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This study analyzed brain imaging data from 1,737 individuals with autism spectrum disorder (ASD) and compared it with gene expression maps to investigate patterns of brain connectivity. The research found that hyperconnectivity (excessive connectivity) and hypoconnectivity (reduced connectivity) in ASD are distinct neurobiological phenomena with different molecular signatures, locations in the brain, and age-related patterns, rather than opposite ends of a single spectrum. Hyperconnectivity was concentrated in higher-order brain regions and more prominent in older participants, while hypoconnectivity was found in subcortical and orbitofrontal systems across all age groups.
Why it matters
These findings could reshape how researchers and clinicians understand autism's neurobiological basis, potentially leading to more targeted interventions that address hyperconnectivity and hypoconnectivity as separate mechanisms. The identification of distinct molecular and genetic profiles associated with each connectivity pattern may inform future development of precision medicine approaches for ASD.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Functional hyperconnectivity and hypoconnectivity in autism spectrum disorder (ASD) are typically treated as opposing expressions of a single circuit-level disturbance, but their molecular and hierarchical basis remains unclear. We combined resting-state fMRI from 1,737 individuals from the Autism Brain Imaging Data Exchange (ABIDE I/II) with gene-expression maps from the Allen Human Brain Atlas and show that hyperconnectivity and hypoconnectivity are dissociable neurobiological phenomena, differing in molecular signatures, cortical-hierarchical embedding, age-group profile, and cognitive associations, rather than a single connectivity axis. Hyperconnectivity was concentrated in higher-order cortical and cerebellar regions and was greater in older participants, while hypoconnectivity was consistent across age groups and localized to subcortical and orbitofrontal systems. ASD was associated with reorganization of the sensory-to-transmodal cortical gradient, most pronounced in association networks. Hyperconnectivity- and hypoconnectivity-associated genes showed partially distinct neurotransmitter profiles and differential embedding within cortical hierarchy, both enriched in transmodal cortex and linked to social-cognitive, perceptual, attentional, and reward-related functions. This dissociation was preserved across developmental stage, sex, and symptom severity. These findings indicate hyperconnectivity and hypoconnectivity are not two poles of one process but two separable components of a reproducible molecular-hierarchical architecture, offering a multi-scale framework linking transcriptomic organization to systems-level brain dysfunction in ASD.