Differential subcortical-cortical circuit reorganization in autism and ADHD

Abstract

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) often co-occur and share symptoms as well as genetic risk factors. While subcortical-cortical networks have been implicated in both conditions, particularly involving thalamic and striatal circuits, patterns of shared and diverging disruptions remain unclear. Here we integrated resting-state functional connectivity (FC) and regression dynamic causal modeling (rDCM) across a transdiagnostic multi-site cohort. We used statistical group comparisons and individualized normative deviation mapping to map network deviations in ASD and ADHD relative to neurotypical controls and against one another. Multivariate associative techniques examined associations to clinical and cognitive phenotypes. Our transdiagnostic analyses revealed significant differentiation of ASD and ADHD across subcortical-cortical circuits. While ASD was characterized by widespread thalamocortical hyperconnectivity and bidirectional elevated coupling across thalamic subdivisions, ADHD exhibited a focal pattern of striatocortical disruption, anchored predominantly within the caudate. Multivariate analyses identified shared and disorder-specific brain-behavior associations. Across both conditions, aberrant striatocortical signaling was associated with reduced overall intelligence measures. Clinically, ASD-related thalamocortical connectivity disruptions mapped onto generalized cognitive impairment, whereas ADHD-related subcortical alterations tracked hyperactive and inattentive symptom dimensions. Our findings differentiate ASD and ADHD through distinct patterns of functional and directional subcortical-cortical dysregulations.