Transcranial magnetic stimulation induced pupil dilations can serve as a cortical excitability measure

The application of non-invasive brain stimulation (NIBS) often relies on proxy estimates of cortical excitability (CE), such as the resting motor threshold (rMT), measured through transcranial magnetic stimulation (TMS). However, estimating the rMT is not always possible, as it requires an intact corticospinal pathway for neural signals to travel from the cortex to the periphery. To broaden the application of NIBS there is a need for additional CE measures. In three experiments combining TMS, transcranial direct current stimulation (tDCS), and eye-tracking, we measured TMS-induced pupil dilations as a potential CE proxy. We present Bayesian evidence (Experiment 1: BF > 9; Experiment 2: BF > 46; Experiment 3: BFs > 6) that TMS-induced pupil dilations serve as an objective CE proxy, with larger pupil size reflecting higher CE. We also show that these effects are not due to auditory, muscle, or sensory confounds. The introduction of this novel measure paves the way for a deeper understanding of CE by enabling objective NIBS measures beyond the motor cortex. Moving away from the reliance on the motor cortex would allow NIBS research and therapy to become more inclusive, allowing access to populations that are affected by damage along the corticospinal pathway.