Fig 1.
The experiment included three recording time points: before cTBS (T0), immediately after cTBS (T1) and 20 minutes after cTBS (T2). Each recording was completed within 20 minutes and included four blocks of stimulation. In two of the four blocks, TMS was delivered to the hand area of the left or right M1 in order to record (1) MEPs from the first dorsal interosseous muscle (FDI) of the contralateral hand and (2) TEPs. In the other two blocks, transcutaneous electrical stimuli were delivered to the left or right median nerve at the level of the wrist in order to record (3) early-latency SEPs. The order of the blocks was identical in T0, T1 and T2 for each experiment.
Fig 2.
Group-level effects of cTBS on the magnitude of MEPs.
(A) cTBS was delivered over M1, using biphasic pulses with an AP-PA or PA-AP current direction. The resting motor threshold (RMT) was significantly lower for TMS pulses delivered in the AP-PA as compared to the PA-AP direction (p<10−5; paired-sample t- test). The latency and amplitude of the MEPs elicited at baseline by AP-PA vs. PA-AP pulses delivered using an intensity of 120% the RMT were not significantly different. (B) Following cTBS delivered in the AP-PA current direction, the magnitude of MEPs elicited by stimulation of the ipsilateral and contralateral M1 tended to increase at both time points (T1 and T2). However, this effect was highly variable across individuals. (C) Similarly, following cTBS delivered in the PA-AP direction, the magnitude of MEPs elicited by stimulation of the ipsilateral and contralateral hemisphere tended to decrease in most participants. However, this effect was also highly variable across individuals. On average, there was no significant group-level effect of cTBS on MEP magnitude.
Table 1.
Effect of cTBS on the magnitude of MEPs, TEPs and SEPs recorded from the ipsilateral and contralateral hemisphere (3-way ANOVA with the factors time [T0, T1, T2], current direction [AP-PA, PA-AP] and hemisphere [ipsilateral or contralateral relative to the hemisphere onto which cTBS was applied]).
Fig 3.
TEPs elicited by TMS delivered over M1 at T0.
(A) Group-level average waveforms of the TEPs recorded before applying cTBS, and elicited by TMS pulses delivered in the AP-PA and PA-AP current direction. The grey areas represent the standard-deviation across individuals. Five peaks were consistently identified: P30, N40, P60, N100 and P190. (B) Group-level average magnitude (±standard deviation) and scalp topography of the P30, N40, P60, N100 and P190 elicited by TMS pulses delivered in the AP-PA and PA-AP directions.
Fig 4.
Group-level average TEP waveforms recorded before (T0) and after (T1, T2) cTBS.
On average, the magnitude of the N100 wave was decreased at both T1 and T2, regardless of the TMS current direction (AP-PA vs. PA-AP) and regardless of whether cTBS was delivered over the ipsilateral or contralateral hemisphere. A point-by-point repeated measures ANOVA with the factors ‘time’ (T0, T1, T2), ‘hemisphere’ (cTBS delibered to the ipsilateral or contralateral hemisphere) and ‘current direction’ was used to assess the effect of cTBS on the entire TEP waveform. The scalp maps show the topographical distribution of the N100 at the different times points and in the different conditions. The bar graphs show the change in N100 magnitude after cTBS (group-level average ± standard deviation). Significant changes are marked by an asterisk (p < .05; t-test against zero).
Fig 5.
SEPs elicited by stimulation of the median nerve at T0.
(a) Group-level average waveforms of the SEPs recorded before applying cTBS. The shaded areas represent the standard-deviation across individuals. Seven peaks were consistently identified at the central electrode contralateral to the stimulated hand (C3/C4): P15, N20, P27, N30, P45, N60 and P100. (b) Group-level average scalp topographies of the N20, P27, N30, P45, N60 and P100 peaks, averaged across conditions.
Fig 6.
Group-level average SEP waveforms recorded before (T0) and after (T1, T2) cTBS.
SEPs recorded from the ipsilateral/contralateral hemisphere were elicited by stimulation of the contralateral/ipsilateral hand, relative to the hemisphere onto which cTBS was applied. A point-by-point repeated measures ANOVA with the factors ‘time’ (T0, T1, T2), ‘hemisphere’ (cTBS delibered to the ipsilateral or contralateral hemisphere) and ‘current direction’ was used to assess the effect of cTBS on the entire SEP waveform. The time intervals showing a significant 3-way interaction between the three factors are shown in green. This included the N20 wave, as well as a longer-lasting period encompassing the late P100 wave. The bar graphs represent the change in magnitude of the N20 wave as well as the late P100 (99.5 ms) (group-level average ± standard deviation). Significant changes are marked by an asterisk (p < .05; t-test against zero). The scalp maps show the topographical distribution of the N20 and later P100 at the different times points and in the different conditions.
Fig 7.
Relationship between MEP latency at T0 and the after-effect of cTBS on the magnitude of MEPs, TEPs and SEPs ipsilateral and contralateral hemisphere relative to the hemisphere onto which cTBS was applied.
(TMS delivered using an AP-PA current direction). (A) At the ipsilateral hemisphere, there was a significant negative correlation between MEP latency at T0 and change in MEP amplitude. Also note, at the contralateral hemisphere, the significant positive correlation between MEP latency and MEP amplitude, as well as (B) TEP N100 amplitude. (C) Finally, note the inverse correlation between MEP latency and the magnitude of the SEP waveform recorded from the ipsilateral and contralateral hemisphere, extending between approximately 50–130 ms, both at T1 and at T2. The grey areas mark the time intervals during which the correlation coefficients obtained at the ipsilateral and contralateral hemisphere were significantly different (p<0.05). (D) At 103.5 ms, the negative correlation between MEP latency at T0 and change in SEP amplitude arrives maximum.
Table 2.
Correlation between MEP latency at T0 and the after-effect of cTBS delivered using an AP-PA or PA-AP current direction on the magnitude of MEPs, TEPs (N100), and SEPs (at 103.5ms) recorded from the ipsilateral or contralateral hemisphere relative to the hemisphere onto which cTBS was applied.
Fig 8.
Relationship between the latency of MEPs obtained at different time points and in different experiments.
(A) Relationship between MEP latencies recorded at T0 and MEP latencies recorded at T1, following stimulation of the ipsilateral and contralateral hemisphere. (B) Relationship between MEP latencies elicited by stimulation of the left and right M1. C. Relationship between MEP latencies recorded at T0 in each of the two experiments, separated by 14–91 days. Left graphs, TMS delivered using an AP-PA current direction. Right graphs: TMS delivered using a PA-AP current direction.