Regional Gray Matter Volume Changes Research Articles

Increased cerebellar vermis volume following repetitive transcranial magnetic stimulation in drug-resistant epilepsy: a voxel-based morphometry study.

Voxel-based morphometry (VBM) was applied to explore structural changes induced by repetitive transcranial magnetic stimulation (rTMS) and the relationship with clinical outcomes. Moreover, the relationship between each segmented regional gray matter (GM) volume was investigated to identify circuits involved in the rTMS treatment process in patients with drug-resistant epilepsy (DRE). Nineteen patients with DRE were finally included in the analysis. A session of rTMS was applied for 5 consecutive days. Participants received either 1,000 or 3,000 pulses, at a frequency of 0.5 Hz and the intensity was set at 90% of the individual's resting motor threshold. VBM analysis was performed to explore regional GM volume changes 2 months after rTMS application. The regional volume change was correlated with seizure reduction rate. Relationships between changes in GM volume in each anatomically parcellated region were analyzed using a fully-automated segmentation pipeline. Compared to the baseline, seizure frequency was reduced, and quality of life was improved after rTMS treatment. Regional volume was increased in the cerebellar vermis 2 months after rTMS application. The increased cerebellar vermis volume correlated with the reduced seizure frequency. Regional volume changes in the cerebellar vermis were correlated with changes in the subcortical and cortical GM regions including the thalamus, caudate, and frontal cortex. These results indicate that rTMS treatment effectively reduced seizure frequency in patients with DRE. Increased volume in the cerebellar vermis and activations of the cerebello-thalamo-cortical circuit may be a crucial mechanism underlying the effectiveness of rTMS application in patients with DRE.

Gray matter alterations in Huntington's disease: A meta-analysis of VBM neuroimaging studies.

Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of voxel-based morphometry (VBM) studies on HD to investigate the evolution of gray matter volume (GMV) alterations and explore the effects of genetic and clinical features on GMV changes. A systematic review was performed to identify the relevant studies. Meta-analyses of whole-brain VBM studies were performed to assess the regional GMV changes in all HD mutation carriers, in presymptomatic HD (pre-HD), and in symptomatic HD (sym-HD). A quantitative comparison was performed between pre-HD and sym-HD. Meta-regression analyses were used to explore the effects of genetic and clinical features on GMV changes. Twenty-eight studies were included, comparing a total of 1811 HD mutation carriers [including 1150 pre-HD and 560 sym-HD] and 969 healthy controls (HCs). Pre-HD showed decreased GMV in the bilateral caudate nuclei, putamen, insula, anterior cingulate/paracingulate gyri, middle temporal gyri, and left dorsolateral superior frontal gyrus compared with HCs. Compared with pre-HD, GMV decrease in sym-HD extended to the bilateral median cingulate/paracingulate gyri, Rolandic operculum and middle occipital gyri, left amygdala, and superior temporal gyrus. Meta-regression analyses found that age, mean lengths of CAG repeats, and disease burden were negatively associated with GMV atrophy of the bilateral caudate and right insula in all HD mutation carriers. This meta-analysis revealed the pattern of GMV changes from pre-HD to sym-HD, prompting the understanding of HD progression. The pattern of GMV changes may be biomarkers for disease progression in HD.

Interactive effects of polygenic risk and cognitive subtype on brain morphology in schizophrenia spectrum and bipolar disorders

Grey matter volume (GMV) may be associated with polygenic risk for schizophrenia (PRS-SZ) and severe cognitive deficits in people with schizophrenia, schizoaffective disorder (collectively SSD), and bipolar disorder (BD). This study examined the interactive effects of PRS-SZ and cognitive subtypes of SSD and BD in relation to GMV. Two-step cluster analysis was performed on 146 clinical cases (69 SSD and 77 BD) assessed on eight cognitive domains (verbal and visual memory, executive function, processing speed, visual processing, language ability, working memory, and planning). Among them, 55 BD, 51 SSD, and 58 healthy controls (HC), contributed to focal analyses of the relationships between cognitive subtypes, PRS-SZ and their interaction on GMV. Two distinct cognitive subtypes were evident among the combined sample of cases: a ‘cognitive deficit’ group (CD; N = 31, 20SSD/11BD) showed severe impairment across all cognitive indices, and a ‘cognitively spared’ (CS; N = 75; 31SSD/44BD) group showed intermediate cognitive performance that was significantly worse than the HC group but better than the CD subgroup. A cognitive subgroup-by-PRS-SZ interaction was significantly associated with GMV in the left precentral gyrus. Moderation analyses revealed a significant negative relationship between PRS-SZ and GMV in the CD group only. At low and average (but not high) PRS-SZ, larger precentral GMV was evident in the CD group compared to both CS and HC groups, and in the CS group compared to HCs. This study provides evidence for a relationship between regional GMV changes and PRS-SZ in psychosis spectrum cases with cognitive deficits, but not in cases cognitively spared.

Regional Gray Matter Volume Changes in Brains of Patients With Ulcerative Colitis.

Ulcerative colitis (UC) and Crohn's disease (CD) are 2 subtypes of inflammatory bowel disease (IBD). Several studies have reported brain abnormalities in IBD patients. This study aims to identify differences of gray matter volume (GMV) between patients with UC and healthy controls (HCs). Fifty-seven patients with UC and 40 HCs underwent structural magnetic resonance imaging. Voxel-based morphometry method was used to detect GMV differences. Receiver operating characteristic (ROC) curve was applied to investigate reliable biomarkers for identifying patients with UC from HCs. Regression analysis was used to examine relationships between the structure alternations and clinical symptoms. Compared with HCs, patients with UC showed decreased GMV in the insula, thalamus, pregenual anterior cingulate cortex, hippocampus/parahippocampus, amygdala, and temporal pole; they showed increased GMV in the putamen, supplementary motor area, periaqueductal gray, hypothalamus, and precentral gyrus. Receiver operating characteristic analysis showed the highest classification power of thalamus. The inclusion of anxiety and depression as covariates eliminated the differences in the right insula, pregenual anterior cingulate cortex, supplementary motor area, and precentral gyrus. Most of the GMV changes were found in active patients with UC, with few changes in patients with UC in remission. We also found significantly negative correlation between UC duration and GMV in several regions. The current neuroimaging findings were involved in visceral sensory pathways and were partially associated with the levels of anxiety and depression and clinical stage of patients with UC. This study might provide evidence for possible neuromechanisms of UC.

Rajyoga Meditation Experience Induces Enhanced Positive Thoughts and Alters Gray Matter Volume of Brain Regions: A Cross-sectional Study

ObjectivesMany studies on various meditation types have reported regional gray matter volume changes using voxel-based morphometric analysis of structural MRI, but there are no studies done on structural MRI of Rajyoga meditators. The objective of the present study is to analyze and compare gray matter volume changes of brain regions in meditators and non-meditators and further study the effects of meditation experience on alterations in various brain regions. These regions were then correlated and compared to positive thought scores of participants.MethodsForty participants in each group (closely matched for age, gender, and handedness) were selected after obtaining their informed consent, and voxel-based morphometric analysis was carried out using their structural MRI scans.ResultsOn voxel-wise comparison of the brain scans, meditators were observed to have significantly higher global gray matter volume and significant regional gray matter volume increases in the right superior frontal gyrus, left inferior orbitofrontal cortex, left inferior parietal gyrus, left posterior cerebellum, left middle temporal gyrus, bilateral precuneus, and cuneus. Additionally, long-term meditators particularly had significantly higher positive thinking scores compared to non-meditators. On multiple regression analysis, gray matter volume of the left superior parietal gyrus and left inferior parietal gyrus had a positive association, whereas the left posterior cerebellum had a negative association with hours of meditation experience. With the positive thoughts score, a significant relationship was found in the right superior temporal gyrus in meditators.ConclusionsThese findings indicate that Rajyoga meditation experience/practice enhances gray matter volume of specific brain regions and positive thoughts.

Regional Gray Matter Volume Changes in Parkinson's Disease with Orthostatic Hypotension.

Neurodegenerative change in the central nervous system has been suggested as one of the pathophysiological mechanisms of autonomic nervous system dysfunction in Parkinson’s disease (PD). We analyzed gray matter (GM) volume changes and clinical parameters in patients with PD to investigate any involvement in the brain structures responsible for autonomic control in patients with PD having orthostatic hypotension (OH). Voxel-based morphometry was applied to compare regional GM volumes between PD patients with and without OH. Multivariate logistic regression analysis using a hierarchical model was carried out to identify clinical factors independently contributing to the regional GM volume changes in PD patients with OH. The Sobel test was used to analyze mediation effects between the independent contributing factors to the GM volume changes. PD patients with OH had more severe autonomic dysfunction and reduction in volume in the right inferior temporal cortex than those without OH. The right inferior temporal volume was positively correlated with the Qualitative Scoring MMSE Pentagon Test (QSPT) score, reflecting visuospatial/visuoperceptual function, and negatively correlated with the Composite Autonomic Severity Score (CASS). The CASS and QSPT scores were found to be factors independently contributing to regional volume changes in the right inferior temporal cortex. The QSPT score was identified as a mediator in which regional GM volume predicts the CASS. Our findings suggest that a decrease in the visuospatial/visuoperceptual process may be involved in the presentation of autonomic nervous system dysfunction in PD patients.

Early and late effects of electroconvulsive therapy associated with different temporal lobe structures

Recent studies examining electroconvulsive therapy (ECT) have reported that early sessions can induce rapid antidepressant and antipsychotic effects, and the early termination of ECT was reported to increase the risk of relapse. We hypothesized that different neural mechanisms associated with the therapeutic effects of ECT may be involved in the different responses observed during the early and late periods of ECT treatment. We investigated whether these antidepressant and antipsychotic effects were associated with temporally and spatially different regional gray matter volume (GMV) changes during ECT. Fourteen patients with major depressive disorder, with or without psychotic features, underwent 3-Tesla structural magnetic resonance imaging scans before (time point [Tp] 1), after the fifth or sixth ECT session (Tp2), and after ECT completion (Tp3). We investigated the regions in which GMV changed between Tp1 and Tp2, Tp2 and Tp3, and Tp1 and Tp3 using voxel-based morphometry. In addition, we investigated the association between regional GMV changes and improvement in depressive or psychotic symptoms. GMV increase in the left superior and inferior temporal gyrus during Tp1–Tp2 was associated with improvement in psychotic symptoms (P < 0.025). GMV increase in the left hippocampus was associated with improvement of depressive symptoms in Tp2–Tp3 (P < 0.05). Our findings suggest that different temporal lobe structures are associated with early antipsychotic and late antidepressant effects of ECT.

Integrative omics analysis identifies differential biological pathways that are associated with regional grey matter volume changes in major depressive disorder.

Major depressive disorder (MDD) is accompanied by alterations in grey matter volume. However, the biological processes associated with regional structural perturbations remain elusive. We applied integrative omics analysis to investigate specialized transcriptome signatures and translational determinants associated with regional grey matter variations in 2737 MDD patients relative to 3098 controls by summarizing the results from gene co-expression network analysis of Allen human brain transcriptome profiles in six donors, enrichment analysis of gene-sets and cellular structure from rodents and mediation analysis of BrainSpan proteome profile in six donors. We found convergent alterations of grey matter volume in MDD were associated with transcriptome profiles enriched for synaptic transmission, metabolism, immune processes and transmembrane transport. Genes with abnormal expression in post-mortem tissue in MDD were also associated with transcriptome signatures. Further gene co-expression network and enrichment analysis of MDD-related genes in these signatures revealed the modules with higher neuronal expression were enriched in the medial temporal cortex and temporo-parietal junction with genes differentially associated with neuronal development and metabolism. Also, the modules with higher non-neuronal (e.g. astrocyte and oligodendrocyte) expression were concentrated in the rostral and dorsal anterior cingulate cortex and were separately associated with immune response and transmembrane transport. Moreover, proteins as the gene expression products mediated the association between transcriptome signatures and brain volume changes in the visual and dorsolateral prefrontal cortex. Our multidimensional analyses offer a novel approach to detect specific biological pathways that capture regional structural variations in MDD, which suggests structural endophenotypes associated with MDD.

Frontoparietal structural properties mediate adult life span differences in executive function

Executive function (EF) refers to a set of cognitive functions that support goal-directed behaviors. Recent findings have suggested that the frontoparietal network (FPN) subserves neural processes that are related to EF. However, the FPN structural and functional network properties that mediate age-related differences in EF components remain unclear. To this end, we used three experimental tasks to test the component processes of EF based on Miyake and Friedman’s model: one common EF component process (incorporating inhibition, shifting, and updating) and two specific EF component processes (shifting and updating). We recruited 126 healthy participants (65 females; 20 to 78 years old) who underwent both structural and functional MRI scanning. We tested a mediation path model of three structural and functional properties of the FPN (i.e., gray matter volume, white matter fractional anisotropy, and intra/internetwork functional connectivity) as mediators of age-related differences in the three EF components. The results indicated that age-related common EF component differences are mediated by regional gray matter volume changes in both hemispheres of the frontal lobe, which suggests that structural changes in the frontal lobe may have an indirect influence on age-related general elements of EF. These findings suggest that the FPN mediates age-related differences in specific components of EF.

The prognosis and changes of regional brain gray matter volume in MDD with gastrointestinal symptoms.

Objective: It is common that major depressive disorder (MDD) is accompanied by gastrointestinal (GI) symptoms. However, few studies have focused on the clinical characteristics and its possible mechanism, while brain gray matter (GM) structure is important in the pathogenesis of GI symptoms. In this study, we aimed to investigate the basic clinical characteristics and regional GM volume changes in MDD accompanied by GI symptoms.Method: Patients with MDD (n=49) and age, gender, and educational level-matched healthy controls (n=30) were recruited. Patients with MDD were divided into two groups based on the GI status: MDD with (n=27) and without (n=22) GI symptoms. The 24-item Hamilton Depression Rating Scale (HAMD) was administered. T1-weighted anatomical images were obtained and analyzed. Correlation analysis was used to identify the possible associations between changed regional GM volume and GI symptoms and depressive symptoms.Results: The HAMD reductive ratio for 2 weeks of treatment in the GI symptoms group was significantly higher than the non-GI symptoms group (P<0.05). The regional GM volume showed significant differences among the three groups (Gaussian Random Field [GRF] correction, voxel-P<0.01, cluster-P <0.05). Compared with non-GI symptoms group, GI symptoms group exhibited significantly increased GM volume in the left hippocampus, left parahippocampal gyrus, right parahippocampal gyrus; and decreased GM volume in the right middle frontal gyrus, right precentral gyrus, right cuneus, right precuneus, right superior occipital gyrus (GRF correction, voxel-P <0.01, cluster-P <0.05). These altered brain areas were correlated with the GI symptoms, not depressive symptoms.Conclusion: The changed regional brain GM volume in GI-MDD group may be the pathogenesis for the GI symptoms. In addition, the GI symptoms may predict the prognosis of MDD.

Risk for affective disorders is associated with greater prefrontal gray matter volumes: A prospective longitudinal study.

BackgroundMajor depression and bipolar disorders aggregates in families and are linked with a wide range of neurobiological abnormalities including cortical gray matter (GM) alterations. Prospective studies of individuals at familial risk may expose the neural mechanisms underlying risk transmission.MethodsWe used voxel based morphometry to investigate changes in regional GM brain volume, over a seven-year period, in 37 initially healthy individuals having a mono- or di-zygotic twin diagnosed with major depression or bipolar disorder (high-risk group; mean age 41.6 yrs.) as compared to 36 individuals with no history of affective disorders in the index twin and first-degree relatives (low-risk group; mean age 38.5 yrs.).ResultsGroups did not differ in regional GM volume changes over time. However, independent of time, high-risk twins had significantly greater GM volumes in bilateral dorsal anterior cingulate, inferior frontal gyrus and temporoparietal regions as compared to low-risk twins. Further, individuals who developed an affective disorder at follow-up (n = 12), had relatively the largest GM volumes, both at baseline and follow-up, in the right dorsal anterior cingulate cortex and right inferior frontal cortex compared to high- and low-risk twins who remained well at follow-up.ConclusionThis pattern of apparently stable grater regional GM volume may constitute a neural marker of an increased risk for developing an affective disorder in individuals at familial risk.

Reproducibility of hormone-driven regional grey matter volume changes in women using SPM8 and SPM12.

Aim of this work was to evaluate the reproducibility of hormone driven regional grey matter volume differences in women, and their correlations with premenstrual symptoms, as determined by voxel-based morphometry (VBM). After data quality control, a total of 138 T1-weighted MR images were included in this longitudinal study, and were analyzed as three different subgroups. Women with a natural menstrual cycle were scanned at three time-points: follicular, ovulatory and luteal phase. Two groups of women, using androgenic and anti-androgenic hormonal contraceptives, respectively, were scanned twice: during the pill-free week and during pill intake. Additionally, subjects were asked to complete a "daily rating of severity of problems" questionnaire, to quantify premenstrual symptoms. All data were analyzed using SPM8 and SPM12 with identical parameter settings. In the natural menstrual cycle group, the regional grey matter volume of the insula is larger at ovulation, as compared to the luteal phase. Premenstrual symptoms correlate differently with regional grey matter volumes between women with a natural cycle and hormonal contraceptive users. Changes in hormonal environment can to various extents affect VBM findings in women. We suggest that researchers take these confounding factors into account while applying this technique, to avoid heterogeneity in data acquisition and to safeguard the sensitivity of findings. Additionally, we suggest validating the consistency of results using more than one software package.

Regional gray matter volume differences and sex-hormone correlations as a function of menstrual cycle phase and hormonal contraceptives use

During the menstrual cycle, hormone-driven functional and morphological changes occur in the female brain. The influence of hormonal contraceptives on these changes has received only little attention in the medical literature. The purpose of our study is to measure regional gray matter volume changes as a function of the cycle phase and use of hormonal contraceptives, in relation to blood concentrations of sex hormones. We performed a prospective study in 30 healthy young women; 15 women had a natural menstrual cycle and 15 were using monophasic combined hormonal contraceptives. MRI examinations were acquired at 2 specific time-points in the cycle (follicular and luteal phase). MRI studies included a T1-weighted, isotropic, high-resolution 3-D gradient echo acquisition, for the purpose of performing voxel based morphometry. Peripheral venous blood samples were obtained to determine concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and progesterone. We found a highly significant negative correlation of regional gray matter volume in the anterior cingulate cortex with estradiol concentrations. To the best of our knowledge, this result has not been described before, and was only present in the natural cycle group, not in women using hormonal contraceptives. The anterior cingulate cortex is involved in emotion processing and there is literature describing behavioral alternations with changing hormone levels. Our findings provide a structural, morphological basis to support these data. Therefore, we advise neuroscientists to take into account the menstrual cycle phase and use of hormonal contraceptives, in order to avoid obtaining heterogeneous data sets, leading to a significant loss of accuracy and precision.

Progression in disability and regional grey matter atrophy in relapsing–remitting multiple sclerosis

Background: In multiple sclerosis (MS) regional grey matter (GM) atrophy has been associated with disability progression. Objective: The aim of this study was to compare regional GM volume changes in relapsing–remitting MS (RRMS) patients with progressive and stable disability, using voxel-based morphometry (VBM). Methods: We acquired baseline and 1-year follow-up 3-dimensional (3D) T1-weighted magnetic resonance imaging (MRI) data of RRMS patients, using two 1.5-Tesla scanners. Patients were matched pair-wise with respect to age, gender, disease duration, medication, scanner and baseline Expanded Disability Status Scale (EDSS) into 13 pairs, with either progressive EDSS (≥ 1 point change y-1) or stable EDSS, as well as into 29 pairs with either progressive Multiple Sclerosis Functional Composite (MSFC) at ≥ 0.25% decrease in y-1 in any component, or stable MSFC. We analysed longitudinal regional differences in GM volumes in the progressive and stable EDSS and MSFC groups, respectively, using VBM. Results: Significant GM volume reductions occurred in the right precuneus, in the progressive EDSS group. Differential between-group effects occurred in the right precuneus and in the postcentral gyrus. Further longitudinal GM volume reductions occurred in the right orbicular gyrus, in the progressive MSFC group, but no between-group differences were observed (non-stationary cluster-wise inference, all Pcorrected < 0.05). Conclusion: These results suggested a direct association of disability progression and regional GM atrophy in RRMS.

Menstrual pain is associated with rapid structural alterations in the brain

Dysmenorrhea is the most prevalent gynecological disorder in women of child-bearing age. Dysmenorrhea is associated with central sensitization and functional and structural changes in the brain. Our recent brain morphometry study disclosed that dysmenorrhea is associated with trait-related abnormal gray matter (GM) changes, even in the absence of menstrual pain, indicating that the adolescent brain is vulnerable to menstrual pain. Here we report rapid state-related brain morphological changes, ie, between pain and pain-free states, in dysmenorrhea. We used T1-weighted anatomic magnetic resonance imaging to investigate regional GM volume changes between menstruation and periovulatory phases in 32 dysmenorrhea subjects and 32 age- and menstrual cycle-matched asymptomatic controls. An optimized voxel-based morphometry analysis was conducted to disclose the possible state-related regional GM volume changes across different menstrual phases. A correlation analysis was also conducted between GM differences and the current menstrual pain experience in the dysmenorrhea group. Compared with the periovulatory phase, the dysmenorrhea subjects revealed greater hypertrophic GM changes than controls during the menstruation phase in regions involved in pain modulation, generation of the affective experience, and regulation of endocrine function, whereas atrophic GM changes were found in regions associated with pain transmission. Volume changes in regions involved in the regulation of endocrine function and pain transmission correlated with the menstrual pain experience scores. Our results demonstrated that short-lasting cyclic menstrual pain is associated not only with trait-related but also rapid state-related structural alterations in the brain. Considering the high prevalence rate of menstrual pain, these findings mandate a great demand to revisit dysmenorrhea with regard to its impact on the brain and other clinical pain conditions.

A voxel-based morphometric analysis of brain gray matter in online game addicts

To explore the possible brain mechanism of online game addiction (OGA) in terms of brain morphology through voxel-based morphometric (VBM) analysis. Seventeen subjects with OGA and 17 age- and gender-matched healthy controls (HC group) were recruited from Department of Psychology at our hospital during February-December 2011. The internet addiction scale (IAS) was used to measure the degree of OGA tendency. Magnetic resonance imaging (MRI) scans were performed to acquire 3-dimensional T1-weighted images. And FSL 4.1 software was employed to confirm regional gray matter volume changes. For the regions where OGA subjects showed significantly different gray matter volumes from the controls, the gray matter volumes of these areas were extracted, averaged and regressed against the scores of IAS. The OGA group had lower gray matter volume in left orbitofrontal cortex (OFC), left medial prefrontal cortex (mPFC), bilateral insula (INS), left posterior cingulate cortex (PCC) and left supplementary motor area (SMA). Gray matter volumes of left OFC and bilateral INS showed a negative correlation with the scores of IAS (r = -0.65, r = -0.78, P < 0.05). Gray matter volume changes are present in online game addicts and they may be correlated with the occurrence and maintenance of OGA.

Progressive gray matter changes in patients with congenital central hypoventilation syndrome

BackgroundCongenital central hypoventilation syndrome (CCHS) patients show brain injury in areas that control chemosensory, autonomic, motor, cognitive, and emotion functions, which are deficient in the condition. Many of these abnormal characteristics are present from the neonatal period; however, it is unclear if tissue injury underlying the characteristics progressively worsens with time. We hypothesized that several brain areas in CCHS subjects would show increased gray matter volume loss over time.MethodsWe collected high-resolution T1-weighted images twice (four years apart) from 7 CCHS (age at first study, 16.1±2.7 years; 4 males) and 3 control subjects (15.9±2.1 years; 3 males) using a 3.0-Tesla MRI scanner, and evaluated regional gray matter volume changes with voxel-based-morphometry procedures.ResultsMultiple brain sites in CCHS, including frontal, prefrontal, insular and cingulate cortices, caudate nuclei and putamen, ventral temporal and parietal cortices, and cerebellar cortices showed significantly reduced gray matter volume over time. Only limited brain areas, including sensory, temporal, and medullary regions emerged with increased gray matter at the later age.ConclusionsCCHS patients show reduced gray matter volume with age progression in autonomic, respiratory, and cognitive regulatory areas, an outcome that may contribute to deterioration of functions found in the syndrome with increasing age.

The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study.

Patients with schizophrenia and related psychoses have an excess of minor neurological abnormalities (neurological soft signs) of unclear neuropathological origin. These include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing complex motor tasks. Neurological soft signs seem not to reflect primary tract or nuclear pathology. It still has to be established whether neurological soft signs result from specific or diffuse brain structural abnormalities. Studying their anatomical correlates can provide not only a better understanding of the aetiopathogenesis of soft signs, but also of the pathophysiology of schizophrenia. Surprisingly few studies have investigated the brain correlates of neurological soft signs. In the present study, we investigated the relationship between brain structure and neurological soft signs in an epidemiologically based sample of 77 first-episode psychosis patients. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of soft neurological signs (both motor and sensory) were associated with a reduction of grey matter volume of subcortical structures (putamen, globus pallidus and thalamus). Signs of sensory integration deficits were additionally associated with volume reduction in the cerebral cortex, including the precentral, superior and middle temporal, and lingual gyri. Neurological soft signs and their associated brain changes were independent of antipsychotic exposure. We conclude that neurological soft signs are associated with regional grey matter volume changes and that they may represent a clinical sign of the perturbed cortical-subcortical connectivity that putatively underlies psychotic disorders.