tDCS Peripheral Nerve Stimulation: A Neglected Mode of Action?

In the November 13, 2020 episode of Shark Tank (Season 12, Episode 5), two earnest entrepreneurs, Ken and Allyson, try to persuade five investors, the “sharks,” to buy into their company. The entrepreneurs sell LIFTiD, a device that applies a small steady current to the forehead. Ken said it’s supposed to improve “productivity, focus, and performance.” Allyson claimed it’s a “smarter way to get a… boost of energy.”

The device is based on transcranial direct current stimulation (tDCS). In 2009 I published an editorial in the journal Clinical Neurophysiology to accompany a paper appearing in the same issue by Pedro Miranda and his colleagues (Clin. Neurophysiol., Volume 120, Pages 1183–1187, 2009), in which they calculated the electric field in the brain caused by a 1 mA current applied to the scalp. I wrote

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)

My participation in the field of transcranial direct current stimulation started and ended with writing this editorial. However, I still follow the literature, and was was fascinated by a recent article by Luuk van Boekholdt and his coworkers in Molecular Psychiatry (Volume 26, Pages 456–461, 2021). Their abstract says

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.

When the sharks tried the LIFTiD device, they each could feel a tingling shock on their scalp. If van Boekholdt et al.’s suggestion is correct, the titillation and annoyance caused by that shock might be responsible for the effects associated with tDCS. In that case, the method would work even if you could somehow make the skull a perfect insulator, so no current whatsoever could enter the brain. I like how van Boekholdt suggests specific, simple experiments that could test their hypothesis.

If you’re trying to buy a device to improve brain performance, you might not care if it works by directly stimulating the brain or just by exciting peripheral nerves. In fact, you might be able to save money by hiring someone to poke you in the back every few seconds. Do whatever it takes to focus your attention.

None of the sharks invested in LIFTiD. My favorite shark, Mark Cuban, claimed the entrepreneurs “tried to sell science without using science.” I couldn’t have said it better myself. 

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