Pupil-linked arousal reflects intracranial aperiodic neural activity in the human auditory cortex

Abstract Disrupted cortical and peripheral neural responses to salient stimuli occur in neural disease states, which may be rooted in pathophysiological neuromodulatory system dynamics. Although low-frequency oscillatory activity is the canonical measure of cortical neuromodulatory state, aperiodic 1/f slope encapsulates the balance between low-frequency and high-frequency activity and could thus provide a more sensitive electrophysiological measure. Here, we simultaneously record pupil diameter as a noninvasive measure of brain state, and intracranial local field potentials (LFP) in the auditory cortex and association regions in humans during an auditory oddball task. We demonstrate a trial-by-trial relationship between pupil and auditory cortical responses that is specific to the high gamma frequency band. We find that pupillary and cortical responses show a state-dependent relationship with aperiodic 1/f slope that is similar to canonical low-frequency measures, but that only the 1/f measure shows a trial-by-trial relationship with tonic and phasic pupil activity. Finally, salient stimuli trigger prolonged shifts in aperiodic 1/f activity after stimulus playback, which associates with altered responses on subsequent trials. Taken together, aperiodic slope captures tonic and phasic components of cortical state at the single trial level, providing mechanistic insight into human saliency responses and a path for pupillometry as a non-invasive readout.