Transcranial direct current stimulation among technologies for low-intensity transcranial electrical stimulation: Classification, history, and terminology

Abstract

This chapters traces the historical developed of transcranial direct current stimulation (tDCS). The application of direct current to modulate human cognition and treat disease dates to the development of the first batteries (circa 1800). The development of electrical devices occurred alongside early electrical medicine using direct current stimulation (circa 1900). Electrical medicine developed throughout the twentieth century with increasingly sophisticated electronics allowing for new technologies that utilized increasingly complex waveforms. The modern era of tDCS commenced in 2000 with the demonstration of polarity-specific and lasting changes in cortical excitability - this work also established a canonical dose of a few mA for tens of minutes applied with large electrodes. With the intent to modulate brain regions associated with patho-physiological excitability, modern tDCS trials have targeted neuropsychiatric disorders. With the intent to promote plasticity, trials in neuro-rehabilitation emerged in 2003. Ongoing trials have developed in breadth of indications, scale and sophistication, now including dozens of randomized controlled trials (RCTs). The safety and tolerably of tDCS has encouraged testing on cognitive function and behavior in healthy volunteers. Animal studies establishing physiological targets for direct current span decades and are consistent with polarity specific modulation of lasting excitability changes, but with nuanced state-dependency. In parallel, dozens of clinical neurophysiology trials have established biomarkers and drug-interactions of response. Over the last decade, the dose response and individual variability of tDCS has been systematically explored and has suggested new approaches to optimize response. Imaging and MRI-derived computational models of current flow have supported hypothesis testing on target engagement and have suggested new techniques such as High-Definition tDCS (HD-tDCS). This chapter introduces tDCS in the context of other transcranial electrical stimulation (tES) techniques that have been historically developed in parallel, while emphasizing the unique role of tDCS in changing the broader trajectory of tES research. Specifically, modern tDCS was developed following rigorous neuro-physiological testing in animals and humans, with behavioral and clinical trials based on specific, mechanistic hypotheses derived from this canonical work. This rigorous and incremental approach has been the foundation of outstanding tDCS studies, and has facilitated in serving as a scientific anchor for the broader (re)discovery of non-invasive electrical stimulation.