Conducting double-blind placebo-controlled clinical trials of transcranial alternating current stimulation (tACS)

Many psychiatric and neurological illnesses can be conceptualized as oscillopathies defined as pathological changes in brain network oscillations. We previously proposed the application of rational design for the development of non-invasive brain stimulation for the modulation and restoration of cortical oscillations as a network therapeutic. Here, we show how transcranial alternating current stimulation (tACS), which applies a weak sine-wave electric current to the scalp, may serve as a therapeutic platform for the treatment of CNS illnesses. Recently, an initial series of double-blind, placebo-controlled treatment trials of tACS have been published. Here, we first map out the conceptual underpinnings of such trials with focus on target identification, engagement, and validation. Then, we discuss practical aspects that need to be considered for successful trial execution, with particular regards to ensuring successful study blind. Finally, we briefly review the few published double-blind tACS trials and conclude with a proposed roadmap to move the field forward with the goal of moving from pilot trials to convincing efficacy studies of tACS.