Developing transcranial direct current stimulation as a neuromodulatory tool: critical considerations on dose, prefrontal stimulation, and safety

Abstract

Transcranial direct current stimulation (tDCS) is a mild form of non-invasive brain stimulation, which involves the use of a weak electric current passed between electrodes placed on the scalp to modulate brain activity. It is an emerging technique that shows promise for the treatment of a variety of neuropsychiatric disorders, including depression. However, several critical gaps in knowledge remain, including the safety of repeated sessions of tDCS delivered over a course of treatment, optimal parameters of use, and identification of simple physiological markers of response to stimulation. The overarching aim of this thesis is to address these gaps and aid in the development of tDCS as a neuromodulatory tool and clinical intervention. This was addressed through studies in healthy participants and through a systematic review and meta-analysis of the existing tDCS safety literature. Study 1 examined whether repeated sessions of tDCS increase the likelihood of adverse events using a meta-analytic approach. Results from this study suggest that repeated sessions do not increase risk of side effects, lending further support in favour of the safety profile of tDCS. Study 2 assessed the dose-response curve of tDCS in healthy participants for enhancement of working memory. Findings suggest that none of the current intensities examined significantly improved cognitive performance. However, neurophysiological outcome measures revealed significant effects of stimulation, with the largest effect size obtained using 1mA stimulation intensity. Study 3 explored the use of a physiological biomarker of autonomic activity, heart rate variability, to objectively measure the neuromodulatory effects of tDCS on cortical activity following a single session of prefrontal stimulation. Results showed that parasympathetic activity increased during and immediately following tDCS, providing evidence that prefrontal cortex functioning is indeed modulated by tDCS, and can be assessed using a simple measure collected from heart rate data. In summary, the studies presented in this thesis contribute to the growing development of tDCS as a neuromodulatory and clinical tool.