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

Area of Science:

• Neuroscience
• Computational Biology
• Genetics

Background:

• Autism pathophysiology involves macroscale connectome miswiring and microcircuit anomalies.
• Understanding the link between global network changes and local circuit dysfunction is crucial for autism research.

Purpose of the Study:

• To investigate the association between macroscale connectome perturbations and microcircuit dysfunctions in autism.
• To explore the relationship between brain network anomalies, genetic expression, and autism symptom severity.

Main Methods:

• Utilized connectome-wide manifold learning and biophysical simulation models on neuroimaging data from individuals with autism and controls.
• Performed transcriptomic association analysis and supervised machine learning to correlate findings with phenotypic data.

Main Results:

• Identified significant differences in structural connectome organization in autism, particularly in somatosensory and association cortices.
• Computational models linked macroscale anomalies to altered excitation/inhibition balance and subcortical inputs in cortical microcircuits.
• Macroscale perturbations correlated with autism symptom severity, as measured by the Autism Diagnostic Observation Schedule.

Conclusions:

• Atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism.
• Findings highlight the interplay between global brain organization and local circuit function in autism pathophysiology.