Myths and Methodologies: How loud is the story told by the transcranial magnetic stimulation-evoked silent period?

Transcranial magnetic stimulation (TMS) of the motor cortex evokes a response in the muscle that can be recorded via electromyography (EMG). One component of this response, when elicited during a voluntary contraction, is a period of EMG silence, termed the silent period (SP), which follows a motor evoked potential (MEP). Modulation of SP duration was long thought to reflect the degree of intracortical inhibition. However, the evidence presented in this review suggests that both cortical and spinal mechanisms contribute to generation of the SP, which makes prefacing SP with 'cortical' misleading. Further investigations with multi-methodological approaches, such as TMS-EEG coupling or interaction of TMS with neuroactive drugs, are needed to make such inferences with greater confidence. A multitude of methodological factors can influence the SP and thus confound the interpretation of this measure; namely, background muscle activity, instructions given to the participant, stimulus intensity and the size of the MEP preceding the SP, and the approach to analysis. A systematic understanding of how the confounding factors influence the interpretation of SP is lacking, which makes standardization of the methodology difficult to conceptualize. Instead, the methodology should be guided through the lens of the research question and the population studied, ensuring greater reproducibility, repeatability and comparability of data sets. Recommendations are provided for the best practice within a given context of the experimental design.