Co-evolutionary Balance State of the Autism inter-Brain Network: A Neurofunctional Framework for Biomarker Discovery

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors; however, objective neurophysiological biomarkers remain lacking. We propose a coevolutionary balance paradigm that quantifies network level energy via a Hamiltonian integrating regional activity measured by fractional amplitude of low frequency fluctuations (fALFF) and resting state functional connectivity (FC). Analysis of resting state fMRI data from 93 adult males with ASD and 93 matched controls revealed that empirical networks showed lower energy than 1000 topology preserving null models (paired t = -4.12, p less than or equal to 1e-4). Participants with ASD exhibited more negative whole brain energy (t = -3.239, p = 0.0015), driven by increased agreement links and reduced imbalanced same motifs. Subnetwork analysis indicated greater energy in the Default Mode Network after false discovery rate correction (p less than 0.016) and enhanced energy between the Default Mode, Salience and Dorsal Attention networks (p less than 0.032). Energy metrics and inter network connectivity correlated with Autism Diagnostic Interview Revised and Autism Diagnostic Observation Schedule severity scores (absolute correlation greater than or equal to 0.29, p less than 0.02). A k nearest neighbors classifier using nine principal features including motif proportions, global node link alignment, inter network fALFF weighted and FC strengths, subnetwork magnetization and pairwise energy achieved an accuracy of 79 percent with balanced sensitivity and specificity. These results demonstrate that coevolutionary energy detects interpretable network disruptions and establishes a robust framework for ASD classification.