Aberrant Structural and Functional Signatures of the Social-Cognitive Brain Network in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is characterized by persistent impairments in social reciprocity and communication, therefore linked to atypical development of the "social brain". It is a distributed network anchored by the temporoparietal junction (TPJ), medial prefrontal cortex (mPFC), and the amygdala. Diagnosis of ASD remains purely behavioral, with no validated biomarker of this circuitry to complement clinical assessment.

The aim of this study is to ask whether structural and functional signatures of amygdala-centered mentalizing circuitry differ between ASD and typically developing individuals, and whether such differences track clinical severity.

Using multi-site neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE), the circuitry was characterized in a large, clinically phenotyped cohort (N = 1112; 539 ASD, 573 controls), combining amygdala surface morphometry, voxelwise general linear modeling of whole-brain effect-size and statistical parametric maps, and dimensional phenotyping via the Autism Diagnostic Observation Schedule (ADOS) and Social Responsiveness Scale (SRS).

Group-level contrasts revealed reduced signal in the left mesial temporal cortex encompassing the amygdala and parahippocampal gyrus in ASD relative to controls, alongside subtle morphometric deviation in amygdala surface topology. SRS scores were markedly elevated in ASD (t = 24.1, p < 0.001), but categorical ADOS severity and dimensional SRS scores were not significantly correlated within the ASD group (r = –0.07, p = 0.51), indicating partially dissociable clinician- and caregiver-rated measures. These findings implicate amygdala-centered mentalizing circuitry in ASD social cognition and motivate a planned EEG extension examining mu rhythm suppression during action observation.