Characterizing the mechanisms that determine the strength of the subjectively perceived discomfort during transcranial magnetic stimulation

This study aimed to assess how facial muscle twitches, acoustic noise, and sensory nerve fiber co-stimulation contribute to the subjective discomfort caused by prefrontal transcranial magnetic stimulation (TMS). Twenty participants underwent two days of testing. Questionnaires were used to characterize the location and magnitude of TMS-induced pain, as well as perceived acoustic noise level. Electromyography (EMG) was used to assess facial muscle activations. On day one, participants received TMS bursts, applying stimulation parameters that are used in approved TMS protocols for treating major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). During the second experimental day, single TMS pulses were used to additionally obtain EMG peak activations at maximal stimulation intensity and input-output curves of facial muscles. Participants localized discomfort predominantly below the coil, with left dorsolateral prefrontal cortex stimulation causing more discomfort than medial prefrontal cortex stimulation. The strength of facial muscle activation did not significantly correlate with subjective discomfort, while perceived acoustic noise levels did. Reducing acoustic noise and optimizing pulse shape to minimize peripheral co-stimulation of sensory fibers might alleviate subjective discomfort. However, optimizing field distribution to minimize facial muscle co-activation appears less pertinent. Our results can help to reduce discomfort in future TMS applications.