The presumed mechanism of tDCS reconsideredTranscranial direct current stimulation (tDCS) is a non-invasive neuromodulation method in which a weak DC current is passed through at least two scalp electrodes. Neuroscientists use tDCS as a tool to study the functional roles of different brain regions, and investigate their behavioral and cognitive correlates. In a clinical context, tDCS is being investigated as treatment for a wide range of conditions, including addiction [1], depression [2], and cognitive decline [3]. Due to this broad potential, combined with its noninvasive nature and low-cost, tDCS is quickly growing in popularity, illustrated by its exponentially growing output of publications [4] and the growing number of consumer tDCS devices on the market.While increasing amounts of research resources are directed towards tDCS's applications, remarkably little is known about the technique's underlying neurophysiological mechanisms. It is widely assumed that effects of tDCS are solely caused by the electric field that it generates in the brain. This weak field is believed to modify functioning of the brain by polarizing the membrane potential of neurons, and thereby altering their excitability [5]. In this opinion piece we would like to suggest that this may be an oversimplified representation of the mechanisms mediating tDCS's effects. In the following paragraphs we discuss evidence which supports this opinion.
BackgroundRecent studies indicate that some transcranial direct current stimulation (tDCS) effects may be caused by indirect stimulation of peripheral nerves in the scalp rather than the electric field in the brain. To address this, we developed a novel tDCS control condition in which peripheral input is blocked using topical anesthetics. We developed a compounded anesthetic gel containing benzocaine and lidocaine (BL10) that blocks peripheral input during tDCS.MethodsIn a blinded randomized cross-over study of 18 healthy volunteers (M/F), we compared the gel's efficacy to EMLA and an inert placebo gel. Subjects used a visual analog scale (VAS) to rate the stimulation sensation in the scalp produced by 10 s of 2 mA tDCS every 2 min during 1 h. In an additional in-vitro experiment, the effect of a DC current on gel resistivity and temperature was investigated.ResultsBoth the BL10 and EMLA gel, lowered the stimulation sensations compared to the placebo gel. The BL10 gel showed a tendency to work faster than the EMLA gel with reported sensations for the BL10 gel being lower than for EMLA for the first 30 min. The DC current caused a drastic increase in gel resistivity for the EMLA gel, while it did not affect gel resistivity for the BL10 and placebo gel, nor did it affect gel temperature.ConclusionsTopical anesthetics reduce stimulation sensations by blocking peripheral nerve input during tDCS. The BL10 gel tends to work faster and is more electrically stable than EMLA gel.Clinical trial registrationThe study is registered at ClinicalTrials.gov with name “Understanding the Neural Mechanisms Behind tDCS” and number NCT04577677.
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