Daniel Z. Wetmore

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

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 under different experimental conditions. The TEN method involved delivering high-frequency pulsed electrical currents to ophthalmic and maxillary divisions of the right trigeminal nerve and cervical spinal nerve afferents. Under resting conditions, TEN significantly suppressed basal sympathetic tone compared to sham as indicated by functional infrared thermography of facial temperatures. In a different experiment, 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 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.

Suppression of human psychophysiological and biochemical stress responses using high-frequency pulse-modulated transdermal electrical neurosignaling

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.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.