Does Transcutaneous Vagal Nerve Stimulation Improves Fear Extinction in Humans (t-VNSext)

A recent study with rats showed that electrical stimulation of the vagus nerve (VNS) facilitates extinction of fear (Pena, Engineer, & McIntyre, Biological Psychiatry, 2013). The hypothesized mechanism is that VNS both enhances memory consolidation (by increasing noradrenergic neurotransmission) and reduces anxiety (thus: preventing fear responses to the CS which may re-consolidate the fear memory). The effect was only apparent when VNS occurred during exposure of the fear conditioned stimulus (CS), and not when stimulation was given immediately following exposure. These results may have implications for the treatment of anxiety disorders in humans. However, until recently, the only means to investigate the effects of VNS on human fear learning would have required the invasive implantation of vagus nerve stimulators. This has fortunately changed, as a non-invasive transcutaneous VNS device has been approved for use in the E.U. for the treatment of psychological disorders.

This study proposes to use a t-VNS to investigate its effects on fear learning and extinction in (healthy) humans. Previous research has only investigated the effects it has on human mood and memory. The results obtained suggest that it reduces negative affect and enhances memory, findings which are consistent with those reported for rats. It is thus reasonable to expect that t-VNS will facilitate the extinction of fear in humans.

The present study aims to answer the following research questions:

Does t-VNS during extinction training:

1. accelerates extinction curves
2. reduces spontaneous recovery of previously extinguished fear
3. reduce re-acquisition of fear
4. reduce generalization of fear to other stimuli that resemble the CS+?
5. facilitates the generalization of inhibitory learning to stimuli that resemble the CS-?

Study Overview

• Status: Unknown
• Conditions: Healthy Adults
• Intervention / Treatment: Device: t-VNS; Device: sham stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Faculty of Psychology and Educational Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy men and women aged 16 - 50 years

Exclusion Criteria:

• current or past psychiatric or neurological disorder
• use of psychopharmaca
• use of medication that affects autonomic nervous functioning (e.g., bèta-blockers)
• current cardiac or respiratory disorder
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: t-VNS; electrical stimulation of the concha of the ear 30sec trains of 0.25msec-duration monophasic square wave pulses at 25Hz, with a stimulation intensity not exceeding 0.5 mA	Device: t-VNS; The device that will be used is approved for systematic use by those with epilepsy and depression in the European Union. It has been used in studies of acute stimulation with healthy participants with no significant changes in heart rate or breathing (Kraus et al., 2007; Busch et al., 2013).; Other Names: NEMOS®, Cerbomed, Erlangen, Germany
Sham Comparator: sham t-VNS; Sham stimulation of the earlobe will be conducted by positioning the electrode upside down 30sec trains of 0.25msec-duration monophasic square wave pulses at 25Hz, with a stimulation intensity not exceeding 0.5 mA	Device: sham stimulation; electrodes will be put upside down; Other Names: NEMOS®, Cerbomed, Erlangen, Germany

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fear response	startle blink EMG skin conductance response ECG respiration self-reports	3 test days

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Ilse Van Diest, PhD, KU Leuven

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: April 10, 2014
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (Estimate): April 14, 2014

Study Record Updates

• Last Update Posted (Estimate): April 14, 2014
• Last Update Submitted That Met QC Criteria: April 11, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: t-VNS extinction