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Timing Considerations for Noninvasive Vagal Nerve Stimulation in Clinical Studies - PubMed

  • ️Wed Jan 01 2020

Clinical Trial

. 2020 Mar 4:2019:1061-1070.

eCollection 2019.

Affiliations

Clinical Trial

Timing Considerations for Noninvasive Vagal Nerve Stimulation in Clinical Studies

Nil Z Gurel et al. AMIA Annu Symp Proc. 2020.

Abstract

Noninvasive vagal nerve stimulation (n-VNS) devices have the potential for widespread applicability in improving the well-being of patients with stress-related psychiatric disorders. n-VNS devices are known to affect physiological signals, and, recently, they have been employed in various protocols involving both acute and longitudinal applications. However, questions regarding response time, "dosage," or optimal treatment paradigms remain open. Prior work evaluated noninvasively obtained biomarkers that quantify the stimulation efficacy based on the changes in autonomic tone in a randomized double-blind study. In this work, we extend the state-of-the-art by investigating the onset of action for n-VNS in these same physiological biomarkers through a three-day clinical trial, including 233 administrations on 24 human participants, with and without immediately preceding acute traumatic stress. Determining n-VNS latency serves as a substantial step toward optimizing stimulation delivery with higher temporal resolution for personalized neuromodulation.

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Figures

Figure 1.
Figure 1.

Simplified representation of n-VNS mechanism of action. The understanding of n-VNS kinetics on noninvasively obtained physiological parameters may enable optimization of n-VNS delivery in unsupervised settings. NTS: nucleus tractus solitarus.

Figure 2.
Figure 2.

Protocol diagram. The protocol included three days: the first day included six traumatic stress prompts followed by immediate n-VNS or sham stimulation and two stimulation administrations without stress. Each of the second and third days included one stimulation administration without stress.

Figure 3.
Figure 3.

Signal processing and feature extraction steps. BPF: bandpass filter; exp. MA: exponential moving average; EA: ensemble average; AO: aortic opening point; PEP: pre-ejection period; HR: heart rate.

Figure 4.
Figure 4.

Annotation diagram. The smoothed instantaneous biomarkers (HR, PEP, PPG amplitude) were plotted from pre-stimulus to post-stimulus. If at least two of the three mentioned changes in the biomarkers occurred, the onset time was marked at the onset of the second change. If no eligible change was observed, the annotation was marked as “absent.”

Figure 5.
Figure 5.

Continuous physiological parameters showing n-VNS without traumatic stress, for one participant undergoing sham (left) and one participant undergoing active n-VNS stimulus (right). Markers represent the extracted data, lines represent the smoothed data. Shaded regions represent stimulus delivery. Dashed lines show the pre-stimulus averages of the measures. The onset time is marked as soon as two of the three annotation criteria mentioned in Figure 4 are detected.

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