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Unique Amygdala Signatures and Shared Prefrontal Deficits in Autism: Mapping Social Heterogeneity via Naturalistic functional MRI

Xin DiiD, Ting XuiD, F. Xavier CastellanosiD, Bharat B. BiswaliD

Abstract

Naturalistic fMRI provides an ecologically valid window into social brain function, yet binary diagnostic labels may obscure neural signatures linked to the continuous spectrum of social deficits. We investigated whether social brain alterations in autism spectrum disorder (ASD) follow a categorical, dimensional, or "dual-track" architecture. We analyzed movie-watching fMRI data from the Healthy Brain Network cohort (ages 5-22) during two films: The Present (n = 327) and Despicable Me (n = 242), using principal component analysis (PCA) to quantify primary (PC1) and secondary (PC2) synchronization and variance partitioning to separate the contributions of categorical diagnosis from continuous symptom severity (Social Responsiveness Scale-2, SRS-2). During The Present, higher SRS-2 scores were associated with widespread reduction in synchronization. In social-motivational hubs (medial prefrontal cortex, caudate), reductions were carried by variance shared between diagnosis and SRS-2 scores, leaving the categorical and dimensional accounts empirically indistinguishable. The left amygdala was the only region with a unique dimensional association independent of diagnosis. Secondary response patterns (PC2) showed further unique dimensional associations in the precuneus, temporoparietal junction, and posterior superior temporal sulcus. No significant associations were detected during Despicable Me; a direct within-participant comparison (n = 198) localized reliable stimulus differences to the medial prefrontal and posterior cingulate cortex, with no difference in the amygdala. These findings identify dimension-specific signatures in the amygdala and in mentalizing-network timing, and indicate that the choice of stimulus affects whether such associations are detectable.

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02 /Specification & Classification

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