Fig. 1.
Effect of iTBS-TDCS on normalised and absolute MEP amplitudes. A) Left, TMS coil orientations for measurements of PA75 and AP45 MEPs; Right, TDCS electrode montages. TDCS electrodes were positioned either side of the hotpot and presumed central sulcus. “A” and “C” represent the anode and cathode. TDCSPA refers to an anode-posterior/cathode-anterior montage, while TDCSAP refers cathode-posterior/anode-anterior. Sham was applied using the TDCSPA montage. (B) Timeline of the protocol. MEPs were recorded twice at baseline (B1 and B2) prior to iTBS-TDCS, and at 10 min intervals following iTBS-TDCS. For the iTBS-TDCSPA, iTBS-TDCSAP and iTBS-TDCSSHAM sessions PA75 MEPs were recorded in 20, 19 and 14 and AP45 MEPs were recorded in 15, 15 and 14 individuals due to some individuals having high TMS thresholds and not returning for the final test session. (C) Absolute PA75 and AP45 MEP amplitudes shown for the three iTBS-TDCS conditions. Paired-sample t-tests were computed on absolute MEP average amplitudes to assess each time point versus averaged baseline MEPs (Bonferroni adjusted significance level, p < 0.0125). iTBS-TDCSPA increased MEPs at all time-points, while a statistical trend was found for iTBS-TDCSSHAM at T30 (p = 0.016). *p < 0.0125, **p < 0.002. (D) Averaged PA75-AP45 MEP amplitudes, normalised to the average of B1 and B2, for the three different conditions. To further assess the time*condition interactions, post-hoc comparisons (Bonferroni adjusted significance level, p < 0.0167) revealed greater MEP amplitudes at T10, T20 and T30 for iTBS-tDCSPA, and a statistical trend at T30 iTBS-TDCSSHAM, in comparison with iTBS-tDCSAP. The grand-average of MEP change (T0-T30) for iTBS-tDCSPA (M = 1.39, N = 19) was significantly greater than iTBS-tDCSAP (M = 0.96, N = 14) (p = 0.001, Cohen's d = 1.33) and tended to be greater than for iTBS-tDCSSHAM (M = 1.20, N = 19) (p = 0.09, Cohen's d = 0.50). A similar trend was observed for iTBS-tDCSSHAM versus iTBS-tDCSAP (p = 0.05, Cohen's d = 0.82). *p < 0.05; + p < 0.017; ++ p < 0.01. (E) Response rates for each condition. Individual average SEM of 20 MEPs from each baseline was computed and averaged across all participants to compute a grand SEM average (±0.15). A significant response to stimulation was considered when it exceeded 95% confidence interval of the SEM (±0.29): opposite responders (OR), <0.71; non-responders (NR), 0.71 > < 1.29; expected responders (ER), >1.29. Compared to iTBS-TDCSSHAM, response rates increased 8% and rates of OR decreased from 21 to 0% for iTBS-TDCSPA. When the DC current was reversed in iTBS-TDCSAP, 79% of individuals were classified as NR and only 7% as ER. (F) Individual grand-average of normalised MEP amplitude (T0-T30). Grey zone represents non-response. Compared to iTBS-TDCSSHAM, 11 of 19 participants displayed an increase in MEP amplitudes following iTBS-TDCSPA. iTBS-TDCSAP was associated with a decrease in MEP amplitudes compared with iTBS-TDCSSHAM and iTBS-TDCSPA in 12 of 14 participants.