Variability and Predictors of Response to Continuous Theta Burst Stimulation: A TMS-EEG Study

Abstract

Continuous theta-burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation paradigm reported to decrease the excitability of the stimulated cortical area and which is thought to reflect a form of inhibitory synaptic plasticity. However, since its introduction, the effect of cTBS has shown a remarkable variability in its effects, which are often quantified by measuring the amplitude of motor evoked potentials (MEPs). Part of this inconsistency in experimental results might be due to an intrinsic variability of TMS effects caused by genetic or neurophysiologic factors. However, it is also possible that MEP only reflect the excitability of a sub-population of output neurons; resting EEG power and measures combining TMS and electroencephalography (TMS-EEG) might represent a more thorough reflection of cortical excitability. The aim of the present study was to verify the robustness of several predictors of cTBS response, such as I wave recruitment and baseline MEP amplitude, and to test cTBS after-effects on multiple neurophysiologic measurements such as MEP, resting EEG power, local mean field power (LMFP), TMS-related spectral perturbation (TRSP), and inter-trial phase clustering (ITPC). As a result, we were not able to confirm either the expected decrease of MEP amplitude after cTBS or the ability of I wave recruitment and MEP amplitude to predict the response to cTBS. Resting EEG power, LMFP, TRSP, and ITPC showed a more consistent trend toward a decrease after cTBS. Overall, our data suggest that the effect of cTBS on corticospinal excitability is variable and difficult to predict with common electrophysiologic markers, while its effect might be clearer when probed with combined TMS and EEG.

The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders

“…For example, a recent study found that the after-effects of cTBS on TMS-evoked EEG responses were more reproducible than the after-effects on TMS-evoked MEPs. 25 One possible reason for this is that the MEP measures the excitability of only a small population of neurones that excite the corticospinal neurones that supply the target muscle, whereas the TMS-evoked EEG response averages the activity of all neurones in a cortical area. 179 In such a case it is quite possible for high variability in the excitability of subpopulations of neurones to coexist with stable average levels of excitability overall.…”

“…Recent studies have shown that the interindividual variability of rTMS is considerable and that most plasticity protocols induce the “expected” effects only in 40% to 60% of participants . It has been proposed that the different response to rTMS might depend on the subset of cortical neurones preferentially recruited or on the excitability of the cortex at the time of the stimulation or may be the result of the outcome measure used to probe plasticity . A further layer of complexity could be added in patients, in which the variability of rTMS effects might be also the result of the different properties of the neural circuits being stimulated …”

“…13,14,17,22,23 It has been proposed that the different response to rTMS might depend on the subset of cortical neurones preferentially recruited 13 or on the excitability of the cortex at the time of the stimulation 24 or may be the result of the outcome measure used to probe plasticity. 25 A further layer of complexity could be added in patients, in which the variability of rTMS effects might be also the result of the different properties of the neural circuits being stimulated. 26 This reassessment of TMS methodology has been performed in studies on healthy individuals.…”

M1 disruption delays motor processes but not deliberation about action choices

“…The disruptive impact of cTBS on cortical activity varies between subjects (Do et al, 2018;Jannati et al, 2017;Rocchi et al, 2018). Here, we aimed at only including individuals in which cTBS effectively disrupted M1.…”

Short interval intracortical inhibition as measured by TMS-EEG

“…Local motor cortical excitability was measured by averaging the TEP waveform in a cluster of four electrodes around the site of stimulation (C1, C3, CP1, CP3). This was performed for each condition and the amplitude of characteristic motor TEP peaks (N15, P30, N45, P60, N100 and P180) was calculated (5,(16)(17)(18)(19)(20)(21).…”