No effect of anodal tDCS on motor cortical excitability and no evidence for responders in a large double-blind placebo-controlled trial

Abstract

Background: Transcranial direct current stimulation (tDCS) has emerged as a non-invasive brain stimulation technique. Most studies show that anodal tDCS increases cortical excitability. However, this effect has been found to be highly variable. Objective: To test the effect of anodal tDCS on cortical excitability and the interaction effect of two participant-specific factors that may explain individual differences in sensitivity to anodal tDCS: the Brain Derived Neurotrophic Factor Val66Met polymorphism (BDNF genotype) and the latency difference between anterior-posterior and lateromedial TMS pulses (APLM latency). Methods: In 62 healthy participants, cortical excitability over the left motor cortex was measured before and after anodal tDCS at 2 mA for 20 min in a pre-registered, double-blind, randomized, placebocontrolled trial with repeated measures. Results: We did not find a main effect of anodal tDCS, nor an interaction effect of the participant-specific predictors. Moreover, further analyses did not provide evidence for the existence of responders and nonresponders. Conclusion:This study indicates that anodal tDCS at 2 mA for 20 min may not reliably affect cortical excitability.

Multimodal Assessment of Precentral Anodal TDCS: Individual Rise in Supplementary Motor Activity Scales With Increase in Corticospinal Excitability

“…Even though TDCS induced MEP changes have been replicated various times (for review Nitsche and Paulus, 2011), many recent reports, including a large doubleblind, placebo-controlled trial, did not show significant effects of anodal TDCS on corticospinal excitability. These recent studies consistently found that the individual change in MEP amplitude was highly variable (Horvath et al, 2014;Lopez-Alonso et al, 2014;Wiethoff et al, 2014;Chew et al, 2015;Strube et al, 2016;Ammann et al, 2017;Lefebvre et al, 2019;Jonker et al, 2020). The number of participants displaying the "classical" anodal TDCS-induced increase ranging only between 30 and 50%, while the other participants showed no or the opposite effect (Lopez-Alonso et al, 2014;Wiethoff et al, 2014).…”

“…MEP measurements are strongly dependent on the investigator holding the coil, even if neuro-navigation and other standard methods are applied. Knowledge about the session type might lead the experimenter to unconsciously influence study outcome and thereby artificially increasing the effect size and studies with a similarly rigorous design have also not shown effects of anodal TDCS on corticospinal excitability, even at significantly higher stimulation intensities (2 mA) (Jonker et al, 2020). A limitation of this study was that mean MEP amplitudes at pre-TDCS baseline were not matched between the real and sham TDCS conditions.…”

“…The method to assess the difference in AP-LM MEP latency may also be relevant. While we used the shortest MEP latency out of 20 superimposed MEP waveforms for each separate coil orientation to determine the AP and LM latency, others calculate the AP and LM latency based on an averaging procedure that takes into account all MEPs (Jonker et al, 2020). Using the latter procedure, a recent larger double-blind trial did not find AP-LM MEP latency differences to reliably predict TDCS-induced aftereffects when using a stimulation intensity of 2 mA (Jonker et al, 2020).…”

“…While we used the shortest MEP latency out of 20 superimposed MEP waveforms for each separate coil orientation to determine the AP and LM latency, others calculate the AP and LM latency based on an averaging procedure that takes into account all MEPs (Jonker et al, 2020). Using the latter procedure, a recent larger double-blind trial did not find AP-LM MEP latency differences to reliably predict TDCS-induced aftereffects when using a stimulation intensity of 2 mA (Jonker et al, 2020). Together, the existing data on, the predictive value of the individual difference in AP-LM MEP latency on TDCS-related aftereffects on corticomotor excitability are highly interesting, but more research on the impact of methodological factors and specific features of the TDCS protocol, such as intensity or montage, is needed to assess the usefulness of the AP-LM MEP latency as predictive variable in future TDCS studies.…”

Is two decades of tDCS work wrong? Commentary on Ahn and Frohlich

“…For this reason, a replication of the protocol within a similarly controlled sample would be highly beneficial for the field, specifically with consideration of the impact of excluding all MEPs under 50 mV. Because this study largely challenges two decades of tDCS work (including many failed attempts to find any effect of tDCS on MEP amplitude; see [9] for a recent example using 2 mA tDCS), I hope that it receives the attention it deserves from the brain stimulation community.…”