Physiological Responses Evoked by Single-Pulse Transcranial Magnetic Stimulation: A Systematic Review of Corticospinal Excitability Measures

Single-pulse transcranial magnetic stimulation (spTMS) is widely used to investigate human corticospinal and cortical physiology, yet individual physiological measures provide only partial information about cortical function. This systematic review aimed to synthesize evidence on human physiological responses evoked by spTMS, with particular emphasis on resting and active motor thresholds, motor-evoked potentials (MEPs), corticospinal silent periods (CSPs), and biological and technical determinants of response variability. The review was conducted in accordance with PRISMA 2020 and searched PubMed, Scopus, Web of Science, and Google Scholar, supplemented by citation tracking. Evidence was synthesized qualitatively because of substantial heterogeneity in stimulation protocols, populations, recording methods, and outcomes. Across the included literature, no single measure fully characterized corticospinal excitability: motor thresholds primarily reflected membrane/axonal excitability, MEPs reflected integrated corticospinal output, and CSPs provided information on intracortical inhibitory processes. Age, sex-related anatomical and hormonal factors, cortical anatomy, coil position and orientation, pulse waveform, stimulation intensity, muscle state, attention, fatigue, sleep, and medication contributed to response variability. The findings support an integrated interpretation of spTMS measures, standardized protocols, and individualized electric field modeling. TMS-evoked EEG potentials (TEPs) methodology is discussed only as complementary contextual information; TEPs were not systematically targeted by the original search strategy and were therefore not included among the outcomes of the systematic synthesis. The exact historical search date could not be reconstructed from the available documentation and is reported transparently as a limitation.