A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience

Abstract

Transcranial magnetic stimulation (TMS) has developed into a powerful tool for studying human brain physiology and brain-behavior relations. When applied in sessions of repeated stimulation, TMS can lead to changes in neuronal activity/excitability that outlast the stimulation itself. Such aftereffects are at the heart of the offline TMS protocols in cognitive neuroscience and neurotherapeutics. However, whether these aftereffects are of applied interest critically depends on their magnitude and duration, which should fall within an experimentally or clinically useful range without increasing risks and adverse effects. In this short review, we survey combined TMS-EEG studies to characterize the TMS-aftereffects as revealed by EEG to contribute to the characterization of the most effective and promising repetitive TMS-parameters. With one session of conventional repetitive TMS (of fixed pulse frequency), aftereffects were consistently comparable in magnitude to EEG-changes reported after learning or with fatigue, and were short-lived (<70 min). The few studies using recently developed protocols (such as theta burst stimulation) suggest comparable effect-size but longer effect-durations. Based on the reviewed data, it is expected that TMS-efficacy can be further promoted by repeating TMS-sessions, by using EEG-gated TMS to tailor TMS to current neuronal state, or by other, non-conventional TMS-protocols. Newly emerging developments in offline TMS research for cognitive neuroscience and neurotherapeutics are outlined.

Figures

Fig. 1

Quantification of TMS-aftereffects in EEG/EPs. a Distribution of protocols. b Aftereffect-direction per study with TMS-effects. Each bar represents one experiment/study. A negative sign (−1) indexes the presence of a suppressive effect on post-TMS relative to pre-TMS or sham EEG/EPs, while a positive sign (+1) indexes facilitative effects. c Aftereffect-size (percent change in amplitude relative to pre-TMS or sham) per study reporting effect-size or from which effect-size could be calculated a posteriori (n = 37). Data are grouped according to TMS protocols (conventional TMS, TBS, PAS) and ordered according to increasing number of applied pulses (see brackets) within 5 subgroups of rTMS (0.2–0.6 Hz, 0.9–1 Hz, 5–20 Hz, TBS, PAS). d Duration of aftereffects across studies having recorded effects until recovery (n = 17, uniformly colored bars) or having reported timing information but terminated EEG recordings before its normalization (n = 21, fading color bars)

Fig. 2

Linear correlations between aftereffect-size [%] and rTMS-parameters. a Aftereffect-size as a function of total number of TMS pulses applied in high-frequency protocols (5–20 Hz rTMS). Regression lines and 95% confidence intervals are shown for analyses including all data points (black lines) and excluding outliers (grey lines, outliers marked by crosses, see also text). b Aftereffect-size as a function of TMS intensity applied in low-frequency protocols (0.9–1 Hz)