Discussion
TBS-induced, ’s active motor threshold
CONTRACTION
In this study we assessed the reliability of TBS-induced neuromodulation of resting-state EEG power using a test–retest design with six stimulation sessions (3 protocols with 2 visits for each protocol) for every subject. We explored the effects of cTBS, iTBS, and sham TBS protocols on modulation of spectral EEG power employing a ROI-specific hypothesis-driven analysis in alpha and beta bands, as well as whole-brain data-driven exploratory analyses across a wide range of frequencies (1–50 Hz) and all cap electrodes. We explored the reliability of TBS-induced spectral power modulation at the group level and individual subject level. We also explored whether rsEEG power and MEP amplitudes are co-modulated by TBS.We found that none of the TBS protocols produced significant group-level effects on ROI-derived rsEEG power. Exploratory whole-brain analysis revealed that cTBS in V2 significantly enhanced relative power in the beta and gamma bands across a broad cortical area; however, these effects were not present in V1. There were no other significant differences between EEG modulation by active and sham TBS protocols. While the reliability of baseline rsEEG power was high across 6 stimulation sessions within individuals, the reliability of TBS-induced neuromodulatory effects was generally low-to-moderate, with substantial inter- and intra-individual variability.Our group has been systematically investigating the reliability of TBS-induced neuromodulation. This work is a continuation of two previous studiesThe results of the present study support conclusions made in our previous worksPrevious studies evaluating TBS modulation of corticospinalThe exact mechanisms underlying TBS effects remain poorly understood. There is evidence suggesting cortical origin of the TBS-induced plasticity and engagement of different physiological mechanisms depending on the type of TBS protocolWe note several limitations of the present study. We delivered TMS to an M1 target and therefore, our results cannot be extended to non-motor regions. The lack of reliable TBS effects on conventional outcome metrics of corticospinal excitability (MEPs) limits our interpretation of the rsEEG neuromodulatory effects. Another methodological limitation of this study is that we applied TBS as a percentage of each subject’s active motor threshold (AMT). This is the conventional approach, which enables direct comparison of our results with most of the previous studies. However, the individual stimulation dose was estimated for the excitability level corresponding to voluntary muscle contraction and differences in the relationship of AMT to RMT across subjects were not consideredCurrent experimental evidence suggests that improvement of our understanding of putative neurophysiological mechanisms underlying TBS neuromodulation is needed to achieve consistent TBS effects, which warrants future systematic and rigorous research. We suggest several potential areas for future studies. (1) Standardization of experimental design and TBS protocols is required to draw conclusions about group-level TBS-induced modulations, 2() EEG recordings may be useful for monitoring and adjustment of stimulation parameters to drive cortical TBS effects in the desired direction. (3) Personalizing TBS protocols by adjusting stimulation frequency to the individual peak frequency or region-specific intrinsic oscillations might enable engagement of the corresponding neural mechanisms. (4) Delivering TBS bursts during particular brain states with closed-loop stimulationIn summary, rsEEG is a noninvasive method to assess modulation of brain activity in response to TBS. This study for the first time systematically investigated effects of active iTBS and cTBS protocols on resting state EEG in the same group of participants and reports no reliable modulation of EEG spectral power using these protocols. We found no significant differences between active and sham TBS. ROI-based and whole-brain analyses did not reveal reproducible rsEEG power changes. Intra- and inter-subject reliability was low-to-moderate. To improve consistency of TBS effects, we suggest that future research should deepen understanding of neural mechanisms underlying TBS effects in different frequency bands and should include standardized methodological practices including appropriate sham control.