortex between first-episode schizophrenic patients with suicide risk and healthy controls.

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    Huiran Zhang

    Full Text Available OBJECTIVE: The schizophrenic patients with high suicide risk are characterized by depression, better cognitive function, and prominent positive symptoms. However, the neurobiological basis of suicide attempts in schizophrenia is not clear. The suicide in schizophrenia is implicated in the defects in emotional process and decision-making, which are associated with prefrontal-cingulate circuit. In order to explore the possible neurobiological basis of suicide in schizophrenia, we investigated the correlation of prefrontal-cingulate circuit with suicide risk in schizophrenia via dynamic casual modelling. METHOD: Participants were 33 first-episode schizophrenic patients comprising of a high suicide risk group (N = 14 and a low suicide risk group (N = 19. A comparison group of healthy controls (N = 15 were matched for age, gender and education. N-back tasking functional magnetic resonance imaging data was collected. RESULTS: Compared with healthy controls group, the two patients groups showed decreased task-related suppression during 2-back task state versus baseline state in the left posterior cingulate and medial prefrontal cortex; the hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex existed in both schizophrenic patients groups, but hypo-connectivity in the opposite direction only existed in the schizophrenic patients group with high suicide risk. CONCLUSIONS: The hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex may suggest that the abnormal effective connectivity was associated with risk for schizophrenia. The hypo-connectivity in the opposite direction may represent a possible correlate of increased vulnerability to suicide attempt.

  6. 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

  7. The GABAA Antagonist DPP-4-PIOL Selectively Antagonises Tonic over Phasic GABAergic Currents in Dentate Gyrus Granule Cells

    DEFF Research Database (Denmark)

    Boddum, Kim; Frølund, Bente; Kristiansen, Uffe

    2014-01-01

    GABAA receptors mediate two different types of inhibitory currents: phasic inhibitory currents when rapid and brief presynaptic GABA release activates postsynaptic GABAA receptors and tonic inhibitory currents generated by low extrasynaptic GABA levels, persistently activating extrasynaptic GABAA...... receptors. The two inhibitory current types are mediated by different subpopulations of GABAA receptors with diverse pharmacological profiles. Selective antagonism of tonic currents is of special interest as excessive tonic inhibition post-stroke has severe pathological consequences. Here we demonstrate...... that phasic and tonic GABAA receptor currents can be selectively inhibited by the antagonists SR 95531 and the 4-PIOL derivative, 4-(3,3-diphenylpropyl)-5-(4-piperidyl)-3-isoxazolol hydrobromide (DPP-4-PIOL), respectively. In dentate gyrus granule cells, SR 95531 was found approximately 4 times as potent...

  8. Ventral simultanagnosia and prosopagnosia for unfamiliar faces due to a right posterior superior temporal sulcus and angular gyrus lesion.

    Science.gov (United States)

    Sakurai, Yasuhisa; Hamada, Kensuke; Tsugawa, Naoya; Sugimoto, Izumi

    2016-01-01

    We report a patient with ventral simultanagnosia, prosopagnosia for "unfamiliar faces" (dorsal prosopagnosia), spatial agraphia, and constructional disorder, particularly on the left spatial side, due to a lesion in the right posterior superior and middle temporal gyri and angular gyrus. The patient showed impairment of fundamental visual and visuospatial recognition, such as in object size, configuration, and horizontal point location, which probably underlay the mechanism of simultanagnosia and prosopagnosia. This case also suggests that the coexistence of simultanagnosia and prosopagnosia results from a right hemispheric insult, and damage to the temporoparietal area interrupts the incorporation of spatial information into object recognition. This disconnection of information flow, together with impaired object recognition per se, may impair the parallel processing of multiple objects, leading to object-by-object or part-by-part recognition.

  9. Properties of doublecortin-(DCX-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

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    Friederike Klempin

    Full Text Available The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise, also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

  10. Neurogenesis in the dentate gyrus depends on ciliary neurotrophic factor and signal transducer and activator of transcription 3 signaling.

    Science.gov (United States)

    Müller, Stephan; Chakrapani, Baby P S; Schwegler, Herbert; Hofmann, Hans-Dieter; Kirsch, Matthias

    2009-02-01

    In the neurogenic areas of the adult rodent brain, neural stem cells (NSCs) proliferate and produce new neurons throughout the lifetime. This requires a permanent pool of NSCs, the size of which needs to be tightly controlled. The gp130-associated cytokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) have been implicated in regulating NSC self-renewal and differentiation during embryonic development and in the adult brain. To study the relevance of the two cytokines in vivo, we analyzed precursor cell proliferation and neurogenesis in the dentate gyrus of CNTF- and LIF-deficient mouse mutants. The number of radial glia-like NSCs, proliferative activity, and generation of new neurons were all reduced in CNTF(-/-) mutants but unaltered in LIF(-/-) animals. Conditional ablation of the signal transducer and activator of transcription 3 (STAT3) gene under the control of the human glial fibrillary acidic protein promoter resulted in a reduction of neurogenesis similar to that in CNTF(-/-) mice. The size of the granule cell layer was decreased in both mutants. Treatment of neurosphere cultures prepared from adult forebrain with CNTF inhibited overall proliferative activity but increased the number of NSCs as indicated by enhanced secondary neurosphere formation and upregulated expression of stem cell markers. Knockdown of STAT3 with short interfering RNA inhibited CNTF effects on neurospheres, and knockdown of suppressor of cytokine signaling 3 (SOCS3) enhanced them. Our results provide evidence that CNTF-induced STAT3 signaling is essential for the formation and/or maintenance of the neurogenic subgranular zone in the adult dentate gyrus and suggest that CNTF is required to keep the balance between NSC self-renewal and the generation of neuronal progenitors.

  11. Association fibers connecting the Broca center and the lateral superior frontal gyrus: a microsurgical and tractographic anatomy.

    Science.gov (United States)

    Kinoshita, Masashi; Shinohara, Harumichi; Hori, Osamu; Ozaki, Noriyuki; Ueda, Fumiaki; Nakada, Mitsutoshi; Hamada, Jun-Ichiro; Hayashi, Yutaka

    2012-02-01

    Recently, intraoperative mapping has disclosed that, in addition to the classic language centers (that is, the Broca and Wernicke centers), other cortical regions may also play an important role in language organization. In the prefrontal cortex, although the lateral superior frontal gyrus (LSFG) could have language-related functions, there are no detailed reports that demonstrate the anatomical connection between the LSFG and other well-known language cortices, such as the Broca center. To show the existence of the structural connection, white matter association fibers between the inferior frontal gyrus (IFG) and the LSFG were examined using fiber dissection (FD) and diffusion tensor (DT) imaging-based tractography. Eight cadaveric cerebral hemispheres were dissected to reveal the association fibers between the IFG and LSFG. The DT imaging-based tractography studies targeting the prefrontal cortex were obtained in 53 right-handed patients who had no organic cerebral lesions. The association fiber tract between Brodmann area 44/45 (the Broca center in the dominant hemisphere) and LSFG were detected in all specimens by FD. In the DT imaging-based tractography studies, the tract was identified in all patients bilaterally, except for the 4 in whom the tract was detected only in the left hemisphere. This tract was spread significantly wider in the left than in the right hemisphere, and left lateralization was evident in male patients. Based on its character, this tract was named the Broca-LSFG pathway. These findings suggest a close relationship between this pathway and language organization. The structural anatomy of the Broca-LSFG pathway may explain speech disturbances induced by LSFG stimulation that are sometimes observed during intraoperative language mapping.

  12. Fusiform gyrus dysfunction is associated with perceptual processing efficiency to emotional faces in adolescent depression: a model-based approach

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    Tiffany Cheing Ho

    2016-02-01

    Full Text Available While the extant literature has focused on major depressive disorder (MDD as being characterized by abnormalities in processing affective stimuli (e.g., facial expressions, little is known regarding which specific aspects of cognition influence the evaluation of affective stimuli, and what are the underlying neural correlates. To investigate these issues, we assessed 26 adolescents diagnosed with MDD and 37 well-matched healthy controls (HCL who completed an emotion identification task of dynamically morphing faces during functional magnetic resonance imaging (fMRI. We analyzed the behavioral data using a sequential sampling model of response time (RT commonly used to elucidate aspects of cognition in binary perceptual decision making tasks: the Linear Ballistic Accumulator (LBA model. Using a hierarchical Bayesian estimation method, we obtained group-level and individual-level estimates of LBA parameters on the facial emotion identification task. While the MDD and HCL groups did not differ in mean RT, accuracy, or group-level estimates of perceptual processing efficiency (i.e., drift rate parameter of the LBA, the MDD group showed significantly reduced responses in left fusiform gyrus compared to the HCL group during the facial emotion identification task. Furthermore, within the MDD group, fMRI signal in the left fusiform gyrus during affective face processing was significantly associated with greater individual-level estimates of perceptual processing efficiency. Our results therefore suggest that affective processing biases in adolescents with MDD are characterized by greater perceptual processing efficiency of affective visual information in sensory brain regions responsible for the early processing of visual information. The theoretical, methodological, and clinical implications of our results are discussed.

  13. Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

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    Eliane C Miotto

    Full Text Available Patients with low-grade glioma (LGG have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR, related-non-structured (RNS, and related-structured words (RS, allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG and middle frontal gyrus (MFG during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

  14. Ictal conduction aphasia and ictal angular gyrus syndrome as rare manifestations of epilepsy: The importance of ictal testing during video-EEG monitoring

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    Johann Philipp Zöllner

    2017-01-01

    Full Text Available The aim of these two case reports is to demonstrate that a predefined, structured, multimodal clinical bed-side testing during seizures in a long-term video-EEG monitoring setting facilitates diagnosis of complex neuropsychological syndromes. To the best of our knowledge, we present the first case of conduction aphasia as the sole ictal semiology, and a patient with focal seizures producing an angular gyrus syndrome in the speech dominant hemisphere. The relevance of diagnosing ictal aphasic and angular gyrus syndromes and localizing the symptomatogenic zone is discussed. Current pathophysiological concepts are presented regarding conduction aphasia and Gerstmann's syndrome.

  15. Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.

    Science.gov (United States)

    Zikopoulos, Basilis; Höistad, Malin; John, Yohan; Barbas, Helen

    2017-05-17

    The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders. SIGNIFICANCE STATEMENT The dialogue between prefrontal cortex and amygdala allows thoughts and emotions to influence actions. The posterior orbitofrontal cortex sends a powerful pathway that targets a special class of amygdalar intercalated mass (IM) inhibitory neurons, whose wiring may help

  16. Role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder: converging evidence from cognitive neuroscience and psychiatric neurosurgery.

    Science.gov (United States)

    McGovern, Robert A; Sheth, Sameer A

    2017-01-01

    OBJECTIVE Advances in understanding the neurobiological basis of psychiatric disorders will improve the ability to refine neuromodulatory procedures for treatment-refractory patients. One of the core dysfunctions in obsessive-compulsive disorder (OCD) is a deficit in cognitive control, especially involving the dorsal anterior cingulate cortex (dACC). The authors' aim was to derive a neurobiological understanding of the successful treatment of refractory OCD with psychiatric neurosurgical procedures targeting the dACC. METHODS First, the authors systematically conducted a review of the literature on the role of the dACC in OCD by using the search terms "obsessive compulsive disorder" and "anterior cingulate." The neuroscience literature on cognitive control mechanisms in the dACC was then combined with the literature on psychiatric neurosurgical procedures targeting the dACC for the treatment of refractory OCD. RESULTS The authors reviewed 89 studies covering topics that included structural and functional neuroimaging and electrophysiology. The majority of resting-state functional neuroimaging studies demonstrated dACC hyperactivity in patients with OCD relative to that in controls, while task-based studies were more variable. Electrophysiological studies showed altered dACC-related biomarkers of cognitive control, such as error-related negativity in OCD patients. These studies were combined with the cognitive control neurophysiology literature, including the recently elaborated expected value of control theory of dACC function. The authors suggest that a central feature of OCD pathophysiology involves the generation of mis-specified cognitive control signals by the dACC, and they elaborate on this theory and provide suggestions for further study. CONCLUSIONS Although abnormalities in brain structure and function in OCD are distributed across a wide network, the dACC plays a central role. The authors propose a theory of cognitive control dysfunction in OCD that

  17. Exposure to blue wavelength light modulates anterior cingulate cortex activation in response to 'uncertain' versus 'certain' anticipation of positive stimuli.

    Science.gov (United States)

    Alkozei, Anna; Smith, Ryan; Killgore, William D S

    2016-03-11

    Blue wavelength light has been used as an effective treatment for some types of mood disorders and circadian rhythm related sleep problems. We hypothesized that acute exposure to blue wavelength light would directly affect the functioning of neurocircuity implicated in emotion regulation (i.e., ventromedial prefrontal cortex, amygdala, insula, and anterior cingulate cortex [ACC]) during 'certain' and 'uncertain' anticipation of negative and positive stimuli. Thirty-five healthy adults were randomized to receive a thirty-minute exposure to either blue (active) or amber (placebo) light, immediately followed by an emotional anticipation task during functional magnetic resonance imaging (fMRI). In contrast to placebo, participants in the blue light group showed significantly reduced activation within the rostral ACC during 'uncertain' anticipation (i.e., uncertainty regarding whether a positive or negative stimulus would be shown) in comparison to 'certain' anticipation of a positive stimulus. These findings may be explicable in terms of interactions between blue light exposure and the influence of specific neuromodulators on ACC-mediated decision-making mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment

    Science.gov (United States)

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-01-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with ‘psychoticism’, a trait associated with a lack of empathic concern and antisocial tendencies, and with ‘need for cognition’, a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others. PMID:23280149

  19. Representing Representation: Integration between the Temporal Lobe and the Posterior Cingulate Influences the Content and Form of Spontaneous Thought.

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    Jonathan Smallwood

    Full Text Available When not engaged in the moment, we often spontaneously represent people, places and events that are not present in the environment. Although this capacity has been linked to the default mode network (DMN, it remains unclear how interactions between the nodes of this network give rise to particular mental experiences during spontaneous thought. One hypothesis is that the core of the DMN integrates information from medial and lateral temporal lobe memory systems, which represent different aspects of knowledge. Individual differences in the connectivity between temporal lobe regions and the default mode network core would then predict differences in the content and form of people's spontaneous thoughts. This study tested this hypothesis by examining the relationship between seed-based functional connectivity and the contents of spontaneous thought recorded in a laboratory study several days later. Variations in connectivity from both medial and lateral temporal lobe regions was associated with different patterns of spontaneous thought and these effects converged on an overlapping region in the posterior cingulate cortex. We propose that the posterior core of the DMN acts as a representational hub that integrates information represented in medial and lateral temporal lobe and this process is important in determining the content and form of spontaneous thought.

  20. Characterization of neuronal intrinsic properties and synaptic transmission in layer I of anterior cingulate cortex from adult mice

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    Li Xiang-Yao

    2012-07-01

    Full Text Available Abstract The neurons in neocortex layer I (LI provide inhibition to the cortical networks. Despite increasing use of mice for the study of brain functions, few studies were reported about mouse LI neurons. In the present study, we characterized intrinsic properties of LI neurons of the anterior cingulate cortex (ACC, a key cortical area for sensory and cognitive functions, by using whole-cell patch clamp recording approach. Seventy one neurons in LI and 12 pyramidal neurons in LII/III were recorded. Although all of the LI neurons expressed continuous adapting firing characteristics, the unsupervised clustering results revealed five groups in the ACC, including: Spontaneous firing neurons; Delay-sAHP neurons, Delay-fAHP neurons, and two groups of neurons with ADP, named ADP1 and ADP2, respectively. Using pharmacological approaches, we found that LI neurons received both excitatory (mediated by AMPA, kainate and NMDA receptors, and inhibitory inputs (which were mediated by GABAA receptors. Our studies provide the first report characterizing the electrophysiological properties of neurons in LI of the ACC from adult mice.

  1. Roles of CREB in the regulation of FMRP by group I metabotropic glutamate receptors in cingulate cortex

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    Wang Hansen

    2012-08-01

    Full Text Available Abstract Background Fragile X syndrome is caused by lack of fragile X mental retardation protein (FMRP due to silencing of the FMR1 gene. The metabotropic glutamate receptors (mGluRs in the central nervous system contribute to higher brain functions including learning/memory, mental disorders and persistent pain. The transcription factor cyclic AMP-responsive element binding protein (CREB is involved in important neuronal functions, such as synaptic plasticity and neuronal survival. Our recent study has shown that stimulation of Group I mGluRs upregulated FMRP and activated CREB in anterior cingulate cortex (ACC, a key region for brain cognitive and executive functions, suggesting that activation of Group I mGluRs may upregulate FMRP through CREB signaling pathway. Results In this study, we demonstrate that CREB contributes to the regulation of FMRP by Group I mGluRs. In ACC neurons of adult mice overexpressing dominant active CREB mutant, the upregulation of FMRP by stimulating Group I mGluR is enhanced compared to wild-type mice. However, the regulation of FMRP by Group I mGluRs is not altered by overexpression of Ca2+-insensitive mutant form of downstream regulatory element antagonist modulator (DREAM, a transcriptional repressor involved in synaptic transmission and plasticity. Conclusion Our study has provided further evidence for CREB involvement in regulation of FMRP by Group I mGluRs in ACC neurons, and may help to elucidate the pathogenesis of fragile X syndrome.

  2. Heritability of brain structure and glutamate levels in the anterior cingulate and left thalamus assessed with MR: A twin study

    DEFF Research Database (Denmark)

    Broberg, Brian Villumsen; Legind, Christian Stefan; Mandl, Rene C W

    included without their siblings. A 3D-T1W structural image and 1H nuclear magnetic resonance spectra (PRESS) was obtained from each subject using a 3 Tesla Philips MRI system. Total brain (TB), Gray matter (GM), white matter (WM), peripheral GM (pGM), ventricular CSF (vCSF) volumes were calculated using......Heritability of brain structure and glutamate levels in the anterior cingulate and left thalamus assessed with MR: A twin study Brian V. Broberg1,2; Christian S. Legind1,2, Rene C. Mandl1,3, Maria H. Jensen1, Simon J. Anhøj1,2, Rikke Hilker1, Egill Rostrup1,2, Birte Y. Glenthøj1 Author affiliations...... the heritability of regional cerebral glutamate levels as well as structural brain volumes. Methods Population: 18 monozygotic, 13 dizygotic twin pairs con- or discordant for schizophrenia (ICD-10, F. 20-29), 16 monozygotic healthy control pairs and 10 dizygotic healthy control pairs. Nine additional twins were...

  3. The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder.

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    Velasquez, Francisco; Wiggins, Jillian Lee; Mattson, Whitney I; Martin, Donna M; Lord, Catherine; Monk, Christopher S

    2017-04-01

    Social deficits in autism spectrum disorder (ASD) are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC) is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR) variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD) completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD) individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. The association between cingulate cortex glutamate concentration and delay discounting is mediated by resting state functional connectivity.

    Science.gov (United States)

    Schmaal, Lianne; Goudriaan, Anna E; van der Meer, Johan; van den Brink, Wim; Veltman, Dick J

    2012-09-01

    Humans vary in their ability to delay gratification and impulsive decision making is a common feature in various psychiatric disorders. The level of delay discounting is a relatively stable psychological trait, and therefore neural processes implicated in delay discounting are likely to be based on the overall functional organization of the brain (under task-free conditions) in which state-dependent shifts from baseline levels occur. The current study investigated whether delay discounting can be predicted by intrinsic properties of brain functioning. Fourteen healthy male subjects performed a delay discounting task. In addition, resting state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (¹H MRS) were used to investigate the relationship between individual differences in delay discounting and molecular and regional measures of resting state (baseline) activity of dorsal anterior cingulate cortex (dACC). Results showed that delay discounting was associated with both dACC glutamate concentrations and resting state functional connectivity of the dACC with a midbrain region including ventral tegmental area and substantia nigra. In addition, a neural pathway was established, showing that the effect of glutamate concentrations in the dACC on delay discounting is mediated by functional connectivity of the dACC with the midbrain. The current findings are important to acknowledge because spontaneous intrinsic brain processes have been proposed to be a potential promising biomarker of disease and impulsive decision making is associated with several psychiatric disorders.

  5. Glutamate/glutamine concentrations in the dorsal anterior cingulate vary with Post-Traumatic Stress Disorder symptoms.

    Science.gov (United States)

    Harnett, Nathaniel G; Wood, Kimberly H; Ference, Edward W; Reid, Meredith A; Lahti, Adrienne C; Knight, Amy J; Knight, David C

    2017-08-01

    Trauma and stress-related disorders (e.g., Acute Stress Disorder; ASD and Post-Traumatic Stress Disorder; PTSD) that develop following a traumatic event are characterized by cognitive-affective dysfunction. The cognitive and affective functions disrupted by stress disorder are mediated, in part, by glutamatergic neural systems. However, it remains unclear whether neural glutamate concentrations, measured acutely following trauma, vary with ASD symptoms and/or future PTSD symptom expression. Therefore, the current study utilized proton magnetic resonance spectroscopy (1H-MRS) to investigate glutamate/glutamine (Glx) concentrations within the dorsal anterior cingulate cortex (ACC) of recently (i.e., within one month) traumatized individuals and non-traumatized controls. Although Glx concentrations within dorsal ACC did not differ between recently traumatized and non-traumatized control groups, a positive linear relationship was observed between Glx concentrations and current stress disorder symptoms in traumatized individuals. Further, Glx concentrations showed a positive linear relationship with future stress disorder symptoms (i.e., assessed 3 months post-trauma). The present results suggest glutamate concentrations may play a role in both acute and future post-traumatic stress symptoms following a traumatic experience. The current results expand our understanding of the neurobiology of stress disorder and suggest glutamate within the dorsal ACC plays an important role in cognitive-affective dysfunction following a traumatic experience. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Exploring individual differences in task switching: Persistence and other personality traits related to anterior cingulate cortex function.

    Science.gov (United States)

    Umemoto, A; Holroyd, C B

    2016-01-01

    Anterior cingulate cortex (ACC) is involved in cognitive control and decision-making but its precise function is still highly debated. Based on evidence from lesion, neurophysiological, and neuroimaging studies, we have recently proposed a critical role for ACC in motivating extended behaviors according to learned task values (Holroyd and Yeung, 2012). Computational simulations based on this theory suggest a hierarchical mechanism in which a caudal division of ACC selects and applies control over task execution, and a rostral division of ACC facilitates switches between tasks according to a higher task strategy (Holroyd and McClure, 2015). This theoretical framework suggests that ACC may contribute to personality traits related to persistence and reward sensitivity (Holroyd and Umemoto, 2016). To explore this possibility, we carried out a voluntary task switching experiment in which on each trial participants freely chose one of two tasks to perform, under the condition that they try to select the tasks "at random" and equally often. The participants also completed several questionnaires that assessed personality trait related to persistence, apathy, anhedonia, and rumination, in addition to the Big 5 personality inventory. Among other findings, we observed greater compliance with task instructions by persistent individuals, as manifested by a greater facility with switching between tasks, which is suggestive of increased engagement of rostral ACC. © 2016 Elsevier B.V. All rights reserved.

  7. Hypo-metabolism of the rostral anterior cingulate cortex associated with working memory impairment in 18 cases of schizophrenia.

    Science.gov (United States)

    Mazgaj, Robert; Tal, Assaf; Goetz, Raymond; Lazar, Mariana; Rothman, Karen; Messinger, Julie Walsh; Malaspina, Dolores; Gonen, Oded

    2016-03-01

    Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions. This retrospective study of 18 schizophrenia cases and 10 matched controls used proton magnetic resonance spectroscopic imaging ((1)H-MRSI, TR/TE = 1800/35 ms, 0.5 cm(3) spatial resolution) to test whether the Work-Mem Index of the Wechsler Adult Intelligence Scale, third edition is associated with differences in the rostral to caudal ACC ratios of N-acetylaspartate (NAA) and creatine (Cr). Higher caudal:rostral ACC Cr (but not NAA) concentrations were associated with decreased Work-Mem Index in cases (r = -0.6, p = 0.02), with a similar trend in controls (r = -0.56, p = 0.10), although caudal:rostral ACC Cr correlated with NAA in cases and controls (r = 0.67 and 0.62, p working memory impairment in schizophrenia. Changes in the rostral (not the expected caudal) subregion underscore the interconnections between the ACC subregions and may offer laboratory markers for treatment trials, etiology studies, and perhaps even enhanced identification of prodromal "at risk" subjects.

  8. Abrupt changes in the patterns and complexity of anterior cingulate cortex activity when food is introduced into an environment

    Directory of Open Access Journals (Sweden)

    Barak Francisco Caracheo

    2013-05-01

    Full Text Available AbstractForaging typically involves two distinct phases, an exploration phase where an organism explores its local environment in search of needed resources and an exploitation phase where a discovered resource is consumed. The behavior and cognitive requirements of exploration and exploitation are quite different and yet organisms can quickly and efficiently switch between them many times during a foraging bout. The present study investigated neural activity state dynamics in the anterior cingulate sub-region of the rat medial prefrontal cortex (mPFC when a reliable food source was introduced into an environment. Distinct and largely independent states were detected using a Hidden Markov Model (HMM when food was present or absent in the environment. Measures of neural entropy or complexity decreased when rats went from exploring the environment to exploiting a reliable food source. Exploration in the absence of food was associated with many weak activity states, while bouts of food consumption were characterized by fewer stronger states. Widespread activity state changes in the mPFC may help to inform foraging decisions and focus behavior on what is currently most prominent or valuable in the environment.

  9. Therapygenetics: anterior cingulate cortex-amygdala coupling is associated with 5-HTTLPR and treatment response in panic disorder with agoraphobia.

    Science.gov (United States)

    Lueken, Ulrike; Straube, Benjamin; Wittchen, Hans-Ulrich; Konrad, Carsten; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Arolt, Volker; Kircher, Tilo; Deckert, Jürgen; Reif, Andreas

    2015-01-01

    Variation in the 5'-flanking promoter region of the serotonin transporter gene SLC6A4, the 5-HTT-linked polymorphic region (5-HTTLPR) has been inconclusively associated with response to cognitive-behavioural therapy (CBT). As genomic functions are stronger related to neural than to behavioural markers, we investigated the association of treatment response, 5-HTTLPR and functional brain connectivity in patients with panic disorder with agoraphobia (PD/AG). Within the national research network PANIC-NET 231 PD/AG patients who provided genetic information underwent a manualized exposure-based CBT. A subset of 41 patients participated in a functional magnetic resonance imaging (fMRI) add-on study prior to treatment applying a differential fear conditioning task. Neither the treatment nor the reduced fMRI sample showed a direct effect of 5-HTTLPR on treatment response as defined by a reduction in the Hamilton Anxiety Scale score ≥50 % from baseline to post assessment. On a neural level, inhibitory anterior cingulate cortex (ACC)-amygdala coupling during fear conditioning that had previously been shown to characterize treatment response in this sample was driven by responders with the L/L genotype. Building upon conclusive evidence from basic and preclinical findings on the association of the 5-HTTLPR polymorphism with emotion regulation and related brain connectivity patterns, present findings translate these to a clinical sample of PD/AG patients and point towards a potential intermediate connectivity phenotype modulating response to exposure-based CBT.

  10. Combined rTMS treatment targeting the Anterior Cingulate and the Temporal Cortex for the Treatment of Chronic Tinnitus

    Science.gov (United States)

    Kreuzer, Peter M.; Lehner, Astrid; Schlee, Winfried; Vielsmeier, Veronika; Schecklmann, Martin; Poeppl, Timm B.; Landgrebe, Michael; Rupprecht, Rainer; Langguth, Berthold

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double-blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group. PMID:26667790

  11. Macro and micro structures in the dorsal anterior cingulate cortex contribute to individual differences in self-monitoring.

    Science.gov (United States)

    Yang, Junyi; Tian, Xue; Wei, Dongtao; Liu, Huijuan; Zhang, Qinglin; Wang, Kangcheng; Chen, Qunlin; Qiu, Jiang

    2016-06-01

    Individual differences in self-monitoring, which are the capability to adjust behavior to adapt to social situations, influence a wide range of social behaviors. However, understanding of focal differences in brain structures related to individual self-monitoring is minimal, particularly when micro and macro structures are considered simultaneously. The present study investigates the relationship between self-monitoring and brain structure in a relatively large sample of young adults. Voxel-based morphometry (VBM) revealed a significant positive correlation between self-monitoring and gray matter volume in the dorsal cingulate anterior cortex (dACC), dorsal lateral prefrontal cortex (DLPFC), and bilateral ventral striatum (VS). Further analysis revealed a significant negative correlation between self-monitoring and white matter (WM) integrity, as indexed by fractional anisotropy (FA) in the anterior cingulum (ACG) bundle. Moreover, there was a significant positive correlation between self-monitoring and mean radius diffusion (RD). These results shed light on the structural neural basis of variation in self-monitoring.

  12. Is dorsal anterior cingulate cortex activation in response to social exclusion due to expectancy violation? An fMRI study.

    Science.gov (United States)

    Kawamoto, Taishi; Onoda, Keiichi; Nakashima, Ken'ichiro; Nittono, Hiroshi; Yamaguchi, Shuhei; Ura, Mitsuhiro

    2012-01-01

    People are typically quite sensitive about being accepted or excluded by others. Previous studies have suggested that the dorsal anterior cingulate cortex (dACC) is a key brain region involved in the detection of social exclusion. However, this region has also been shown to be sensitive to non-social expectancy violations. We often expect other people to follow an unwritten rule in which they include us as they would expect to be included, such that social exclusion likely involves some degree of expectancy violation. The present event-related functional magnetic resonance imaging (fMRI) study sought to separate the effects of expectancy violation from those of social exclusion, such that we employed an "overinclusion" condition in which a player was unexpectedly overincluded in the game by the other players. With this modification, we found that the dACC and right ventrolateral prefrontal cortex (rVLPFC) were activated by exclusion, relative to overinclusion. In addition, we identified a negative correlation between exclusion-evoked brain activity and self-rated social pain in the rVLPFC, but not in the dACC. These findings suggest that the rVLPFC is critical for regulating social pain, whereas the dACC plays an important role in the detection of exclusion. The neurobiological basis of social exclusion is different from that of mere expectancy violation.

  13. Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex.

    Directory of Open Access Journals (Sweden)

    Kep Kee Loh

    Full Text Available Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today's society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM analyses: Individuals with higher Media Multitasking Index (MMI scores had smaller gray matter density in the anterior cingulate cortex (ACC. Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences.

  14. Network profiles of the dorsal anterior cingulate and dorsal prefrontal cortex in schizophrenia during hippocampal-based associative memory

    Directory of Open Access Journals (Sweden)

    Eric eWoodcock

    2016-04-01

    Full Text Available Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n=12 and healthy control subjects (n=10 participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC and the dorsal anterior cingulate cortex (dACC as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance with seed (dPFC vs. dACC, group (patients vs. controls, and memory process (encoding vs. retrieval as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness’ characterization as a disconnection syndrome.

  15. Network Profiles of the Dorsal Anterior Cingulate and Dorsal Prefrontal Cortex in Schizophrenia During Hippocampal-Based Associative Memory.

    Science.gov (United States)

    Woodcock, Eric A; Wadehra, Sunali; Diwadkar, Vaibhav A

    2016-01-01

    Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC) and the dorsal anterior cingulate cortex (dACC) as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance (ANOVA) with seed (dPFC vs. dACC), group (patients vs. controls), and memory process (encoding and retrieval) as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness' characterization as a disconnection syndrome.

  16. The effect of regulatory mode on procrastination: Bi-stable parahippocampus connectivity with dorsal anterior cingulate and anterior prefrontal cortex.

    Science.gov (United States)

    Zhang, Chenyan; Ni, Yan; Feng, Tingyong

    2017-06-30

    Previous research has elucidated that procrastination can be influenced by regulatory mode orientations. However, the neural mechanism of regulatory modes affecting procrastination is not well understood. To address this question, we employed resting-state functional magnetic resonance imaging (RS-fMRI) to test the influence of two regulatory modes (assessment and locomotion) on procrastination. The behavioral results showed that procrastination was positively correlated with assessment orientation but negatively correlated with locomotion orientation. Neuroimaging results indicated that the functional connectivity between parahippocampal cortex (PHC) and dorsal anterior cingulate (dACC) was negatively correlated with assessment scores, while the functional connectivity between anterior prefrontal cortex (aPFC) and parahippocampal cortex (PHC) was negatively correlated with locomotion scores. Critically, mediation analysis showed that the different effects of two distinct regulatory modes on procrastination were mediated by PHC-dACC and aPFC-PHC functional connectivity respectively. These results suggested that people's procrastination could be predicted by regulatory mode orientations, which is mediated by PHC connectivity with dACC and aPFC respectively. The present study extends our knowledge on procrastination and provides neural mechanism for understanding the link between regulatory mode orientations and procrastination. Copyright © 2017. Published by Elsevier B.V.

  17. The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Francisco Velasquez

    2017-04-01

    Full Text Available Social deficits in autism spectrum disorder (ASD are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task.

  18. A Chan Dietary Intervention Enhances Executive Functions and Anterior Cingulate Activity in Autism Spectrum Disorders: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Agnes S. Chan

    2012-01-01

    Full Text Available Executive dysfunctions have been found to be related to repetitive/disinhibited behaviors and social deficits in autism spectrum disorders (ASDs. This study aims to investigate the potential effect of a Shaolin-medicine-based dietary modification on improving executive functions and behavioral symptoms of ASD and exploring the possible underlying neurophysiological mechanisms. Twenty-four children with ASD were randomly assigned into the experimental (receiving dietary modification for one month and the control (no modification groups. Each child was assessed on his/her executive functions, behavioral problems based on parental ratings, and event-related electroencephalography (EEG activity during a response-monitoring task before and after the one month. The experimental group demonstrated significantly improved mental flexibility and inhibitory control after the diet modification, which continued to have a large effect size within the low-functioning subgroup. Such improvements coincided with positive evaluations by their parents on social communication abilities and flexible inhibitory control of daily behaviors and significantly enhanced event-related EEG activity at the rostral and subgenual anterior cingulate cortex. In contrast, the control group did not show any significant improvements. These positive outcomes of a one-month dietary modification on children with ASD have implicated its potential clinical applicability for patients with executive function deficits.

  19. Right anterior cingulate cortical thickness and bilateral striatal volume correlate with child behavior checklist aggressive behavior scores in healthy children.

    Science.gov (United States)

    Ducharme, Simon; Hudziak, James J; Botteron, Kelly N; Ganjavi, Hooman; Lepage, Claude; Collins, D Louis; Albaugh, Matthew D; Evans, Alan C; Karama, Sherif

    2011-08-01

    The anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. Data from 193 representative 6- to 18-year-old healthy children were obtained from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development after a blinded quality control. Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist. AGG scores were regressed against cortical thickness and basal ganglia volumes using first- and second-order linear models while controlling for age, gender, scanner site, and total brain volume. Gender by AGG interactions were analyzed. There were positive associations between bilateral striatal volumes and AGG scores (right: r = .238, p = .001; left: r = .188, p = .01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p right ACC cortex. An AGG by gender interaction trend was found in bilateral OFC and ACC associations with AGG scores. This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender-specific patterns of association in OFC/ACC gray matter. These results may guide research on oppositional-defiant and conduct disorders. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Functional Alterations of Postcentral Gyrus Modulated by Angry Facial Expressions during Intraoral Tactile Stimuli in Patients with Burning Mouth Syndrome: A Functional Magnetic Resonance Imaging Study

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    Atsuo Yoshino

    2017-11-01

    Full Text Available Previous findings suggest that negative emotions could influence abnormal sensory perception in burning mouth syndrome (BMS. However, few studies have investigated the underlying neural mechanisms associated with BMS. We examined activation of brain regions in response to intraoral tactile stimuli when modulated by angry facial expressions. We performed functional magnetic resonance imaging on a group of 27 BMS patients and 21 age-matched healthy controls. Tactile stimuli were presented during different emotional contexts, which were induced via the continuous presentation of angry or neutral pictures of human faces. BMS patients exhibited higher tactile ratings and greater activation in the postcentral gyrus during the presentation of tactile stimuli involving angry faces relative to controls. Significant positive correlations between changes in brain activation elicited by angry facial images in the postcentral gyrus and changes in tactile rating scores by angry facial images were found for both groups. For BMS patients, there was a significant positive correlation between changes in tactile-related activation of the postcentral gyrus elicited by angry facial expressions and pain intensity in daily life. Findings suggest that neural responses in the postcentral gyrus are more strongly affected by angry facial expressions in BMS patients, which may reflect one possible mechanism underlying impaired somatosensory system function in this disorder.

  1. Poor receptive joint attention skills are associated with atypical gray matter asymmetry in the posterior superior temporal gyrus of chimpanzees (Pan troglodytes)

    DEFF Research Database (Denmark)

    Hopkins, William D; Misiura, Maria; Reamer, Lisa A

    2014-01-01

    Clinical and experimental data have implicated the posterior superior temporal gyrus as an important cortical region in the processing of socially relevant stimuli such as gaze following, eye direction, and head orientation. Gaze following and responding to different socio-communicative signals i...

  2. Evidence of a posterior cingulate involvement (Brodmann area 31) in dyslexia: a study based on source localization algorithm of event-related potentials.

    Science.gov (United States)

    Stoitsis, John; Giannakakis, Giorgos A; Papageorgiou, Charalabos; Nikita, Konstantina S; Rabavilas, Andreas; Anagnostopoulos, Dimitris

    2008-04-01

    The study investigates the differences regarding the position of intracranial generators of P50 component of ERPs in 38 dyslexic children aged 11.47+/-2.12 years compared with their 19 healthy siblings aged 12.21+/-2.25. The dipoles were extracted by solving the inverse electromagnetic problem according to the recursively applied and projected multiple signal classification (RAP-MUSIC) algorithm approach. For improved localization of the main dipole the solutions were optimized using genetic algorithms. The statistical analysis revealed differences regarding the position of intracranial generators of low frequency of P50. Particularly, dyslexics showed main activity being located at posterior cingulate cortex (Brodmann's area 31) while controls exhibited main activity being located at retrosplenial cortex (Brodmann's area 30). These results may indicate a role for the posterior cingulate cortex in the pre-attentive processing operation of dyslexia beyond of its traditional function in terms of spatial attention and motor intention.

  3. Interleukin-1β increases neuronal death in the hippocampal dentate gyrus associated with status epilepticus in the developing rat.

    Science.gov (United States)

    Rincón-López, C; Tlapa-Pale, A; Medel-Matus, J-S; Martínez-Quiroz, J; Rodríguez-Landa, J F; López-Meraz, M-L

    Interleukin-1β (IL-1β) increases necrotic neuronal cell death in the CA1 area after induced status epilepticus (SE) in developing rats. However, it remains uncertain whether IL-1β has a similar effect on the hippocampal dentate gyrus (DG). In this study, we analysed the effects of IL-1β on 14-day-old Wistar rats experiencing DG neuronal death induced by SE. SE was induced with lithium-pilocarpine. Six hours after SE onset, a group of pups was injected with IL-1β (at 0, 0.3, 3, 30, or 300ng/μL) in the right ventricle; another group was injected with IL-1β receptor (IL-1R1) antagonist (IL-1Ra, at 30ng/μL) of IL-1RI antagonist (IL-1Ra) alone, and additional group with 30ng/μL of IL-1Ra plus 3ng/μL of IL-1β. Twenty-four hours after SE onset, neuronal cell death in the dentate gyrus of the dorsal hippocampus was assessed using haematoxylin-eosin staining. Dead cells showed eosinophilic cytoplasm and condensed and fragmented nuclei. We observed an increased number of eosinophilic cells in the hippocampal DG ipsilateral to the site of injection of 3ng/μL and 300ng/μL of IL-1β in comparison with the vehicle group. A similar effect was observed in the hippocampal DG contralateral to the site of injection of 3ng/μL of IL-1β. Administration of both of IL-1β and IL-1Ra failed to prevent an increase in the number of eosinophilic cells. Our data suggest that IL-1β increases apoptotic neuronal cell death caused by SE in the hippocampal GD, which is a mechanism independent of IL-1RI activation. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Effects of Environmental Enrichment on Doublecortin and BDNF Expression along the Dorso-Ventral Axis of the Dentate Gyrus.

    Science.gov (United States)

    Gualtieri, Fabio; Brégère, Catherine; Laws, Grace C; Armstrong, Elena A; Wylie, Nicholas J; Moxham, Theo T; Guzman, Raphael; Boswell, Timothy; Smulders, Tom V

    2017-01-01

    Adult hippocampal neurogenesis (AHN) in the dentate gyrus is known to respond to environmental enrichment, chronic stress, and many other factors. The function of AHN may vary across the septo-temporal axis of the hippocampus, as different subdivisions are responsible for different functions. The dorsal pole regulates cognitive-related behaviors, while the ventral pole mediates mood-related responses through the hypothalamic-pituitary-adrenal (HPA) axis. In this study, we investigate different methods of quantifying the effect of environmental enrichment on AHN in the dorsal and ventral parts of the dentate gyrus (dDG and vDG). To this purpose, 11-week-old female CD-1 mice were assigned for 8 days to one of two conditions: the Environmental Enrichment (E) group received (i) running wheels, (ii) larger cages, (iii) plastic tunnels, and (iv) bedding with male urine, while the Control (C) group received standard housing. Dorsal CA (Cornu Ammonis) and DG regions were larger in the E than the C animals. Distance run linearly predicted the volume of the dorsal hippocampus, as well as of the intermediate and ventral CA regions. In the dDG, the amount of Doublecortin (DCX) immunoreactivity was significantly higher in E than in C mice. Surprisingly, this pattern was the opposite in the vDG (C > E). Real-time PCR measurement of Dcx mRNA and DCX protein analysis using ELISA showed the same pattern. Brain Derived Neurotrophic Factor (BDNF) immunoreactivity and mRNA displayed no difference between E and C, suggesting that upregulation of DCX was not caused by changes in BDNF levels. BDNF levels were higher in vDG than in dDG, as measured by both methods. Bdnf expression in vDG correlated positively with the distance run by individual E mice. The similarity in the patterns of immunoreactivity, mRNA and protein for differential DCX expression and for BDNF distribution suggests that the latter two methods might be effective tools for more rapid quantification of AHN.

  5. Dentate Gyrus Contributes to Retrieval as well as Encoding: Evidence from Context Fear Conditioning, Recall, and Extinction.

    Science.gov (United States)

    Bernier, Brian E; Lacagnina, Anthony F; Ayoub, Adam; Shue, Francis; Zemelman, Boris V; Krasne, Franklin B; Drew, Michael R

    2017-06-28

    Dentate gyrus (DG) is widely thought to provide a teaching signal that enables hippocampal encoding of memories, but its role during retrieval is poorly understood. Some data and models suggest that DG plays no role in retrieval; others encourage the opposite conclusion. To resolve this controversy, we evaluated the effects of optogenetic inhibition of dorsal DG during context fear conditioning, recall, generalization, and extinction in male mice. We found that (1) inhibition during training impaired context fear acquisition; (2) inhibition during recall did not impair fear expression in the training context, unless mice had to distinguish between similar feared and neutral contexts; (3) inhibition increased generalization of fear to an unfamiliar context that was similar to a feared one and impaired fear expression in the conditioned context when it was similar to a neutral one; and (4) inhibition impaired fear extinction. These effects, as well as several seemingly contradictory published findings, could be reproduced by BACON (Bayesian Context Fear Algorithm), a physiologically realistic hippocampal model positing that acquisition and retrieval both involve coordinated activity in DG and CA3. Our findings thus suggest that DG contributes to retrieval and extinction, as well as to the initial establishment of context fear. SIGNIFICANCE STATEMENT Despite abundant evidence that the hippocampal dentate gyrus (DG) plays a critical role in memory, it remains unclear whether the role of DG relates to memory acquisition or retrieval. Using contextual fear conditioning and optogenetic inhibition, we show that DG contributes to both of these processes. Using computational simulations, we identify specific mechanisms through which the suppression of DG affects memory performance. Finally, we show that DG contributes to fear extinction learning, a process in which learned fear is attenuated through exposures to a fearful context in the absence of threat. Our data resolve a

  6. Glutamate Levels and Resting Cerebral Blood Flow in Anterior Cingulate Cortex Are Associated at Rest and Immediately Following Infusion of S-Ketamine in Healthy Volunteers

    OpenAIRE

    Kirsten Borup Bojesen; Kirsten Borup Bojesen; Kasper Aagaard Andersen; Kasper Aagaard Andersen; Kasper Aagaard Andersen; Sophie Nordahl Rasmussen; Sophie Nordahl Rasmussen; Sophie Nordahl Rasmussen; Lone Baandrup; Line Malmer Madsen; Birte Yding Glenthøj; Birte Yding Glenthøj; Egill Rostrup; Brian Villumsen Broberg

    2018-01-01

    Progressive loss of brain tissue is seen in some patients with schizophrenia and might be caused by increased levels of glutamate and resting cerebral blood flow (rCBF) alterations. Animal studies suggest that the normalisation of glutamate levels decreases rCBF and prevents structural changes in hippocampus. However, the relationship between glutamate and rCBF in anterior cingulate cortex (ACC) of humans has not been studied in the absence of antipsychotics and illness chronicity. Ketamine i...

  7. Efferents of anterior cingulate areas 24a and 24b and midcingulate areas 24a' and 24b' in the mouse.

    Science.gov (United States)

    Fillinger, Clémentine; Yalcin, Ipek; Barrot, Michel; Veinante, Pierre

    2017-12-06

    The anterior cingulate cortex (ACC), constituted by areas 25, 32, 24a and 24b in rodents, plays a major role in cognition, emotion and pain. In a previous study, we described the afferents of areas 24a and 24b and those of areas 24a' and 24b' of midcingulate cortex (MCC) in mice and highlighted some density differences among cingulate inputs (Fillinger et al., Brain Struct Funct 222:1509-1532, 2017). To complete this connectome, we analyzed here the efferents of ACC and MCC by injecting anterograde tracers in areas 24a/24b of ACC and 24a'/24b' of MCC. Our results reveal a common projections pattern from both ACC and MCC, targeting the cortical mantle (intracingulate, retrosplenial and parietal associative cortex), the non-cortical basal forebrain, (dorsal striatum, septum, claustrum, basolateral amygdala), the hypothalamus (anterior, lateral, posterior), the thalamus (anterior, laterodorsal, ventral, mediodorsal, midline and intralaminar nuclei), the brainstem (periaqueductal gray, superior colliculus, pontomesencephalic reticular formation, pontine nuclei, tegmental nuclei) and the spinal cord. In addition to an overall denser ACC projection pattern compared to MCC, our analysis revealed clear differences in the density and topography of efferents between ACC and MCC, as well as between dorsal (24b/24b') and ventral (24a/24a') areas, suggesting a common functionality of these two cingulate regions supplemented by specific roles of each area. These results provide a detailed analysis of the efferents of the mouse areas 24a/24b and 24a'/24b' and achieve the description of the cingulate connectome, which bring the anatomical basis necessary to address the roles of ACC and MCC in mice.

  8. Regional Metabolic Changes in the Hippocampus and Posterior Cingulate Area Detected with 3-Tesla Magnetic Resonance Spectroscopy in Patients with Mild Cognitive Impairment and Alzheimer Disease

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    Zhiqun Wang; Cheng Zhao; Kuncheng Li (Dept. of Radiology, Xuanwu Hospital, Capital Medical Univ., Beijing (China)); Lei Yu; Weidong Zhou (Dept. of Neurology, Xuanwu Hospital, Capital Medical Univ., Beijing (China))

    2009-04-15

    Background: Magnetic resonance spectroscopy (MRS) plays an important role in early diagnosis of Alzheimer disease (AD). There are many reports on MRS studies among individuals with AD and mild cognitive impairment (MCI). However, very few studies have compared spectroscopic data of different limbic regions among AD and MCI subjects. Purpose: To compare metabolite changes of different regions in the brain of AD and MCI patients by using 3.0T short-echo-time MRS. Material and Methods: Metabolite ratios in the hippocampus and posterior cingulate area were compared in a group of patients with AD (n=16), MCI (n=16), and normal subjects as a control group (n=16). Clinical neuropsychological tests were measured in all subjects. Results: In the hippocampus, there were significant differences in N-acetylaspartate (NAA)/creatine (Cr), myo-inositol (mI)/Cr, and mI/NAA ratios among the three groups. However, there were no significant differences in choline (Cho)/Cr ratio among the three groups. In the posterior cingulate area, there were no significant differences in the NAA/Cr, Cho/Cr, and mI/Cr ratios among the three groups. However, there were significant differences in mI/NAA ratio between patients with AD and the control group, and between the AD and MCI groups. In addition, there was significant correlation between mI/NAA ratio and Mini Mental Status Exam (MMSE) score in subjects with AD and MCI. Conclusion: The study reveals that the elevation of mI/NAA ratio in the hippocampus is more significant than that in the posterior cingulate area, which corresponds to the pathologic procession of AD. The ratios of mI/NAA in the hippocampus and in the posterior cingulate area together provide valuable discrimination among the three groups (AD, MCI, and controls). There is a significant correlation between mI/NAA ratio and cognitive decline.

  9. Low serotonin1B receptor binding potential in the anterior cingulate cortex in drug-free patients with recurrent major depressive disorder.

    Science.gov (United States)

    Tiger, Mikael; Farde, Lars; Rück, Christian; Varrone, Andrea; Forsberg, Anton; Lindefors, Nils; Halldin, Christer; Lundberg, Johan

    2016-07-30

    The pathophysiology of major depressive disorder (MDD) is not fully understood and the diagnosis is largely based on history and clinical examination. So far, several lines of preclinical data and a single imaging study implicate a role for the serotonin1B (5-HT1B) receptor subtype. We sought to study 5-HT1B receptor binding in brain regions of reported relevance in patients with MDD. Subjects were examined at the Karolinska Institutet PET centre using positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369. Ten drug-free patients with recurrent MDD and ten control subjects matched for age and sex were examined. The main outcome measure was [(11)C]AZ10419369 binding in brain regions of reported relevance in the pathophysiology of MDD. The [(11)C]AZ10419369 binding potential was significantly lower in the MDD group compared with the healthy control group in the anterior cingulate cortex (20% between-group difference), the subgenual prefrontal cortex (17% between-group difference), and in the hippocampus (32% between-group difference). The low anterior cingulate [(11)C]AZ10419369 binding potential in patients with recurrent MDD positions 5-HT1B receptor binding in this region as a putative biomarker for MDD and corroborate a role of the anterior cingulate cortex and associated areas in the pathophysiology of recurrent MDD. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  10. Proton magnetic resonance spectroscopy assessment of metabolite status of the anterior cingulate cortex in chronic pain patients and healthy controls

    Directory of Open Access Journals (Sweden)

    Ito T

    2017-01-01

    Full Text Available Takahiro Ito,1 Sachiko Tanaka-Mizuno,2,3 Narihito Iwashita,4 Ikuo Tooyama,5 Akihiko Shiino,6 Katsuyuki Miura,1,7 Sei Fukui4 1Department of Public Health, Shiga University of Medical Science, 2Department of Medical Statistics, Shiga University of Medical Science, Otsu, Japan; 3The Center for Data Science Education and Research, Shiga University, Hikone, Japan; 4Department of Anesthesiology, Interdisciplinary Pain Management Center, Shiga University of Medical Science Hospital, 5Molecular Neuroscience Research Center, Shiga University of Medical Science, 6Biomedical MR Science Center, Shiga University of Medical Science, 7Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan Background: Chronic pain is a common cause of reduced quality of life. Recent studies suggest that chronic pain patients have a different brain neurometabolic status to healthy people. Proton magnetic resonance spectroscopy (1H-MRS can determine the concentrations of metabolites in a specific region of the brain without being invasive. Patients and methods: We recruited 56 chronic pain patients and 60 healthy controls to compare brain metabolic characteristics. The concentrations of glutamic acid (Glu, myo-inositol (Ins, N-acetylaspartate (NAA, Glu + glutamine (Glx, and creatine + phosphocreatine (total creatine [tCr] in the anterior cingulate cortex of participants were measured using 1H-MRS. We used age- and gender-adjusted general linear models and receiver-operating characteristic analyses for this investigation. Patients were also assessed using the Hospital Anxiety and Depression Scale (HADS to reveal the existence of any mental health issues. Results: Our analysis indicates that pain patients have statistically significantly higher levels of Glu/tCr (p=0.039 and Glx/tCr (p<0.001 and lower levels of NAA/tCr than controls, although this did not reach statistical significance (p=0.052. Receiver-operating characteristic analysis

  11. Fatty acid composition of the anterior cingulate cortex indicates a high susceptibility to lipid peroxidation in Parkinson's disease.

    Science.gov (United States)

    Abbott, Sarah K; Jenner, Andrew M; Spiro, Adena S; Batterham, Marijka; Halliday, Glenda M; Garner, Brett

    2015-01-01

    Oxidative stress contributes to Parkinson's disease (PD) etiology. Although previous studies have focused on sources of free radical formation in brain regions affected by PD, less is known regarding changes in lipid composition and the implications for susceptibility to peroxidation. To assess fatty acid profiles from control and PD tissues that are susceptible to PD pathology but devoid of severe destruction. We used gas chromatography methods to assess fatty acid profiles from control (n = 10) and PD (n = 9) postmortem tissues. We focused on the anterior cingulate cortex (ACC), a region that accumulates alpha-synuclein, but does not undergo severe destruction, and compared this to the occipital cortex, a region that is pathologically spared. Our data indicate a significant 33% increase in the proportion of polyunsaturated fatty acids (mol%) present in the PD ACC as compared to control ACC. Increases in highly unsaturated 22:5n-6 and 22:6n-3 fatty acids were particularly pronounced (109% and 73%, respectively). Calculation of a peroxidation index (accounting for total fatty acyl double bounds) indicated a 44% increase in susceptibility of the PD ACC to lipid peroxidation compared to control ACC. Such differences were not detected in the occipital cortex from the same donors. Assessment of F2-isprostane levels confirmed that PD tissue lipids were more oxidized than controls. The global composition of fatty acids in the PD ACC is altered in a way that increases susceptibility to peroxidation in a region-specific manner. This has important implications for PD, supporting the oxidative stress hypothesis of PD pathogenesis.

  12. Meditation reduces pain-related neural activity in the anterior cingulate cortex, insula, secondary somatosensory cortex, and thalamus.

    Directory of Open Access Journals (Sweden)

    Hiroki eNakata

    2014-12-01

    Full Text Available Recent studies have shown that meditation inhibits or relieves pain perception. To clarify the underlying mechanisms for this phenomenon, neuroimaging methods, such as functional magnetic resonance imaging (fMRI, and neurophysiological methods, such as magnetoencephalography (MEG and electroencephalography (EEG, have been used. However, it has been difficult to interpret the results, because there is some paradoxical evidence. For example, some studies reported increased neural responses to pain stimulation during meditation in the anterior cingulate cortex (ACC and insula, whereas others showed a decrease in these regions. There have been inconsistent findings to date. Moreover, in general, since the activities of the ACC and insula are correlated with pain perception, the increase in neural activities during meditation would be related to the enhancement of pain perception rather than its reduction. These contradictions might directly contribute to the ‘mystery of meditation’. In this review, we presented previous findings for brain regions during meditation and the anatomical changes that occurred in the brain with long-term meditation training. We then discussed the findings of previous studies that examined pain-related neural activity during meditation. We also described the brain mechanisms responsible for pain relief during meditation, and possible reasons for paradoxical evidence among previous studies. By thoroughly overviewing previous findings, we hypothesized that meditation reduces pain-related neural activity in the ACC, insula, secondary somatosensory cortex, and thalamus. We suggest that the characteristics of the modulation of this activity may depend on the kind of meditation and/or number of years of experience of meditation, which were associated with paradoxical findings among previous studies that investigated pain-related neural activities during meditation.

  13. Interference and conflict monitoring in individuals with amnestic mild cognitive impairment: A structural study of the anterior cingulate cortex.

    Science.gov (United States)

    Borsa, Virginia M; Della Rosa, Pasquale A; Catricalà, Eleonora; Canini, Matteo; Iadanza, Antonella; Falini, Andrea; Abutalebi, Jubin; Iannaccone, Sandro

    2016-05-04

    Amnestic mild cognitive impairment (aMCI) is a clinical condition characterized by memory impairment in the absence of any other cognitive impairment and is commonly associated with high conversion to Alzheimer's disease. Recent evidence shows that executive functions and selective attention mechanisms could also be impaired in aMCI. In this study, we investigated performance differences (i.e., reaction times [RTs] and accuracy) between a group of aMCI participants and a group of age-matched healthy individuals on the attentional network task (ANT) focusing on situations with increased interference. In particular, we assessed the relationship between interference and conflict effects and grey matter volumes (GMVs) of the anterior cingulate cortex (ACC)/pre-supplementary motor area in the entire sample because of its crucial role in conflict monitoring. When compared with controls, aMCI participants were less accurate on the ANT, showing increased interference and conflict effects, but no differences in RTs. In addition, aMCI participants exhibited lower GMV in the ACC than controls. While better accuracy for interference and conflict effects was associated with an increase of GMV in the ACC for both groups, RTs from the interference effect were negatively correlated with GMV of the ACC only in aMCI participants. In other words, lower GMV values of the ACC were paralleled with significantly impaired performance in terms of interference resolution. In conclusion, our study suggests the presence of a selective impairment in interference and conflict monitoring in aMCI, which in turn is associated with decreased GMVs in the ACC. © 2016 The British Psychological Society.

  14. Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice

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    Willias Masocha

    2015-10-01

    Full Text Available Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP in animal models. We examined glial fibrillary acidic protein (GFAP; an astrocyte marker immunoreactivity and gene expression of GFAP, glutamate transporters and receptor subunits by real time PCR in the anterior cingulate cortex (ACC at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. The ACC, an area in the brain involved in pain perception and modulation, was chosen because changes in this area might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold and GFAP immunoreactivity increased in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2 quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1 were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, with no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP.

  15. Comparison of anterior cingulate versus insular cortex as targets for real-time fMRI regulation during pain stimulation

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    Kirsten eEmmert

    2014-10-01

    Full Text Available Real-time functional magnetic resonance imaging (rt-fMRI neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network i.e. the anterior insular cortex (AIC and the anterior cingulate cortex (ACC.Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the feedback signal in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis.At the behavioral level, pain ratings significantly decreased during feedback versus localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28 in both task-related and functional connectivity analysis. The functional connectivity towards the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex.Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain

  16. Women's Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex.

    Science.gov (United States)

    Nakagawa, Jun; Takahashi, Muneyoshi; Okada, Rieko; Matsushima, Eisuke; Matsuda, Tetsuya

    2015-01-01

    Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman's perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift's social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift's social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant's attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods--preference for the member is a powerful modulator of social reward processing.

  17. Women's Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex.

    Directory of Open Access Journals (Sweden)

    Jun Nakagawa

    Full Text Available Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman's perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1 the giver and (2 the type of the gift (the gift's social meaning. In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift's social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1 the female participant's attitude toward the male acquaintance (liked vs. uninteresting and (2 the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]. We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC, an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods--preference for the member is a powerful modulator of social reward processing.

  18. Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making.

    Science.gov (United States)

    Khani, Abbas; Kermani, Mojtaba; Hesam, Soghra; Haghparast, Abbas; Argandoña, Enrike G; Rainer, Gregor

    2015-06-01

    Despite the evidence for altered decision making in cannabis abusers, the role of the cannabinoid system in decision-making circuits has not been studied. Here, we examined the effects of cannabinoid modulation during cost-benefit decision making in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), key brain areas involved in decision making. We trained different groups of rats in a delay-based and an effort-based form of cost-benefit T-maze decision-making task. During test days, the rats received local injections of either vehicle or ACEA, a cannabinoid type-1 receptor (CB1R) agonist in the ACC or OFC. We measured spontaneous locomotor activity following the same treatments and characterized CB1Rs localization on different neuronal populations within these regions using immunohistochemistry. We showed that CB1R activation in the ACC impaired decision making such that rats were less willing to invest physical effort to gain high reward. Similarly, CB1R activation in the OFC induced impulsive pattern of choice such that rats preferred small immediate rewards to large delayed rewards. Control tasks ensured that the effects were specific for differential cost-benefit tasks. Furthermore, we characterized widespread colocalizations of CB1Rs on GABAergic axonal ends but few colocalizations on glutamatergic, dopaminergic, and serotonergic neuronal ends. These results provide first direct evidence that the cannabinoid system plays a critical role in regulating cost-benefit decision making in the ACC and OFC and implicate cannabinoid modulation of synaptic ends of predominantly interneurons and to a lesser degree other neuronal populations in these two frontal regions.

  19. Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients.

    Science.gov (United States)

    Carmi, Lior; Alyagon, Uri; Barnea-Ygael, Noam; Zohar, Joseph; Dar, Reuven; Zangen, Abraham

    Obsessive Compulsive Disorder (OCD) is a chronic and disabling disorder with poor response to pharmacological treatments. Converging evidences suggest that OCD patients suffer from dysfunction of the cortico-striato-thalamo-cortical (CSTC) circuit, including in the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC). To examine whether modulation of mPFC-ACC activity by deep transcranial magnetic stimulation (DTMS) affects OCD symptoms. Treatment resistant OCD participants were treated with either high-frequency (HF; 20 Hz), low-frequency (LF; 1 Hz), or sham DTMS of the mPFC and ACC for five weeks, in a double-blinded manner. All treatments were administered following symptoms provocation, and EEG measurements during a Stroop task were acquired to examine changes in error-related activity. Clinical response to treatment was determined using the Yale-Brown-Obsessive-Compulsive Scale (YBOCS). Interim analysis revealed that YBOCS scores were significantly improved following HF (n = 7), but not LF stimulation (n = 8), compared to sham (n = 8), and thus recruitment for the LF group was terminated. Following completion of the study, the response rate in the HF group (n = 18) was significantly higher than that of the sham group (n = 15) for at least one month following the end of the treatment. Notably, the clinical response in the HF group correlated with increased Error Related Negativity (ERN) in the Stroop task, an electrophysiological component that is attributed to ACC activity. HF DTMS over the mPFC-ACC alleviates OCD symptoms and may be used as a novel therapeutic intervention. Notwithstanding alternative explanations, this may stem from DTMS ability to directly modify ACC activity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Effects of microinjection of histamine into the anterior cingulate cortex on pain-related behaviors induced by formalin in rats.

    Science.gov (United States)

    Hamzeh-Gooshchi, Nasrin; Tamaddonfard, Esmaeal; Farshid, Amir Abbas

    2015-06-01

    The present study was aimed to investigate the effects of microinjection of histamine and its H1, H2 and H3 receptor antagonists, mepyramine, ranitidine and thioperamide, respectively, into the anterior cingulate cortex (ACC) on pain-related behaviors induced by formalin in rats. Two stainless steel guide canulas were bilaterally implanted into the ACC of anaesthetized rats. For induction of pain, intraplantar (ipl) injection of a 2.5% formalin solution was performed. The duration of paw licking/biting and the number of paw flinching were recorded in 5 min blocks for 60 min. Locomotor activity was assessed using an open-field test. Formalin produced a marked biphasic pattern of pain. Histamine reduced the second phases of paw licking/biting and flinching. Mepyramine (2 μg/side) prevented the suppressive effect of histamine (1 μg/side) on second phase of pain, but at a dose of 8 μg/side it did not inhibit the suppressive effects of 4 μg/side of histamine. Ranitidine at doses of 2 and 8 μg/side prevented histamine (1 and 4 μg/side)-induced antinociception. Thioperamide not only suppressed the second phases of pain, but also increased the suppressive effect of histamine. Naloxone prevented suppressive effects of histamine and thioperamide on pain. Mepyramine (8 μg/side) suppressed locomotor activity. The results of the present study showed pain suppressing effects for histamine. Histamine H2 and H3, and to a lesser extent, H1 receptors might be involved in histamine-induced antinociception. Opioid receptors might be involved in suppressive effects of histamine and thioperamide. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. Role of Anterior Cingulate Cortex in Instrumental Learning: Blockade of Dopamine D1 Receptors Suppresses Overt but Not Covert Learning

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    Mayada Aly-Mahmoud

    2017-05-01

    Full Text Available HIGHLIGHTSBlockade of dopamine D1 receptors in ACC suppressed instrumental learning when overt responding was required.Covert learning through observation was not impaired.After treatment with a dopamine antagonist, instrumental learning recovered but not the rat's pretreatment level of effort tolerance.ACC dopamine is not necessary for acquisition of task-relevant cues during learning, but regulates energy expenditure and effort based decision.Dopamine activity in anterior cingulate cortex (ACC is essential for various aspects of instrumental behavior, including learning and effort based decision making. To dissociate learning from physical effort, we studied both observational (covert learning, and trial-and-error (overt learning. If ACC dopamine activity is required for task acquisition, its blockade should impair both overt and covert learning. If dopamine is not required for task acquisition, but solely for regulating the willingness to expend effort for reward, i.e., effort tolerance, blockade should impair overt learning but spare covert learning. Rats learned to push a lever for food rewards either with or without prior observation of an expert conspecific performing the same task. Before daily testing sessions, the rats received bilateral ACC microinfusions of SCH23390, a dopamine D1 receptor antagonist, or saline-control infusions. We found that dopamine blockade suppressed overt responding selectively, leaving covert task acquisition through observational learning intact. In subsequent testing sessions without dopamine blockade, rats recovered their overt-learning capacity but not their pre-treatment level of effort tolerance. These results suggest that ACC dopamine is not required for the acquisition of conditioned behaviors and that apparent learning impairments could instead reflect a reduced level of willingness to expend effort due to cortical dopamine blockade.

  2. Differential regulation of observational fear and neural oscillations by serotonin and dopamine in the mouse anterior cingulate cortex.

    Science.gov (United States)

    Kim, Byung Sun; Lee, Junghee; Bang, Minji; Seo, Bo Am; Khalid, Arshi; Jung, Min Whan; Jeon, Daejong

    2014-11-01

    The aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known. We investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity. An observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D1 receptor antagonist), or haloperidol (DA D2 receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo. The microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment. The current results demonstrated that DA D2 receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations.

  3. Role of Anterior Cingulate Cortex in Instrumental Learning: Blockade of Dopamine D1 Receptors Suppresses Overt but Not Covert Learning.

    Science.gov (United States)

    Aly-Mahmoud, Mayada; Carlier, Pascal; Salam, Sherine A; Houari Selmani, Mariam; Moftah, Marie Z; Esclapez, Monique; Boussaoud, Driss

    2017-01-01

    HIGHLIGHTS Blockade of dopamine D1 receptors in ACC suppressed instrumental learning when overt responding was required.Covert learning through observation was not impaired.After treatment with a dopamine antagonist, instrumental learning recovered but not the rat's pretreatment level of effort tolerance.ACC dopamine is not necessary for acquisition of task-relevant cues during learning, but regulates energy expenditure and effort based decision. Dopamine activity in anterior cingulate cortex (ACC) is essential for various aspects of instrumental behavior, including learning and effort based decision making. To dissociate learning from physical effort, we studied both observational (covert) learning, and trial-and-error (overt) learning. If ACC dopamine activity is required for task acquisition, its blockade should impair both overt and covert learning. If dopamine is not required for task acquisition, but solely for regulating the willingness to expend effort for reward, i.e., effort tolerance, blockade should impair overt learning but spare covert learning. Rats learned to push a lever for food rewards either with or without prior observation of an expert conspecific performing the same task. Before daily testing sessions, the rats received bilateral ACC microinfusions of SCH23390, a dopamine D1 receptor antagonist, or saline-control infusions. We found that dopamine blockade suppressed overt responding selectively, leaving covert task acquisition through observational learning intact. In subsequent testing sessions without dopamine blockade, rats recovered their overt-learning capacity but not their pre-treatment level of effort tolerance. These results suggest that ACC dopamine is not required for the acquisition of conditioned behaviors and that apparent learning impairments could instead reflect a reduced level of willingness to expend effort due to cortical dopamine blockade.

  4. Cortical thinning in the anterior cingulate cortex predicts multiple sclerosis patients' fluency performance in a lateralised manner.

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    Geisseler, Olivia; Pflugshaupt, Tobias; Bezzola, Ladina; Reuter, Katja; Weller, David; Schuknecht, Bernhard; Brugger, Peter; Linnebank, Michael

    2016-01-01

    Cognitive impairment is as an important feature of Multiple Sclerosis (MS), and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters - including cortical thinning and T2 lesion load - to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal - but not figural - fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology.

  5. Meditation reduces pain-related neural activity in the anterior cingulate cortex, insula, secondary somatosensory cortex, and thalamus

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    Nakata, Hiroki; Sakamoto, Kiwako; Kakigi, Ryusuke

    2014-01-01

    Recent studies have shown that meditation inhibits or relieves pain perception. To clarify the underlying mechanisms for this phenomenon, neuroimaging methods, such as functional magnetic resonance imaging, and neurophysiological methods, such as magnetoencephalography and electroencephalography, have been used. However, it has been difficult to interpret the results, because there is some paradoxical evidence. For example, some studies reported increased neural responses to pain stimulation during meditation in the anterior cingulate cortex (ACC) and insula, whereas others showed a decrease in these regions. There have been inconsistent findings to date. Moreover, in general, since the activities of the ACC and insula are correlated with pain perception, the increase in neural activities during meditation would be related to the enhancement of pain perception rather than its reduction. These contradictions might directly contribute to the ‘mystery of meditation.’ In this review, we presented previous findings for brain regions during meditation and the anatomical changes that occurred in the brain with long-term meditation training. We then discussed the findings of previous studies that examined pain-related neural activity during meditation. We also described the brain mechanisms responsible for pain relief during meditation, and possible reasons for paradoxical evidence among previous studies. By thoroughly overviewing previous findings, we hypothesized that meditation reduces pain-related neural activity in the ACC, insula, secondary somatosensory cortex, and thalamus. We suggest that the characteristics of the modulation of this activity may depend on the kind of meditation and/or number of years of experience of meditation, which were associated with paradoxical findings among previous studies that investigated pain-related neural activities during meditation. PMID:25566158

  6. Anterior cingulate volume predicts response to psychotherapy and functional connectivity with the inferior parietal cortex in major depressive disorder.

    Science.gov (United States)

    Sambataro, Fabio; Doerig, Nadja; Hänggi, Jürgen; Wolf, Robert Christian; Brakowski, Janis; Holtforth, Martin Grosse; Seifritz, Erich; Spinelli, Simona

    2018-01-01

    In major depressive disorder (MDD), the anterior cingulate cortex (ACC) has been associated with clinical outcome as well as with antidepressant treatment response. Nonetheless, the association between individual differences in ACC structure and function and the response to cognitive behavioral therapy (CBT) is still unexplored. For this aim, twenty-five unmedicated patients with MDD were scanned with structural and resting state functional magnetic resonance imaging before the beginning of CBT treatment. ACC morphometry was correlated with clinical changes following psychotherapy. Furthermore, whole-brain resting state functional connectivity with the ACC was correlated with clinical measures. Greater volume in the left subgenual (subACC), the right pregenual (preACC), and the bilateral supragenual (supACC) predicted depressive symptoms improvement after CBT. Greater subACC volume was related to stronger functional connectivity with the inferior parietal cortex and dorsolateral prefrontal cortex. Stronger subACC-inferior parietal cortex connectivity correlated with greater adaptive rumination. Greater preACC volume was associated with stronger functional connectivity with the inferior parietal cortex and ventrolateral prefrontal cortex. In contrast, greater right supACC volume was related to lower functional connectivity with the inferior parietal cortex. These results suggest that ACC volume and its functional connectivity with the fronto-parietal cortex are associated with CBT response in MDD, and this may be mediated by adaptive forms of rumination. Our findings support the role of the subACC as a potential predictor for CBT response. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  7. Cortical thinning in the anterior cingulate cortex predicts multiple sclerosis patients' fluency performance in a lateralised manner

    Directory of Open Access Journals (Sweden)

    Olivia Geisseler

    2016-01-01

    Full Text Available Cognitive impairment is as an important feature of Multiple Sclerosis (MS, and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters – including cortical thinning and T2 lesion load – to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal – but not figural – fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology.

  8. Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia.

    Science.gov (United States)

    Cordes, Julia S; Mathiak, Krystyna A; Dyck, Miriam; Alawi, Eliza M; Gaber, Tilman J; Zepf, Florian D; Klasen, Martin; Zvyagintsev, Mikhail; Gur, Ruben C; Mathiak, Klaus

    2015-01-01

    Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF) seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC), a central hub for cognitive processing, is one of the brain regions known to be dysfunctional in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI) in patients with schizophrenia to enable them to control their ACC activity. Training was performed over 3 days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI). Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. In a stepwise regression analysis, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, patients with schizophrenia can learn to regulate localized brain activity. However, cognitive strategies and neural network location differ from healthy controls. These data emphasize that for therapeutic interventions in patients with schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social NF based on fMRI may be one method to accomplish precise learning targets.

  9. Activation of the serotonergic system by pedaling exercise changes anterior cingulate cortex activity and improves negative emotion.

    Science.gov (United States)

    Ohmatsu, Satoko; Nakano, Hideki; Tominaga, Takanori; Terakawa, Yuzo; Murata, Takaho; Morioka, Shu

    2014-08-15

    Pedaling exercise (PE) of moderate intensity has been shown to ease anxiety and discomfort; however, little is known of the changes that occur in brain activities and in the serotonergic (5-HT) system after PE. Therefore, this study was conducted for the following reasons: (1) to localize the changes in the brain activities induced by PE using a distributed source localization algorithm, (2) to examine the changes in frontal asymmetry, as used in the Davidson model, with electroencephalography (EEG) activity, and (3) to examine the effect of PE on the 5-HT system. A 32-channel EEG was used to record before and after PE. Profile of Mood States tests indicated that there was a significant decrease in tension-anxiety and a significant increase in vigor after PE. A standardized low-resolution brain electromagnetic tomography analysis showed a significant decrease in brain activities after PE in the alpha-2 band (10-12.5 Hz) in the anterior cingulate cortex (ACC). Moreover, a significant increase in frontal EEG asymmetry was observed after PE in the alpha-1 band (7.5-10 Hz). Urine 5-HT levels significantly increased after PE. Urine 5-HT levels positively correlated with the degree of frontal EEG asymmetry in the alpha-1 band and negatively correlated with brain activity in ACC. Our results suggested that PE activates the 5-HT system and consequently induces increases in frontal EEG asymmetry in the alpha-1 band and reductions of brain activity in the alpha-2 band in the ACC region. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Inflammatory pain by carrageenan recruits low-frequency local field potential changes in the anterior cingulate cortex.

    Science.gov (United States)

    Harris-Bozer, Amber L; Peng, Yuan B

    2016-10-06

    The anterior cingulate cortex (ACC) has been extensively cited as a key area for processing pain affect. While local field potential (LFP) studies in other fields have yielded a great deal of information about neural oscillations, there is a poverty in the pain literature about the neural LFP profile related to pain, particularly in freely moving animals. In this study, we revealed the LFP profile in the ACC in freely moving rats during carrageenan inflammation. Mechanical allodynia was recorded before and after unilateral injection of carrageenan/saline in the left hindpaw. LFP activity in the ACC was recorded at baseline, after injection, and after injection with mechanical stimulation to the paw using a von Frey filament. This study uniquely reveals that carrageenan injection significantly recruited ACC LFP activity in delta, theta, and alpha bands (0-13Hz). Application of von Frey mechanical stimulation to the carrageenan-injected paw resulted in a significant increase in delta, theta, and alpha bands over and above what was recruited by carrageenan alone and further expanded the LFP range to additionally include beta activity (13-30Hz). Taken together, these data reveal significant changes in the lowest-frequency activities in the LFP range during painful inflammation, which merit attention. LFP is a powerful window to reveal wide-range, integrated synaptic processing by low-frequency cellular events during behavior. Information about LFP during pain broadens the scope of our understanding of pain mechanisms, our greatest resource for designing management approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure

    Science.gov (United States)

    Migliorini, Robyn; Moore, Eileen M.; Glass, Leila; Infante, M. Alejandra; Tapert, Susan F.; Jones, Kenneth Lyons; Mattson, Sarah N.; Riley, Edward P.

    2015-01-01

    Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure correlates of this deficit have not been determined with sufficient detail. We examined the hypothesis that the structure of the anterior cingulate cortex (ACC) relates to inhibition performance in youth with histories of heavy prenatal alcohol exposure (AE, n = 32) and non-exposed controls (CON, n = 21). Adolescents (12–17 years) underwent structural magnetic resonance imaging yielding measures of gray matter volume, surface area, and thickness across four ACC subregions. A subset of subjects were administered the NEPSY-II Inhibition subtest. MANCOVA was utilized to test for group differences in ACC and inhibition performance and multiple linear regression was used to probe ACC-inhibition relationships. ACC surface area was significantly smaller in AE, though this effect was primarily driven by reduced right caudal ACC (rcACC). AE also performed significantly worse on inhibition speed but not on inhibition accuracy. Regression analyses with the rcACC revealed a significant group × ACC interaction. A smaller rcACC surface area was associated with slower inhibition completion time for AE but was not significantly associated with inhibition in CON. After accounting for processing speed, smaller rcACC surface area was associated with worse (i.e., slower) inhibition regardless of group. Examining processing speed independently, a decrease in rcACC surface area was associated with faster processing speed for CON but not significantly associated with processing speed in AE. Results support the theory that caudal ACC may monitor reaction time in addition to inhibition and highlight the possibility of delayed ACC neurodevelopment in prenatal alcohol exposure. PMID:26025509

  12. Assessment of Anterior Cingulate Cortex (ACC and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS.

    Directory of Open Access Journals (Sweden)

    Aya Goji

    Full Text Available Proton magnetic resonance spectroscopy (1H MRS is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger's syndrome (AS is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder.Study participants consisted of 34 children with AS (2-12 years old; mean age 5.2 (±2.0; 28 boys and 19 typically developed children (2-11 years old; mean age 5.6 (±2.6; 12 boys who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC and left cerebellum.In the ACC, levels of N-acetylaspartate (NAA, total creatine (tCr, total choline-containing compounds (tCho and myo-Inositol (mI were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions.The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.

  13. Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Julia S Cordes

    2015-06-01

    Full Text Available Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC, a central hub for cognitive processing, is one of the dysfunctional brain regions in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI in patients with schizophrenia to enable them to control their ACC activity. Training was performed over three days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI. Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: Patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. However, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, schizophrenia patients can learn to regulate localized brain activity. Cognitive strategies and neural network location differ, however, from healthy controls. These data emphasize that for therapeutic interventions in schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social neurofeedback based on fMRI may be one method to accomplish precise learning targets.

  14. Enhancing verbal creativity: modulating creativity by altering the balance between right and left inferior frontal gyrus with tDCS.

    Science.gov (United States)

    Mayseless, N; Shamay-Tsoory, S G

    2015-04-16

    Creativity is the production of novel ideas that have value. Previous research indicated that while regions in the right hemisphere are implicated in the production of new ideas, damage to the left inferior frontal gyrus (IFG) is associated with increased creativity, indicating that the left IFG damage may have a "releasing" effect on creativity. To examine this, in the present study we used transcranial direct current stimulation (tDCS) to modulate activity of the right and the left IFG. In the first experiment we show that whereas anodal tDCS over the right IFG coupled with cathodal tDCS over the left IFG increases creativity as measured by a verbal divergent thinking task, the reverse stimulation does not affect creative production. To further confirm that only altering the balance between the two hemispheres is crucial in modulating creativity, in the second experiment we show that stimulation targeting separately the left IFG (cathodal stimulation) or the right IFG (anodal stimulation) did not result in changes in creativity as measured by verbal divergent thinking. These findings support the balance hypothesis, according to which verbal creativity requires a balance of activation between the right and the left frontal lobes, and more specifically, between the right and the left IFG. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

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    Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Nakagawa, Shin [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takamura, Naoki [Pharmaceutical Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka (Japan); Kato, Akiko [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takebayashi, Minoru [Department of Psychiatry, National Hospital Organization Kure Medical Center, Kure (Japan); Hisaoka-Nakashima, Kazue [Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima (Japan); Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  16. Fatty acid synthase as a factor required for exercise-induced cognitive enhancement and dentate gyrus cellular proliferation.

    Science.gov (United States)

    Chorna, Nataliya E; Santos-Soto, Iván J; Carballeira, Nestor M; Morales, Joan L; de la Nuez, Janneliz; Cátala-Valentin, Alma; Chornyy, Anatoliy P; Vázquez-Montes, Adrinel; De Ortiz, Sandra Peña

    2013-01-01

    Voluntary running is a robust inducer of adult hippocampal neurogenesis. Given that fatty acid synthase (FASN), the key enzyme for de novo fatty acid biosynthesis, is critically involved in proliferation of embryonic and adult neural stem cells, we hypothesized that FASN could mediate both exercise-induced cell proliferation in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhancement of spatial learning and memory. In 20 week-old male mice, voluntary running-induced hippocampal-specific upregulation of FASN was accompanied also by hippocampal-specific accumulation of palmitate and stearate saturated fatty acids. In experiments addressing the functional role of FASN in our experimental model, chronic intracerebroventricular (i.c.v.) microinfusions of C75, an irreversible FASN inhibitor, and significantly impaired exercise-mediated improvements in spatial learning and memory in the Barnes maze. Unlike the vehicle-injected mice, the C75 group adopted a non-spatial serial escape strategy and displayed delayed escape latencies during acquisition and memory tests. Furthermore, pharmacologic blockade of FASN function with C75 resulted in a significant reduction, compared to vehicle treated controls, of the number of proliferative cells in the DG of running mice as measured by immunoreactive to Ki-67 in the SGZ. Taken together, our data suggest that FASN plays an important role in exercise-mediated cognitive enhancement, which might be associated to its role in modulating exercise-induced stimulation of neurogenesis.

  17. Fatty acid synthase as a factor required for exercise-induced cognitive enhancement and dentate gyrus cellular proliferation.

    Directory of Open Access Journals (Sweden)

    Nataliya E Chorna

    Full Text Available Voluntary running is a robust inducer of adult hippocampal neurogenesis. Given that fatty acid synthase (FASN, the key enzyme for de novo fatty acid biosynthesis, is critically involved in proliferation of embryonic and adult neural stem cells, we hypothesized that FASN could mediate both exercise-induced cell proliferation in the subgranular zone (SGZ of the dentate gyrus (DG and enhancement of spatial learning and memory. In 20 week-old male mice, voluntary running-induced hippocampal-specific upregulation of FASN was accompanied also by hippocampal-specific accumulation of palmitate and stearate saturated fatty acids. In experiments addressing the functional role of FASN in our experimental model, chronic intracerebroventricular (i.c.v. microinfusions of C75, an irreversible FASN inhibitor, and significantly impaired exercise-mediated improvements in spatial learning and memory in the Barnes maze. Unlike the vehicle-injected mice, the C75 group adopted a non-spatial serial escape strategy and displayed delayed escape latencies during acquisition and memory tests. Furthermore, pharmacologic blockade of FASN function with C75 resulted in a significant reduction, compared to vehicle treated controls, of the number of proliferative cells in the DG of running mice as measured by immunoreactive to Ki-67 in the SGZ. Taken together, our data suggest that FASN plays an important role in exercise-mediated cognitive enhancement, which might be associated to its role in modulating exercise-induced stimulation of neurogenesis.

  18. Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu

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    Jeremy D. Coplan

    2014-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1, and body mass index (BMI in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.

  19. Reward memory relieves anxiety-related behavior through synaptic strengthening and protein kinase C in dentate gyrus.

    Science.gov (United States)

    Lei, Zhuofan; Liu, Bei; Wang, Jin-Hui

    2016-04-01

    Anxiety disorders are presumably associated with negative memory. Psychological therapies are widely used to treat this mental deficit in human beings based on the view that positive memory competes with negative memory and relieves anxiety status. Cellular and molecular processes underlying psychological therapies remain elusive. Therefore, we have investigated its mechanisms based on a mouse model in which food reward at one open-arm of the elevated plus-maze was used for training mice to form reward memory and challenge the open arms. Mice with the reward training showed increased entries and stay time in reward open-arm versus neutral open-arm as well as in open-arms versus closed-arms. Accompanying with reward memory formation and anxiety relief, glutamatergic synaptic transmission in dentate gyrus in vivo and dendritic spines in granule cells became upregulated. This synaptic up-regulation was accompanied by the expression of more protein kinase C (PKC) in the dendritic spines. The inhibition of PKC by chelerythrine impaired the formation of reward memory, the relief of anxiety-related behavior and the up-regulation of glutamate synapses. Our results suggest that reward-induced positive memory relieves mouse anxiety-related behavior by strengthening synaptic efficacy and PKC in the hippocampus, which imply the underlying cellular and molecular processes involved in the beneficial effects of psychological therapies treating anxiety disorders. © 2015 Wiley Periodicals, Inc.

  20. Loss of Ensemble Segregation in Dentate Gyrus, but Not in Somatosensory Cortex, during Contextual Fear Memory Generalization

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    Marie Yokoyama

    2016-11-01

    Full Text Available The details of contextual or episodic memories are lost and generalized with the passage of time. Proper generalization may underlie the formation and assimilation of semantic memories and enable animals to adapt to ever-changing environments, whereas overgeneralization of fear memory evokes maladaptive fear responses to harmless stimuli, which is a symptom of anxiety disorders such as post-traumatic stress disorder (PTSD. To understand the neural basis of fear memory generalization, we investigated the patterns of neuronal ensemble reactivation during memory retrieval when contextual fear memory expression is generalized using transgenic mice that allowed us to visualize specific neuronal ensembles activated during memory encoding and retrieval. We found preferential reactivations of neuronal ensembles in the primary somatosensory cortex, when mice were returned to the conditioned context to retrieve their memory 1 day after conditioning. In the hippocampal dentate gyrus (DG, exclusively separated ensemble reactivation was observed when mice were exposed to a novel context. These results suggest that the DG as well as the somatosensory cortex were likely to distinguish the two different contexts at the ensemble activity level when memory is not generalized at the behavioral level. However, 9 days after conditioning when animals exhibited generalized fear, the unique reactivation pattern in the DG, but not in the somatosensory cortex, was lost. Our results suggest that the alternations in the ensemble representation within the DG, or in upstream structures that link the sensory cortex to the hippocampus, may underlie generalized contextual fear memory expression.

  1. Effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus of hippocampal formation in rats

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    Ghasem Zarei

    2014-01-01

    Full Text Available Background: Several studies have been shown that antidepressant drugs have contradictory effects on cognitive processes. Therefore, the aim of this study was to investigate the effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus (DG of the hippocampal formation in rat. Materials and Methods: Experimental groups were the control, the fluoxetine, and amitriptyline. The rats were treated for 21 days and then, paired pulse facilitation/inhibition (PPF/I and long-term potentiation (LTP in perforant path-DG synapses were assessed (by 400 Hz tetanization. Field excitatory post-synaptic potential (fEPSP slope and population spike (PS amplitude were measured. Results: The results of PPF/I showed that PS amplitude ratios were increased in 10-70 ms inter-stimulus intervals in the amitriptyline group compared to the control group. In the fluoxetine group, EPSP slope ratios were decreased in intervals 30, 40, and 50 ms inter-stimulus intervals compared to the control group. The PS-LTP was significantly lower in the fluoxetine and the amitriptyline groups with respect to the control group. Conclusion: The results showed that fluoxetine and amitriptyline affect synaptic plasticity in the hippocampus and these effects is probably due to the impact on the number of active neurons.

  2. Age-related changes in glutamate release in the CA3 and dentate gyrus of the rat hippocampus

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    Stephens, Michelle L.; Quintero, Jorge E.; Pomerleau, Francois; Huettl, Peter; Gerhardt, Greg A.

    2012-01-01

    The present studies employed a novel microelectrode array recording technology to study glutamate release and uptake in the dentate gyrus, CA3 and CA1 hippocampal subregions in anesthetized young, late-middle aged and aged male Fischer 344 rats. The mossy fiber terminals in CA3 showed a significantly decreased amount of KCl-evoked glutamate release in aged rats compared to both young and late-middle-aged rats. Significantly more KCl-evoked glutamate release was seen from perforant path terminals in the DG of late-middle-aged rats compared young and aged rats. The DG of aged rats developed an increased glutamate uptake rate compared to the DG of young animals, indicating a possible age-related change in glutamate regulation to deal with increased glutamate release that occurred in late-middle age. No age-related changes in resting levels of glutamate were observed in the DG, CA3 and CA1. Taken together, these data support dynamic changes to glutamate regulation during aging in subregions of the mammalian hippocampus that are critical for learning and memory. PMID:19535175

  3. Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus

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    Kunze, Albrecht; Congreso, Marga Rubenecia; Hartmann, Christian; Wallraff-Beck, Anke; Hüttmann, Kerstin; Bedner, Peter; Requardt, Robert; Seifert, Gerald; Redecker, Christoph; Willecke, Klaus; Hofmann, Andreas; Pfeifer, Alexander; Theis, Martin; Steinhäuser, Christian

    2009-01-01

    In the adult dentate gyrus, radial glia-like cells represent putative stem cells generating neurons and glial cells. Here, we combined patch-clamp recordings, biocytin filling, immunohistochemistry, single-cell transcript analysis, and mouse transgenics to test for connexin expression and gap junctional coupling of radial glia-like cells and its impact on neurogenesis. Radial glia-like cells were identified in mice expressing EGFP under control of the nestin and gfap promoters. We show that a majority of Radial glia-like cells are coupled and express Cx43. Neuronal precursors were not coupled. Mice lacking Cx30 and Cx43 in GFAP-positive cells displayed almost complete inhibition of proliferation and a significant decline in numbers of radial glia-like cells and granule neurons. Inducible virus-mediated ablation of connexins in the adult hippocampus also reduced neurogenesis. These findings strongly suggest the requirement of connexin expression by radial glia-like cells for intact neurogenesis in the adult brain and point to possible communication pathways of these cells. PMID:19549869

  4. The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

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    Yan, Bing Chun; Yoo, Ki-Yeon; Park, Joon Ha; Lee, Choong Hyun; Choi, Jung Hoon

    2011-01-01

    Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 mg/kg EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice. PMID:22025974

  5. Dentate gyrus expression of nestin-immunoreactivity in patients with drug-resistant temporal lobe epilepsy and hippocampal sclerosis.

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    D'Alessio, L; Konopka, H; Escobar, E; Acuña, A; Oddo, S; Solís, P; Seoane, E; Kochen, S

    2015-04-01

    Granule cells pathology in dentate gyrus, have received considerable attention in terms of understanding the pathophysiology of temporal lobe epilepsy with hippocampal sclerosis. The aim of this study was to determine the nestin (an intermediate filament protein expressed by newly formed cells), immunoreactivity (IR) in granular cells layers of hippocampal tissue extirpated during epilepsy surgical procedure, in patients with drug-resistant epilepsy. Hippocampal sections of 16 patients with hippocampal sclerosis and drug-resistant temporal lobe epilepsy were processed using immunoperoxidase with antibody to nestin. Archival material from 8 normal post-mortem hippocampus, were simultaneously processed. Reactive area for nestin-IR, the total number of positive nestin cells per field (20×), and the MGV (mean gray value) was determined by computerized image analysis (ImageJ), and compared between groups. Student's t test was used for statistical analysis. Nestin-IR cells were found in granule cells layers of both controls and patients. Larger reactive somas (p sclerosis (p sclerosis. Further studies are required to determine the clinical implications on memory an emotional alterations such as depression. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. Abnormal functional connectivity of the posterior cingulate cortex is associated with depressive symptoms in patients with Alzheimer’s disease

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    Zhang J

    2017-10-01

    Full Text Available Jiangtao Zhang,1,2 Zhongwei Guo,2 Xiaozheng Liu,3 Xize Jia,4 Jiapeng Li,2 Yaoyao Li,1,5 Danmei Lv,1,5 Wei Chen1,5 1Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine and the Collaborative Innovation Center for Brain Science, Hangzhou, Zhejiang, China; 2Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China; 3China-USA Neuroimaging Research Institute & Department of Radiology, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; 4Center for Cognitive Brain Disorders & Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou Normal University, Hangzhou, China; 5Key Laboratory of Medical Neurobiology of Chinese Ministry of Health, Hangzhou, Zhejiang, China Background: Depressive symptoms are significant and very common psychiatric complications in patients with Alzheimer’s disease (AD, which can aggravate the decline in social function. However, changes in the functional connectivity (FC of the brain in AD patients with depressive symptoms (D-AD remain unclear.Objective: To investigate whether any differences exist in the FC of the posterior cingulate cortex (PCC between D-AD patients and non-depressed AD patients (nD-AD.Materials and methods: We recruited 15 D-AD patients and 17 age-, sex-, educational level-, and Mini-Mental State Examination (MMSE-matched nD-AD patients to undergo tests using the Neuropsychiatric Inventory, Hamilton Depression Rating Scale, and 3.0T resting-state functional magnetic resonance imaging. Bilateral PCC were selected as the regions of interest and between-group differences in the PCC FC network were assessed using Student’s t-test.Results: Compared with the nD-AD group, D-AD patients showed increased PCC FC in the right amygdala, right parahippocampus, right superior temporal pole, right middle temporal lobe, right middle temporal pole, and right hippocampus (AlphaSim correction; P<0.05. In the nD-AD group, MMSE

  7. Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions

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    Victoria eHolec

    2014-01-01

    Full Text Available The rat anterior cingulate cortex (ACC mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., courage. As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the high reward arm. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain

  8. The neural basis of humour comprehension and humour appreciation: The roles of the temporoparietal junction and superior frontal gyrus.

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    Campbell, Darren W; Wallace, Marc G; Modirrousta, Mandana; Polimeni, Joseph O; McKeen, Nancy A; Reiss, Jeffrey P

    2015-12-01

    Psychological well-being and social acumen benefit from the recognition of humourous intent and its enjoyment. The enjoyment of humour requires recognition, but humour recognition is not necessarily accompanied by humour enjoyment. Humour recognition is crucial during social interactions, while the associated enjoyment is less critical. Few neuroimaging studies have explicitly differentiated between the neural foundations of humour comprehension and humour appreciation. Among such studies, design limitations have obscured the specification of neural correlates to humour comprehension or appreciation. We implemented a trichotomous response option to address these design limitations. Twenty-four participants rated 120 comics (90 unaltered with humourous intent and 30 caption-altered without humourous intent) as either funny jokes (FJ), not funny jokes but intended to be funny (NFJ), or not intended to be funny or non-jokes (NJ). We defined humour comprehension by NFJ minus NJ and humour appreciation by FJ minus NFJ. We measured localized blood oxygen level dependent (BOLD) neural responses with a 3T MRI scanner. We tested for BOLD responses in humour comprehension brain regions of interest (ROIs), humour appreciation ROIs, and across the whole-brain. We found significant NFJ-NJ BOLD responses in our humour comprehension ROIs and significant FJ-NFJ BOLD responses in select humour appreciation ROIs. One key finding is that comprehension accuracy levels correlated with humour-comprehension responses in the left temporo-parietal junction (TPJ). This finding represents a novel and precise neural linkage to humour comprehension. A second key finding is that the superior frontal gyrus (SFG) was uniquely associated with humour-appreciation. The SFG response suggests that complex cognitive processing underlies humour appreciation and that current models of humour appreciation be revised. Finally, our research design provides an operational distinction between humour

  9. Stress and Corticosteroids Aggravate Morphological Changes in the Dentate Gyrus after Early-Life Experimental Febrile Seizures in Mice

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    Jolien S. van Campen

    2018-01-01

    Full Text Available Stress is the most frequently self-reported seizure precipitant in patients with epilepsy. Moreover, a relation between ear stress and epilepsy has been suggested. Although ear stress and stress hormones are known to influence seizure threshold in rodents, effects on the development of epilepsy (epileptogenesis are still unclear. Therefore, we studied the consequences of ear corticosteroid exposure for epileptogenesis, under highly controlled conditions in an animal model. Experimental febrile seizures (eFS were elicited in 10-day-old mice by warm-air induced hyperthermia, while a control group was exposed to a normothermic condition. In the following 2 weeks, mice received either seven corticosterone or vehicle injections or were left undisturbed. Specific measures indicative for epileptogenesis were examined at 25 days of age and compared with vehicle injected or untreated mice. We examined structural [neurogenesis, dendritic morphology, and mossy fiber sprouting (MFS] and functional (glutamatergic postsynaptic currents and long-term potentiation plasticity in the dentate gyrus (DG. We found that differences in DG morphology induced by eFS were aggravated by repetitive (mildly stressful vehicle injections and corticosterone exposure. In the injected groups, eFS were associated with decreases in neurogenesis, and increases in cell proliferation, dendritic length, and spine density. No group differences were found in MFS. Despite these changes in DG morphology, no effects of eFS were found on functional plasticity. We conclude that corticosterone exposure during early epileptogenesis elicited by eFS aggravates morphological, but not functional, changes in the DG, which partly supports the hypothesis that ear stress stimulates epileptogenesis.

  10. The Right Supramarginal Gyrus Is Important for Proprioception in Healthy and Stroke-Affected Participants: A Functional MRI Study

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    Ben-Shabat, Ettie; Matyas, Thomas A.; Pell, Gaby S.; Brodtmann, Amy; Carey, Leeanne M.

    2015-01-01

    Human proprioception is essential for motor control, yet its central processing is still debated. Previous studies of passive movements and illusory vibration have reported inconsistent activation patterns related to proprioception, particularly in high-order sensorimotor cortices. We investigated brain activation specific to proprioception, its laterality, and changes following stroke. Twelve healthy and three stroke-affected individuals with proprioceptive deficits participated. Proprioception was assessed clinically with the Wrist Position Sense Test, and participants underwent functional magnetic resonance imaging scanning. An event-related study design was used, where each proprioceptive stimulus of passive wrist movement was followed by a motor response of mirror ­copying with the other wrist. Left (LWP) and right (RWP) wrist proprioception were tested separately. Laterality indices (LIs) were calculated for the main cortical regions activated during proprioception. We found proprioception-related brain activation in high-order sensorimotor cortices in healthy participants especially in the supramarginal gyrus (SMG LWP z = 4.51, RWP z = 4.24) and the dorsal premotor cortex (PMd LWP z = 4.10, RWP z = 3.93). Right hemispheric dominance was observed in the SMG (LI LWP mean 0.41, SD 0.22; RWP 0.29, SD 0.20), and to a lesser degree in the PMd (LI LWP 0.34, SD 0.17; RWP 0.13, SD 0.25). In stroke-affected participants, the main difference in proprioception-related brain activation was reduced laterality in the right SMG. Our findings indicate that the SMG and PMd play a key role in proprioception probably due to their role in spatial processing and motor control, respectively. The findings from stroke-­affected individuals suggest that decreased right SMG function may be associated with decreased proprioception. We recommend that clinicians pay particular attention to the assessment and rehabilitation of proprioception following right hemispheric

  11. Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats.

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    Balietti, Marta; Giorgetti, Belinda; Fattoretti, Patrizia; Grossi, Yessica; Di Stefano, Giuseppina; Casoli, Tiziana; Platano, Daniela; Solazzi, Moreno; Orlando, Fiorenza; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2008-06-01

    Ketogenic diets (KDs) have beneficial effects on several diseases, such as epilepsy, mitochondriopathies, cancer, and neurodegeneration. However, little is known about their effects on aging individuals. In the present study, late-adult (19-month-old) rats were fed for 8 weeks with two medium chain triglycerides (MCT)-KDs, and the following morphologic parameters reflecting synaptic plasticity were evaluated in stratum moleculare of hippocampal CA1 region (SM CA1) and outer molecular layer of hippocampal dentate gyrus (OML DG): average area (S), numeric density (Nv(s)), and surface density (Sv) of synapses, and average volume (V), numeric density (Nv(m)), and volume density (Vv) of synaptic mitochondria. In SM CA1, MCT-KDs induced the early appearance of the morphologic patterns typical of old animals (higher S and V, and lower Nv(s) and Nv(m)). On the contrary, in OML DG, Sv and Vv of MCT-KDs-fed rats were higher (as a result of higher Nv(s) and Nv(m)) versus controls; these modifications are known to improve synaptic function and metabolic supply. The opposite effects of MCT-KDs might reflect the different susceptibility to aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar metabolic properties. Present findings provide the first evidence that MCT-KDs may cause opposite morphologic modifications, being potentially harmful for SM CA1 and potentially advantageous for OML DG. This implies risks but also promising potentialities for their therapeutic use during aging.

  12. Schizophrenia affects speech-induced functional connectivity of the superior temporal gyrus under cocktail-party listening conditions.

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    Li, Juanhua; Wu, Chao; Zheng, Yingjun; Li, Ruikeng; Li, Xuanzi; She, Shenglin; Wu, Haibo; Peng, Hongjun; Ning, Yuping; Li, Liang

    2017-09-17

    The superior temporal gyrus (STG) is involved in speech recognition against informational masking under cocktail-party-listening conditions. Compared to healthy listeners, people with schizophrenia perform worse in speech recognition under informational speech-on-speech masking conditions. It is not clear whether the schizophrenia-related vulnerability to informational masking is associated with certain changes in FC of the STG with some critical brain regions. Using sparse-sampling fMRI design, this study investigated the differences between people with schizophrenia and healthy controls in FC of the STG for target-speech listening against informational speech-on-speech masking, when a listening condition with either perceived spatial separation (PSS, with a spatial release of informational masking) or perceived spatial co-location (PSC, without the spatial release) between target speech and masking speech was introduced. The results showed that in healthy participants, but not participants with schizophrenia, the contrast of either the PSS or PSC condition against the masker-only condition induced an enhancement of functional connectivity (FC) of the STG with the left superior parietal lobule and the right precuneus. Compared to healthy participants, participants with schizophrenia showed declined FC of the STG with the bilateral precuneus, right SPL, and right supplementary motor area. Thus, FC of the STG with the parietal areas is normally involved in speech listening against informational masking under either the PSS or PSC conditions, and declined FC of the STG in people with schizophrenia with the parietal areas may be associated with the increased vulnerability to informational masking. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Interaction between Cannabinoid Type 1 and Type 2 Receptors in the Modulation of Subventricular Zone and Dentate Gyrus Neurogenesis

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    Rui S. Rodrigues

    2017-08-01

    Full Text Available Neurogenesis in the adult mammalian brain occurs mainly in two neurogenic niches, the subventricular zone (SVZ and the subgranular zone (SGZ of the dentate gyrus (DG. Cannabinoid type 1 and 2 receptors (CB1R and CB2R have been shown to differently modulate neurogenesis. However, low attention has been given to the interaction between CB1R and CB2R in modulating postnatal neurogenesis (proliferation, neuronal differentiation and maturation. We focused on a putative crosstalk between CB1R and CB2R to modulate neurogenesis and cultured SVZ and DG stem/progenitor cells from early postnatal (P1-3 Sprague-Dawley rats. Data showed that the non-selective cannabinoid receptor agonist WIN55,212-2 promotes DG cell proliferation (measured by BrdU staining, an effect blocked by either CB1R or CB2R selective antagonists. Experiments with selective agonists showed that facilitation of DG cell proliferation requires co-activation of both CB1R and CB2R. Cell proliferation in the SVZ was not affected by the non-selective receptor agonist, but it was enhanced by CB1R selective activation. However, either CB1R or CB2R selective antagonists abolished the effect of the CB1R agonist in SVZ cell proliferation. Neuronal differentiation (measured by immunocytochemistry against neuronal markers of different stages and calcium imaging was facilitated by WIN55,212-2 at both SVZ and DG. This effect was mimicked by either CB1R or CB2R selective agonists and blocked by either CB1R or CB2R selective antagonists, cross-antagonism being evident. In summary, our findings indicate a tight interaction between CB1R and CB2R to modulate neurogenesis in the two major neurogenic niches, thus contributing to further unraveling the mechanisms behind the action of endocannabinoids in the brain.

  14. Effects of rapamycin treatment after controlled cortical impact injury on neurogenesis and synaptic reorganization in the mouse dentate gyrus

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    Corwin R Butler

    2015-11-01

    Full Text Available Post-traumatic epilepsy (PTE is one consequence of traumatic brain injury (TBI. A prominent cell signaling pathway activated in animal models of both TBI and epilepsy is the mammalian target of rapamycin (mTOR. Inhibition of mTOR with rapamycin has shown promise as a potential modulator of epileptogenesis in several animal models of epilepsy, but cellular mechanisms linking mTOR expression and epileptogenesis are unclear. In this study, the role of mTOR in modifying functional hippocampal circuit reorganization after focal TBI induced by controlled cortical impact was investigated. Rapamycin (3 or 10 mg/kg, an inhibitor of mTOR signaling, was administered by intraperitoneal injection beginning on the day of injury and continued daily until tissue collection. Relative to controls, rapamycin treatment reduced dentate granule cell area in the hemisphere ipsilateral to the injury two weeks post-injury. Brain injury resulted in a significant increase in doublecortin immunolabeling in the dentate gyrus ipsilateral to the injury, indicating increased neurogenesis shortly after TBI. Rapamycin treatment prevented the increase in doublecortin labeling, with no overall effect on Fluoro-Jade B staining in the ipsilateral hemisphere, suggesting that rapamycin treatment reduced posttraumatic neurogenesis but did not prevent cell loss after injury. At later times post-injury (8-13 weeks, evidence of mossy fiber sprouting and increased recurrent excitation of dentate granule cells was detected, which were attenuated by rapamycin treatment. Rapamycin treatment also diminished seizure prevalence relative to vehicle-treated controls after TBI. Collectively, these results support a role for adult neurogenesis in PTE development and suggest that suppression of epileptogenesis by mTOR inhibition includes effects on post-injury neurogenesis.

  15. Organization of auditory areas in the superior temporal gyrus of marmoset monkeys revealed by real-time optical imaging.

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    Nishimura, Masataka; Takemoto, Makoto; Song, Wen-Jie

    2017-11-28

    The prevailing model of the primate auditory cortex proposes a core-belt-parabelt structure. The model proposes three auditory areas in the lateral belt region; however, it may contain more, as this region has been mapped only at a limited spatial resolution. To explore this possibility, we examined the auditory areas in the lateral belt region of the marmoset using a high-resolution optical imaging technique. Based on responses to pure tones, we identified multiple areas in the superior temporal gyrus. The three areas in the core region, the primary area (A1), the rostral area (R), and the rostrotemporal area, were readily identified from their frequency gradients and positions immediately ventral to the lateral sulcus. Three belt areas were identified with frequency gradients and relative positions to A1 and R that were in agreement with previous studies: the caudolateral area, the middle lateral area, and the anterolateral area (AL). Situated between R and AL, however, we identified two additional areas. The first was located caudoventral to R with a frequency gradient in the ventrocaudal direction, which we named the medial anterolateral (MAL) area. The second was a small area with no obvious tonotopy (NT), positioned between the MAL and AL areas. Both the MAL and NT areas responded to a wide range of frequencies (at least 2-24 kHz). Our results suggest that the belt region caudoventral to R is more complex than previously proposed, and we thus call for a refinement of the current primate auditory cortex model.

  16. Spinal cord infusion of stem cells in amyotrophic lateral sclerosis: Magnetic resonance spectroscopy shows metabolite improvement in the precentral gyrus.

    Science.gov (United States)

    García Santos, José M; Inuggi, Alberto; Gómez Espuch, Joaquín; Vázquez, Carlos; Iniesta, Francisca; Blanquer, Miguel; María Moraleda, José; Martínez, Salvador

    2016-06-01

    We aimed to investigate whether magnetic resonance spectroscopy (MRS) metabolite ratios change in the precentral gyrus of patients with amyotrophic lateral sclerosis (ALS) after spinal cord surgical injection of bone marrow mononuclear cells, as well as their relationship with disability and survival. Stem cells were surgically injected in the spinal cord of 11 spinal-onset amyotrophic lateral sclerosis patients (group 1); 21 matched patients were the control group (group 2), comprising ALS patients with an intrathecal saline infusion. Single-voxel 1.5T MRS was performed in both precentral gyri just after inclusion/baseline (before surgery in group 1) and a year later (7 patients in group 1 and 11 in group 2). The spectroscopy data, time of survival and clinical parameters (ALS Functional Rating Scale, forced vital capacity [FVC], Medical Research Council Score) were longitudinally assessed and correlated in both groups. Only in group 1was there a significant N-acetyl-aspartate/creatine (NAA/Cr) increase with time in the dominant side (P = 0.024). NAA/Cr also correlated with years of survival in the nondominant side (r = 0.808, P = 0.026). Except for FVC, all group 1 clinical parameters at 12 months correlated with baseline NAA/Cr on both sides (P <0.05); this was not the case in group 2. In view of these results, we speculate on a distant beneficial effect of bone marrow stem cells injected at the spinal cord over the upper motor neuron at the precentral gyri in the brain. Spinal cord injection of stem cells shows metabolic improvement in the brain that might be related to longer survival and less disability. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. Anatomical pathways for auditory memory II: Information from rostral superior temporal gyrus to dorsolateral temporal pole and medial temporal cortex.

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    Monica eMunoz-Lopez

    2015-05-01

    Full Text Available Auditory recognition memory in non-human primates differs from recognition memory in other sensory systems. Monkeys learn the rule for visual and tactile delayed matching-to-sample within a few sessions, and then show one-trial recognition memory lasting 10-20 minutes. In contrast, monkeys require hundreds of sessions to master the rule for auditory recognition, and then show retention lasting no longer than 30-40 seconds. Moreover, unlike the severe effects of rhinal lesions on visual memory, such lesions have no effect on the monkeys’ auditory memory performance. It is possible, therefore, that the anatomical pathways differ. Long-term visual recognition memory requires anatomical connections from the visual association area TE with areas 35 and 36 of the perirhinal cortex (PRC. We examined whether there is a similar anatomical route for auditory processing, or that poor auditory recognition memory may reflect the lack of such a pathway. Our hypothesis is that an auditory pathway for recognition memory originates in the higher order processing areas of the rostral superior temporal gyrus (rSTG, and then connects via the dorsolateral temporal pole to access the rhinal cortex of the medial temporal lobe. To test this, we placed retrograde (3% FB and 2% DY and anterograde (10% BDA 10,000 MW tracer injections in rSTG and the dorsolateral area 38DL of the temporal pole. Results showed that area 38DL receives dense projections from auditory association areas Ts1, TAa, TPO of the rSTG, from the rostral parabelt and, to a lesser extent, from areas Ts2-3 and PGa. In turn, area 38DL projects densely to area 35 of PRC, entorhinal cortex, and to areas TH/TF of the posterior parahippocampal cortex. Significantly, this projection avoids most of area 36r/c of PRC. This anatomical arrangement may contribute to our understanding of the poor auditory memory of rhesus monkeys.

  18. Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats

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    Denise eManahan-Vaughan

    2011-03-01

    Full Text Available Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an 8-arm radial maze. Basal synaptic transmission was stable over a 24h period in both rat strains, and the input-output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the Hooded Lister strain when pulses were given 40-100 msec apart. Low frequency stimulation at 1Hz evoked long-term depression (>24h in Wistar and short-term depression (<2h in HL rats; 200Hz stimulation induced long-term potentiation (>24h in Wistar, and a transient, significantly smaller potentiation (<1h in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10d in an 8-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8-10 days of training. Wistar rats were less active and more anxious than HL rats.These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however.

  19. Activation of β-adrenoceptor facilitates active avoidance learning through enhancement of glutamate levels in the hippocampal dentate gyrus.

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    Lv, Jing; Feng, Hao; Chen, Ling; Wang, Wei-Yao; Yue, Xue-Ling; Jin, Qing-Hua

    2017-10-18

    Long-term potentiation (LTP) is widely accepted as the best studied model for neurophysiological mechanisms that could underlie learning and memory formation. Despite a number of studies indicating that β-adrenoceptors in the hippocampal dentate gyrus (DG) is involved in the modulation of learning and memory as well as LTP, few studies have used glutamate release as a visual indicator in awake animals to explore the role of β-adrenoceptors in learning-dependent LTP. Therefore, in the present study, the effects of propranolol (an antagonist of β-adrenoceptor) and isoproterenol (an agonist of β-adrenoceptor) on extracellular concentrations of glutamate and amplitudes of field excitatory postsynaptic potential were measured in the DG region during active avoidance learning in freely moving conscious rats. In the control group, the glutamate level in the DG was significantly increased during the acquisition of active avoidance behavior and returned to basal level following extinction training. In propranolol group, antagonism of β-adrenoceptors in the DG significantly reduced the change in glutamate level, and the acquisition of the active avoidance behavior was significantly inhibited. In contrast, the change in glutamate level was significantly enhanced by isoproterenol, and the acquisition of the active avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in glutamate level were accompanied by corresponding changes in field excitatory postsynaptic potential amplitude and active avoidance behavior. Our results suggest that activation of β-adrenoceptors in the hippocampal DG facilitates active avoidance learning by modulations of glutamate level and synaptic efficiency in rats.

  20. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors.

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    Zhang, D; Wang, X; Wang, B; Garza, J C; Fang, X; Wang, J; Scherer, P E; Brenner, R; Zhang, W; Lu, X-Y

    2017-07-01

    Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. Whole-cell patch-clamp recordings in brain slices revealed that intrinsic excitability of DG granule neurons was enhanced by adiponectin deficiency and suppressed after treatment with the adiponectin mimetic AdipoRon, which were associated with increased input resistance and hyperpolarized resting membrane potential, respectively. Moreover, deletion of AdipoR2, but not AdipoR1 in the DG, resulted in augmented fear expression and reduced extinction, accompanied by intrinsic hyperexcitability of DG granule neurons. Adiponectin and AdipoRon failed to induce facilitation of fear extinction and elicit inhibition of intrinsic excitability of DG neurons in AdipoR2 knockout mice. These results indicated that adiponectin action via AdipoR2 was both necessary and sufficient for extinction of contextual fear and intrinsic excitability of DG granule neurons, implying that enhancing or dampening DG neuronal excitability may cause resistance to or facilitation of extinction. Therefore, our findings provide a functional link between adiponectin/AdipoR2 activation, DG neuronal excitability and contextual fear extinction, and suggest that targeting adiponectin/AdipoR2 may be used to strengthen extinction-based exposure therapies for PTSD.

  1. Different patterns of amygdala priming differentially affect dentate gyrus plasticity and corticosterone, but not CA1 plasticity.

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    Rose-Marie eVouimba

    2013-05-01

    Full Text Available Stress-induced activation of the amygdala is involved in the modulation of memory processes in the hippocampus. However, stress effects on amygdala and memory remain complex. The activation of the basolateral amygdala (BLA was found to modulate plasticity in other brain areas, including the hippocampus. We previously demonstrated a differential effect of BLA priming on LTP in the CA1 and the dentate gyrus (DG. While BLA priming suppressed long term potentiation (LTP in CA1, it was found to enhance it in the DG. However, since the amygdala itself is amenable to experience-induced plasticity it is thus conceivable that when activity within the amygdala is modified this will have impact on the way the amygdala modulates activity and plasticity in other brain areas. In the current study we examined the effects of different patterns of BLA activation on the modulation of LTP in the DG and CA1, as well as on serum corticosterone (CORT. In CA1, BLA priming impaired LTP induction as was reported before. In contrast, in the DG, varying BLA stimulation intensity and frequency resulted in differential effects on LTP, ranging from no effect to strong impairment or enhancement. Varying BLA stimulation patterns resulted in also differential alterations in Serum CORT, leading to higher CORT levels being positively correlated with LTP magnitude in DG but not in CA1.The results support the notion of a differential role for the DG in aspects of memory, and add to this view the possibility that DG-associated aspects of memory will be enhanced under more emotional or stressful conditions. It is interesting to think of BLA patterns of activation and the differential levels of circulating CORT as two arms of the emotional and stress response that attempt to synchronize brain activity to best meet the challenge. It is foreseeable to think of abnormal such synchronization under extreme conditions, which would lead to the development of maladaptive behavior.

  2. Acute restraint stress decreases c-fos immunoreactivity in hilar mossy cells of the adult dentate gyrus

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    Moretto, Jillian N.; Duffy, Áine M.

    2017-01-01

    Although a great deal of information is available about the circuitry of the mossy cells (MCs) of the dentate gyrus (DG) hilus, their activity in vivo is not clear. The immediate early gene c-fos can be used to gain insight into the activity of MCs in vivo, because c-fos protein expression reflects increased neuronal activity. In prior work, it was identified that control rats that were perfusion-fixed after removal from their home cage exhibited c-fos immunoreactivity (ir) in the DG in a spatially stereotyped pattern: ventral MCs and dorsal granule cells (GCs) expressed c-fos protein (Duffy et al., Hippocampus 23:649–655, 2013). In this study, we hypothesized that restraint stress would alter c-fos-ir, because MCs express glucocorticoid type 2 receptors and the DG is considered to be involved in behaviors related to stress or anxiety. We show that acute restraint using a transparent nose cone for just 10 min led to reduced c-fos-ir in ventral MCs compared to control rats. In these comparisons, c-fos-ir was evaluated 30 min after the 10 min-long period of restraint, and if evaluation was later than 30 min c-fos-ir was no longer suppressed. Granule cells (GCs) also showed suppressed c-fos-ir after acute restraint, but it was different than MCs, because the suppression persisted for over 30 min after the restraint. We conclude that c-fos protein expression is rapidly and transiently reduced in ventral hilar MCs after a brief period of restraint, and suppressed longer in dorsal GCs. PMID:28190104

  3. Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

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    Roman Smidak

    2017-11-01

    Full Text Available Fragile X mental retardation protein (FMRP encoded by Fragile X mental retardation 1 (FMR1 gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG from young (17 weeks and aging (22 months Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM and CUG-BP, Elav-like (CELF family, and YTH N(6-methyladenosine RNA-binding proteins (YTHDF. The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process.