Voxel Based Morphometry

This study utilizes voxel-based morphometry to examine the neural basis of developmental changes in transitive reasoning in parietal regions. Two groups of participants (young adolescents and adults) performed a transitive reasoning task, subsequent to undergoing anatomical MRI brain scans. Behaviorally, adults performed better on the transitive reasoning task than the young adolescents. Grey matter analysis of their brains showed the expected thinning/pruning of grey matter in BA 7 and a significantly greater correlation between the performance of the adults and grey matter density than the performance of adolescents and grey matter density in this area. These results support the idea that developmental anatomical changes in parietal cortex facilitate developmental changes in transitive reasoning.

Background: Major Depressive Disorder (MDD) is one of the most common mental disorders. Converging evidence suggests that the insula plays an important role in the pathophysiology of MDD. Little is known regarding in which insula subregion volume alterations occur in patients with MDD. Methods: We analyzed voxel-based morphometry in T1weighted MRI scans of unmedicated DSM-IV MDD patients (n=26) and in age, education, and sex matched healthy controls (HC, n=26). Furthermore, we performed a quantitative metaanalysis across 14 structural MRI MDD studies by applying the anatomical likelihood estimation technique to identify concordant volume reductions in MDD in the insula cortex. We found significantly reduced grey matter volumes (GMV) in patients with MDD compared to HCs in the left midinsula and in the right and left caudate nucleus. The left midinsular volume reduction in our sample was consistent with the coordinate-based meta-analysis results. Limitations: The small number of MRI studies investigating heterogeneous MDD samples included in the meta-analysis may have resulted in low statistical power. The findings highlight the role of the mid-insula in the psychopathology of MDD. The mid-insula sub-region might be associated with reduced interoceptive abilities in patients with MDD that is the ability to process information of "how the body feels". In addition, the caudate nucleus has been described as being part of a network that mediates emotional and motivational processes which seems to be affected in MDD.

Objectives: To examine associations between low cognitive-performance and regional-and network-level brain changes at ages 9–10 in very-preterm, moderately-preterm, and full-term children, and explore whether these
alterations predict ASD/ADHD symptoms at age 12.
Methods: This longitudinal population-based study included 9–10-year-old U.S. children from ABCD Study. Children underwent brain imaging and cognitive assessment using NIH Toolbox. Cortical thickness and
subcortical volumes of preterm-children with low cognitive-performance (NIH composite score < -1SD and > -2SD) were compared with preterm and full-term peers with typical performance (≥-1SD). Structural covariance
networks were also examined.
Results: Among 7281 children (mean age 9.9 ±0.6 years; 52.2 % boys), 71 were very-preterm, 151 moderately-preterm, and 7056 full-term. Low cognitive-performance was most prevalent in very-preterm children (29.6 %),
followed by moderately-preterm (24.0 %) and full-term children (16.2 %).
Very-preterm children with low cognitive-performance had thinner inferior temporal cortex (β =-0.58; p =0.03), thinner fusiform gyrus (β =-0.62; p =0.02), and larger amygdala volumes (β =0.41; p =0.05) compared to very-preterm children with typical performance. Moderately-preterm children with low cognitive-performance had smaller hippocampal volumes (β =-0.32; p =0.01). Similar patterns were observed when comparing preterm children with low cognitive-performance to full-term peers with typical performance.
Structural covariance network analysis revealed stronger covariance between the precuneus-postcentral gyrus pair among moderately-preterm children with low cognitive-performance. Individualized Differential Structural
Covariance Network values extracted from this pair were positively associated with ASD/ADHD symptoms, though not statistically significance.
Conclusion: Low cognitive performance in preterm children is associated with distinct regional and network-level brain differences, differing by prematurity. Stronger hub covariance may reflect compensatory mechanisms, highlighting the need for prematurity-tailored interventions.

AUTISM is a biological disorder which affects social cognition, and understanding brain abnormalities of the former will elucidate the brain basis of the latter. We report structural MRI data on 15 high-functioning individuals with autistic disorder. A voxel-based whole brain analysis identi®ed grey matter differences in an amygdala centered system relative to 15 age-and IQmatched controls. Decreases of grey matter were found in anterior parts of this system (right paracingulate sulcus, left inferior frontal gyrus). Increases were found in posterior parts (amygdala/peri-amygdaloid cortex, middle temporal gyrus, inferior temporal gyrus), and in regions of the cerebellum. These structures are implicated in social cognition by animal, imaging and histopathological studies. This study therefore provides converging evidence of the physiological basis of social cognition. NeuroReport 10:1647±1651 # 1999 Lippincott Williams & Wilkins.

Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammation in vivo in patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite all imaging data accumulated on neuroinflammation across the past three decades, an overview of the imaging evidence of neuroinflammation in migraine is still missing. We conducted a systematic review in the Pubmed and Embase databases to evaluate existing imaging data on inflammation in migraine, and to identify gaps in the literature. We included 20 studies investigating migraine without aura (N = 4), migraine with aura (N = 8), both migraine with and without aura (N = 3), or hemiplegic migraine (N = 5). In migraine without aura, macrophage activation was not evident. In migraine with aura, imaging evidence suggested microglial and parameningeal inflammatory activity. Increased vascular permeability was mostly found in hemiplegic migraine, and was atypical in migraine with and without aura. Based on the weight of existing and emerging data, we show that most studies have concentrated on demonstrating increased vascular permeability as a marker of neuroinflammation, with tools that may not have been optimal. In the future, novel, more sensitive techniques, as well as imaging tracers delineating specific inflammatory pathways may further bridge the gap between preclinical and clinical findings.

Magnetic resonance imaging (MRI) has improved the diagnosis and management of patients with multiple sclerosis (MS). Montreal Cognitive Assessment (MoCA) is a brief, sensitive test that has been recommended by National Institute of Neurological Diseases and Stroke and Canadian Stroke Network (NINDS-CSN) as a reliable tool to detect mild cognitive impairments. This study aimed to evaluate the relationship between MoCA test and its sub-items with brain abnormalities in MRI of MS patients. Based on MRI scans of 46 MS patients, third ventricle and white matter lesions volumes were measured. Disease duration and expanded disability status scale (EDSS) were recorded in each patient. In addition, cognitive domains of the patients were evaluated by Montreal cognitive assessment (MoCA) test. We analyzed data using t-test or Mann-Whitney U test, Pearson correlation coefficient, and non-parametric Spearman test. Furthermore, multiple linear regression model was applied to evaluate the associat...

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There is still much debate about the exact nature and frequency of developmental dyscalculia, and about how it should be defined. This article examines several key questions in turn: Is developmental dyscalculia a distinct disorder, or should it be seen as the lower end of a continuumor possibly more than one continuum-of numerical ability? Do individuals with developmental dyscalculia show atypical brain structure or function? Does the study of acquired dyscalculia have anything to teach us about developmental dyscalculia? In studying dyscalculia, should we look less at arithmetical ability as a single entity, and more at separable components of arithmetical ability? How heterogeneous is developmental dyscalculia, and how important is it to study individual profiles? To what extent is developmental dyscalculia influenced by domain-specific versus domain-general abilities? The conclusion is that, though a significant amount has been discovered through existing research, and though this has some important implications for screening and diagnosis of dyscalculia, there is much more research that still needs to be conducted if we are to answer all of these questions fully. In particular, the study of developmental dyscalculia must be more integrated with the study of individual differences in mathematics in the population as a whole.

Background: The phenotypic expression of 22q11.2 deletion syndrome (22q11.2DS) is variable and may include cognitive, psychiatric, and neurological manifestations, e.g., parkinsonism. We investigated brain structural alterations in patients with 22q11.2DS with and without parkinsonism (Park+ and Park−) in comparison with healthy controls (HCs). Methods: Voxel-based morphometry was performed on 3D T1-weighted MR images to explore gray matter volume (GMV) differences between 29 patients (15 Park+, 14 Park−), selected from a consecutive series of 56 adults diagnosed with 22q11.2DS, and 24 HCs. One-way ANOVA and multiple linear regression analyses were performed to explore group differences in GMV and correlations between clinical scores (MDS-UPDR-III and MoCA scores) and structural alterations. Results: Significant between-group differences in GMV were found in the cerebellum, specifically in bilateral lobes VIII and left Crus II, as well as in the left superior occipital gyrus. Althou...

Pain is a highly personal experience that varies substantially among individuals. In search of an anatomical correlate of pain sensitivity we used voxel-based morphometry (VBM) to investigate the relationship between grey matter density across the whole brain and inter-individual differences in pain sensitivity in 116 healthy volunteers (62 females, 54 males). Structural MRI and psychophysical data from 10 previous fMRI studies were used. Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates. Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49°C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship. No regions exhibited a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure.

Language ability and handedness are likely to be associated with asymmetry of the cerebral cortex (grey matter) and connectivity (white matter). Grey matter asymmetry, most likely linked to language has been identified with voxel-based morphometry (VBM) using T 1 -weighted images. Differences in white matter obtained with this technique are less consistent, probably due to the relative insensitivity of the T 1 contrast to the ultrastructure of white matter. Furthermore, previous VBM studies failed to find differences related to handedness in either grey or white matter. We revisited these issues and investigated two independent groups of subjects with diffusion-tensor imaging (DTI) for asymmetries in white matter composition. Using voxel-based statistical analyses an asymmetry of the arcuate fascicle was observed, with higher fractional anisotropy in the left hemisphere. In addition, we show differences related to handedness in the white matter underneath the precentral gyrus contralateral to the dominant hand. Remarkably, these findings were very robust, even when investigating small groups of subjects. This highlights the sensitivity of DTI for white matter tissue differences, making it an ideal tool to study small patient populations.

ABSTRACTBackgroundCharles Bonnet syndrome (CBS) is a prototype phenomenon for investigating complex visual hallucination. Our research focuses on resting state neural networks features of CBS patients with a comparison of patients with equally matched visual loss and healthy subjects in order to investigate the mechanism behind complex visual hallucinations.Material and MethodsFour CBS patients CBS(+), three patients with visual loss but no visual hallucinations CBS(-) and 15 healthy individuals (HS) undergo resting state fMRI recordings and their resting state data is analyzed for Default Mode Network (DMN) changes through dual regression analysis. Cognitive functions of the participants were also evaluated through Mini Mental State Examination and University of Miami - Parkinson’s Disease Hallucination Questionnaire (um-PDHQ)ResultsAlthough we found no difference in Default Mode Networks between CBS(-) and CBS(+), and between the CBS(-) and HC groups, we detected decreased connect...

Objectives. To address the role of latent T. gondii infection in schizophrenia we studied the infl uence of latent toxoplasmosis on brain morphology. Methods. An optimized voxel-based morphometry of magnetic resonance imaging was analyzed by analysis of variance with diagnosis and seropositivity as factors in 44 schizophrenic patients (12 T. gondii positive) and 56 controls (13 T. gondii positive). Results. Grey matter (GM) volume was reduced in schizophrenia patients compared with controls in the cortical regions, hippocampus and in the caudate. In the schizophrenia sample we found a signifi cant reduction of GM volume in T. gondii positive comparing with T. gondii -negative patients bilaterally in the caudate, median cingulate, thalamus and occipital cortex and in the left cerebellar hemispheres. T. gondii -positive and -negative controls did not differ in any cluster. Among participants seropositive to T. gondii the reduction of GM in the schizophrenia subjects was located in the same regions when comparing the entire sample (11,660 over-threshold voxels ( P Յ 0.05, FWR corrected). The differences between T. gondii -negative patients and controls consisted only of 289 voxels in temporal regions. Conclusions. Our study is the fi rst to document that latent toxoplasmosis reduces GM in schizophrenia but not in controls.

With the widespread increase in elderly populations, the quality of life and mental health in old age are issues of great interest. The human brain changes with age, and the brain aging process is biologically complex and varies widely among individuals. In this cross-sectional study, to clarify the effects of mental health, as well as common metabolic factors (e.g., diabetes) on healthy brain aging in late life, we analyzed structural brain MRI findings to examine the relationship between predicted brain age and life satisfaction, depressive symptoms, resilience, and lifestyle-related factors in elderly community-living individuals with unimpaired cognitive function. We extracted data from a community-based cohort study in Arakawa Ward, Tokyo. T1-weighted images of 773 elderly participants aged ≥65 years were analyzed, and the predicted brain age of each subject was calculated by machine learning from anatomically standardized gray-matter images. Specifically, we examined the relat...

Introduction: Progressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%-70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing-remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol-treated compared to placebo-treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes. Methods: Sixty-two estriol-and forty-nine placebo-treated RRMS patients underwent clinical evaluations and brain MRI. Voxel-based morphometry (VBM) was used to evaluate voxelwise GM sparing from high-resolution T1-weighted scans. Results: A region of treatment-induced sparing (TIS) was defined as the areas where GM was spared in estriol-as compared to placebo-treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disabilityspecific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol-treated subjects that was associated with better performance on the PASAT. Conclusions: Discovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.

Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear. Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed. GM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in ...

We aimed to find structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients. The volumes of the cerebrum, hippocampus and frontal lobe and the area of the corpus callosum&#39;s subdivisions were all semiautomatically measured, and then optimized voxel-based morphometry (VBM) was performed in 19 JME patients and 19 age/gender matched normal controls. The rostrum and rostral body of the corpus callosum and the left hippocampus were significantly smaller than those of the normal controls, whereas the volume of the JME&#39;s left frontal lobe was significantly larger than that of the controls. The area of the rostral body had a significant positive correlation with the age of seizure onset (r = 0.56, p = 0.012), and the volume of the right frontal lobe had a significant negative correlation with the duration of disease (r = -0.51, p = 0.025). On the VBM, the gray matter concentration of the prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior mi...

To investigate the effects of various intracranial volume (ICV) measurement methods on the sensitivity of hippocampal volumetry and modulated voxel-based morphometry (mVBM) in female patients with major depressive disorder (MDD). Materials and Methods : T1 magnetic resonance imaging (MRI) data for 41 female subjects (21 MDD patients, 20 normal subjects) were analyzed. Hippocampal volumes were measured manually, and ICV was measured manually and automatically using the FreeSurfer package. Gray and white matter volumes were measured separately. Results : Manual ICV normalization provided the greatest sensitivity in hippocampal volumetry and mVBM, followed by FreeSurfer ICV, GWMV, and GMV. Manual and FreeSurfer ICVs were similar in normal subjects (p = 0.696), but distinct in MDD patients (p = 0.000002). Manual ICV-corrected total gray matter volume (p = 0.0015) and Manual ICV-corrected bilateral hippocampal volumes (right, p = 0.014; left, p = 0.004) were decreased significantly in MDD patients, but the differences of hippocampal volumes corrected by FreeSurfer ICV, GWMV, or GMV were not significant between two groups (p > 0.05). Only manual ICV-corrected mVBM analysis was significant after correction for multiple comparisons. The method of ICV measurement greatly affects the sensitivity of hippocampal volumetry and mVBM. Manual ICV normalization showed the ability to detect differences between women with and without MDD for both methods.

Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age-and gender-matched non-smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error-corrected clusters, P < 0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre-existing differences in these areas may predispose individuals to the development of nicotine dependence.

Repeated hospitalizations are a characteristic of severe disease courses in patients with affective disorders (PAD). To elucidate how a hospitalization during a nine-year follow-up in PAD affects brain structure, a longitudinal case-control study (mean [SD] follow-up period 8.98 [2.20] years) was conducted using structural neuroimaging. We investigated PAD (N = 38) and healthy controls (N = 37) at two sites (University of Münster, Germany, Trinity College Dublin, Ireland). PAD were divided into two groups based on the experience of in-patient psychiatric treatment during follow-up. Since the Dublin-patients were outpatients at baseline, the rehospitalization analysis was limited to the Münster site (N = 52). Voxel-based morphometry was employed to examine hippocampus, insula, dorsolateral prefrontal cortex and whole-brain gray matter in two models: (1) group (patients/controls)×time (baseline/follow-up) interaction; (2) group (hospitalized patients/not-hospitalized patients/controls)×time interaction. Patients lost significantly more whole-brain gray matter volume of superior temporal gyrus and temporal pole compared to HC (p FWE = 0.008). Patients hospitalized during follow-up lost significantly more insular volume than healthy controls (p FWE = 0.025) and more volume in their hippocampus compared to not-hospitalized patients (p FWE = 0.023), while patients without re-hospitalization did not differ from controls. These effects of hospitalization remained stable in a smaller sample excluding patients with bipolar disorder. PAD show gray matter volume decline in temporo-limbic regions over nine years. A hospitalization during follow-up comes with intensified gray matter volume decline in the insula and hippocampus. Since hospitalizations are a correlate of severity, this finding corroborates and extends the hypothesis that a severe course of disease has detrimental long-term effects on temporo-limbic brain structure in PAD.

Cognition has been reported to be involved in patients with multiple system atrophy (MSA), although initially it was considered an exclusion in the diagnosis of MSA. We assessed cognition in these patients and compared it with age and education matched healthy controls and correlated with the gray matter volume using voxel-based morphometry (VBM). This was a prospective, case-control, single-center study. Thirty patients with MSA (20 MSA-C (cerebellar variant) and 10 MSA-P (Parkinsonian variant)) and 25 age-and educational level-matched healthy controls were included. All the patients and controls underwent detailed neuropsychological tests and MRI brain. A battery of neuropsychological tests like Stroop test, digit span forward and backward, digit symbol substitution time test, animal naming test, color trail test and auditory verbal learning test were used to assess the various domain of cognition, which include mainly attention, executive function, memory, new learning, mental and motor speed. The gray matter volume was determined using VBM and correlated with neuropsychological scores. Attention, execution, verbal and visual memory, verbal fluency, and new learning were impaired in patients with MSA. MSA-P had more impairment in motor and mental speed, working memory, executive functions, and focused attention compared to MSA-C. Patients with MSA-C had more impairment in new learning, immediate recall, verbal fluency, and sustained attention compared to MSA-P. However, it was not statistically significant. There was a significant correlation between the various cognitive domains and atrophy of frontotemporal cortical areas, insula, caudate, thalamus, and cerebellum. Cognition is impaired in patients with MSA-C and MSA-P and is likely due to the neurodegenerative process involving the cortical and subcortical structures. Long-term follow-up studies are required to find out the progression of these cognitive changes.

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric condition that is common in veterans returning from combat operations. While the symptoms of PTSD have been extensively characterized, the neural mechanisms that underlie PTSD are only vaguely understood. In this study, we examined the neurophysiology of PTSD using magnetoencephalography (MEG) in a sample of veterans with and without PTSD. Our primary hypothesis was that veterans with PTSD would exhibit aberrant activity across multiple brain networks, especially those involving medial temporal and frontal regions. To this end, we examined a total of 51 USA combat veterans with a battery of clinical interviews and tests. Thirty-one of the combat veterans met diagnostic criteria for PTSD and the remaining 20 did not have PTSD. All participants then underwent high-density MEG during an eyes-closed resting-state task, and the resulting data were analyzed using a Bayesian image reconstruction method. Our results indicate...

The human sense of smell is closely associated with morphological differences of the fronto-limbic system, specifically the piriform cortex and medial orbitofrontal cortex (mOFC). Still it is unclear whether cortical volume in the core olfactory areas and connected brain regions are shaped differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI) matched with sixteen normosmic controls. All subjects underwent whole-brain magnetic resonance imaging, and voxel-based morphometry was used to estimate regional variations in grey matter volume. The analyses showed that relative to controls, COI subjects had significantly larger grey matter volumes in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks" test, was positively associated with larger grey matter volume in right posterior cingulate and parahippocampal cortices whereas the opposite relationship was observed in controls. Across COI subjects and controls, better olfactory detection threshold was associated with smaller volume in right piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory.

for their input during the questionnaire development. Also, we want to thank our co-interviewers Rosie De Vidts and Lisa Thibau for their time and dedication to this project. Many thanks to the staff of the Old Age Psychiatry Departments of AZ Sint-Jan Bruges-Ostend AV, Psychiatric Hospital Karus and Psychiatric Hospital Alexianen Zorggroep Tienen for their support during the data collection process. Finally, we would like to thank Dr. Howard Ryland for his help with the language editing.

Background: Many research papers claim that patients with specific psychiatric disorders (major depressive disorder, posttraumatic stress disorder, borderline personality disorder, alcohol use disorder, and others) have smaller hippocampi, but most of those reports compared patients to healthy controls. We hypothesized that if psychiatrically matched controls (psychiatric control, matched for demographics and psychiatric comorbidities) were used, much of the biomarker literature in psychiatric research would not replicate. We used hippocampus and amygdala volume only as examples, as these are very commonly replicated results in psychiatry biomarker research. We propose that psychiatry biomarker research could benefit from using psychiatric controls, as the use of healthy controls results in data that are not disorder-specific. Method: Hippocampus/amygdala volumes were compared between major depressive disorder, sex-/age-/race-matched healthy control, and psychiatric control (N ¼ 126/group). Similar comparisons were performed for posttraumatic stress disorder (N ¼ 67), borderline personality disorder (N ¼ 111), and alcohol use disorder (N ¼ 136). Results: Major depressive disorder patients had smaller left (p ¼ 8.79 Â 10 À3 ) and right (p ¼ 3.13 Â 10 À3 ) hippocampal volumes than healthy control. Posttraumatic stress disorder had smaller left (p ¼ 0.018) and right (p ¼ 8.64 Â 10 À4 ) hippocampi than healthy control. Borderline personality disorder had smaller right hippocampus (p ¼ 7.90 Â 10 À3 ) and amygdala (p ¼ 1.49 Â 10 À3 ) than healthy control. Alcohol use disorder had smaller right hippocampus (p ¼ 0.034) and amygdala (p ¼ .024) than healthy control. No differences were found between any of the four diagnostic groups and psychiatric control. Conclusion: When psychiatric controls were used, there was no difference in hippocampal or amygdalar volume between any of the diagnoses studied and controls. This strategy (keeping all possible relevant variables matched between experimental groups) has been used to advance science for hundreds of years, and we propose should also be used in biomarker psychiatry research.

Widespread regional gray matter volume (GMV) alterations have been reported in bipolar disorder (BD). Structural networks, which are thought to better reflect the complex multivariate organization of the brain, and their clinical and psychological function have not been investigated yet in BD. 24 patients with BD type-I (BD-I), and 30 with BD type-II (BD-II), and 45 controls underwent MRI scan. Voxel-based morphometry and source-based morphometry (SBM) were performed to extract structural covariation patterns of GMV. SBM components associated with morphometric differences were compared among diagnoses. Executive function and emotional processing correlated with morphometric characteristics. Compared to controls, BD-I showed reduced GMV in the temporo-insular-parieto-occipital cortex and in the culmen. An SBM component spanning the prefrontal-temporal-occipital network exhibited significantly lower GMV in BD-I compared to controls, but not between the other groups. The structural network covariance in BD-I was associated with the number of previous manic episodes and with worse executive performance. Compared to BD-II, BD-I showed a loss of GMV in the temporal-occipital regions, and this was correlated with impaired emotional processing. Altered prefrontal-temporal-occipital network structure could reflect a neural signature associated with visuospatial processing and problem-solving impairments as well as emotional processing and illness severity in BD-I.

Chronic alcoholism and its related cognitive impairments are associated with increased social, relational, and professional deficits which have a variable overall impact on social integration. These impairments are known to have varying severities and have rarely been studied among healthy alcohol-dependent subjects with preserved psychosocial functioning. Thus, the objective of this study is to describe neuropsychological performance in this particular population. Twenty-nine socially adjusted alcohol-dependent men, hospitalized for a first or second withdrawal and abstinent for 3 weeks minimum, were compared to 29 healthy non-alcoholic controls. All subjects underwent clinical and psychiatric examination, neuropsychological tests of memory (M), working memory (WM), and executive functions (EF). Comparisons were performed using Student&#39;s t-tests or Mann-Whitney U tests. No group differences were found on the Self-Reported Social Adjustment Scale (SAS-SR) or in the Mini-Mental S...

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch–Boonstra–Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction....

Objective: To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES). Method: Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively. Results: Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts. Conclusion: These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome.

In recent years, cerebellar abnormalities have gained increasing attention as possible physiopathological substratum of idiopathic cervical dystonia (ICD), but a consistent pattern of cerebellar structural modifications has not yet been established. We systematically investigated the presence of volumetric alterations of cerebellar gray (GM) and white matter (WM) in ICD patients, as well as their clinical relevance. Methods In this two-centers prospective cross-sectional study, from May 2013 to December 2017, 27 patients with ICD and 27 age-and sex-comparable healthy controls underwent brain MRI including 3D T1-weighted sequences for volumetric analyses. Between-group differences in terms of gray matter and cerebellar peduncles volumes were investigated using both region of interest (ROI)-based and voxel-based approaches using the SUIT tool (SPM12), and significant volumetric changes were correlated with clinical impairment (as measured with the Tsui score) and presence of tremor. Results ICD patients showed significant volumetric reduction of cerebellar GM in the anterior lobe and lobule VI, resulting from both ROI-based (p≤0.009) and voxel-based (p≤0.04) analyses, while small clusters of reduced WM volume were found in the right cerebellum and left midbrain (p=0.04), along with reduced volume of the bilateral superior (p=0.04) and middle (p=0.03) cerebellar peduncles. Furthermore, higher middle cerebellar peduncles volume was associated with the presence of tremor (p=0.04). Our data show evidence of a specific pattern of cerebellar structural abnormalities in ICD patients, with volume loss mainly involving cortical GM regions related to the somatotopic representation of the affected body parts and, to a lesser extent, cerebellar peduncles.

Objective: Memory decline commonly occurs among elderly individuals. This observation is often attributed to early neurodegenerative changes in the hippocampus and related brain regions. However, the contribution of vascular lesions, such as brain infarcts, to hippocampal integrity and age-associated memory decline remains unclear. We studied 658 elderly participants without dementia from a prospective, communitybased study on aging and dementia who received high-resolution structural MRI. Cortical and subcortical infarcts were identified, and hippocampal and relative brain volumes were calculated following standard protocols. Summary scores reflecting performance on tasks of memory, language, processing speed, and visuospatial function were derived from a comprehensive neuropsychological battery. We used multiple regression analyses to relate cortical and subcortical infarcts, hippocampal and relative brain volume, to measures of cognitive performance in domains of memory, language, processing speed, and visuospatial ability. Results: Presence of brain infarcts was associated with a smaller hippocampus. Smaller hippocampus volume was associated with poorer memory specifically. Brain infarcts were associated with poorer memory and cognitive performance in all other domains, which was independent of hippocampus volume. Both hippocampal volume and brain infarcts independently contribute to memory performance in elderly individuals without dementia. Given that age-associated neurodegenerative conditions, such as Alzheimer disease, are defined primarily by impairment in memory, these findings have clinical implications for prevention and for identification of pathogenic factors associated with disease symptomatology. Neurology ® 2012;78:38-46 GLOSSARY AD ϭ Alzheimer disease; FLAIR ϭ fluid-attenuated inversion recovery; FOV ϭ field of view; MCI ϭ mild cognitive impairment; PCA ϭ posterior cerebral artery; SRT ϭ Selective Reminding Test; TE ϭ echo time; TI ϭ inversion time; TR ϭ repetition time.

Aims. The relationship between freezing of gait (FOG) and regional brain atrophy has been intensively investigated, but it is still not clearly understood. The study objective was to test whether grey matter (GM) atrophy contributes to FOG in Parkinson´s disease (PD) using a surface-based algorithm. Methods. We investigated 21 patients with PD, 11 with FOG and 10 without FOG. Both groups were assessed using a FOG questionnaire and Hoehn and Yahr staging. High resolution T1-weighted brain images were acquired for each subject using a 1.5T MRI scanner. A surface-based method implemented in FreeSurfer was used to quantify the GM atrophy. A vertex-wise and region of interest (ROI) comparison of spatially normalized subject data using a general linear model and the Wilcoxon rank sum test were to assess significant group differences. Results. Higher global levels of cortical atrophy were detected in freezers, although this was not statistically significant. The vertex-wise analysis revealed significant local reduction in grey matter thickness in the left supplementary motor area, m iddle/anterior cingulate cortex, temporal pole and right frontal operculum in freezers at P<0.001, uncorrected. The ROI analysis of average thickness confirmed the regional atrophy in bilateral anterior and posterior cingulate cortices. No significant relative regional cortical atrophy was observed in non-freezers. Conclusion. FOG was associated with regional cortical atrophy, especially in mesial frontal and cingulate cortices. Our findings provide additional evidence that the development of FOG in patients with PD is associated with local structural cortical changes.

Psychogenic non-epileptic seizures (PNES) -time-limited disturbances of consciousness and motor-sensory control, not accompanied by ictal activity on electroencephalogram (EEG) -are best conceptualized as atypical neurophysiological responses to emotional distress, physiological stressors and danger. Patients and families find the diagnosis of PNES difficult to understand; the transition from neurology (where the diagnosis is made) to mental health services (to which patients are referred for treatment) can be a bumpy one. This study reports how diagnostic formulations constructed for 60 consecutive children and adolescents with PNES were used to inform both the explanations about PNES that were given to them and their families and the clinical interventions that were used to help patients gain control over PNES. Families were able to accept the diagnosis of PNES and engage in treatment when it was explained how emotional distress, illness and states of high arousal could activate atypical defence responses in the body and brain -with PNES being an unwanted by-product of this process. Patients and their families made good use of therapeutic interventions. A total of 75% of children/adolescents (45/60) regained normal function and attained full-time return to school. Global Assessment of Functioning scores increased from 41 to 67 (t(54) = 10.09; p < .001). Outcomes were less favourable in children/ adolescents who presented with chronic PNES and in those with a chronic, comorbid mental

SummaryObjectiveIntelligence quotient (IQ) outcomes after pediatric epilepsy surgery show significant individual variation. Clinical factors such as seizure cessation or antiepileptic medication discontinuation have been implicated, but do not fully account for the heterogeneity seen. Less is known about the impact of neurobiological factors, such as brain development and resection location. This study examines clinical and neuroimaging factors associated with cognitive outcome after epilepsy surgery in childhood.MethodsFifty‐two children (28 boys, 24 girls) were evaluated for epilepsy surgery and reassessed on average 7.7 years later. In the intervening time, 13 were treated pharmacologically and 39 underwent focal surgery (17 temporal, 16 extratemporal, six multilobar; mean age at surgery = 14.0 years). Pre‐ and postsurgical assessments included IQ tests and T1‐weighted brain images. Predictors of IQ change were investigated, including voxel‐based analyses of resection location, a...

Developmental dyslexia (DD) is a highly prevalent neurodevelopmental disorder, which is devastating for individuals in modern societies in which fluent reading skill is mandatory for leading a normal life. Research on the neural origins of DD has continued for half a century, yielding, however, inconsistent results. It has also lacked a thorough characterization of the association between abnormal neuroanatomy and skills vital for reading. The current study was set out to determine abnormalities of grey and white matter volumes in adults with DD and associations between brain structures and reading and related skills. To this end, we conducted a whole-brain voxel based morphometry following current guidelines on state-of-the-art analysis approaches and rigorous neuropsychological testing. We found decreased volumes of grey matter in DD, comprising a left-hemispheric network including superior temporal and inferior frontal gyri, insula, the limbic system, and basal ganglia, and white...

Improving quality of life has been recognized as an important outcome for schizophrenia treatment, although the fundamental determinants are not well understood. In this study, we investigated the association between brain structural abnormalities and objective quality of life in schizophrenia patients. Thirty-three schizophrenia patients and 42 age-, sex-, and education-matched healthy participants underwent magnetic resonance imaging. The Quality of Life Scale was used to measure objective quality of life in schizophrenia patients. Voxel-based morphometry was performed to identify regional brain alterations that correlate with Quality of Life Scale score in the patient group. Schizophrenia patients showed gray matter reductions in the frontal, temporal, limbic, and subcortical regions. We then performed voxel-based multiple regression analysis in these regions to identify any correlations between regional gray matter volume and Quality of Life Scale scores. We found that among four subcategories of the scale, the Instrumental Role category score correlated with gray matter volume in the right anterior insula in schizophrenia patients. In addition, this correlation was shown to be mediated by negative symptoms. Our findings suggest that the neural basis of objective quality of life might differ topographically from that of subjective QOL in schizophrenia.

The purpose of this coordinate based meta-analysis (CBMA) was to summarise the available evidence related to regional grey matter (GM) changes in patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS). CBMA is a way to find the consistent results across multiple independent studies that are otherwise not easily comparable due to methodological differences. The coordinate based random effect size (CBRES) meta-analysis method utilizes the reported coordinates (foci of the clusters of GM loss) and Z score standardised by number of subjects, controlling type I error rate by false cluster discovery rate (FCDR). Thirty-four published articles reporting forty-five independent studies using voxel-based morphometry (VBM) for the assessment of GM atrophy between MS or CIS patients and healthy controls were identified from electronic databases. The primary meta-analysis identified clusters of spatially consistent crossstudy reporting of GM atrophy; subgroup analyses and meta-regression were also performed. This meta-analysis demonstrates consistent areas of GM loss in MS or CIS, in the form of significant clusters. Some clusters also demonstrate correlation with disease duration. Coordinate based meta-analysis, voxel-based morphometry, grey matter atrophy, MS, CIS .

Though routine neuroimaging is usually normal in essential tremor (ET) there is clinical evidence of widespread involvement of central nervous system. This study aimed at determining morphological changes in brain of patients with ET using voxel-based morphometry (VBM) analysis and also compare the subtypes of ET. Clinical and imaging data of 20 patients (5 women, 15 men; mean age 38.2 ± 16.5 years) of ET were collected prospectively. To determine areas of gray matter (GM) atrophy, T1W volumetric MRI data of patients were compared with 17 matched control subjects using VBM analysis with Statistical Parametric Mapping 5. Voxel-wise analysis of patients with and without head tremor showed widespread areas of GM atrophy in cerebral hemispheres of patients with head tremor. No difference was observed between the familial and nonfamilial subgroups of ET. Multiple regression analysis revealed relationship between GM atrophy and tremor severity score. Patients with ET showed widespread areas of atrophy in both cerebellum and cerebral GM, which supports the current concept of the progressive and diffuse nature of ET. Patients with additional head tremor may represent a distinct subgroup of ET.

Results Increasing age was associated with a decrease in global GM [r(62)=0.214, p=.051] but not WM [r(62)=0.063, p=.313]. GM atrophy varied as a function of age and sex in several regions. As shown in figure 2, age-related GM atrophy was greater for males in the frontal lobes compared to females (p&lt;0.005). Conversely, old females exhibited greater age-related GM atrophy in temporal lobe brain areas (p&lt;0.005). WM atrophy also varied with age and sex (fig 3). Atrophy of the internal capsula was significant and common to both males and females (p&lt;0.005), but females exhibited greater atrophy of the alveus of the hippocampus relative to males (p&lt;0.005). By contrast, WM atrophy of the optic nerve bundle was predominant in old male dogs (p&lt;0.005). Discussion The present study is the first successful application of VBM techniques for assessing changes in brain morphometry in a canine model of aging. Consistent with earlier manual-based ROI analyses [3], significant frontal ...

Background: With the increasing efforts to a better understanding of psychiatric diseases, detection of brain morphological alterations are necessary. This study compared two methods-voxel based morphometry (VBM) and region of interest (ROI) analyses- to identify significant gray matter changes of patients with bipolar disorder type I (BP I). Methods: The structural MRI were obtained in a total of 50 subjects (25 healthy subjects with a mean age of 34.48±8.32 years as a control group and 25 patients with a mean age of 37.68±10.88 years). We compared the gray matter alteration results obtained by VBM analysis using the DARTEL approach with those obtained using ROI analysis which applies three probabilistic brain atlases namely, hammers, lpba40, and neuromorphometrics atlases. All analyses were conducted via the Computational Anatomy Toolbox (CAT12) implemented in Statistical Parametric Mapping (SPM12) software package. Results: The VBM findings suggested that gray matter reductions i...

BackgroundNegative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES).MethodsT1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were compar...

Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits is not well understood. Abnormal brain structure, including increased total brain volume, white matter (WM) and grey matter (GM) abnormalities have been reported in the NF1 brain. These previous studies employed univariate model-driven methods preventing detection of subtle and spatially distributed differences in brain anatomy. Multivariate pattern analysis allows the combination of information from multiple spatial locations yielding a discriminative power beyond that of single voxels. Here we investigated for the first time subtle anomalies in the NF1 brain, using a multivariate data-driven classification approach. We used support vector machines (SVM) to classify whole-brain GM and WM segments of structural T 1 -weighted MRI scans from 39 participants with NF1 and 60 non-affected individuals, divided in children/adolescents and adults groups. We also employed voxel-based morphometry (VBM) as a univariate gold standard to study brain structural differences. SVM classifiers correctly classified 94% of cases (sensitivity 92%; specificity 96%) revealing the existence of brain structural anomalies that discriminate NF1 individuals from controls. Accordingly, VBM analysis revealed structural differences in agreement with the SVM weight maps representing the most relevant brain regions for group discrimination. These included the hippocampus, basal ganglia, thalamus, and visual cortex. This multivariate datadriven analysis thus identified subtle anomalies in brain structure in the absence of visible pathology. Our results provide further insight into the neuroanatomical correlates of known features of the cognitive phenotype of NF1.

Cannabis consumption is temporally associated with the development of first episode psychosis (FEP). Whether or not the chronic use of this substance induces structural brain changes that may be responsible for the cognitive and psychological disturbances in this disorder is still matter of debate. To address this issue, we compared the magnetic resonance imaging (MRI)-assessed grey (GM) and white matter (WM) changes in young FEP patients between users versus non-users of cannabis. This prospective study included 50 consecutive FEP subjects: 33 users (22.7 ± 4.1 years, 4 women) and 17 non-users (23.9 ± 4.2 years, 10 women). Users were further divided into 15 heavy (23.3 ± 4.5 years, 2 women) and 18 light users (22.2 ± 3.8 years, 2 women) according to their lifetime cannabis use. Voxel-based-morphometry (VBM) analysis of GM and tract-based-spatial-statistics (TBSS) analysis of WM were performed. Age and gender were used as non-explanatory co-regressors. There were no supra-threshold differences between user and non-user groups for both GM and WM parameters. This was also the case when only heavy users were compared to non-users. Multivariate models controlling for age and gender confirmed these findings. We found no evidence for cannabis consumption related alterations in GM or WM in FEP subjects. Due to the strict correction for multiple comparisons and sample size, we cannot formally exclude subtle morphometric changes associated with cannabis consumption. However, even if present, such potential alterations would be of low magnitude.

Hallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD. In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM). We prospectively collected a sample of 46 non-demented PD patients, with (N=17) and without (n=29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function.

Body processing has been associated functionally to the so called extrastriate body area (EBA) which is located in the lateral occipital cortex. As body image disturbance is one of the main diagnostic criteria in anorexia nervosa (AN) this study aimed at looking for alterations in gray matter density in women with (AN) especially in the EBA. High resolution T1 images from 15 women with AN and 15 age matched healthy controls women were contrasted using voxel based morphometry (VBM). Additionally functional localizer scans were used to determine functionally the EBA of each participant. In general, total gray matter volumes did differ between groups. VBM results yielded evidence for a reduction of gray matter density in the left EBA. This reduction, which resulted from whole brain analysis, was localised within the activation cluster of the EBA localizer scan. The current results provide for the first time evidence for structural alterations in the EBA in patients with AN which might suggest that body image distortion is related at least in part to structural alteration in the EBA.

PURPOSE The purpose of this study was to determine the optimal computational options in voxel-based morphometry (VBM) for discrimination between Alzheimer&#39;s disease (AD) patients and healthy control (HC) subjects. MATERIALS AND METHODS Structural magnetic resonance images of 24 AD patients and 26 HC subjects were analyzed using VBM to determine brain regions with significant gray matter (GM) loss due to AD. The VBM analyses were performed with 4 different computational options: gray matter concentration (GMC) analysis with and without global normalization, and gray matter volume (GMV) analysis, with and without global normalization. Statistical maps calculated with the 4 computational options were obtained at 3 different P-value thresholds (P &lt; 0.001, P &lt; 0.0005, and P &lt; 0.0001, uncorrected for multiple comparisons), yielding a total of 12 sets of maps, from which regions-of-interest (ROI) were generated for subsequent analyses of performance in terms of discrimination ...