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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. 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.

Stressful life events (SLEs) in adulthood are a risk factor for various disorders such as depression, cancer or infections. Part of this risk is mediated through pathways altering brain physiology and structure. There is a lack of longitudinal studies examining associations between SLEs and brain structural changes. High‐resolution structural magnetic resonance imaging data of 212 healthy subjects were acquired at baseline and after 2 years. Voxel‐based morphometry was used to identify associations between SLEs using the Life Events Questionnaire and grey matter volume (GMV) changes during the 2‐year period in an ROI approach. Furthermore, we assessed adverse childhood experiences as a possible moderator of SLEs‐GMV change associations. SLEs were negatively associated with GMV changes in the left medial prefrontal cortex. This association was stronger when subjects had experienced adverse childhood experiences. The medial prefrontal cortex has previously been associated with stress‐related disorders. The present findings represent a potential neural basis of the diathesis‐stress model of various disorders.

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole‐brain, voxel‐based, multi‐tissue mega‐analytic approach, thereby extending our recent surface‐based region of interest findings on a nearly matching sample using a complementary methodological approach. T1‐weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel‐based morphometry. The effects of group, sex, group‐by‐sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group‐by‐sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group‐by‐sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo‐occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD. We aimed to characterize the sex differences in gray matter and white matter correlates of alcohol use disorder using a whole‐brain, voxel‐based, multi‐tissue mega‐analytic approach. We found that individuals with AUD relative to controls had lower GM volume in widespread brain clusters. Group‐by‐sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males.

ABSTRACT Neuroeconomic findings show that interoceptive sensitivity contributes to the typical overweighting of prospective losses over gains known as “loss aversion.” Whether the latter is related to the morphometric properties of the insula—a key node for interoception—remains, however, debated, due to previous conflicting evidence of both positive and negative correlations between their respective metrics. We combined a well‐established behavioral modeling approach with a comprehensive morphometric protocol to explore both a linear and quadratic relationship between loss aversion and distinct voxel‐based and surface‐based cortical features in a sample of 208 healthy young individuals. Both univariate and multivariate analyses highlighted a positive quadratic (i.e., U‐shaped) relationship between loss aversion and distinct morphometric features of the posterior insula and somatosensory‐parietal cortex. These results first suggest that previous inconsistent findings might reflect methodological differences across studies, facilitating the detection of either the descending or ascending sectors of a U‐shaped relationship between loss aversion and structural features. Moreover, they provide novel insights into the interoceptive modulation of choice‐related evaluations guiding decision‐making towards or away from loss avoidance, thus paving the way to studies investigating alterations of this mechanism in neuro‐psychiatric conditions and its susceptibility to different types of intervention including neuromodulation. Univariate and multivariate analyses highlighted a positive, “U‐shaped”, quadratic relationship between loss aversion and posterior insular/somatosensory morphometric features. These results provide novel insights into the interoceptive modulation of choice‐related evaluations guiding decision‐making towards or away from loss avoidance, paving the way to studies investigating alterations of this mechanism in neuro‐psychiatric conditions.

Understanding how function and structure are organized and their coupling with clinical traits in individuals with autism spectrum disorder (ASD) is a primary goal in network neuroscience research for ASD. Atypical brain functional networks and structures in individuals with ASD have been reported, but whether these associations show heterogeneous hierarchy modeling in adolescents and adults with ASD remains to be clarified. In this study, 176 adolescent and 74 adult participants with ASD without medication or comorbidities and sex, age matched healthy controls (HCs) from 19 research groups from the openly shared Autism Brain Imaging Data Exchange II database were included. To investigate the relationship between the functional gradient, structural changes, and clinical symptoms of brain networks in adolescents and adults with ASD, functional gradient and voxel‐based morphometry (VBM) analyses based on 1000 parcels defined by Schaefer mapped to Yeo's seven‐network atlas were performed. Pearson's correlation was calculated between the gradient scores, gray volume and density, and clinical traits. The subsystem‐level analysis showed that the second gradient scores of the default mode networks and frontoparietal network in patients with ASD were relatively compressed compared to adolescent HCs. Adult patients with ASD showed an overall compression gradient of 1 in the ventral attention networks. In addition, the gray density and volumes of the subnetworks showed no significant differences between the ASD and HC groups at the adolescent stage. However, adults with ASD showed decreased gray density in the limbic network. Moreover, numerous functional gradient parameters, but not VBM parameters, in adolescents with ASD were considerably correlated with clinical traits in contrast to those in adults with ASD. Our findings proved that the atypical changes in adolescent ASD mainly involve the brain functional network, while in adult ASD, the changes are more related to brain structure, including gray density and volume. These changes in functional gradients or structures are markedly correlated with clinical traits in patients with ASD. Our study provides a novel understanding of the pathophysiology of the structure–function hierarchy in ASD. The brain atypical changes in adolescent participants with autism mainly involve the brain functional network. In adult participants with autism, the brain changes are more related to brain structure including grey density and volume. These changes in functional gradients or structures were correlated with parts of clinical traits in autism spectrum disorder.

ABSTRACT Background Myelin oligodendrocyte glycoprotein antibody‐associated disease can manifest as a relapsing or monophasic condition. Although several MRI studies have shown evident gray and white matter atrophy compared to healthy controls, little is known about regional brain volume dynamics in myelin oligodendrocyte glycoprotein antibody‐associated disease over time. Methods In this study, we performed an explorative voxel‐based morphometry to detect brain volumetric differences between myelin oligodendrocyte glycoprotein antibody‐associated disease (N = 27), relapsing multiple sclerosis (N = 40)—both in early disease stages—and healthy controls (N = 45). Furthermore, we investigated the longitudinal brain volume changes over a 2‐year follow‐up period in myelin oligodendrocyte glycoprotein antibody‐associated disease (N = 15) and relapsing multiple sclerosis (N = 40). Results We identified distinct patterns of regional brain volume loss in the patient subgroups compared to healthy controls. In multiple sclerosis patients, bilateral thalamic atrophy was observed, whereas patients with myelin oligodendrocyte glycoprotein antibody‐associated disease showed atrophy of the bilateral fornix and stria terminalis. Our results confirmed longitudinal volume loss in thalamic and infratentorial regions in the relapsing multiple sclerosis group, which was partly related to clinical relapses during the 2‐year follow‐up period. In contrast, no longitudinal gray or white matter changes were found in the myelin oligodendrocyte glycoprotein antibody‐associated disease group. Conclusions To our knowledge, this is the first MRI study demonstrating no evidence of regional brain volume loss over time in patients with myelin oligodendrocyte glycoprotein antibody‐associated disease using voxel‐based morphometry, suggesting a different—probably not progressive—pathophysiological background compared to relapsing multiple sclerosis.

Imaging studies of subthreshold depression (StD) have reported structural and functional abnormalities in a variety of spatially diverse brain regions. However, there is no consensus among different studies. In the present study, we applied a multimodal meta‐analytic approach, the Activation Likelihood Estimation (ALE), to test the hypothesis that StD exhibits spatially convergent structural and functional brain abnormalities compared to healthy controls. A total of 31 articles with 25 experiments were included, collectively representing 1001 subjects with StD. We found consistent differences between StD and healthy controls mainly in the left insula across studies with various neuroimaging methods. Further exploratory analyses found structural atrophy and decreased functional activities in the right pallidum and thalamus in StD, and abnormal spontaneous activity converged to the middle frontal gyrus. Coordinate‐based meta‐analysis found spatially convergent structural and functional impairments in StD. These findings provide novel insights for understanding the neural underpinnings of subthreshold depression and enlighten the potential targets for its early screening and therapeutic interventions in the future. Subthreshold depression is a threatening precursor and risk factor for major depressive disorder. CBMA found spatially convergent structural and functional impairments in subthreshold depression mainly in the left insula. And abnormal spontaneous brain activity converged to the middle frontal gyrus in subthreshold depression.

Pain thresholds vary considerably across individuals and are influenced by a number of behavioral, genetic and neurobiological factors. However, the neurobiological underpinnings that account for individual differences remain to be fully elucidated. In this study, we used voxel‐based morphometry (VBM) and graph theory, specifically the local clustering coefficient (CC) based on resting‐state connectivity, to identify brain regions, where regional gray matter volume and network properties predicted individual pain thresholds. As a main finding, we identified a cluster in the left posterior insular cortex (IC) reaching into the left parietal operculum, including the secondary somatosensory cortex, where both regional gray matter volume and the local CC correlated with individual pain thresholds. We also performed a resting‐state functional connectivity analysis using the left posterior IC as seed region, demonstrating that connectivity to the pre‐ as well as postcentral gyrus bilaterally; that is, to the motor and primary sensory cortices were correlated with individual pain thresholds. To our knowledge, this is the first study that applied VBM in combination with voxel‐based graph theory in the context of pain thresholds. The co‐location of the VBM and the local CC cluster provide first evidence that both structure and function map to the same brain region while being correlated with the same behavioral measure; that is, pain thresholds. The study highlights the importance of the posterior IC, not only for pain perception in general, but also for the determination of individual pain thresholds. Pain thresholds vary considerably across individuals. In our study both regional gray matter volume and specific network properties in the left posterior insula and secondary somatosensory cortex correlated with individual pain thresholds, so did functional resting state connectivity of this region with the primary somatosensory cortices.

Although regular physical exercise has multiple positive benefits for the general population, excessive exercise may lead to exercise dependence (EXD), which is harmful to one's physical and mental health. Increasing evidence suggests that stress is a potential risk factor for the onset and development of EXD. However, little is known about the neural substrates of EXD and the underlying neuropsychological mechanism by which stress affects EXD. Herein, we investigate these issues in 86 individuals who exercise regularly by estimating their cortical gray matter volume (GMV) utilizing a voxel‐based morphometry method based on structural magnetic resonance imaging. Whole‐brain correlation analyses and prediction analyses showed negative relationships between EXD and GMV of the right orbitofrontal cortex (OFC), left subgenual cingulate gyrus (sgCG), and left inferior parietal lobe (IPL). Furthermore, mediation analyses found that the GMV of the right OFC was an important mediator between stress and EXD. Importantly, these results remained significant even when adjusting for sex, age, body mass index, family socioeconomic status, general intelligence and total intracranial volume, as well as depression and anxiety. Collectively, the results of the present study provide crucial evidence of the neuroanatomical basis of EXD and reveal a potential neuropsychological pathway in predicting EXD in which GMV mediates the relationship between stress and EXD. EXD was negatively correlated with the GMV of the right OFC, left sgCG, and left IPL. The GMV of the right OFC was associated with stress. The GMV of the right OFC served as a mediator between stress and EXD.

ABSTRACT It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD‐PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole‐brain voxel‐by‐voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD‐PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD‐PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD‐PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals. We used brain structural imaging, genome‐wide gene polymorphism data, and creativity data as measured by divergent thinking. And we showed that a higher genetic risk of bipolar disorder is associated with higher creativity and prefrontal cortical gray matter/white matter volume in young adults.