scholarly journals Widespread decrease of cerebral vimentin-immunoreactive astrocytes in depressed suicides

2020 ◽  
Author(s):  
Liam Anuj O’Leary ◽  
Claudia Belliveau ◽  
Maria Antonietta Davoli ◽  
Jie Christopher Ma ◽  
Arnaud Tanti ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
White Matter ◽  
Blood Vessels ◽  
Close Association ◽  
Brain Regions ◽  
Quantitative Comparison ◽  
Postmortem Brain ◽  
Dorsomedial Prefrontal Cortex ◽  
Morphometric Features ◽  
Fine Morphology

1AbstractPostmortem investigations have implicated cerebral astrocytes immunoreactive (-IR) for glial fibrillary acidic protein (GFAP) in the etiopathology of depression and suicide. However, it remains unclear whether astrocytic subpopulations IR for other astrocytic markers are similarly affected. Astrocytes IR to vimentin (VIM) display different regional densities than GFAP-IR astrocytes in the healthy brain, and so may be differently altered in depression and suicide. To investigate this, we compared the densities of GFAP-IR astrocytes and VIM-IR astrocytes in postmortem brain samples from depressed suicides and matched non-psychiatric controls in three brain regions (dorsomedial prefrontal cortex, dorsal caudate nucleus and mediodorsal thalamus). A quantitative comparison of the fine morphology of VIM-IR astrocytes was also performed in the same regions and subjects. Finally, given the close association between astrocytes and blood vessels, we also assessed densities of CD31-IR blood vessels. Like for GFAP-IR astrocytes, VIM-IR astrocyte densities were found to be globally reduced in depressed suicide relative to controls. By contrast, CD31-IR blood vessel density and VIM-IR astrocyte morphometric features in these regions were similar between groups, except in prefrontal white matter, in which vascularization was increased and astrocytes displayed fewer primary processes. By revealing a widespread reduction of cerebral VIM-IR astrocytes in cases vs. controls, these findings further implicate astrocytic dysfunctions in depression and suicide.

scholarly journals Widespread Decrease of Cerebral Vimentin-Immunoreactive Astrocytes in Depressed Suicides

2021 ◽  
Vol 12 ◽  
Author(s):  
Liam Anuj O'Leary ◽  
Claudia Belliveau ◽  
Maria Antonietta Davoli ◽  
Jie Christopher Ma ◽  
Arnaud Tanti ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Blood Vessels ◽  
Close Association ◽  
Brain Regions ◽  
Quantitative Comparison ◽  
Post Mortem ◽  
Dorsomedial Prefrontal Cortex ◽  
Post Mortem Brain ◽  
Morphometric Features ◽  
Fine Morphology

Post-mortem investigations have implicated cerebral astrocytes immunoreactive (-IR) for glial fibrillary acidic protein (GFAP) in the etiopathology of depression and suicide. However, it remains unclear whether astrocytic subpopulations IR for other astrocytic markers are similarly affected. Astrocytes IR to vimentin (VIM) display different regional densities than GFAP-IR astrocytes in the healthy brain, and so may be differently altered in depression and suicide. To investigate this, we compared the densities of GFAP-IR astrocytes and VIM-IR astrocytes in post-mortem brain samples from depressed suicides and matched non-psychiatric controls in three brain regions (dorsomedial prefrontal cortex, dorsal caudate nucleus and mediodorsal thalamus). A quantitative comparison of the fine morphology of VIM-IR astrocytes was also performed in the same regions and subjects. Finally, given the close association between astrocytes and blood vessels, we also assessed densities of CD31-IR blood vessels. Like for GFAP-IR astrocytes, VIM-IR astrocyte densities were found to be globally reduced in depressed suicides relative to controls. By contrast, CD31-IR blood vessel density and VIM-IR astrocyte morphometric features in these regions were similar between groups, except in prefrontal white matter, in which vascularization was increased and astrocytes displayed fewer primary processes. By revealing a widespread reduction of cerebral VIM-IR astrocytes in cases vs. controls, these findings further implicate astrocytic dysfunctions in depression and suicide.

scholarly journals Characterizing the Theory of Mind Network in Schizophrenia Reveals a Sparser Network Structure

2020 ◽  
Author(s):  
Florian Bitsch ◽  
Philipp Berger ◽  
Arne Nagels ◽  
Irina Falkenberg ◽  
Benjamin Straube
Keyword(s):  
Prefrontal Cortex ◽  
Social Functioning ◽  
Network Structure ◽  
Functional Integration ◽  
Signs And Symptoms ◽  
Brain Regions ◽  
Interpersonal Behavior ◽  
Single Subject ◽  
Dorsomedial Prefrontal Cortex ◽  
The Right

AbstractImpaired social functioning is a hallmark of schizophrenia and altered functional integration between distant brain regions are expected to account for signs and symptoms of the disorder. The functional neuroarchitecture of a network relevant for social functioning, the mentalizing network, is however poorly understood. In this study we examined dysfunctions of the mentalizing network in patients with schizophrenia compared to healthy controls via dynamic causal modelling and an interactive social decision-making game. Network characteristics were analyzed on a single subject basis whereas graph theoretic metrics such as in-degree, out-degree and edge-connectivity per network node were compared between the groups. The results point to a sparser network structure in patients with schizophrenia and highlight the dorsomedial prefrontal cortex as a disconnected network hub receiving significantly less input from other brain regions in the network. Further analyses suggest that integrating pathways from the right and the left temporo-parietal junction into the dorsomedial prefrontal cortex were less frequently found in patients with schizophrenia. Brain and behavior analyses further suggest that the connectivity-intactness within the entire network is associated with functional interpersonal behavior during the task. Thus, the neurobiological alterations within the mentalizing network in patients with schizophrenia point to a specific integration deficit between core brain regions underlying the generation of higher-order representations and thereby provide a potential treatment target.

scholarly journals Dorsolateral and dorsomedial prefrontal cortex track distinct properties of dynamic social behavior

2020 ◽  
Vol 15 (4) ◽  
pp. 383-393
Author(s):  
Kelsey R McDonald ◽  
John M Pearson ◽  
Scott A Huettel
Keyword(s):  
Prefrontal Cortex ◽  
Video Game ◽  
Brain Regions ◽  
Neural Mechanisms ◽  
Strategic Action ◽  
General Role ◽  
Temporoparietal Junction ◽  
Dorsomedial Prefrontal Cortex ◽  
Decision Neuroscience ◽  
Dorsolateral Prefrontal

Abstract Understanding how humans make competitive decisions in complex environments is a key goal of decision neuroscience. Typical experimental paradigms constrain behavioral complexity (e.g. choices in discrete-play games), and thus, the underlying neural mechanisms of dynamic social interactions remain incompletely understood. Here, we collected fMRI data while humans played a competitive real-time video game against both human and computer opponents, and then, we used Bayesian non-parametric methods to link behavior to neural mechanisms. Two key cognitive processes characterized behavior in our task: (i) the coupling of one’s actions to another’s actions (i.e. opponent sensitivity) and (ii) the advantageous timing of a given strategic action. We found that the dorsolateral prefrontal cortex displayed selective activation when the subject’s actions were highly sensitive to the opponent’s actions, whereas activation in the dorsomedial prefrontal cortex increased proportionally to the advantageous timing of actions to defeat one’s opponent. Moreover, the temporoparietal junction tracked both of these behavioral quantities as well as opponent social identity, indicating a more general role in monitoring other social agents. These results suggest that brain regions that are frequently implicated in social cognition and value-based decision-making also contribute to the strategic tracking of the value of social actions in dynamic, multi-agent contexts.

scholarly journals Hippocampal regenerative medicine: neurogenic implications for addiction and mental disorders

2021 ◽  
Author(s):  
Lee Peyton ◽  
Alfredo Oliveros ◽  
Doo-Sup Choi ◽  
Mi-Hyeon Jang
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Executive Function ◽  
General Population ◽  
Mental Disorders ◽  
Psychiatric Illness ◽  
Neural Circuitry ◽  
Brain Regions ◽  
Neuropsychiatric Disease ◽  
Motivated Behavior

AbstractPsychiatric illness is a prevalent and highly debilitating disorder, and more than 50% of the general population in both middle- and high-income countries experience at least one psychiatric disorder at some point in their lives. As we continue to learn how pervasive psychiatric episodes are in society, we must acknowledge that psychiatric disorders are not solely relegated to a small group of predisposed individuals but rather occur in significant portions of all societal groups. Several distinct brain regions have been implicated in neuropsychiatric disease. These brain regions include corticolimbic structures, which regulate executive function and decision making (e.g., the prefrontal cortex), as well as striatal subregions known to control motivated behavior under normal and stressful conditions. Importantly, the corticolimbic neural circuitry includes the hippocampus, a critical brain structure that sends projections to both the cortex and striatum to coordinate learning, memory, and mood. In this review, we will discuss past and recent discoveries of how neurobiological processes in the hippocampus and corticolimbic structures work in concert to control executive function, memory, and mood in the context of mental disorders.

scholarly journals Pairwise maximum entropy model explains the role of white matter structure in shaping emergent co-activation states

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Arian Ashourvan ◽  
Preya Shah ◽  
Adam Pines ◽  
Shi Gu ◽  
Christopher W. Lynn ◽  
...  
Keyword(s):  
White Matter ◽  
Maximum Entropy ◽  
Large Scale ◽  
Structural Connectivity ◽  
Quantitative Relationship ◽  
Brain Regions ◽  
Maximum Entropy Model ◽  
Entropy Model ◽  
Activation Patterns ◽  
Co Activation

AbstractA major challenge in neuroscience is determining a quantitative relationship between the brain’s white matter structural connectivity and emergent activity. We seek to uncover the intrinsic relationship among brain regions fundamental to their functional activity by constructing a pairwise maximum entropy model (MEM) of the inter-ictal activation patterns of five patients with medically refractory epilepsy over an average of ~14 hours of band-passed intracranial EEG (iEEG) recordings per patient. We find that the pairwise MEM accurately predicts iEEG electrodes’ activation patterns’ probability and their pairwise correlations. We demonstrate that the estimated pairwise MEM’s interaction weights predict structural connectivity and its strength over several frequencies significantly beyond what is expected based solely on sampled regions’ distance in most patients. Together, the pairwise MEM offers a framework for explaining iEEG functional connectivity and provides insight into how the brain’s structural connectome gives rise to large-scale activation patterns by promoting co-activation between connected structures.

scholarly journals Retrospective analysis of hemispheric structural network change as a function of location and size of glioma

2020 ◽  
Author(s):  
Shawn D’Souza ◽  
Lisa Hirt ◽  
David R Ormond ◽  
John A Thompson
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Temporal Lobe ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Structural Network ◽  
Tumour Location ◽  
The Impact ◽  
Tractography Data ◽  
Diffusion Tensor Imaging Tractography

Abstract Gliomas are neoplasms that arise from glial cell origin and represent the largest fraction of primary malignant brain tumours (77%). These highly infiltrative malignant cell clusters modify brain structure and function through expansion, invasion and intratumoral modification. Depending on the growth rate of the tumour, location and degree of expansion, functional reorganization may not lead to overt changes in behaviour despite significant cerebral adaptation. Studies in simulated lesion models and in patients with stroke reveal both local and distal functional disturbances, using measures of anatomical brain networks. Investigations over the last two decades have sought to use diffusion tensor imaging tractography data in the context of intracranial tumours to improve surgical planning, intraoperative functional localization, and post-operative interpretation of functional change. In this study, we used diffusion tensor imaging tractography to assess the impact of tumour location on the white matter structural network. To better understand how various lobe localized gliomas impact the topology underlying efficiency of information transfer between brain regions, we identified the major alterations in brain network connectivity patterns between the ipsilesional versus contralesional hemispheres in patients with gliomas localized to the frontal, parietal or temporal lobe. Results were indicative of altered network efficiency and the role of specific brain regions unique to different lobe localized gliomas. This work draws attention to connections and brain regions which have shared structural susceptibility in frontal, parietal and temporal lobe glioma cases. This study also provides a preliminary anatomical basis for understanding which affected white matter pathways may contribute to preoperative patient symptomology.

scholarly journals A pilot trial of repetitive transcranial magnetic stimulation of the dorsomedial prefrontal cortex in anorexia nervosa: resting fMRI correlates of response

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
D. Blake Woodside ◽  
Katharine Dunlop ◽  
Charlene Sathi ◽  
Eileen Lam ◽  
Brigitte McDonald ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Prefrontal Cortex ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Trial Registration ◽  
Angular Gyrus ◽  
Open Label ◽  
Compulsive Disorder ◽  
Dorsomedial Prefrontal Cortex

Abstract Background Patients with anorexia nervosa (AN) face severe and chronic illness with high mortality rates, despite our best currently available conventional treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown increasing efficacy in treatment-refractory cases across a variety of psychiatric disorders comorbid with AN, including major depression, Obsessive Compulsive Disorder (OCD), and Post traumatic Stress Disorder (PTSD). However, to date few studies have examined the effects of a course of rTMS on AN pathology itself. Methods Nineteen patients with AN underwent a 20–30 session open-label course of dorsomedial prefrontal rTMS for comorbid Major Depressive Disorder (MDD) ± PTSD. Resting-state functional MRI was acquired at baseline in 16/19 patients. Results Following treatment, significant improvements were seen in core AN pathology on the EDE global scale, and to a lesser extent on the shape and weight concerns subscales. Significant improvements in comorbid anxiety, and to a lesser extent depression, also ensued. The greatest improvements were seen in patients with lower baseline functional connectivity from the dorsomedial prefrontal cortex (DMPFC) target to regions in the right frontal pole and left angular gyrus. Conclusions Despite the limited size of this preliminary, open-label study, the results suggest that rTMS is safe in AN, and may be useful in addressing some core domains of AN pathology. Other targets may also be worth studying in this population, in future sham-controlled trials with larger sample sizes. Trial registration Trial registration ClinicalTrials.gov NCT04409704. Registered May 282,020. Retrospectively registered.

scholarly journals Convergence of heteromodal lexical retrieval in the lateral prefrontal cortex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander A. Aabedi ◽  
Sofia Kakaizada ◽  
Jacob S. Young ◽  
Jasleen Kaur ◽  
Olivia Wiese ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Picture Naming ◽  
Cognitive Rehabilitation ◽  
Tumor Model ◽  
Brain Regions ◽  
Support Vector ◽  
Lexical Retrieval ◽  
Lateral Prefrontal Cortex ◽  
Lesion Symptom Mapping ◽  
Single Construct

AbstractLexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.

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