Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism

The pathophysiology of autism has been suggested to involve a combination of both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. We studied neuroimaging and phenotypic data in 47 individuals with autism and 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences in structural connectome organization in individuals with autism relative to controls, with strong between-group effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models reveal that the degree of macroscale anomalies is related to atypical increases of recurrent excitation/inhibition, as well as subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic association analysis based on postmortem datasets identifies genes expressed in cortical and thalamic areas from childhood to young adulthood. Finally, supervised machine learning finds that the macroscale perturbations are associated with symptom severity scores on the Autism Diagnostic Observation Schedule. Together, our analyses suggest that atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism. Autism is increasingly recognized to impact multiple scales of neural organization. Here, the authors show alterations in individuals with autism relative to typically developing controls, with findings particularly pointing to atypically organized subcortical-cortical networks.

Automated summary

The study suggests that there are significant differences in structural connectome organization in individuals with autism compared to typically developing controls, particularly in low-level somatosensory regions and high-level association cortices. Computational models reveal that macroscale anomalies are related to atypical increases in recurrent excitation/inhibition and subcortical inputs into cortical microcircuits in sensory and motor areas.