Spectral Fingerprints of Cortical Neuromodulation.

Pupil size has been established as a versatile marker of noradrenergic and cholinergic neuromodulation, which has profound effects on neuronal processing, cognition, and behavior. However, little is known about the cortical control and effects of pupil-linked neuromodulation. Here, we show that pupil dynamics are tightly coupled to temporally, spectrally, and spatially specific modulations of local and large-scale cortical population activity in the human brain. We quantified the dynamics of band-limited cortical population activity in resting human subjects using magnetoencephalography and investigated how neural dynamics were linked to simultaneously recorded pupil dynamics. Our results show that pupil-linked neuromodulation does not merely affect cortical population activity in a stereotypical fashion. Instead, we identified three frontal, precentral, and occipitoparietal networks, in which local population activity with distinct spectral profiles in the theta, beta, and alpha bands temporally preceded and followed changes in pupil size. Furthermore, we found that amplitude coupling at ∼16 Hz in a large-scale frontoparietal network predicted pupil dynamics. Our results unravel network-specific spectral fingerprints of cortical neuromodulation in the human brain that likely reflect both the causes and effects of neuromodulation. Brain function is constantly affected by modulatory neurotransmitters. Pupil size has been established as a versatile marker of noradrenergic and cholinergic neuromodulation. However, because the cortical correlates of pupil dynamics are largely unknown, fundamental questions remain unresolved. Which cortical networks control pupil-linked neuromodulation? Does neuromodulation affect cortical activity in a stereotypical or region-specific fashion? To address this, we quantified the dynamics of cortical population activity in human subjects using magnetoencephalography. We found that pupil dynamics are coupled to highly specific modulations of local and large-scale cortical activity in the human brain. We identified four cortical networks with distinct spectral profiles that temporally predicted and followed pupil size dynamics. These effects likely reflect both the cortical control and effect of neuromodulation.