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bioRxiv · 10.64898/2025.12.18.694946

Physiological Arousal as a Predominant Source of Individual Differences in Functional Brain Networks

Hill, J. A.·Zhai, T.·Korponay, C.·Welsh, J.·Salmeron, B. J.·Ross, T. J.·Yang, Y.·Frederick, B.·Janes, A.
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Abstract

Individual differences in brain network function and organization are promising targets for fMRI-based biomarkers in precision psychiatry, yet the sources of individual variability remain poorly understood. We show that arousal, assessed by systemic low-frequency oscillation (sLFO) amplitude in the fMRI signal, accounts for a substantial portion of variance in brain network properties (e.g.: R= 0.70 for default mode network (DMN)-dorsal attention connectivity; R= -0.63 for DMN dynamics). These relationships replicated across sessions, across independent samples, and when assessed with traditional arousal indices. Critically, associations persisted after sLFO denoising, indicating a genuine brain-physiology relationship rather than hemodynamic artifact. Pharmacological manipulation showed that drug-induced sLFO-assessed arousal changes were accompanied by corresponding shifts in network connectivity and dynamics. This work identifies arousal as a prominent determinant of variability in functional brain networks, providing a new perspective on brain-based individual differences while offering an approach to measure arousal directly from fMRI data.

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Hill, J. A., Zhai, T., Korponay, C., Welsh, J., Salmeron, B. J., Ross, T. J., Yang, Y., Frederick, B., Janes, A.. 2025-12-22. Physiological Arousal as a Predominant Source of Individual Differences in Functional Brain Networks. https://doi.org/10.64898/2025.12.18.694946

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