Pupil self-regulation modulates markers of cortical excitability and cortical arousal

The brains arousal state (i.e., central arousal) is regulated by multiple neuromodulatory nuclei in the brainstem and significantly influences high-level cognitive processes. By exploiting the mechanistic connection between the locus coeruleus (LC), a key regulator of central arousal, and pupil dynamics, we recently demonstrated that participants can gain volitional control over arousal-regulating centers including the LC using a pupil-based biofeedback approach. Here, we test whether pupil-based biofeedback modulates electrophysiological markers of cortical excitability, cortical arousal, and phasic LC activity. Combining pupil-based biofeedback with single-pulse TMS, EEG recordings, and an auditory oddball task revealed three main results: pupil self-regulation significantly modulates (i) cortical excitability, (ii) the EEG spectral slope, a marker of cortical arousal, and (iii) the P300 response to target tones, an event-related potential suggested to be tightly linked to phasic LC activity. Interestingly, pupil self-regulation strength was linearly linked to the modulation of the spectral slope, suggesting a common physiological mechanism. Here, we have shown that pupil-based biofeedback modulates fundamental aspects of brain function. Whether this method could further be used to modulate these aspects in case of disturbances associated with neurological and psychiatric disorders needs to be investigated in future studies.