AROUSAL FLUCTUATIONS MODULATE CORTICAL-SUBCORTICAL DYNAMICS IN THE HUMAN BRAIN

Compared to purely cortical processes, subcortical-cortical interactions remain relatively understudied. Recent work (Nazzi et al., 2025) showed that infraslow functional connectivity changes are synchronized in the cortex and the subcortex, with two ‘clusters’ of subcortical regions (comprising, respectively, hippocampus/amygdala and thalamus/basal ganglia) displaying synchronized changes in their connectivity pattern with cortical regions. We hypothesized that this coordinated cortical-subcortical dynamics might be related to fluctuations in arousal. Arousal, driven by ascending neuromodulatory projections that broadly innervate both the cortex and subcortical structures, exhibits periodic fluctuations on the order of seconds that are mirrored in pupil diameter and EEG vigilance indices. Simultaneous fMRI-pupillometry and fMRI-EEG studies have demonstrated that these arousal shifts significantly modulate the BOLD signal (Wong et al., 2013), driving global, low-dimensional fluctuations in brain dynamics. However, their impact on subcortical regions and cortico-cortical interaction remains relatively unexplored. Specifically, it is unclear whether the recently identified dichotomy in subcortical connectivity reflects a differential sensitivity, or different responses to arousal. To address this gap, we leveraged high-resolution 7T fMRI and simultaneous eye-tracking data from the Human Connectome Project to test these hypotheses.