Modulating cortical excitability and cortical arousal by pupil self-regulation

Marieke Lieve Weijs (), Silvia Missura, Weronika Potok-Szybińska, Marc Bächinger, Bianca Badii, Manuel Carro-Domínguez, Nicole Wenderoth () and Sarah Nadine Meissner
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Marieke Lieve Weijs: ETH Zurich
Silvia Missura: ETH Zurich
Weronika Potok-Szybińska: ETH Zurich
Marc Bächinger: ETH Zurich
Bianca Badii: ETH Zurich
Manuel Carro-Domínguez: ETH Zurich
Nicole Wenderoth: ETH Zurich
Sarah Nadine Meissner: ETH Zurich

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract The brain’s 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, a key regulator of central arousal, and pupil dynamics, we recently demonstrated that participants could gain volitional control over arousal-regulating centers including the locus coeruleus using a pupil-based biofeedback approach. Here, we test whether pupil-based biofeedback modulates electrophysiological markers of cortical excitability, cortical arousal, and P300 responses. Combining pupil-based biofeedback with single-pulse transcranial magnetic stimulation, electroencephalography, and an auditory oddball task reveals three main results: pupil self-regulation significantly modulates (i) cortical excitability, (ii) the electroencephalogram spectral slope, a marker of cortical arousal, and (iii) the P300 response to target tones, an event-related potential suggested to be linked to phasic locus coeruleus activity. Here, we show that pupil-based biofeedback modulates fundamental aspects of brain function. Whether this method can further be used to modulate these aspects in case of disturbances associated with neurological and psychiatric disorders needs to be investigated in future studies.

Date: 2025
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DOI: 10.1038/s41467-025-59837-5

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