Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans |
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Affiliation: | 1. Human Engineering Research Laboratories, VA RR&D Center of Excellence, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA;2. Rehabilitation Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, USA;3. Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA;4. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA;5. Department of Communication Science and Disorders, University of Pittsburgh, Pittsburgh, PA, USA;6. Department of Mechanical Engineering and the Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA, USA |
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Abstract: | BackgroundTranscutaneous stimulation of the external ear is thought to recruit afferents of the auricular vagus nerve, providing a means to activate noradrenergic pathways in the central nervous system. Findings from human studies examining the effects of auricular stimulation on noradrenergic biomarkers have been mixed, possibly relating to the limited and variable parameter space explored to date.ObjectiveWe tested the extent to which brief pulse trains applied to locations of auricular innervation (canal and concha) elicit acute pupillary responses (PRs) compared to a sham location (lobe). Pulse amplitude and frequency were varied systematically to examine effects on PR features.MethodsParticipants (n = 19) underwent testing in three separate experiments, each with stimulation applied to a different external ear location. Perceptual threshold (PT) was measured at the beginning of each experiment. Pulse trains (∼600 ms) consisting of different amplitude (0.0xPT, 0.8xPT, 1.0xPT, 1.5xPT, 2.0xPT) and frequency (25 Hz, 300 Hz) combinations were administered during eye tracking procedures.ResultsStimulation to all locations elicited PRs which began approximately halfway through the pulse train and peaked shortly after the final pulse (≤1 s). PR size and incidence increased with pulse amplitude and tended to be greatest with canal stimulation. Higher pulse frequency shortened the latency of PR onset and peak dilation. Changes in pupil diameter elicited by pulse trains were weakly associated with baseline pupil diameter.Conclusion(s): Auricular stimulation elicits acute PRs, providing a basis to synchronize neuromodulator release with task-related neural spiking which preclinical studies show is a critical determinant of therapeutic effects. Further work is needed to dissociate contributions from vagal and non-vagal afferents mediating activation of the biomarker. |
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Keywords: | Vagus nerve Vagus nerve stimulation Pupillometry Noradrenaline Norepinephrine Locus coeruleus |
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