Recent Progress and Emerging Perspectives on How Technical Parameters of Transcranial Magnetic Stimulation Shape Cortical Measures Derived from Concurrent Electroencephalography

Objectives. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) offers a unique opportunity to probe cortical dynamics by capturing transcranial magnetic stimulation (TMS)-evoked potentials (TEPs). Although TEPs are increasingly used as biomarkers of cortical function, their physiological interpretation is complicated by substantial methodologic variability across studies. Among the critical factors that influence TEPs is the often arbitrary choice of technical parameters for TMS administration, such as pulse waveform, width, or coil orientation, which determine the direction of the induced current in the brain, with essential implications for both basic and clinical research. Materials and Methods. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review that collated evidence from studies manipulating TMS pulse waveform, pulse width, or current direction in healthy participants and explored the effects of these methodologic modulations on TEPs. Our search on Scopus, Web of Science, and MEDLINE databases identified 9 TMS-EEG studies that systematically evaluated the impact of these parameters on cortical measures recorded concurrently with EEG. Results. Across the available literature, the direction of the TMS-induced current exerts the most decisive influence on TEPs, particularly for early components (< 50 milliseconds), supporting the selective activation of distinct circuits and networks when different coil orientations are used to target the same brain site. The pulse waveform further modulated these direction-specific effects, with monophasic pulses exhibiting greater specificity in activation patterns than biphasic ones. Even if this investigation was primarily conducted within the motor system, similar parameter-dependent changes were also observed when premotor and associative regions were stimulated, affecting TEP morphology, oscillatory activity, and functional connectivity. Conclusions. Findings from these studies underscore the critical role of TMS technical parameters in shaping cortical responses, highlighting the need to carefully consider these variables to optimize neurostimulation/modulation protocols targeting specific cortical networks or pathways and more broadly to improve the reproducibility of TMS aftereffects.