Reliability of transcranial magnetic stimulation evoked potentials to detect the effects of theta-burst stimulation of the prefrontal cortex

Abstract

Background: Transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) is a novel method for assessing cortical properties outside the motor region. Theta burst stimulation (TBS), a form of repetitive TMS, can non-invasively modulate cortical excitability and has been increasingly used to treat psychiatric disorders by targetting the dorsolateral prefrontal cortex (DLPFC). The TMS-evoked potentials (TEPs) and local mean field power (LMFP) analyses have been used to evaluate local cortical excitability changes after TBS. However, it remains unclear whether TEPs can detect the neuromodulatory effects of TBS.

Objectives: To confirm the reliability of TEP components and LMFP within and between sessions and to measure changes in neural excitability induced by intermittent (iTBS) and continuous TBS (cTBS) applied to the left DLPFC.

Methods: Test-retest reliability of TEPs/LMFP and TBS-induced changes in cortical excitability were assessed in twenty-four healthy participants by stimulating the DLPFC in five separate sessions, once with sham and twice with iTBS and cTBS. EEG responses were recorded of 100 single TMS pulses before and after TBS, and the reproducibility measures were quantified with the concordance correlation coefficient (CCC).

Results: The N100 and P200 components presented substantial reliability within the baseline block (CCCs>0.8) and moderate concordance between sessions (CCC_max> 0.6). Both N40 and P60 TEP amplitudes showed little concordance between sessions. Similar results were achieved using LMFP responses. Changes in TEP amplitudes after iTBS were marginally reliable for N100 (CCC_max = 0.52), P200 (CCC_max = 0.47) and P60 (CCC_max = 0.40), presenting only fair levels of concordance at specific time points. LMFP changes showed poor reproducibility after iTBS and cTBS.

Conclusions: The present findings show that only the N100 and P200 components had good concordance between sessions. The reliability of earlier TEP components and LMF responses may have been affected by a sub-optimal removal of TMS-related artefacts. The poor reliability in detecting changes in neural excitability induced by TBS indicates that TEPs/LMFP do not provide a precise estimate of the changes in excitability in the DLPFC or, alternatively, that TBS did not induce consistent changes in neural excitability.

Keywords: Dorsolateral prefrontal cortex; Electroencephalography; Test-retest reliability; Theta burst stimulation; Transcranial magnetic stimulation-evoked potentials.

Fig. 1

TMS-evoked potential and LMFP following single-pulse stimulation over the left dorsolateral prefrontal cortex pre-TBS. TEPs were combined across all experimental sessions. The grey box indicates removed data points due to TMS-related artefacts and cleaning steps. (A) Butterfly plot from all electrodes with major peaks (N40, P60, N100, P200) indicated in the text. The red lines indicate the waveform obtained from the mean of four electrodes (F3, FC3, F1, FC1) around the stimulation site. (B) Local mean field power pre-TBS in the DLPFC averaged across all experimental sessions. Dotted lines represent the boundaries of the three time windows of interest: 30–60 ms (“early”), 60–125 ms (“mid”) and 125–265 ms (“late”). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Concordance of TMS-evoked potentials within and between the baseline blocks. A) Concordance correlation coefficient between odds and even trials of baseline block. B) Concordance correlation coefficient between the first and second half of the baseline block. C) Concordance correlation coefficient between the baseline block across five separate sessions. Shaded regions in grey show the 95% CI of the null distribution. The three lines show the different latency strategies used for amplitude extraction, and the x-axis shows the number of trials used for estimating the CCC. Horizontal lines at 0.4, 0.6 and 0.8 are the lower limits for the fair, moderate and substantial reliability categories, respectively.

Fig. 3

Neuromodulatory effects induced by iTBS on the N100 component. Concordance correlation coefficients (CCC) of the amount of neuromodulatory effects induced by iTBS between each post-iTBS block minus pre-across trial numbers and latency strategies used for amplitude extraction.

Fig. 4

The concordance correlation coefficient for each component using TEP amplitudes extracted based on the block latencies and LMFP. A) CCC is plotted for the three levels of comparisons: within the baseline block (odd vs even and half 1 vs half 2) and between the baseline block across five separate sessions. B) LMFP CCC for the three levels of comparisons. All CCC values shown in the figure are calculated for 35 trials except the 4th value for the between sessions' CCC, which is also presented for 70 trials. Horizontal lines at 0.1, 0.4, 0.6 and 0.8 are the lower limits for the slight, fair, moderate, and substantial reliability categories, respectively. Each TEP component and LMFP time window is colour coded according to the legend inside the figures. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)