Neuromodulatory influences on propagation of traveling waves along the unimodal-transmodal gradient.

Understanding the factors underlying brain activity fluctuation is important to understand the flexible nature of the brain and cognition. Growing evidence indicates that functional magnetic resonance imaging (fMRI) activity travels as waves around global signal peaks following a unimodal-transmodal gradient. This may explain the organization of brain activity into functional networks, but why the strength of integration between networks fluctuates is uncertain. Given that arousal-related neuromodulatory systems affect network integration and that traveling waves are modulated by arousal, we aimed to assess the hypothesis that an increase in neuromodulatory tone can affect network integration by modulating the speed of propagation of traveling waves. We tested this hypothesis using pharmacological fMRI/pupil measurements during rest and tasks. Atomoxetine, which increases extracellular catecholamine levels, was associated with faster traveling waves, and faster traveling waves correlated with more network integration. We also examined temporal variations in pupil size, a signature of transient changes in neuromodulatory activity, and found that the periods of traveling waves were characterized by larger pupil size. Our results suggest that neuromodulatory tone affects traveling wave propagation, and that this arousal-modulated propagation shapes integrated functional connectivity features, highlighting specific effects of prolonged and transient neuromodulatory influences on slow brain dynamics.