Tardiff, Nathan; John D. Medaglia; Danielle S. Bassett and Sharon L. Thompson-Schill

There is growing interest in how neuromodulators shape brain networks. Recent neuroimaging studies provide evidence that brainstem arousal systems, such as the locus coeruleus-norepinephrine system (LC-NE), influence functional connectivity and brain network topology, suggesting they have a role in flexibly reconfiguring brain networks in order to adapt behavior and cognition to environmental demands. To date, however, the relationship between brainstem arousal systems and functional connectivity has not been assessed within the context of a task with an established relationship between arousal and behavior, with most prior studies relying on incidental variations in arousal or pharmacological manipulation and static brain networks constructed over long periods of time. These factors have likely contributed to a heterogeneity of effects across studies. To address these issues, we took advantage of the association between LC-NE-linked arousal and exploration to probe the relationships between exploratory choice, arousal -as measured indirectly via pupil diameter -and brain network dynamics. Exploration in a bandit task was associated with a shift toward fewer, more weakly connected modules that were more segregated in terms of connectivity and topology but more integrated with respect to the diversity of cognitive systems represented in each module. Functional connectivity strength decreased, and changes in connectivity were correlated with changes in pupil diameter, in line with the hypothesis that brainstem arousal systems influence the dynamic reorganization of brain networks. More broadly, we argue that carefully aligning dynamic network analyses with task designs can increase the temporal resolution at which behaviorally-and cognitively-relevant modulations can be identified, and offer these results as a proof of concept of this approach.