Transcranial Electrical Stimulation and Behavioral Change: The Intermediary Influence of the Brain

Numerous studies have shown that transcranial electrical stimulation (tES) can modulate a wide-range of behavioral processes (Coffman et al., 2014; Harty et al., 2014; Sarkar et al., 2014; Pasqualotto, 2016), and ameliorate deficits in several neuropsychiatric disorders (for reviews see Kekic et al., 2016; Lefaucheur et al., 2017). These promising outcomes, in conjunction with the fact that the approach is safe and inexpensive, have generated enthusiasm for its viability as both an investigative and neuroenhancement tool. However, concerns about the variability and reproducibility of tES effects have constrained progression with its application (Jacobson et al., 2012; Berlim et al., 2013; Horvath et al., 2015). Many factors may contribute to the variability and poor reproducibility of findings. Some of these have already been discussed elsewhere such as insufficient statistical power, methodological differences across studies, experimenter error, inadequate sensitivity and test-retest reliability of the outcome measures (Horvath et al., 2015; Open Science Collaboration, 2015). However, one factor that we believe has received insufficient consideration to date concerns the extent to which the assumptions relating to the targeted brain region are supported (Bikson and Rahman, 2013; Miniussi et al., 2013; Plewnia et al., 2015; Harty et al., 2017). In the present article, we highlight the importance of accounting for states and traits of the neurophysiological milieu when assessing the effects of interventions such as tES on behavior. We present hypothetical scenarios relating to the use of transcranial direct current stimulation (tDCS), but the discussed logic equally applies to other electrical and magnetic stimulation techniques.We additionally propose that mediation andmoderation analyses constitute valuable and elegant statistical approaches for assessing the dynamic interaction between these interventions, the brain, and behavior.