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      Functional Connectivity Changes in Obsessive–Compulsive Disorder Correspond to Interference Control and Obsessions Severity

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          Abstract

          Introduction: Deficits in neurocognitive mechanisms such as inhibition control and cognitive flexibility have been suggested to mediate the symptoms in obsessive–compulsive disorder (OCD). These mechanisms are proposedly controlled by the “affective” and “executive” orbitofronto-striato-thalamo-cortical (CSTC) circuits with well-documented morphological and functional alterations in OCD that are associated with OCD symptoms. The precuneus region has been suggested in OCD as another key structure associated with the mechanism of “thought–action fusion.” Our study aimed to elucidate the association of the altered functional coupling of the CSTC nodes (and precuneus), the OCD symptoms, and interference control/cognitive flexibility.

          Methods: In a group of 36 (17 medicated and 19 drug-free) OCD patients and matched healthy volunteers, we tested functional connectivity (FC) within the constituents of the dorsolateral prefrontal cortex “executive” CSTC, the orbitofrontal cortex/anterior cingulate “affective” CSTC, and precuneus. The functional connections showing the strongest effects were subsequently entered as explanatory variables to multiple regression analyses to identify possible associations between observed alterations of functional coupling and cognitive (Stroop test) and clinical measures (obsessions, compulsions, and anxiety level).

          Results: We observed increased FC (FWE p < 0.05 corr.) between CSTC seeds and regions of the parieto-occipital cortex, and between the precuneus and the angular gyrus and dorsolateral prefrontal cortex. Decreased FC was observed within the CSTC loop (caudate nucleus and thalamus) and between the anterior cingulate cortex and the limbic lobe. Linear regression identified a relationship between the altered functional coupling of thalamus with the right somatomotor parietal cortex and the Stroop color–word score. Similar association of thalamus FC has been identified also for obsessions severity. No association was observed for compulsions and anxiety.

          Conclusions: Our findings demonstrate altered FC in OCD patients with a prevailing increase in FC originating in CSTC regions toward other cortical areas, and a decrease in FC within the constituents of CSTC loops. Moreover, our results support the role of precuneus in OCD. The association of the cognitive and clinical symptoms with the FC between the thalamus and somatomotor cortex indicates that cognitive flexibility and inhibitory control are strongly linked and both mechanisms might contribute to the symptomatology of OCD.

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          The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology.

          The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex.
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            Voxel-wise meta-analysis of grey matter changes in obsessive-compulsive disorder.

            Specific cortico-striato-thalamic circuits are hypothesised to mediate the symptoms of obsessive-compulsive disorder (OCD), but structural neuroimaging studies have been inconsistent. To conduct a meta-analysis of published and unpublished voxel-based morphometry studies in OCD. Twelve data-sets comprising 401 people with OCD and 376 healthy controls met inclusion criteria. A new improved voxel-based meta-analytic method, signed differential mapping (SDM), was developed to examine regions of increased and decreased grey matter volume in the OCD group v. control group. Results No between-group differences were found in global grey matter volumes. People with OCD had increased regional grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, as well as decreased volumes in bilateral dorsal medial frontal/anterior cingulate gyri. A descriptive analysis of quartiles, a sensitivity analysis as well as analyses of subgroups further confirmed these findings. Meta-regression analyses showed that studies that included individuals with more severe OCD were significantly more likely to report increased grey matter volumes in the basal ganglia. No effect of current antidepressant treatment was observed. Conclusions The results support a dorsal prefrontal-striatal model of the disorder and raise the question of whether functional alterations in other brain regions commonly associated with OCD, such as the orbitofrontal cortex, may reflect secondary compensatory strategies. Whether the reported differences between participants with OCD and controls precede the onset of the symptoms and whether they are specific to OCD remains to be established.
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              Functional significance of the cortico-subthalamo-pallidal 'hyperdirect' pathway.

              How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. The cortico-subthalamo-pallidal 'hyperdirect' pathway conveys powerful excitatory effects from the motor-related cortical areas to the globus pallidus, bypassing the striatum, with shorter conduction time than effects conveyed through the striatum. We emphasize the functional significance of the 'hyperdirect' pathway and propose a dynamic 'center-surround model' of basal ganglia function in the control of voluntary limb movements. When a voluntary movement is about to be initiated by cortical mechanisms, a corollary signal conveyed through the cortico-subthalamo-pallidal 'hyperdirect' pathway first inhibits large areas of the thalamus and cerebral cortex that are related to both the selected motor program and other competing programs. Then, another corollary signal through the cortico-striato-pallidal 'direct' pathway disinhibits their targets and releases only the selected motor program. Finally, the third corollary signal possibly through the cortico-striato-external pallido-subthalamo-internal pallidal 'indirect' pathway inhibits their targets extensively. Through this sequential information processing, only the selected motor program is initiated, executed and terminated at the selected timing, whereas other competing programs are canceled.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                20 August 2020
                2020
                : 11
                : 568
                Affiliations
                [1] 1National Institute of Mental Health (NIMH) , Klecany, Czechia
                [2] 2Third Faculty of Medicine, Charles University , Prague, Czechia
                [3] 3Institute of Computer Science, Czech Academy of Sciences , Prague, Czechia
                Author notes

                Edited by: Ovidiu Lungu, Université de Montréal, Canada

                Reviewed by: Yann Quidé, University of New South Wales, Australia; Tomas Kasparek, Masaryk University, Czechia

                *Correspondence: Iveta Fajnerova iveta.fajnerova@ 123456nudz.cz

                This article was submitted to Applied Neuroimaging, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2020.00568
                7468468
                32973642
                7a4b11fa-f276-4307-9a9f-7530b35cc78c
                Copyright © 2020 Fajnerova, Gregus, Francova, Noskova, Koprivova, Stopkova, Hlinka and Horacek.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 July 2019
                : 19 May 2020
                Page count
                Figures: 1, Tables: 5, Equations: 0, References: 80, Pages: 13, Words: 10044
                Funding
                Funded by: Agentura Pro Zdravotnickí Výzkum Ceské Republiky 10.13039/501100009553
                Award ID: 17-30833A
                Award ID: NU20-04-00147
                Categories
                Neurology
                Original Research

                Neurology
                obsessive–compulsive disorder,functional connectivity,resting state,inhibitory/interference control,stroop test,obsessions and compulsions,anxiety

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