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Vagus nerve stimulation as a tool for enhancing extinction in exposure-based therapies

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Abstract

Rationale

Emotionally traumatic experiences can lead to maladaptive memories that are enduring and intrusive. The goal of exposure-based therapies is to extinguish conditioned fears through repeated, unreinforced exposures to reminders of traumatic events. The extinction of conditioned fear depends upon the consolidation of new memories made during exposure to reminders. An impairment in extinction recall, observed in certain patient populations, can interfere with progress in exposure-based therapies, and the drive to avoid thoughts and reminders of the trauma can undermine compliance and increase dropout rate. Effective adjuncts to exposure-based therapies should improve the consolidation and maintenance of the extinction memory or improve the tolerability of the therapy. Under stressful conditions, the vagus nerve responds to elevations in epinephrine and signals the brain to facilitate the storage of new memories while, as part of the parasympathetic nervous system, it slows the sympathetic response.

Objective

Here, we review studies relevant to fear extinction, describing the anatomical and functional characteristics of the vagus nerve and mechanisms of vagus nerve stimulation (VNS)-induced memory enhancement and plasticity.

Results

We propose that stimulation of the left cervical vagus nerve during exposure to conditioned cues signals the brain to store new memories just as epinephrine or emotional arousal would do, but bypasses the peripheral sympathetic “fight-or-flight” response.

Conclusions

In support of this hypothesis, we have found that VNS accelerates extinction and prevents reinstatement of conditioned fear in rats. Finally, we propose future studies targeting the optimization of stimulation parameters and the search for biomarkers of VNS effectiveness that may improve exposure therapy outcomes.

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Funding

This work was sponsored by the National Institutes of Mental Health (NIMH - MH10 MH105014) and the Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO) ElectRx program under the auspices of Dr. Doug Weber and Eric Van Gieson through the Space and Naval Warfare Systems Center, Pacific Grant/Contract No. N66001-15-2-4057. Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the funding agencies.

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  1. School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX, 75080, USA

    Lindsey J. Noble, Rimenez R. Souza & Christa K. McIntyre

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  1. Lindsey J. Noble
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  2. Rimenez R. Souza
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  3. Christa K. McIntyre
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Lindsey J. Noble and Rimenez R Souza reported no biomedical financial interests or potential conflicts of interest. Christa K. McIntyre is an author of a patent entitled “Enhancing Fear Extinction using Vagus Nerve Stimulation.”

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This article belongs to a Special Issue on Psychopharmacology of Extinction.

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Noble, L.J., Souza, R.R. & McIntyre, C.K. Vagus nerve stimulation as a tool for enhancing extinction in exposure-based therapies. Psychopharmacology 236, 355–367 (2019). https://doi.org/10.1007/s00213-018-4994-5

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