Debunking the Myth of Excitatory and Inhibitory Repetitive Transcranial Magnetic Stimulation in Cognitive Neuroscience Research.

Repetitive TMS (rTMS) is a powerful neuroscientific tool with the potential to noninvasively identify brain-behavior relationships in humans. Early work suggested that certain rTMS protocols (e.g., continuous theta-burst stimulation, intermittent theta-burst stimulation, high-frequency rTMS, low-frequency rTMS) predictably alter the probability that cortical neurons will fire action potentials (i.e., change cortical excitability). However, despite significant methodological, conceptual, and technical advances in rTMS research over the past few decades, overgeneralization of early rTMS findings has led to a stubbornly persistent assumption that rTMS protocols by their nature induce behavioral and/or physiological inhibition or facilitation, even when they are applied to nonmotor cortical sites or under untested circumstances. In this Perspectives article, we offer a "public service announcement" that summarizes problems with these assumptions, highlighting limitations of seminal studies that inspired them and results of contemporary studies that violate them. Next, we discuss problems associated with holding these assumptions, including making brain-behavior inferences without confirming the locality and directionality of neurophysiological changes. Then, we emphasize results of recent studies showing that the effects of rTMS on neurophysiological metrics and their associated behaviors can be caused by mechanisms other than binary changes in excitability of the stimulated brain region or network. Finally, we provide recommendations for researchers to eliminate the misguided assumption that specific rTMS protocols are inherently excitatory or inhibitory when designing and interpreting their own work. Collectively, we contend that no rTMS protocol is by its nature either excitatory or inhibitory, and that researchers must use caution with these terms when forming experimental hypotheses and testing brain-behavior relationships.