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

I read with great interest the article recently published by Ahn and Fr€ ohlich [1] reporting that 10 minutes of 2 mA transcranial direct current stimulation (tDCS) over human primarymotor cortex (M1) can induce extraordinary modulations to corticospinal excitability, as indicated by changes in the amplitude of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). The observed effects on excitability (MEP ratio; mean MEP amplitude post-/pre-tDCS) were predictive of a range of EEG measures, including mu power and cortical reactivity to TMS (TMSevoked potentials; TEPs). The effects reported in the article are worthy of attention, not just for their magnitude, but for their place in a field so often plagued by subtle effects with large variability both between and within participants [2e4]. The experiment by Ahn and Fr€ ohlich is well-considered for a number of reasons: a fully-repeated measures design probed the effect of tDCS across 3 double-blinded sessions (all 18 participants received anodal, sham, and cathodal tDCS; counterbalanced order), and great care was taken to reduce variability both between and within participants (e.g., 100 MEPs were elicited before and after tDCS, structural scans were acquired for electric field modelling, M1 hotspots were targeted with neuronavigation, and only male participants aged 18e35 years were recruited). The sample sizedresulting in 54 analysable datasetsdis highly respectable (especially considering concurrent EEG was recorded), and their study protocol was registered a priori. To further minimise MEP variability across stimuli, neuronavigation was used to track TMS pulse locations in real-time and used to verify hotspot targeting. However, all MEPs with amplitudes below 50 mV were removed (4.4 ± 7.2 of 100 MEPs), irrespective of hotspot validity. Their effort to control multiple sources of variability was seemingly rewarded by a strong effect of tDCS on MEP ratio [F2,28 1⁄4 255, h2 1⁄4 0.906]. Indeed, the authors themselves seem surprised by the size of this effect, stating that it is “higher than [the average] effect size (0.67) from a recent meta-analysis.” However, this statement does a disservice to the truly remarkable size of their observed effects: the value (0.67) pulled from [5] was not h2 but rather the standardised mean difference (SMD), akin to Cohen’s d. Converted to SMD, Ahn and Fr€ ohlich actually show an effect size of 3.55 for anodal tDCS (a-tDCS; relative to sham) and 4.32 for cathodal tDCS (c-tDCS; relative to sham). To put these effects into perspective, they exist far outside the 95% confidence intervals for the SMD of a-tDCS [0.49, 0.86] and ctDCS [e0.78, 0.39] established across studies spanning the past