RT Journal Article SR Electronic T1 Suppression of human psychophysiological and biochemical stress responses using high-frequency pulse-modulated transdermal electrical neurosignaling JF bioRxiv FD Cold Spring Harbor Laboratory SP 015032 DO 10.1101/015032 A1 William J. Tyler A1 Alyssa M. Boasso A1 Jonathan D. Charlesworth A1 Michelle A. Marlin A1 Kirsten Aebersold A1 Linh Aven A1 Daniel Z. Wetmore A1 Sumon K. Pal YR 2015 UL http://biorxiv.org/content/early/2015/02/08/015032.abstract AB We have developed a neuromodulation approach that targets peripheral nerves and utilizes their afferents as signaling conduits to influence brain function. We investigated the effects of this transdermal electrical neurosignaling (TEN) approach on physiological responses to acute stress induction. TEN was targeted to the ophthalmic and maxillary divisions of the right trigeminal nerve and cervical spinal nerve afferents (C2/C3) using high-frequency, pulse-modulated electrical currents. Compared to active sham stimulation, TEN significantly suppressed sympathetic activity in response to acute stress without impeding cognitive performance. This sympatholytic action of TEN was indicated by significant suppression of heart rate variability changes, galvanic skin responses, and salivary α-amylase levels in response to stress. These observations are consistent with the hypothesis that TEN acted partially by modulating activity in the locus coeruleus and subsequent noradrenergic signaling. Dampening sympathetic tone using TEN in such a manner represents a promising approach to managing daily stress and improving brain health.