Spontaneous brain activity captured with functional magnetic resonance imaging (fMRI) at rest engages in distinct coupling modes over time, transiently forming functional networks. While these networks show promise as biomarkers for psychiatric conditions, our limited understanding of their fundamental organizing principles has constrained the development of network-targeted therapeutic interventions.

In this study, Leading Eigenvector Dynamics Analysis (LEiDA) is applied to fMRI scans from n=945 participants from the Autism Brain Imaging Data Exchange (ABIDE I), demonstrating sensitivity to discriminate Autism Spectrum Disorder (ASD) subtypes and neurotypical controls. Compared to neurotypical controls (n=508), participants with Autistic Disorder subtype (n=331) exhibited reduced occurrence of both the Default Mode Network, DMN, and the Frontoparietal Network. In contrast, participants with Pervasive Developmental Disorder subtype (n=31) show increased occurrence of a more diffuse DMN configuration involving temporal areas and a Salience-Somatomotor network, whereas participants with Asperger subtype (n=75) show a subtle reduction of Frontoparietal Network occupancy.

By detecting phase-alignment modes—a fundamental physical phenomenon characteristic of standing waves—LEiDA provides a novel perspective on how brain networks self-organize at rest. Building on this mechanistic foundation, LEiDA successfully identified reproducible differences in functional network occupancy among the distinct ASD subtype classifications. Beyond its demonstrated utility as a diagnostic tool, these findings reveal LEiDA’s ability to characterize the principles through which brain networks achieve their complex spatiotemporal organization. Through its publicly available MATLAB and Python implementations, LEiDA offers researchers a powerful framework for investigating the physical mechanisms that shape functional brain dynamics in both health and disease.

The authors have declared no competing interest.

This study was funded by La Caixa Foundation, Spain (LCF/BQ/PR22/11920014) and the Foundation for Science and Technology, Portugal (UIDB/50026/2020, UIDP/50026/2020).

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All fMRI data used in this study is from Autism Brain Imaging Data Exchange (ABIDE) released under the Preprocessed Connectomes Project (PCP) and available publicly at http://preprocessed-connectomes-project.org/abide/index.html.

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