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      Structural and functional brain alterations in anorexia nervosa:A multimodal meta‐analysis of neuroimaging studies

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          Abstract

          Anorexia nervosa (AN) is a complex psychiatric disorder with poorly understood etiology. Numerous voxel‐based morphometry (VBM) and resting‐state functional imaging studies have provided strong evidence of abnormal brain structure and intrinsic and functional activities in AN, but with inconsistent conclusions. Herein, a whole‐brain meta‐analysis was conducted on VBM (660 patients with AN, and 740 controls) and resting‐state functional imaging (425 patients with AN, and 461 controls) studies that measured differences in the gray matter volume (GMV) and intrinsic functional activity between patients with AN and healthy controls (HCs). Overall, patients with AN displayed decreased GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex), and left middle occipital gyrus (extending to the left inferior parietal lobe). In resting‐state functional imaging studies, patients with AN displayed decreased resting‐state functional activity in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increased resting‐state functional activity in the right parahippocampal gyrus. This multimodal meta‐analysis identified reductions of gray matter and functional activity in the anterior and median cingulate in patients with AN, which contributes to further understanding of the pathophysiology of AN.

          Abstract

          This meta‐analysis demonstrated a significant reduction in the functional activity and gray matter in the cingulate cortex in patients with AN, particularly in the ACC and MCC, which imply that structural changes may underlie functional alterations. These results expand the current understanding of functional and structural brain abnormalities in AN patients, which would provide additional potential targets for therapeutic intervention.

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          Contributions of anterior cingulate cortex to behaviour

          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 cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT TRUNCATED AT 400 WORDS)
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            Cognitive and emotional influences in anterior cingulate 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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                Author and article information

                Contributors
                johneil@vip.sina.com
                Journal
                Hum Brain Mapp
                Hum Brain Mapp
                10.1002/(ISSN)1097-0193
                HBM
                Human Brain Mapping
                John Wiley & Sons, Inc. (Hoboken, USA )
                1065-9471
                1097-0193
                23 July 2021
                15 October 2021
                : 42
                : 15 ( doiID: 10.1002/hbm.v42.15 )
                : 5154-5169
                Affiliations
                [ 1 ] Medical Imaging Center First Affiliated Hospital of Jinan University Guangzhou China
                [ 2 ] Institute of Molecular and Functional Imaging Jinan University Guangzhou China
                [ 3 ] Department of Radiology Six Affiliated Hospital of Sun Yat‐sen University Guangzhou China
                [ 4 ] Department of Applied Psychology Guangdong University of Foreign Studies Guangzhou China
                Author notes
                [*] [* ] Correspondence

                Ying Wang, Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China.

                Email: johneil@ 123456vip.sina.com

                Author information
                https://orcid.org/0000-0003-3935-5821
                https://orcid.org/0000-0002-0388-4177
                Article
                HBM25602
                10.1002/hbm.25602
                8449099
                34296492
                5ad578bd-0f0b-419a-888c-6fe117283a90
                © 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 July 2021
                : 09 April 2021
                : 12 July 2021
                Page count
                Figures: 3, Tables: 3, Pages: 16, Words: 13234
                Funding
                Funded by: National Key Research and Development Program of China , doi 10.13039/501100012166;
                Award ID: 2020YFC2005700
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81671670
                Award ID: 81671597
                Funded by: Planned Science and Technology Project of Guangzhou
                Award ID: 201905010003
                Funded by: Basic Research and Applied Basic Research in General Colleges and Universities of Guangdong
                Award ID: 2018KZDXM009
                Categories
                Review Article
                Review Article
                Custom metadata
                2.0
                October 15, 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.7 mode:remove_FC converted:18.09.2021

                Neurology
                anorexia nervosa,meta‐analysis,multimodal,resting‐state functional imaging,voxel‐based morphometry

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