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Transdermal neuromodulation of noradrenergic activity suppresses psychophysiological and biochemical stress responses in humans

William J. Tyler, Alyssa M. Boasso, Hailey M. Mortimore, Rhonda S. Silva, Jonathan D. Charlesworth, Michelle A. Marlin, Kirsten Aebersold, Linh Aven, Daniel Z. Wetmore, Sumon K. Pal
doi: https://doi.org/10.1101/015032
William J. Tyler
Thync, Inc. Boston, MA USA 02199
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  • For correspondence: jamie@thync.com sumon@thync.com
Alyssa M. Boasso
Thync, Inc. Boston, MA USA 02199
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Hailey M. Mortimore
Thync, Inc. Boston, MA USA 02199
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Rhonda S. Silva
Thync, Inc. Boston, MA USA 02199
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Jonathan D. Charlesworth
Thync, Inc. Boston, MA USA 02199
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Michelle A. Marlin
Thync, Inc. Boston, MA USA 02199
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Kirsten Aebersold
Thync, Inc. Boston, MA USA 02199
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Linh Aven
Thync, Inc. Boston, MA USA 02199
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Daniel Z. Wetmore
Thync, Inc. Boston, MA USA 02199
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Sumon K. Pal
Thync, Inc. Boston, MA USA 02199
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  • For correspondence: jamie@thync.com sumon@thync.com
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Abstract

We engineered a transdermal neuromodulation approach that targets peripheral (cranial and spinal) nerves and utilizes their afferent pathways as signaling conduits to influence brain function. We investigated the effects of this transdermal electrical neurosignaling (TEN) method on sympathetic physiology in human volunteers under different experimental conditions. In all cases, the TEN involved delivering high-frequency pulsed electrical currents to ophthalmic and maxillary divisions of the right trigeminal nerve (V1/V2) and cervical spinal nerve afferents (C2/C3). Under resting conditions when subjects were not challenged or presented with environmental stimuli, TEN significantly suppressed basal sympathetic tone compared to sham as indicated by functional infrared thermography of facial temperatures. In a different experiment conducted under similar resting conditions, subjects treated with TEN reported significantly lower levels of tension and anxiety on the Profile of Mood States scale compared to sham. In a third experiment when subjects were experimentally stressed by a classical fear conditioning paradigm and a series of time-constrained cognitive tasks, TEN produced a significant suppression of heart rate variability, galvanic skin conductance, and salivary α-amylase levels compared to sham. Collectively these observations demonstrate TEN can dampen basal sympathetic tone and attenuate sympathetic activity in response to acute stress induction. Our physiological and biochemical observations are consistent with the hypothesis that TEN modulates noradrenergic signaling to suppress sympathetic activity. We conclude that dampening sympathetic activity in such a manner represents a promising approach to managing daily stress.

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Posted June 03, 2015.
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Transdermal neuromodulation of noradrenergic activity suppresses psychophysiological and biochemical stress responses in humans
William J. Tyler, Alyssa M. Boasso, Hailey M. Mortimore, Rhonda S. Silva, Jonathan D. Charlesworth, Michelle A. Marlin, Kirsten Aebersold, Linh Aven, Daniel Z. Wetmore, Sumon K. Pal
bioRxiv 015032; doi: https://doi.org/10.1101/015032
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Transdermal neuromodulation of noradrenergic activity suppresses psychophysiological and biochemical stress responses in humans
William J. Tyler, Alyssa M. Boasso, Hailey M. Mortimore, Rhonda S. Silva, Jonathan D. Charlesworth, Michelle A. Marlin, Kirsten Aebersold, Linh Aven, Daniel Z. Wetmore, Sumon K. Pal
bioRxiv 015032; doi: https://doi.org/10.1101/015032

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