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tDCS peripheral nerve stimulation: a neglected mode of action?


Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method widely used by neuroscientists and clinicians for research and therapeutic purposes. tDCS is currently under investigation as a treatment for a range of psychiatric disorders. Despite its popularity, a full understanding of tDCS’s underlying neurophysiological mechanisms is still lacking. tDCS creates a weak electric field in the cerebral cortex which is generally assumed to cause the observed effects. Interestingly, as tDCS is applied directly on the skin, localized peripheral nerve endings are exposed to much higher electric field strengths than the underlying cortices. Yet, the potential contribution of peripheral mechanisms in causing tDCS’s effects has never been systemically investigated. We hypothesize that tDCS induces arousal and vigilance through peripheral mechanisms. We suggest that this may involve peripherally-evoked activation of the ascending reticular activating system, in which norepinephrine is distributed throughout the brain by the locus coeruleus. Finally, we provide suggestions to improve tDCS experimental design beyond the standard sham control, such as topical anesthetics to block peripheral nerves and active controls to stimulate non-target areas. Broad adoption of these measures in all tDCS experiments could help disambiguate peripheral from true transcranial tDCS mechanisms.

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Fig. 1: Comparison of the tDCS transcranial and transcutaneous mechanisms.
Fig. 2: TDCS transcutaneous mechanism.


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LvB wrote the article. SK, AK, and BA contributed to discussing, editing, and writing the article. MMcL formulated the central hypothesis in the article and contributed to discussing, editing, and writing it.

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Correspondence to Myles Mc Laughlin.

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van Boekholdt, L., Kerstens, S., Khatoun, A. et al. tDCS peripheral nerve stimulation: a neglected mode of action?. Mol Psychiatry 26, 456–461 (2021).

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