Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans,Brain Stimulation

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Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans
Brain Stimulation ( IF 7.7 ) Pub Date : 2021-06-18 , DOI: 10.1016/j.brs.2021.06.002
Michael A Urbin ₁ , Charles W Lafe ₂ , Tyler W Simpson ₃ , George F Wittenberg ₄ , Bharath Chandrasekaran ₅ , Douglas J Weber ₆

Affiliation

Human Engineering Research Laboratories, VA RR&D Center of Excellence, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; Rehabilitation Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, USA; Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
Human Engineering Research Laboratories, VA RR&D Center of Excellence, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; Rehabilitation Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, USA.
Rehabilitation Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, USA; Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
Human Engineering Research Laboratories, VA RR&D Center of Excellence, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; Rehabilitation Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Communication Science and Disorders, University of Pittsburgh, Pittsburgh, PA, USA.
Rehabilitation Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, USA; Department of Mechanical Engineering and the Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA, USA.

Background

Transcutaneous 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.

Objective

We 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.

Methods

Participants (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.

Results

Stimulation 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.

中文翻译：

外耳的电刺激急性激活人类的去甲肾上腺素能机制

背景

外耳的经皮刺激被认为会募集耳廓迷走神经的传入神经，从而提供一种激活中枢神经系统中去甲肾上腺素能通路的手段。人类研究检查耳刺激对去甲肾上腺素能生物标志物的影响的结果喜忧参半，可能与迄今为止探索的有限和可变参数空间有关。

客观的

我们测试了与假位置（叶）相比，应用于耳廓神经支配（耳道和外耳）位置的简短脉冲序列引起急性瞳孔反应 (PR) 的程度。系统地改变脉冲幅度和频率以检查对 PR 特征的影响。

方法

参与者（n = 19）在三个独立的实验中进行了测试，每个实验都将刺激应用于不同的外耳位置。在每个实验开始时测量感知阈值 (PT)。在眼动追踪过程中管理由不同幅度（0.0xPT、0.8xPT、1.0xPT、1.5xPT、2.0xPT）和频率（25 Hz、300 Hz）组合组成的脉冲串（~600 ms）。