Pupil-based states of brain integration across cognitive states

Abstract

Arousal is a potent mechanism that provides the brain with functional flexibility and adaptability to external conditions. Within the wake state, arousal levels driven by activity in the neuromodulatory systems are related to specific signatures of neural activation and brain synchrony. However, direct evidence is still lacking on the varying effects of arousal on macroscopic brain characteristics and across a variety of cognitive states in humans. Using a concurrent fMRI-pupillometry approach, we used pupil size as a proxy for arousal and obtained patterns of brain integration associated with increasing arousal levels. We carried out this analysis on resting-state data and data from two attentional tasks implicating different cognitive processes. We found that an increasing level of arousal was related to a non-linear pattern of brain integration, with increasing brain integration from intermediate to larger arousal levels. This effect was prominent in the salience network in all tasks, while other regions showed task-specificity. Furthermore, task performance was also related to arousal level, with accuracy being highest at intermediate levels of arousal across tasks. Taken together, our study provides evidence in humans for pupil size as an index of brain network state, and supports the role of arousal as a switch that drives brain coordination in specific brain regions according to the cognitive state.

Mapping the bioimaging marker of Alzheimer’s disease based on pupillary light response-driven brain-wide fMRI in awake mice

“…Combining whole-brain fMRI with real-time pupillometry provides a non-invasive mapping scheme to identify pupil-fMRI relationships across different species. Existing human fMRI studies with pupillometry have revealed pupil dynamic changes associated with the activation of subcortical brain nuclei along the ascending arousal network, as well as the salience network including the cingulate cortex and insula 32,[41][42][43][44][45][46][47][48][49] . Interestingly, opposite arousal correlation features between eye movements and resting-state fMRI have been revealed between the cortex and subcortical nuclei in both non-human primates and rodent brains [50][51][52] .…”

Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation

“…Resting state fMRI (rs-fMRI) studies have uncovered global pupil-fMRI correlation patterns in human brains as well as revealed that the pupil dynamics-fMRI relationship changed under different lighting conditions or when subjects engaged in mental imagery (22,26). The dynamic functional connectivity changes detected by fMRI, possibly modulated by the interplay of cholinergic and noradrenergic systems (41), are also reflected by pupil dynamics both at rest (42) and in task conditions (43). Furthermore, rs-fMRI has been used to display a differential correlation pattern with brainstem noradrenergic nuclei, e.g., A5 cell group, depending on the cortical crossfrequency coupling state in the animal model (23).…”