Motor and extra-motor gray matter integrity may underlie neurophysiologic parameters of motor function in amyotrophic lateral sclerosis: a combined voxel-based morphometry and transcranial stimulation study

The association between gray matter (GM) density and neurophysiologic changes is still unclear in amyotrophic lateral sclerosis (ALS). We evaluated the relationship between GM density and motor system integrity combining voxel-based morphometry (VBM) and transcranial magnetic stimulation (TMS) in ALS. We included 17 ALS patients and 22 healthy controls (HC) who underwent 3D-T1-weighted imaging. Among the ALS group, we applied left motor cortex single-pulse TMS. We used whole-brain VBM comparing ALS and HC in GM density. We also conducted regression analysis to examine correlations between GM density and the following TMS parameters: motor evoked potential (MEP)/M ratio and central motor conduction time (CMCT). We found significantly decreased GM density in ALS patients in several frontal, temporal, parietal/occipital and cerebellar regions (p?<?0.001 uncorrected; cluster-extent threshold k?=?100 voxels per cluster). With regards to TMS parameters, ALS patients showed mostly increased MEP/M ratio and modest prolongation of CMCT. MEP/M ratio was associated with GM density in (a) rolandic operculum/inferior frontal gyrus/precentral gyrus; anterior cingulate gyrus; inferior temporal gyrus; superior parietal lobule; cuneus; superior occipital gyrus and cerebellum (positive association) and (b) paracentral lobule/supplementary motor area (negative association). CMCT was associated with GM density in (a) inferior frontal gyrus and middle cingulated gyrus (positive association) and (b) superior parietal lobule; cuneus and cerebellum (negative association). Our findings support a significant interaction between motor and extra-motor structural and functional changes and highlight that motor and extra-motor GM integrity may underlie TMS parameters of motor function in ALS patients.     

Gray matter volume deficits and correlation with insight and negative symptoms in first-psychotic-episode subjects

Bergé D, Carmona S, Rovira M, Bulbena A, Salgado P, Vilarroya O. Gray matter volume deficits and correlation with insight and negative symptoms in first‐psychotic‐episode subjects. Objective: To determine brain areas reduced in first episode of psychotic subjects and its association with lack of insight and negative symptoms. Method: Twenty‐one drug naive first‐episode subjects and 20 controls underwent a structural MRI scan and were clinically assessed. Optimized voxel‐based‐morphometry analysis (VBM) was implemented to find between‐group differences and correlations between GM volume and: (i) lack of insight and (ii) negative symptoms. Results: Patients showed GM reduction in prefrontal and left temporal areas. A significant correlation was found between insight and GM volume in the cerebellum (corrected P = 0.01), inferior temporal gyrus (corrected P = 0.022), medial superior frontal gyrus (corrected P < 0.001), and inferior frontal gyrus (corrected P = 0.012), as the insight decreased, the volume decreased. Negative symptoms correlated with decreased GM volume at cerebellum (corrected P = 0.037) and frontal inferior regions (corrected P < 0.001), the more negative symptoms, the less volume. Conclusion: Our findings support an association between prefrontal, temporal, and cerebellar deficits and lack of insight in schizophrenia and confirm previous findings of GM deficits in patients since the first episode of psychosis.     

Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study

Women with ovarian cancer often undergo chemotherapy involving multiple agents. However, little is known about treatment-related central neurotoxicity in this population. The goal of this cross-sectional study was to assess brain structure and function and neurocognitive abilities in patients with ovarian cancer following first-line chemotherapy. Eighteen patients with ovarian, peritoneal and fallopian tube cancer and eighteen healthy controls matched for gender, age and education participated in the study. The patients were evaluated 1–4 months following completion of first-line taxane/platinum chemotherapy. All participants underwent structural and functional magnetic resonance imaging (MRI), and completed neuropsychological tests of attention, memory and executive functions. Neuroimaging assessments included voxel-based morphometry (VBM) for measuring gray matter (GM) volume, and functional MRI (fMRI) during the N-back working memory task. The results of VBM showed that patients had significantly reduced GM volume compared to healthy controls in the right middle/superior frontal gyrus, and in the left supramarginal gyrus and left inferior parietal lobule. fMRI results indicated significantly decreased activation in patients relative to healthy controls in the left middle frontal gyrus and left inferior parietal lobule during the N-back task (1/2/3-back >0-back). There were no statistically significant differences between the two groups on the neuropsychological tests. This is the first study showing structural and functional alterations involving frontal and parietal regions in patients with ovarian cancer treated with first-line chemotherapy. These findings are congruent with studies involving women with breast cancer, and provide additional supporting evidence for central neurotoxicity associated with taxane/platinum chemotherapy.     

Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study

The aim of the current study was to use whole brain voxel-based morphometry（VBM）to assess the gray matter（GM）changes in unmedicated patients with obsessive-compulsive disorder（OCD）compared with normal controls.We compared the GM volumes in28 patients with 22 matched healthy controls using a1.5T MRI.Three-dimensional T1-weighted magnetic resonance images were obtained from all participants.VBM was performed to detect GM volume differences between the two groups.We detected increased regional GM volumes in the bilateral middle temporal gyri,bilateral middle occipital gyri,bilateral globus pallidus,right inferior parietal gyrus,left superior parietal gyrus,right parahippocampus,right supramarginal gyrus,right medial superior frontal gyrus,and left inferior frontal opercular cortex in the OCD patients relative to controls（P〈0.001,uncorrected,cluster size〉100 voxels）.No decreased GM volume was found in the OCD group compared with normal controls.Our findings suggest that structural changes in the GM are not limited to fronto-striato-thalamic circuits in the pathogenesis of OCD.Temporo-parietal cortex may also play an important role.     

Gray Matter Reduction in the Vermis and CRUS-II Is Associated with Social and Interaction Deficits in Low-Functioning Children with Autistic Spectrum Disorders: a VBM-DARTEL Study

Voxel-based morphometry (VBM) studies have reported abnormalities in brain regions involved in functions that are commonly impaired in autism spectrum disorders (ASD). However, little is known about brain structure anomalies in low-functioning (LF) young children with ASD. A VBM analysis was carried out to assess brain regions involved in ASD LF children, and a multiple regression analysis was used to examine the relationship between regional volume changes and autism symptom measures. Twenty-six LF ASD children (2–10 years) were compared with 21 controls. A VBM-Diffeomorphic Anatomical Registration analysis using Exponentiated Lie algebra (DARTEL) was used to evaluate gray matter (GM) and white matter alterations, covaried with Intelligence Quotient, age, and total brain volume. The resulting altered regions were correlated with Autism Diagnostic Interview (ADI)-Revised and Autism Diagnostic Observation Schedule (ADOS)-Generic scores. GM bilateral reduction was noted in the cerebellum (Crus II and vermis) and in the hippocampi in ASD group. GM reduction was also detected in the inferior and superior frontal gyri, in the occipital medial and superior gyri, and in the inferior temporal gyrus of the left cerebral hemisphere. In the right hemisphere, GM reduction was found in the post-central cortex and in the occipital inferior gyrus. Multiple regression analysis showed a correlation between alterations in GM volume in the cerebellum (Crus II and vermis) and ADI-communication and ADOS-total (communication and interaction) scores. These findings seem to confirm that the cerebellum is involved in integrating and regulating emotional and cognitive functions which are impaired in ASD.     

Effect of the BDNF Val66Met Polymorphism on Regional Gray Matter Volumes and Cognitive Function in the Chinese Population

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is common and influences the activity-dependent secretion of BDNF, which is critical for neuronal plasticity and survival. This study investigated the genetic effect of the BDNF Val66Met polymorphism on cognitive function and regional gray matter (GM) volume in a healthy Chinese population (n = 330). Voxel-based morphometry (VBM)-optimized analysis was used. There was no significant difference in the neuropsychological performances among the three BDNF genotypic groups. VBM analyses demonstrated that Met homozygotes had greater GM volumes than Val homozygotes in the left medial frontal gyrus, the left middle temporal gyrus, the left cerebellum, and the right middle temporal gyrus, and had larger GM volumes than Val/Met heterozygotes in the left middle temporal gyrus, the left inferior temporal gyrus, and the right superior frontal gyrus. Our findings suggest that the presence of two Met alleles has a protective effect on regional GM volumes in the Chinese population.     

Regional gray matter changes in bipolar disorder: a voxel-based morphometric study

OBJECTIVE: To investigate structural abnormalities in bipolar disorder (BD) using optimized voxel-based morphometry (VBM) in closely matched patients and controls, and to examine the relationship of clinical features with regional gray matter (GM) volumes. METHODS: Twenty-four patients (six male) aged 19-59 years (mean=38.21 years, SD=11.04 years) with DSM-IV bipolar I disorder were compared with 25 control subjects, matched on age, sex, and years of education. VBM analyses were conducted on high-resolution T1-weighted brain magnetic resonance imaging to detect regional GM volume differences between groups, ensuring statistical correlation for age, sex and total intracranial volumes. Within the patient groups, regional GM changes were also investigated. RESULTS: Compared to controls, BD patients had increased GM volume in left parahippocampal gyrus and decreased GM volume in left middle temporal gyrus. Family history, psychotic symptoms and lithium status were associated with regional GM abnormalities in BD patients. CONCLUSIONS: This study presents evidence of gray matter volume abnormalities in adults with bipolar I disorder. Regional variation in relation to clinical factors suggests a neurobiological basis for clinical heterogeneity and posits the possibility of trait deficits.     

Exploring cortical atrophy and its clinical and biochemical correlates in Wilson’s disease using voxel based morphometry

ObjectivesTo determine cortical grey matter (GM) changes and their clinical and biochemical correlates in patients with Wilson’s disease using voxel based morphometry (VBM).MethodsClinical and imaging data of 10 patients (all male, mean age 16.0 ± 6.3years) with Wilson’s Disease were analyzed. T1W volumetric MRI data of patients without obvious cortical atrophy or signal changes on conventional MRI was compared with MRI of 11 matched control subjects using VBM analysis with Statistical Parametric Mapping 8. Results were expressed at statistical threshold of p < 0.05 (FWE corrected) and p < 0.001 (uncorrected). Multiple regression analysis was done to analyze possible relation between GM atrophy, duration of disease and biochemical abnormalities.ResultsCompared to controls, patients showed scattered areas of reduced GM volume in bilateral caudate head, medial part of right globus pallidus and body of right caudate (FWE corrected p < 0.05). At p < 0.001(uncorrected) widespread areas of cortical atrophy were also noted involving the frontal and temporal lobes, lentiform nuclei, cerebellum and thalamus. Significant positive correlation (uncorrected p < 0.001) were noted between (i) duration of disease and cortical GM volume of frontal, parietal and temporal lobes and cerebellum (ii) serum copper levels and GM volume of right medial frontal gyrus and paracentral lobule.ConclusionsTo the best of our knowledge, this is the first VBM study in patients with Wilson’s disease. In spite of apparently normal cortex on visual inspection of MRI, decreased cortical GM volume was detected using VBM. In addition, serum copper may act as surrogate marker of cortical abnormalities in Wilson’s disease.     

Voxel‐wise meta‐analysis of gray matter abnormalities in idiopathic Parkinson’s disease

Structural neuroimaging studies on idiopathic Parkinson’s disease (IPD) with voxel‐based morphometry (VBM) yielded variable and conflicting findings. A systematic review of VBM studies of patients with IPD and healthy control (HC) subjects published in PubMed, ISI Web of Science, Embase, and Medline databases from 1995 to 25 October 2010 was conducted. Coordinates were extracted from clusters of significant gray matter (GM) difference between patients with IPD and HC subjects. Meta‐analysis was performed using signed differential mapping. A total of 17 VBM studies involving 498 patients with IPD and 375 HC subjects met the inclusion criteria. A significant regional GM volume decrease was detected in the left inferior frontal gyrus (BA47) extending to the left superior temporal gyrus (BA38) and the left insula (BA13) of patients with IPD compared with HC subjects. The findings of this study remain largely unchanged in quartile and jackknife sensitivity analyses and in subgroup analyses. Robust GM reductions in the inferior frontal/orbitofrontal gyrus (BA47) are implicated in IPD, and the reductions may be related to the mediation of the non‐motor IPD symptoms, such as cognitive, emotional, and autonomic functions. Further studies must be conducted to determine whether the findings are specific to all IPD subtypes or different from the atypical Parkinsonism.     

Voxel-based morphometric analysis on the volume of gray matter in bipolar I disorder

A number of previous studies have found that bipolar disorder is associated with abnormalities of brain structure. In this study we used optimized voxel-based morphometry (VBM) to compare gray matter volume between patients with bipolar I disorder and healthy controls. Twenty-four bipolar I patients (15 males and nine females) and 36 healthy controls (21 males and 15 females), who were well matched for age and gender, were scanned using structural magnetic resonance imaging. Gray matter volume was assessed and compared using optimized VBM, and the correlation between duration of illness/number of episodes and regional volumes was analyzed. There was no difference in whole-brain gray matter volume between the two groups. Optimized vVBM showed that subjects with bipolar I disorder had smaller volumes in the left inferior parietal lobule, right superior temporal gyrus, right middle frontal gyrus and left caudate. Only the volume of the right middle frontal gyrus was correlated with duration of illness and number of episodes in patients. These results suggest widespread gray matter defects in bipolar I disorder, which may play an important role in onset of the illness.     

Anatomical signatures of dyslexia in children: unique information from manual and voxel based morphometry brain measures

Thirteen male control and thirteen male dyslexic children (age, 121-152 months) were studied to determine if voxel based morphometry (VBM) could identify anatomical differences in the right cerebellar anterior lobe, and right and left pars triangularis that were identified with manual measures of the same children. VBM demonstrated significant gray and white matter differences in these three brain regions. In contrast to the manual results, these differences were not significant after controlling for brain volume, suggesting the manual measures captured additional important variance that distinguished the groups. Post-hoc VBM comparisons demonstrated white matter volume differences in a left temporal-parietal region that are consistent in location with results from diffusion tensor imaging studies of dyslexia. The VBM analyses also identified, gray matter volume differences in the left and right lingual gyrus, left inferior parietal lobule and cerebellum, areas that had not been examined with manual methods. We conclude that manual and automated methods provide valuable and complementary approaches to the search for functionally significant neurobiological characteristics of dyslexia.     

Assessment of cortical degeneration in patients with Parkinson's disease by voxel-based morphometry, cortical folding, and cortical thickness

Noninvasive brain imaging methods provide useful information on cerebral involution and degenerative processes. Here we assessed cortical degeneration in 20 nondemented patients with Parkinson's disease (PD) and 20 healthy controls using three quantitative neuroanatomical approaches: voxel‐based morphometry (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We examined the relationship between global and regional gray matter (GM) volumes, sulcal indices, and thickness measures derived from the previous methods as well as their association with cognitive performance, age, severity of motor symptoms, and disease stage. VBM analyses showed GM volume reductions in the left temporal gyrus in patients compared with controls. Cortical folding measures revealed significant decreases in the left frontal and right collateral sulci in patients. Finally, analysis of cortical thickness showed widespread cortical thinning in right lateral occipital, parietal and left temporal, frontal, and premotor regions. We found that, in patients, all global anatomical measures correlated with age, while GM volume and cortical thickness significantly correlated with disease stage. In controls, a significant association was found between global GM volume and cortical folding with age. Overall these results suggest that the three different methods provide complementary and related information on neurodegenerative changes occurring in PD, however, surface‐based measures of cortical folding and especially cortical thickness seem to be more sensitive than VBM to identify regional GM changes associated to PD. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis

Background

Individual structural imaging studies in the pre-psychotic phases deliver contrasting findings and are unable to definitively characterize the neuroanatomical correlates of an increased liability to psychosis and to predict transition to psychosis.

Method

Ninenteen voxel-based morphometry (VBM) studies of subjects at enhanced risk for psychosis and healthy controls were included in an activation likelihood estimation (ALE) meta-analysis.

Results

The overall sample consisted of 701 controls and 896 high risk subjects. Subjects at high risk for psychosis showed reduced gray matter (GM) volume as compared to controls in the right superior temporal gyrus, left precuneus, left medial frontal gyrus, right middle frontal gyrus, bilateral parahippocampal/hippocampal regions and bilateral anterior cingulate. High risk subjects who later developed a psychotic episode showed baseline GM volume reductions in the right inferior frontal gyrus and in the right superior temporal gyrus.

Conclusions

GM volume reductions in temporo-parietal, bilateral prefrontal and limbic cortex are neuroanatomical correlates of an enhanced vulnerability to psychosis. Baseline GM reductions in superior temporal and inferior frontal areas are associated with later transition to psychosis.     

Cortical brain atrophy and intra-individual variability in neuropsychological test performance in HIV disease

To characterize the relationship between dispersion-based intra-individual variability (IIV_d) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV-) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIV_d was measured by computing intra-individual standard deviations (ISD’s) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Total gray matter (GM) volume was inversely associated with IIV_d. Among all subjects, IIV_d -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIV_d -related GM atrophy. IIV_d in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests.     

Spatiotemporal distribution pattern of white matter lesion volumes and their association with regional grey matter volume reductions in relapsing‐remitting multiple sclerosis

The association of white matter (WM) lesions and grey matter (GM) atrophy is a feature in relapsing‐remitting multiple sclerosis (RRMS). The spatiotemporal distribution pattern of WM lesions, their relations to regional GM changes and the underlying dynamics are unclear. Here we combined parametric and non‐parametric voxel‐based morphometry (VBM) to clarify these issues. MRI data from RRMS patients with progressive (PLV, n = 45) and non‐progressive WM lesion volumes (NPLV, n = 44) followed up for 12 months were analysed. Cross‐sectionally, the spatial WM lesion distribution was compared using lesion probability maps (LPMs). Longitudinally, WM lesions and GM volumes were studied using FSL‐VBM and SPM5‐VBM, respectively. WM lesions clustered around the lateral ventricles and in the centrum semiovale with a more widespread pattern in the PLV than in the NPLV group. The maximum local probabilities were similar in both groups and higher for T2 lesions (PLV: 27%, NPLV: 25%) than for T1 lesions (PLV: 15%, NPLV 14%). Significant WM lesion changes accompanied by cortical GM volume reductions occured in the corpus callosum and optic radiations (P = 0.01 corrected), and more liberally tested (uncorrected P < 0.01) in the inferior fronto‐occipital and longitudinal fasciculi, and corona radiata in the PLV group. Not any WM or GM changes were found in the NPLV group. In the PLV group, WM lesion distribution and development in fibres, was associated with regional GM volume loss. The different spatiotemporal distribution patterns of patients with progressive compared to patients with non‐progressive WM lesions suggest differences in the dynamics of pathogenesis. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Neural correlates of communication skill and symptom severity in autism: A voxel-based morphometry study

Although many studies have compared the brains of normal controls and individuals with autism, especially older, higher-functioning individuals with autism, little is known of the neural correlates of the vast clinical heterogeneity characteristic of the disorder. In this study, we used voxel-based morphometry (VBM) to examine gray matter correlates of variation in communication skill and symptom severity within a heterogeneous group of 33 children with autism ranging in age from 3.4 to 11.4 years. Greater gray matter (GM) volume was associated with better communication skills in numerous frontal regions, especially in the left middle frontal gyrus. Further, greater GM volume in the right inferior frontal gyrus was associated with reduced severity of symptoms of autism. However, increased total GM volume was correlated with more severe symptoms of autism at a trend level, consistent with other studies, suggesting that while increased total GM volume is generally predictive of greater autistic severity, specific local increases in GM volume result in a reduction in symptoms. Our results suggest that communication and symptom severity have distinct neuroanatomic correlates and draw attention to the importance of studying the neuroanatomy of clinical heterogeneity within the autistic population.     

Altered Gray Matter Volume in Stable Chronic Obstructive Pulmonary Disease with Subclinical Cognitive Impairment: an Exploratory Study

Gray matter volume deficits have been identified in cognitively impaired patients with chronic obstructive pulmonary disease (COPD). However, it remains unknown whether the gray matter volume is altered in COPD patients with subclinical cognitive impairment. To determine whether any gray matter abnormalities are present in these patients, neuropsychological tests and structural MRI data were analyzed from 60 patients with COPD and 60 age-, gender-, education-, and handedness-matched normal controls (NCs). The COPD patients had similar Mini-Mental State Examination (MMSE) scores compared with the NCs. However, they had reduced Montreal Cognitive Assessment (MoCA) scores for visuospatial and executive and naming and memory functions (P < 0.001). Voxel-based morphometry (VBM) analysis revealed that the COPD patients had significantly lowered gray matter volumes in several brain regions, including the left precuneus (PrCU), bilateral calcarine (CAL), right superior temporal gyrus/middle temporal gyrus (STG/MTG), bilateral fusiform gyrus (FG), and right inferior parietal lobule (IPL) (P < 0.01, corrected). Importantly, the forced vital capacity (FVC) was found to be associated with the gray matter volume in the calcarine. The present study confirmed that brain structural changes were present in stable COPD patients with subclinical cognitive impairment. These findings may provide new insights into the pathogenesis of COPD.     

Temporal Lobe Volume Abnormalities Precede the Prodrome: A Study of Children Presenting Antecedents of Schizophrenia

Distributed abnormalities of gray matter (GM) and white matter (WM) volume characterize individuals experiencing their first episode of schizophrenia. Regions of abnormality are present already, albeit less extensively, during the prodromal phase of illness. This study aimed to determine whether putatively at-risk children, aged 9–12 years, who present multiple antecedents of schizophrenia (ASz), display GM and WM volume abnormalities relative to typically developing (TD) children presenting no antecedents. Structural magnetic resonance images were acquired for 20 ASz children and 20 TD children matched on age, sex, and IQ. Whole-brain differences in GM and WM volume were determined using voxel-based morphometry. Relative to the TD group, ASz children showed significantly decreased GM volume in the right middle temporal gyrus (MTG) and increased GM volume in the left superior-middle temporal gyri (P < 0.05, cluster correction). WM volume was significantly increased in ASz children relative to TD children in a cluster encompassing the left inferior parietal lobe, occipital lobe, and superior temporal gyrus. Post-hoc analyses indicated that these abnormalities were not limited to ASz children who self-reported auditory hallucinations on questionnaire. Our findings suggest that children aged 9–12 years who present multiple ASz are characterized by abnormalities of GM and WM volume in the temporal lobes, comprising a subset of the regions affected in first-episode schizophrenia and in the prodromal phase of illness. These preliminary findings indicate that structural brain abnormalities associated with schizophrenia may be detected in putatively at-risk, preprodromal children. Prospective studies following the brain development of at-risk children are needed.Key words: psychosis, high risk, MRI, VBM, biomarkers, brain structure     

Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia

The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n=146) were compared with normal control subjects (n=36) and first episode schizophrenic subjects (n=34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis.