Richetin, S. | Search bioRxiv

bioRxiv2025

Social, cognitive and sensory dimensions of cortical network overconnectivity in young children with autism spectrum disorder

The heterogeneity in both the neurobiological mechanisms and the phenotypic presentation of autism spectrum disorder (ASD) poses a major challenge to clinical and translational research. Early inefficiencies in functional connectivity (FC) have been associated with ASD, yet it remains unclear whether and how abnormal brain network properties may account for individual differences across ASD-related symptomatology and behaviors. We applied source-level reconstruction to resting-state high-definition EEG data in a cohort of 113 young children (40 with ASD) to identify early global and local alterations of cortical network connectivity. We subsequently used regularized canonical correlation analysis (rCCA) to characterize specific FC patterns linked to variation in cognitive, social and sensory dimensions within the autism spectrum. We found increased low-frequency FC in frontotemporal cross-hemispheric networks and lateral-occipital regions of young ASD children. RCCA revealed three distinct FC patterns in recurrent ASD-related networks, each contributing to predict individual differences in cognitive, social and sensory features. These linked FC-behavior dimensions may shed light on atypical brain network topology conferring risk for specific phenotypic manifestations of ASD, which may implicate unique underlying neurobiological mechanisms.

neuroscience↗

bioRxiv2022

Rare CNVs and phenome-wide profiling: a tale of brain-structural divergence and phenotypical convergence

Copy number variations (CNVs) are rare genomic deletions and duplications that can exert profound effects on brain and behavior. Previous reports of pleiotropy in CNVs imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, studies to date have primarily examined single CNV loci in small clinical cohorts. It remains unknown how distinct CNVs escalate the risk for the same developmental and psychiatric disorders. Here, we quantitatively dissect the impact on brain organization and behavioral differentiation across eight key CNVs. In 534 clinical CNV carriers from multiple sites, we explored CNV-specific brain morphology patterns. We extensively annotated these CNV-associated patterns with deep phenotyping assays through the UK Biobank resource. Although the eight CNVs cause disparate brain changes, they are tied to similar phenotypic profiles across [~]1000 lifestyle indicators. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

genetics↗