tDCS Peripheral Nerve Stimulation: A Neglected Mode of Action?

Although Miranda et al.’s paper is useful and enlightening, one crucial issue is not addressed: the mechanism of tDCS. In other words, how does the electric field interact with the neurons to modulate their excitability? Miranda et al. calculate a current density in the brain on the order of 0.01 mA/cm2, which corresponds to an electric field of about 0.3 V/m (a magnitude that is consistent with other studies (Wagner et al., 2007)). Such a small electric field should polarize a neuron only slightly. Hause’s model of a single neuron predicts that a 10 V/m electric field would induce a transmembrane potential of 6–8 mV (Hause, 1975), implying that the 0.3 V/m electric field during tDCS should produce a transmembrane potential of less than 1 mV. Can such a small polarization significantly influence neuron excitability? If so, how? These questions perplex me, yet answers are essential for understanding tDCS. Detailed models of the cortical geometry and brain heterogeneities may be necessary to address this issue (Silva et al., 2008), but ultimately the response of the neuron (or network of neurons) to the electric field must be included in the model in order to unravel the mechanism. Moreover, because the effect of tDCS can last for up to an hour after the current turns off (Nitsche et al., 2008), the mechanism is likely to be more complicated than just neural polarization.

van Boekholdt et al. (2021)

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.

LIFTiD Neurostimulation Personal Brain Stimulator; https://www.youtube.com/watch?v=hFzihXprRUM

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