Reliability of resting-state EEG modulation by continuous and intermittent theta burst stimulation of the primary motor cortex: A sham-controlled study

Abstract

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation designed to induce changes of cortical excitability that outlast the period of TBS application. In this study, we explored the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) versus sham TBS stimulation, applied to the primary motor cortex, on modulation of resting state electroencephalography (rsEEG) power. We first conducted hypothesis-driven region-of-interest (ROI) analyses examining changes in alpha (8-12 Hz) and beta (13-21 Hz) bands over the left and right motor cortex. Additionally, we performed data-driven whole-brain analyses across a wide range of frequencies (1-50 Hz) and all electrodes. Finally, we assessed the reliability of TBS effects across two sessions approximately 1 month apart. None of the protocols produced significant group-level effects in the ROI. Whole-brain analysis revealed that cTBS significantly enhanced relative power between 19-43 Hz over multiple sites in both hemispheres. However, these results were not reliable across visits. There were no significant differences between EEG modulation by active and sham TBS protocols. Between-visit reliability of TBS-induced neuromodulatory effects was generally low-to-moderate. We discuss confounding factors and potential approaches for improving the reliability of TBS-induced rsEEG modulation.

Figure 1.

Neuromodulatory effects of cTBS, iTBS and sham TBS on relative power in the initial visit (V1) in ROI Left. a) Group power spectrum (averages across all participants) at 1–50 Hz frequency band for each stimulation protocol in pre-TBS, black line – group mean, grey shaded area – 95% confidence intervals, b) log-transformed ratios post-TBS/pre-TBS in alpha and beta 1 bands for each protocol and post-TBS time point. Black triangles – mean group values for T0, T15 and T25 post-TBS time points, grey round markers – corresponding individual subject values.

Figure 2.

Neuromodulatory effects of cTBS across all electrodes and frequency bands. a) t values associated with whole-brain analysis of relative power using paired t tests comparing T15 and pre-TBS in the retest V2 cTBS visit across 1–50 Hz frequency band (x-axis) and electrodes (y-axis). The color scale is applied only to t-values surviving cluster-based multiple comparisons correction (shown in shades of red), all nonsignificant values are masked in green; b) topographic representation of the t values averaged across the significant frequencies (19–43 Hz) and electrodes (black dots).

Figure 3.

Test-retest reliability of TBS-induced modulation of rsEEG relative power in ROI Left; a) mean post-TBS/pre-TBS ratios at T0, T15 and T25 in V1 and V2 visits in alpha and beta 1 frequency bands. b) Cronbach’s alpha coefficients of consistency between V1 and V2. Spectral power in different frequency bands is shown in different colors: alpha – black, beta 1 – red; error bars - standard error of the mean.

Figure 4.

Types of TBS-induced changes of relative EEG power in ROI Left; a) numerical proportions of types in the initial (V1) and retest (V2) visits in alpha and beta 1 bands expressed as percentage; b) conversion plots show types of change in each participant in V1 and V2. Different types of change are given in different colors: magenta - increase of relative power in post-TBS in comparison to pre-TBS, blue – decrease of power, green - mixed change including increase and decrease at different post-TBS time points, grey - no change, white – missing data.

Figure 5.

Relationships between modulation of EEG spectral power in beta 1 band and subsequent changes of corticospinal excitability. Scatter plots depicting relationship between normalized log-transformed relative power (post-TBS/pre-TBS ratios) and normalized MEP amplitudes (post-TBS/pre-TBS ratios) in iTBS V1 (EEG at T15 post-TBS and MEP at T20 post-TBS), sham TBS V1 (EEG at T0 post-TBS and MEP at T5 post-TBS), sham TBS V2 (same as in sham V1), dots – individual data points, lines denote linear fit, r - Pearson’s r coefficients.