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.

Effects of a short and intensive transcranial direct current stimulation treatment in children and adolescents with developmental dyslexia: A crossover clinical trial

“…Finally, starting from our previous results (Lazzaro et al, 2021c) and in accordance with studies indicating that preexisting factors (e.g., age) may contribute to improvements after tDCS treatment (for a review, see Vergallito et al, 2022), we explored the association between age and reading improvement.…”

“…Regarding correlations, we found that as age decreased, the NW reading speed improved immediately after and 1 month after the end of the active tDCS condition. A large body of literature has shown that age -and the related thickness of the skull, maturation of brain regions, hormonal disturbances, and neurotransmitter activity -is a determinant of neuroplasticity (Vergallito et al, 2022). Neural plasticity is one of the main mechanisms involved in the stimulation effects, which depends on the personal propensity to induce plasticity (Bandeira et al, 2021).…”

“…Second, existing results are fundamentally heterogeneous (Costanzo et al, 2016b(Costanzo et al, , 2019Rios et al, 2018) probably due to high inter-subject variability. Indeed, it has been widely recognized that the influence of stable factors (demographical, neuroanatomical, and genetical), or transient/contextual factors such as vigilance, hormonal activity, participant engagement or task predisposition can significantly produce heterogeneous results and alter the generalizability of findings observed in tDCS studies (for a review, see Vergallito et al, 2022).…”

How to Test the Association Between Baseline Performance Level and the Modulatory Effects of Non-Invasive Brain Stimulation Techniques

“…A consistent body of independent and recent evidence suggests that baseline performance modulates TMS effects (Schwarzkopf et al, 2011;Painter et al, 2015;Emrich et al, 2017;Juan et al, 2017;Paracampo et al, 2018;Silvanto et al, 2018). Furthermore, also the effects of others brain stimulation techniques, such as transcranial direct current stimulation (tDCS) or transcranial random noise stimulation (tRNS), seem to interact with baseline performance level (Jones and Berryhill, 2012;Tseng et al, 2012;Hsu et al, 2014Hsu et al, , 2016Benwell et al, 2015;Learmonth et al, 2015;Juan et al, 2017;Penton et al, 2017;Schaal et al, 2017;Yang and Banissy, 2017; see also Vergallito et al, 2022 for a recent review). Together these findings have been interpreted as indicative of the importance of adopting an individual differences approach, when describing the effect of NIBS.…”

Are we really targeting and stimulating DLPFC by placing transcranial electrical stimulation (tES) electrodes over F3/F4?

“…Previous works pointed out the importance of inter-individual variability of the EF and submaximal stimulation dose at the intended target [25], suggesting the need for a systematic analysis of dosage in targeted and non-targeted regions. EF variation has been linked to substantial differences in morphological features (e.g., skull thickness, cortex morphology, and gyrification [26,27]). These differences may explain why cortical EF is not restricted to a region "under" the electrode; understanding the distribution of the peak current density and its cortical location in a large sample may help to design more optimal protocols and better interpret stimulation outcomes at both individual and group-levels.…”