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Few studies have examined the association between conduct problems and cerebral cortical development. Herein, we characterize the association between age-related brain change and conduct problems in a large longitudinal, community-based sample of adolescents. 1,039 participants from the IMAGEN study possessed psychopathology and surface-based morphometric data at study baseline (M = 14.42 years, SD = 0.40; 559 females) and 5-year follow-up. Self-reports of conduct problems were obtained using the Strengths and Difficulties Questionnaire (SDQ). Vertex-level linear mixed effects models were implemented using the Matlab toolbox, SurfStat. To investigate the extent to which cortical thickness maturation was qualified by dimensional measures of conduct problems, we tested for an interaction between age and SDQ Conduct Problems (CP) score. There was no main effect of CP score on cortical thickness; however, a significant "Age by CP" interaction was revealed in bilateral insulae, left inferior frontal gyrus, left rostral anterior cingulate, left posterior cingulate, and bilateral inferior parietal cortices. Across regions, follow-up analysis revealed higher levels of CP were associated with accelerated age-related thinning. Findings were not meaningfully altered when controlling for alcohol use, co-occurring psychopathology, and socioeconomic status. Results may help to further elucidate neurodevelopmental patterns linking adolescent conduct problems with adverse adult outcomes., Competing Interests: Declaration of Competing Interest Dr. Banaschewski has served as an advisor or consultant to Bristol-Myers Squibb, Desitin Arzneimittel, Eli Lilly, Medice, Novartis, Pfizer, Shire, UCB, and Vifor Pharma; he has received conference attendance support, conference support, or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire, and UCB; and he is involved in clinical trials conducted by Eli Lilly, Novartis, and Shire; the present work is unrelated to these relationships. The other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The relationship between structural changes of the cerebral cortex revealed by Magnetic Resonance Imaging (MRI) and gene expression in the human fetal brain has not been explored. In this study, we aimed to test the hypothesis that relative regional thickness (a measure of cortical evolving organization) of fetal cortical compartments (cortical plate [CP] and subplate [SP]) is associated with expression levels of genes with known cortical phenotype. Mean regional SP/CP thickness ratios across age measured on in utero MRI of 25 healthy fetuses (20-33 gestational weeks [GWs]) were correlated with publicly available regional gene expression levels (23-24 GW fetuses). Larger SP/CP thickness ratios (more pronounced cortical evolving organization) was found in perisylvian regions. Furthermore, we found a significant association between SP/CP thickness ratio and expression levels of the FLNA gene (mutated in periventricular heterotopia, congenital heart disease, and vascular malformations). Further work is needed to identify early MRI biomarkers of gene expression that lead to abnormal cortical development., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The MNI CIVET pipeline for automated extraction of cortical surfaces and evaluation of cortical thickness from in-vivo human MRI has been extended for processing macaque brains. Processing is performed based on the NIMH Macaque Template (NMT), as the reference template, with the anatomical parcellation of the surface following the D99 and CHARM atlases. The modifications needed to adapt CIVET to the macaque brain are detailed. Results have been obtained using CIVET-macaque to process the anatomical scans of the 31 macaques used to generate the NMT and another 95 macaques from the PRIME-DE initiative. It is anticipated that the open usage of CIVET-macaque will promote collaborative efforts in data collection and processing, sharing, and automated analyses from which the non-human primate brain imaging field will advance., Competing Interests: Declaration of Competing Interest The authors report no competing interest., (Copyright © 2020. Published by Elsevier Inc.)

Background: Longitudinal studies of first episode of psychosis (FEP) patients are critical to understanding the dynamic clinical factors influencing functional outcomes; negative symptoms and verbal memory (VM) deficits are two such factors that remain a therapeutic challenge. This study uses white-gray matter contrast at the inner edge of the cortex, in addition to cortical thickness, to probe changes in microstructure and their relation with negative symptoms and possible intersections with verbal memory., Methods: T1-weighted images and clinical data were collected longitudinally for patients (N = 88) over a two-year period. Cognitive data were also collected at baseline. Relationships between baseline VM (immediate/delayed recall) and rate of change in two negative symptom dimensions, amotivation and expressivity, were assessed at the behavioral level, as well as at the level of brain structure., Results: VM, particularly immediate recall, was significantly and positively associated with a steeper rate of expressivity symptom decline (r = 0.32, q = 0.012). Significant interaction effects between baseline delayed recall and change in expressivity were uncovered in somatomotor regions bilaterally for both white-gray matter contrast and cortical thickness. Furthermore, interaction effects between immediate recall and change in expressivity on cortical thickness rates were uncovered across higher-order regions of the language processing network., Conclusions: This study shows common neural correlates of language-related brain areas underlying expressivity and VM in FEP, suggesting deficits in these domains may be more linked to speech production rather than general cognitive capacity. Together, white-gray matter contrast and cortical thickness may optimally inform clinical investigations aiming to capture peri-cortical microstructural changes.

In recent years, replicability of neuroscientific findings, specifically those concerning correlates of morphological properties of gray matter (GM), have been subject of major scrutiny. Use of different processing pipelines and differences in their estimates of the macroscale GM may play an important role in this context. To address this issue, here, we investigated the cortical thickness estimates of three widely used pipelines. Based on analyses in two independent large-scale cohorts, we report high levels of within-pipeline reliability of the absolute cortical thickness-estimates and comparable spatial patterns of cortical thickness-estimates across all pipelines. Within each individual, absolute regional thickness differed between pipelines, indicating that in-vivo thickness measurements are only a proxy of actual thickness of the cortex, which shall only be compared within the same software package and thickness estimation technique. However, at group level, cortical thickness-estimates correlated strongly between pipelines, in most brain regions. The smallest between-pipeline correlations were observed in para-limbic areas and insula. These regions also demonstrated the highest interindividual variability and the lowest reliability of cortical thickness-estimates within each pipeline, suggesting that structural variations within these regions should be interpreted with caution., (© The Author(s) 2020. Published by Oxford University Press.)

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V, and VI. In contrast, motor-frontal cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness from motor to frontal association cortices. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness, and, ultimately, functional neuroanatomy., Competing Interests: The authors have declared that no competing interests exist.

There is growing evidence that psychosis is characterized by brain network abnormalities. Analyzing morphological abnormalities with T1-weighted structural MRI may be limited in discovering the extent of deviations in cortical associations. We assess whether structural associations of either cortical white-gray contrast (WGC) or cortical thickness (CT) allow for a better understanding of brain structural relationships in first episode of psychosis (FEP) patients. Principal component and structural covariance analyses were applied to WGC and CT derived from T1-weighted MRI for 116 patients and 88 controls, to explore sets of brain regions that showed group differences, and associations with symptom severity and cognitive ability in patients. We focused on 2 principal components: one encompassed primary somatomotor regions, which showed trend-like group differences in WGC, and the second included heteromodal cortices. Patients' component scores were related to general psychopathology for WGC, but not CT. Structural covariance analyses with WGC revealed group differences in pairwise correlations across widespread brain regions, mirroring areas derived from PCA. More group differences were uncovered with WGC compared with CT. WGC holds potential as a proxy measure of myelin from commonly acquired T1-weighted MRI and may be sensitive in detecting systems-level aberrations in early psychosis, and relationships with clinical/cognitive profiles., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Few studies have investigated the link between putative biomarkers of attention-deficit/hyperactivity disorder (ADHD) symptomatology and genetic risk for ADHD. To address this, we investigate the degree to which ADHD symptomatology is associated with white matter microstructure and cerebral cortical thickness in a large population-based sample of adolescents. Critically, we then test the extent to which multimodal correlates of ADHD symptomatology are related to ADHD polygenic risk score (PRS). Neuroimaging, genetic, and behavioral data were obtained from the IMAGEN study. A dimensional ADHD composite score was derived from multi-informant ratings of ADHD symptomatology. Using tract-based spatial statistics, whole brain voxel-wise regressions between fractional anisotropy (FA) and ADHD composite score were calculated. Local cortical thickness was regressed on ADHD composite score. ADHD PRS was based on a very recent genome-wide association study, and calculated using PRSice. ADHD composite score was negatively associated with FA in several white matter pathways, including bilateral superior and inferior longitudinal fasciculi (p < 0.05, corrected). ADHD composite score was negatively associated with orbitofrontal cortical thickness (p < 0.05, corrected). The ADHD composite score was correlated with ADHD PRS (p < 0.001). FA correlates of ADHD symptomatology were significantly associated with ADHD PRS, whereas cortical thickness correlates of ADHD symptomatology were unrelated to ADHD PRS. Variation in hyperactive/inattentive symptomatology was associated with white matter microstructure, which, in turn, was related to ADHD PRS. Results suggest that genetic risk for ADHD symptomatology may be tied to biological processes affecting white matter microstructure.

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

The peri-infarct cortex (PIC) is the site of long-term physiologic changes after ischemic stroke. Traditional methods for delineating the peri-infarct gray matter (GM) have used a volumetric Euclidean distance metric to define its extent around the infarct. This metric has limitations in the case of cortical stroke, i.e., those where ischemia leads to infarction in the cortical GM, because the vascularization of the cerebral cortex follows the complex, folded topology of the cortical surface. Instead, we used a geodesic distance metric along the cortical surface to subdivide the PIC into equidistant rings emanating from the infarct border and compared this new approach to a Euclidean distance metric definition. This was done in 11 patients with [F-18]-Flumazenil ([18-F]-FMZ) positron emission tomography (PET) scans at 2 weeks post-stroke and at 6 month follow-up. FMZ is a PET radiotracer with specific binding to the alpha subunits of the type A γ-aminobutyric acid (GABAA) receptor. Additionally, we used partial-volume correction (PVC) of the PET images to compensate for potential cortical thinning and long-term neuronal loss in follow-up images. The difference in non-displaceable binding potential (BP ND ) between the stroke unaffected and affected hemispheres was 35% larger in the geodesic versus the Euclidean peri-infarct models in initial PET images and 48% larger in follow-up PET images. The inter-hemispheric BP ND difference was approximately 17-20% larger after PVC when compared to uncorrected PET images. PET studies of peri-infarct GM in cortical strokes should use a geodesic model and include PVC as a preprocessing step. Hum Brain Mapp 38:326-338, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Cerebral cortical folding becomes dramatically more complex in the fetal brain during the 3rd trimester of gestation; the process continues in a similar fashion in children who are born prematurely. To quantify this morphological development, it is necessary to extract the interface between gray matter and white matter, which is particularly challenging due to changing tissue contrast during brain maturation. We employed the well-established CIVET pipeline to extract this cortical surface, with point correspondence across subjects, using a surface-based spherical registration. We then developed a variant of the pipeline, called NEOCIVET, that quantified cortical folding using mean curvature and sulcal depth while addressing the well-known problems of poor and temporally-varying gray/white contrast as well as motion artifact in neonatal MRI. NEOCIVET includes: i) a tissue classification technique that analyzed multi-atlas texture patches using the nonlocal mean estimator and subsequently applied a label fusion approach based on a joint probability between templates, ii) neonatal template construction based on age-specific sub-groups, and iii) masking of non-interesting structures using label-fusion approaches. These techniques replaced modules that might be suboptimal for regional analysis of poor-contrast neonatal cortex. The proposed segmentation method showed more accurate results in subjects with various ages and with various degrees of motion compared to state-of-the-art methods. In the analysis of 158 preterm-born neonates, many with multiple scans (n=231; 26-40weeks postmenstrual age at scan), NEOCIVET identified increases in cortical folding over time in numerous cortical regions (mean curvature: +0.003/week; sulcal depth: +0.04mm/week) while folding did not change in major sulci that are known to develop early (corrected p<0.05). The proposed pipeline successfully mapped cortical structural development, supporting current models of cerebral morphogenesis, and furthermore, revealed impairment of cortical folding in extremely preterm newborns relative to relatively late preterm newborns, demonstrating its potential to provide biomarkers of prematurity-related developmental outcome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Fronto-amygdalar networks are implicated in childhood psychiatric disorders characterized by high rates of externalizing (aggressive, noncompliant, oppositional) behavior. Although externalizing behaviors are distributed continuously across clinical and nonclinical samples, little is known about how brain variations may confer risk for problematic behavior. Here, we studied cortical thickness, amygdala volume, and cortico-amygdalar network correlates of externalizing behavior in a large sample of healthy children., Methods: Two hundred ninety-seven healthy children (6-18 years; mean = 12 ± 3 years), with 517 magnetic resonance imaging scans, from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development, were studied. Relationships between externalizing behaviors (measured with the Child Behavior Checklist) and cortical thickness, amygdala volume, and cortico-amygdalar structural networks were examined using first-order linear mixed-effects models, after controlling for age, sex, scanner, and total brain volume. Results significant at p ≤ .05, following multiple comparison correction, are reported., Results: Left orbitofrontal, right retrosplenial cingulate, and medial temporal cortex thickness were negatively correlated with externalizing behaviors. Although amygdala volume alone was not correlated with externalizing behaviors, an orbitofrontal cortex-amygdala network predicted rates of externalizing behavior. Children with lower levels of externalizing behaviors exhibited positive correlations between orbitofrontal cortex and amygdala structure, while these regions were not correlated in children with higher levels of externalizing behavior., Conclusions: Our findings identify key cortical nodes in frontal, cingulate, and temporal cortex associated with externalizing behaviors in children; and indicate that orbitofrontal-amygdala network properties may influence externalizing behaviors, along a continuum and across healthy and clinical samples., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

One dimension of insight in psychosis is the ability to attribute correctly one's symptoms to a mental disorder. Recent work suggests that gray matter volumes of the orbitofrontal cortex (OFC) are correlated with aggregate symptom attribution scores in first-episode schizophrenia. Whether regions beyond the OFC are important for symptom attribution remains to be established. Further, whether common or separable neural systems underlie attribution of specific symptoms (e.g., delusions, asociality) has not been studied. In the current magnetic resonance imaging study, 52 people with a first-episode psychosis (FEP) were rated with the Scale for Assessment of Unawareness of Mental Disorder on attribution of hallucinations, delusions, flat affect and asociality. Attribution ratings were regressed on cortical thickness at 81,924 vertices. Mapping statistics revealed that delusion misattribution was associated with thickness in the OFC [Brodmann's area (BA) 11/47]. Delusion, flat affect and asociality misattribution were associated with cortical thinness in the dorsolateral prefrontal cortex (BA 9/46). Differential associations emerged between each attribution item and cortical thickness/thinness in a variety of frontal, temporal, parietal and occipital areas. The results imply a selective role for the OFC in delusion misattribution in FEP. Evidence for cortical thickness covariation in a variety of regions suggests partial independence in the neural architecture underlying attribution for different symptoms in FEP., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Regional cortical thickness was evaluated using CIVET processing of 3D T1-weighted images (i) to compare the variation in cortical thickness between 33 participants with fetal alcohol spectrum disorders (FASD) aged 6-30 years (mean age 12.3 years) versus 33 age/sex/hand-matched controls, and (ii) to examine developmental changes in cortical thickness with age from children to young adults in both groups. Significant cortical thinning was found in the participants with FASD in large areas of the bilateral middle frontal lobe, pre- and post- central areas, lateral and inferior temporal and occipital lobes compared to controls. No significant cortical thickness increases were observed for the FASD group. Cortical thinning with age in a linear model was observed in both groups, but the locations were different for each group. FASD participants showed thinning with age in the left middle frontal, bilateral precentral, bilateral precuneus and paracingulate, left inferior occipital and bilateral fusiform gyri; while controls showed decreases with age in the bilateral middle frontal gyrus, right inferior frontal gyrus, bilateral precuneus gyrus, and bilateral occipital gyrus. A battery of cognitive assessments of memory, attention, motor, and verbal abilities was conducted with many of the FASD participants, but no significant correlations were found between these cognitive scores and regional cortical thickness. Non-invasive measurements of cortical thickness in children to young adults with FASD have identified both key regions of cortex that may be more deleteriously affected by prenatal alcohol exposure as well as cortical changes with age that differ from normal developmental thinning., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Context: Whether cortical thickness changes in schizophrenia over time are more pronounced relative to the changes that can be attributed to normal aging has not been studied., Objective: To compare patients with schizophrenia and healthy control participants on cortical thickness change., Design: A 5-year longitudinal study comparing schizophrenic patients and healthy controls using 2 magnetic resonance images of the brain., Setting: Patients were recruited from the Department of Psychiatry at the University Medical Centre Utrecht and from other psychiatric hospitals in the Netherlands. Healthy controls were recruited via advertisement in newspapers and notice boards., Participants: Ninety-six schizophrenic patients and 113 healthy controls aged 16 to 56 years., Main Outcome Measures: Cortical thickness and change in cortical thickness on a vertex-by-vertex basis across the cortical mantle, measures of functional and symptomatic outcome, and cumulative intake of antipsychotics during the scan interval., Results: At baseline, the schizophrenic patients had thinner left orbitofrontal and right parahippocampal and superior temporal cortices and a thicker superior parietal lobule and occipital pole compared with the controls. Mean cortical thickness did not differ between the groups. Over time, excessive cortical thinning was found in widespread areas on the cortical mantle, most pronounced bilaterally in the temporal cortex and in the left frontal area. Poor outcome in patients was associated with more pronounced cortical thinning. Higher cumulative intake of typical antipsychotics during the scan interval was associated with more pronounced cortical thinning, whereas higher cumulative intake of atypical antipsychotic medication was associated with less pronounced cortical thinning., Conclusions: In schizophrenia, the cortex shows excessive thinning over time in widespread areas of the brain, most pronounced in the frontal and temporal areas, and progresses across the entire course of the illness. The excessive thinning of the cortex appears related to outcome and medication intake.

Through conceptualizing poor insight in psychotic disorders as a form of anosognosia (neurological deficit), frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. Whether non-frontal brain regions are important for insight remains to be investigated. We used a multi-method approach to examine the neural morphometry of all cortical regions for insight in first-episode psychosis. Insight was rated in 79 people with a first-episode psychosis with the awareness of illness and awareness of treatment need and efficacy items of the Scale for assessment of Unawareness of Mental Disorder. Participants were assessed with magnetic resonance imaging. Cortical thickness analysis and voxel-based morphometry were utilized to identify the possible neuroanatomical basis of insight. Cortical thickness technique revealed that poorer awareness of illness was associated with regional thinning in left middle frontal and inferior temporal gyri. Poorer awareness of treatment need and efficacy was associated with cortical thinning in left medial frontal gyrus, precuneus and temporal gyri. No significant associations emerged between any insight measure and gray matter density using voxel-based morphometry. The results confirm predictions derived from the anosognosia/neuropsychology account and assert that regional thickness in frontal cortex is associated with awareness of illness in the early phase of psychosis. The fact that prominent thickness reductions emerged in non-frontal regions of the brain in parietal and temporal cortices for both awareness of illness and awareness of treatment need and efficacy suggests that the neural signature of insight involves a network of brain structures, and not only the frontal lobes as previously suggested., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Prevailing psychometric theories of intelligence posit that individual differences in cognitive performance are attributable to three main sources of variance: the general factor of intelligence (g), cognitive ability domains, and specific test requirements and idiosyncrasies. Cortical thickness has been previously associated with g. In the present study, we systematically analyzed associations between cortical thickness and cognitive performance with and without adjusting for the effects of g in a representative sample of children and adolescents (N=207, Mean age=11.8; SD=3.5; Range=6 to 18.3 years). Seven cognitive tests were included in a measurement model that identified three first-order factors (representing cognitive ability domains) and one second-order factor representing g. Residuals of the cognitive ability domain scores were computed to represent g-independent variance for the three domains and seven tests. Cognitive domain and individual test scores as well as residualized scores were regressed against cortical thickness, adjusting for age, gender and a proxy measure of brain volume. g and cognitive domain scores were positively correlated with cortical thickness in very similar areas across the brain. Adjusting for the effects of g eliminated associations of domain and test scores with cortical thickness. Within a psychometric framework, cortical thickness correlates of cognitive performance on complex tasks are well captured by g in this demographically representative sample., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Cerebral grey matter volume reductions are progressive in schizophrenia, with larger grey matter volume decreases associated with cannabis use. It is unknown whether this grey matter loss is globally distributed over the entire brain or more pronounced in specific cortical brain regions. Fifty-one patients with recent-onset schizophrenia and 31 matched healthy subjects were included. For all subjects, magnetic resonance imaging scans were obtained at inclusion and at 5-year follow-up. Nineteen patients (ab-)used cannabis but no other illicit drugs; 32 patients and the healthy comparison subjects did not use any drugs during the 5-year follow-up. At follow-up, clinical outcome was measured. To evaluate the local differences in cortical thickness change over five years between the two groups regression analysis was carried out over the cortical surface. At inclusion cortical thickness did not differ between patients and controls and between cannabis-using and non-using patients. Over the follow-up period we found excessive thinning of the right supplementary motor cortex, inferior frontal cortex, superior temporal gyrus, angular gyrus, occipital and parietal lobe in patients relative to controls after controlling for cannabis use. Patients who used cannabis showed additional thinning in the left dorsolateral prefrontal cortex (DLPFC), left anterior cingulate cortex (ACC) and left occipital lobe as compared to those patients that did not use cannabis during the scan interval. First-episode schizophrenia patients who use cannabis show a more pronounced cortical thinning than non-using patients in areas known for their high density of CB1 receptors, such as the ACC and the DLPFC., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Multicenter structural MRI studies can have greater statistical power than single-center studies. However, across-center differences in contrast sensitivity, spatial uniformity, etc., may lead to tissue classification or image registration differences that could reduce or wholly offset the enhanced statistical power of multicenter data. Prior work has validated volumetric multicenter MRI, but robust methods for assessing reliability and power of multisite analyses with voxel-based morphometry (VBM) and cortical thickness measurement (CORT) are not yet available. We developed quantitative methods to investigate the reproducibility of VBM and CORT to detect group differences and estimate heritability when MRI scans from different scanners running different acquisition protocols in a multicenter setup are included. The method produces brain maps displaying information such as lowest detectable effect size (or heritability) and effective number of subjects in the multicenter study. We applied the method to a five-site multicenter calibration study using scanners from four different manufacturers, running different acquisition protocols. The reliability maps showed an overall good comparability between the sites, providing a reasonable gain in sensitivity in most parts of the brain. In large parts of the cerebrum and cortex scan pooling improved heritability estimates, with "effective-N" values upto the theoretical maximum. For some areas, "optimal-pool" maps indicated that leaving out a site would give better results. The reliability maps also reveal which brain regions are in any case difficult to measure reliably (e.g., around the thalamus). These tools will facilitate the design and analysis of multisite VBM and CORT studies for detecting group differences and estimating heritability., (Copyright © 2010 Wiley-Liss, Inc.)

Context: Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data., Objective: To delineate the development of cortical asymmetry in children with and without ADHD., Design: Longitudinal study., Setting: Government Clinical Research Institute., Participants: A total of 218 children with ADHD and 358 typically developing children, from whom 1133 neuroanatomical magnetic resonance images were acquired prospectively., Main Outcome Measures: Cortical thickness was estimated at 40 962 homologous points in the left and right hemispheres, and the trajectory of change in asymmetry was defined using mixed-model regression., Results: In right-handed typically developing individuals, a mean (SE) increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age of 0.011 (0.0018) mm per year (t(337) = 6.2, P < .001) was balanced against a relative left-hemispheric increase in the occipital cortical regions of 0.013 (0.0015) mm per year (t(337) = 8.1, P < .001). Age-related change in asymmetry in non-right-handed typically developing individuals was less extensive and was localized to different cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost., Conclusions: These findings explain the way that, in typical development, the increased dimensions of the right frontal and left occipital cortical regions emerge in adulthood from the reversed pattern of childhood cortical asymmetries. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders.

In addition to the positive and negative symptoms, schizophrenia is associated with a variety of cognitive impairments, and in particular with episodic memory deficits. Functional neuroimaging studies have begun exploring the potential neural correlates of memory deficits but there are few reports of structural brain abnormalities underlying memory impairment in schizophrenia. We investigated the potential association between morphological brain abnormalities as revealed by cortical thickness measures and episodic memory performance on a face recognition task. Differences in regional cortical thickness between 27 patients with a DSM-IV diagnosis of schizophrenia and 28 control matched subjects were investigated using MRI T1 images and computer image analysis (CIVET pipeline; Lerch and Evans, 2005). Cortical thickness was estimated as the shortest distance between the pial surface of the cerebral cortex and the white-matter/gray-matter interface surface at numerous points (40 962 vertices) across the cortical mantle. Consistent with previous studies, a group comparison revealed thinner cortex in the patient group relative to controls in the right prefrontal cortex and parahippocampal gyrus. Interestingly, a significant positive correlation between memory performance and cortical thickness of the anterior cingulate, bilaterally as well as the right parahippocampal gyrus was noted in the schizophrenia group. That is, the thinner the cortex in those regions, the more impaired the patients were in terms of memory performance as compared to healthy participants. [Copyright &y& Elsevier]