Biology subjects

Voineskos, A.

Publications and source records attributed to Voineskos, A..

9 recordsLinked to original sources

bioRxiv2024

Sex differences in deep brain shape and asymmetry persist across schizophrenia and healthy individuals: A meta-analysis from the ENIGMA-Schizophrenia Working Group

BackgroundSchizophrenia (SCZ) is characterized by a disconnect from reality that manifests as various clinical and cognitive symptoms, and persistent neurobiological abnormalities. Sex-related differences in clinical presentation imply separate brain substrates. The present study characterized deep brain morphology using shape features to understand the independent effects of diagnosis and sex on the brain, and to determine whether the neurobiology of schizophrenia varies as a function of sex. MethodsThis study analyzed multi-site archival data from 1,871 male (M) and 955 female (F) participants with SCZ, and 2,158 male and 1,877 female healthy controls (CON) from twenty-three cross-sectional samples from the ENIGMA Schizophrenia Workgroup. Harmonized shape analysis protocols were applied to each sites data for seven deep brain regions obtained from T1-weighted structural MRI scans. Effect sizes were calculated for the following main contrasts: 1) Sex effects;2) Diagnosis-by-Sex interaction; 3) within sex tests of diagnosis; 4) within diagnosis tests of sex differences. Meta-regression models between brain structure and clinical variables were also computed separately in men and women with schizophrenia. ResultsMass univariate meta-analyses revealed more concave-than-convex shape differences in all regions for women relative to men, across diagnostic groups (d = -0.35 to 0.20, SE = 0.02 to 0.07); there were no significant diagnosis-by-sex interaction effects. Within men and women separately, we identified more-concave-than-convex shape differences for the hippocampus, amygdala, accumbens, and thalamus, with more-convex-than-concave differences in the putamen and pallidum in SCZ (d = -0.30 to 0.30, SE = 0.03 to 0.10). Within CON and SZ separately, we found more-concave-than-convex shape differences in the thalamus, pallidum, putamen, and amygdala among females compared to males, with mixed findings in the hippocampus and caudate (d = -0.30 to 0.20, SE = 0.03 to 0.09). Meta-regression models revealed similarly small, but significant relationships, with medication and positive symptoms in both SCZ-M and SCZ-F. ConclusionsSex-specific variation is an overriding feature of deep brain shape regardless of disease status, underscoring persistent patterns of sex differences observed both within and across diagnostic categories, and highlighting the importance of including it as a critical variable in studies of neurobiology. Future work should continue to explore these dimensions independently to determine whether these patterns of brain morphology extend to other aspects of neurobiology in schizophrenia, potentially uncovering broader implications for diagnosis and treatment. Key PointsO_LIStatistical analyses revealed significant main effects for diagnosis and sex in deep brain shape morphology. Among patients with schizophrenia, there was a pattern of thinning and surface contraction in the bilateral hippocampus, amygdala, accumbens, and thalamus, and a pattern of significant thickening and surface expansion in the bilateral putamen and pallidum compared to healthy control participants. Between males and females, there was a pattern of significant thinning and surface contraction in the bilateral thalamus, pallidum, putamen, and amygdala in females compared to males. C_LIO_LIThere was no significant interaction between diagnosis and biological sex, suggesting that sex differences in deep brain shape and asymmetry among patients with schizophrenia reflect those observed in healthy individuals. C_LIO_LISmall but statistically significant relationships exist between brain structure and clinical correlates of schizophrenia were similar for both men and women with the disease, such that higher CPZ was associated with shape-derived thinning and surface contraction in the caudate, accumbens, hippocampus, amygdala, and thalamus, and elevated positive symptoms were associated with shape-derived thinning and surface contraction in the bilateral caudate, right hippocampus, and right amygdala. C_LI

neuroscience↗

bioRxiv2023

Comparing the stability and reproducibility of brain-behaviour relationships found using Canonical Correlation Analysis and Partial Least Squares within the ABCD Sample

IntroductionCanonical Correlation Analysis (CCA) and Partial Least Squares Correlation (PLS) detect associations between two data matrices based on computing a linear combination between the two matrices (called latent variables; LVs). These LVs maximize correlation (CCA) and covariance (PLS). These different maximization criteria may render one approach more stable and reproducible than the other when working with brain and behavioural data at the population-level. This study compared the LVs which emerged from CCA and PLS analyses of brain-behaviour relationships from the Adolescent Brain Cognitive Development (ABCD) dataset and examined their stability and reproducibility. MethodsStructural T1-weighted imaging and behavioural data were accessed from the baseline Adolescent Brain Cognitive Development dataset (N > 9000, ages = 9-11 years). The brain matrix consisted of cortical thickness estimates in different cortical regions. The behavioural matrix consisted of 11 subscale scores from the parent-reported Child Behavioral Checklist (CBCL) or 7 cognitive performance measures from the NIH Toolbox. CCA and PLS models were separately applied to the brain-CBCL analysis and brain-cognition analysis. A permutation test was used to assess whether identified LVs were statistically significant. A series of resampling statistical methods were used to assess stability and reproducibility of the LVs. ResultsWhen examining the relationship between cortical thickness and CBCL scores, the first LV was found to be significant across both CCA and PLS models (singular value: CCA = .13, PLS = .39, p < .001). LV1 from the CCA model found that covariation of CBCL scores was linked to covariation of cortical thickness. LV1 from the PLS model identified decreased cortical thickness linked to lower CBCL scores. There was limited evidence of stability or reproducibility of LV1 for both CCA and PLS. When examining the relationship between cortical thickness and cognitive performance, there were 6 significant LVs for both CCA and PLS (p < .01). The first LV showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p < .001). ConclusionCCA and PLS identify different brain-behaviour relationships with limited stability and reproducibility when examining the relationship between cortical thickness and parent-reported behavioural measures. However, both methods identified relatively similar brain-behaviour relationships that were stable and reproducible when examining the relationship between cortical thickness and cognitive performance. The results of the current study suggest that stability and reproducibility of brain-behaviour relationships identified by CCA and PLS are influenced by characteristics of the analyzed sample and the included behavioural measurements when applied to a large pediatric dataset.

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bioRxiv2023

Connectome architecture shapes large-scale cortical reorganization in schizophrenia: a worldwide ENIGMA study

While schizophrenia is considered a prototypical network disorder characterized by widespread brain-morphological alterations, it still remains unclear whether distributed structural alterations robustly reflect underlying network layout. Here, we tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2,439 adults with schizophrenia and 2,867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n=207), we evaluated structural alterations of schizophrenia against two network susceptibility models: i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; ii) epicenter mapping, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Schizophrenia-related structural alterations co-localized with interconnected functional and structural hubs and harbored temporo-paralimbic and frontal epicenters. Findings were robust across sites and related to individual symptom profiles. We observed localized unique epicenters for first-episode psychosis and early stages, and transmodal epicenters that were shared across first-episode to chronic stages. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, yielding insights in pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work contributes to recognizing potentially common pathways to better understand macroscale structural alterations, and inter-individual variability in schizophrenia.

neuroscience↗

bioRxiv2021

Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders

BackgroundExternalizing and internalizing behaviors are common and contribute to impairment in children with neurodevelopmental disorders (NDDs). Associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in children with and without clinically significant internalizing/externalizing behaviors. This study examined whether such associations are present across children with different NDDs. MethodsMulti-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6-18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (n range=157-346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined. ResultsNo significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results. ConclusionsThe current study provides evidence in favour of the absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with various NDDs and TDC. Detecting shared brain-behavior relationships in children with NDDs may benefit from the use of different methodological approaches, including incorporation of multi-dimensional behavioral data (i.e. behavioral assessments, neurocognitive tasks, task-based fMRI) or clustering approaches to delineate whether subgroups of individuals with different brain-behavior profiles are present within heterogeneous cross-disorder samples.

neuroscience↗

bioRxiv2018

White matter microstructure in women with acute and remitted anorexia nervosa: an exploratory neuroimaging study

Anorexia nervosa (AN) is a highly heritable psychiatric disorder characterized by starvation and emaciation and associated with changes in brain structure. The precise nature of these changes remains unclear, as does their developmental time course and capacity for reversal with weight restoration. In this exploratory neuroimaging study, we sought to characterize changes in white matter microstructure in women with acute and remitted AN. Diffusion-weighted MRI data was collected from underweight women with a current diagnosis of AN (acAN: n=23), weight-recovered women with a past diagnosis of AN (recAN: n=23), and age-matched healthy control women (HC: n=24). Image processing and analysis were performed with Tract-Based Spatial Statistics, part of FSL, and group differences in voxel-wise, brain-wide fractional anisotropy (FA) and mean diffusivity (MD), indices of white matter microstructure, were tested with nonparametric permutation and threshold free cluster enhancement. No significant main effect of group on FA was identified. A significant main effect of group on MD was observed in a large cluster covering 9.2% of white matter and including substantial portions of the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus, and post hoc analyses revealed similar effects of group on axial diffusivity (AD) and radial diffusivity (RD). Cluster-wise MD was significantly higher in acAN participants (+3.8%) and recAN participants (+2.9%) than healthy controls, and the same was true for cluster-wise AD and RD. Trait-based increases in diffusivity, consistent with atypical myelination and impaired axon integrity, suggest a link between altered white matter microstructure and vulnerability to AN, and evidence of reduced oligodendrocyte density in AN provides further support for this hypothesis. Potential mechanisms of action include atypical neurodevelopment and systemic inflammation.

neuroscience↗

bioRxiv2018

Neuroanatomical correlates of temperament and cognitive function in women with and without anorexia nervosa

Brain-behavior relationships that could provide insight into risk-associated pathophysiology have not been thoroughly assessed in anorexia nervosa (AN). Therefore, we sought to identify grey and white matter signatures of AN symptoms and risk factors (trait anxiety, set-shifting impairment) in a sample enriched for AN vulnerability, including acute and remitted AN patients and their unaffected sisters (n = 72, aged 18 - 48 years). MRI/DTI data were acquired on a 3T scanner and processed with Freesurfer and FSL TBSS. Relationships between clinical variables of interest and regional subcortical volume, vertex-wise cortical surface architecture (thickness, surface area, local gyrification), and voxel-wise white matter microstructure (FA, MD) were tested with separate linear regressions, including age, BMI, lifetime AN diagnosis, and intracranial volume as covariates, where appropriate. Significance was determined using a Bonferroni-corrected threshold, p(t) [≤] 0.001. We detected distinct associations linking AN symptoms to lateral occipital cortical thickness and insular/cingulate gyrification and trait anxiety to lingual cortical thickness and superior parietal gyrification, and we detected overlapping associations linking AN symptoms and set-shifting impairment to frontoparietal gyrification. No other brain-behavior relationships emerged. Our findings suggest that variations in site-specific cortical morphology could give rise to core features of AN and shared temperamental and cognitive-behavioral risk factors for AN.

neuroscience↗

bioRxiv2018

Deep Learning for Quality Control of Subcortical Brain 3D Shape Models

We present several deep learning models for assessing the morphometric fidelity of deep grey matter region models extracted from brain MRI. We test three different convolutional neural net architectures (VGGNet, ResNet and Inception) over 2D maps of geometric features. Further, we present a novel geometry feature augmentation technique based on parametric spherical mapping. Finally, we present an approach for model decision visualization, allowing human raters to see the areas of subcortical shapes most likely to be deemed of failing quality by the machine. Our training data is comprised of 5200 subjects from the ENIGMA Schizophrenia MRI cohorts, and our test dataset contains 1500 subjects from the ENIGMA Major Depressive Disorder cohorts. Our final models reduce human rater time by 46-70%. ResNet outperforms VGGNet and Inception for all of our predictive tasks.

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bioRxiv2017

Machine Learning for Large-Scale Quality Control of 3D Shape Models in Neuroimaging

As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.

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bioRxiv2017

Personalized intrinsic network topography mapping and functional connectivity deficits in Autism Spectrum Disorder

BackgroundRecent advances demonstrate individually specific variation in brain architecture in healthy individuals using fMRI data. To our knowledge, the effects of individually specific variation in complex brain disorders have not been previously reported.\n\nMethodsWe developed a novel approach (Personalized Intrinsic Network topography, PINT) for localizing individually specific resting state networks using conventional resting state fMRI scans. Using cross-sectional data from participants with ASD (n=393) and TD controls (n=496) across 15 sites we tested: 1) effect of diagnosis and age on the variability of intrinsic network locations and 2) whether prior findings of functional connectivity differences in ASD as compared to TD remain after PINT application.\n\nResultsWe found greater variability in the spatial locations of resting state networks within individuals with ASD as compared to TD. In TD participants, variability decreased from childhood into adulthood, and increased again in late-life, following a U-shaped pattern, which was not present in those with ASD. Comparison of intrinsic connectivity between groups revealed that the application of PINT decreased the number of hypo-connected regions in ASD.\n\nConclusionsOur results provide a new framework for measuring altered brain functioning in neurodevelopmental disorders that may have implications for tracking developmental course, phenotypic heterogeneity, and ultimately treatment response. We underscore the importance of accounting for individual variation in the study of complex brain disorders.

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