Inter-Individual Variability in tDCS Effects: A Narrative Review on the Contribution of Stable, Variable, and Contextual Factors

Abstract

Due to its safety, portability, and cheapness, transcranial direct current stimulation (tDCS) use largely increased in research and clinical settings. Despite tDCS's wide application, previous works pointed out inconsistent and low replicable results, sometimes leading to extreme conclusions about tDCS's ineffectiveness in modulating behavioral performance across cognitive domains. Traditionally, this variability has been linked to significant differences in the stimulation protocols across studies, including stimulation parameters, target regions, and electrodes montage. Here, we reviewed and discussed evidence of heterogeneity emerging at the intra-study level, namely inter-individual differences that may influence the response to tDCS within each study. This source of variability has been largely neglected by literature, being results mainly analyzed at the group level. Previous research, however, highlighted that only a half-or less-of studies' participants could be classified as responders, being affected by tDCS in the expected direction. Stable and variable inter-individual differences, such as morphological and genetic features vs. hormonal/exogenous substance consumption, partially account for this heterogeneity. Moreover, variability comes from experiments' contextual elements, such as participants' engagement/baseline capacity and individual task difficulty. We concluded that increasing knowledge on inter-dividual differences rather than undermining tDCS effectiveness could enhance protocols' efficiency and reproducibility.

Keywords: inter-individual differences; inter-subject variability; noninvasive brain stimulation; reproducibility; tDCS.

Figure 1

Patterns of responders and non-responders across the four TMS-EEG studies from our lab. The upper panel represents the interindividual variability of the modulatory effects of tDCS in early (0–50 ms), middle (50–100 ms), and late (100–150 ms) latency TEPs components, represented by the pink, green, and blue boxes, respectively. The effect was computed by dividing post-tDCS by pre-tDCS local mean-field power values so that values above 1 represent an increase in post-tDCS response. Cathodal results are reversed for graphical reasons. The bottom panel represents the percentage of responders (green) and non-responders (red) calculated as participants showing the outcome modulation of at least 20% of the pre-tDCS values on early, middle, and late TEPs components, represented by the inner, intermediate, and outer circles.