The Pupil‐Brain System at Rest: Spontaneous Pupil Fluctuations as Markers of Neuromodulatory and Network Dynamics

Summary

Spontaneous pupil fluctuations during rest offer a non-invasive, low-cost index of central arousal dynamics. This review synthesizes evidence on the resting-state pupil-brain system, focusing on central neuromodulatory circuits and large-scale cortical networks. It examines the relationship between pupil fluctuations and the ascending arousal system, including noradrenergic, cholinergic, serotonergic, and dopaminergic nuclei, and details coupling with intrinsic functional networks—default mode, salience, and sensorimotor systems. Converging evidence from animal and human neuroimaging studies reveals robust spatiotemporal and spectral coupling between pupil fluctuations and neural activity across micro- and macro-scales. The findings support a systems-level framework where pupil fluctuations serve as integrative markers linking subcortical neuromodulation with large-scale cortical dynamics, with potential utility as biomarkers for neuropsychiatric conditions and altered states of consciousness.

Study at a glance

Abstract

Spontaneous pupil fluctuations (SPFs) during rest provide a non-invasive, low-cost index of central arousal dynamics, independent of cognitive task demands. These features position SPFs as promising markers for baseline neurophysiological activity in both basic and translational research. This review synthesizes current evidence on the resting-state pupil-brain system, focusing on its core components: central neuromodulatory circuits and large-scale cortical networks. We first examine the relationship between SPFs and distributed elements of the ascending arousal system, including noradrenergic, cholinergic, serotonergic, and dopaminergic nuclei. We then detail SPF coupling with intrinsic functional networks-default mode, salience, and sensorimotor systems-highlighting their role in mediating transitions between internally- and externally-oriented brain states. Finally, we discuss the spectral and directional properties of pupil-brain interactions, emphasizing analytical approaches suited for assessing directionality and outlining implications for clinical and translational applications. Converging evidence from animal and human neuroimaging studies reveals robust spatiotemporal and spectral coupling between SPFs and neural activity across micro- and macro-scales. These findings support a systems-level framework in which SPFs serve as integrative markers linking subcortical neuromodulation with large-scale cortical dynamics. We conclude that SPFs offer a sensitive window into arousal regulation and body-brain integration, with potential utility as biomarkers for neuropsychiatric conditions and altered states of consciousness.

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