Modulation of fear extinction processes using transcranial electrical stimulation.

R Abend,T Shechner,D S Pine,R Sar-El,I Jalon,T Hendler,G Gurevitch,Y Bar-Haim

doi:10.1038/tp.2016.197

R Abend, T Shechner + Show 6 more

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https://doi.org/10.1038/tp.2016.197

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Abstract

Research associates processes of fear conditioning and extinction with treatment of anxiety and stress-related disorders. Manipulation of these processes may therefore be beneficial for such treatment. The current study examines the effects of electrical brain stimulation on fear extinction processes in healthy humans in order to assess its potential relevance for treatment enhancement. Forty-five participants underwent a 3-day fear conditioning and extinction paradigm. Electrical stimulation targeting the medial prefrontal cortex was applied during the extinction-learning phase (Day 2). Participants were randomly assigned to three stimulation conditions: direct-current (DC) stimulation, aimed at enhancing extinction-learning; low-frequency alternating-current (AC) stimulation, aimed at interfering with reconsolidation of the activated fear memory; and sham stimulation. The effect of stimulation on these processes was assessed in the subsequent extinction recall phase (Day 3), using skin conductance response and self-reports. Results indicate that AC stimulation potentiated the expression of fear response, whereas DC stimulation led to overgeneralization of fear response to non-reinforced stimuli. The current study demonstrates the capability of electrical stimulation targeting the medial prefrontal cortex to modulate fear extinction processes. However, the stimulation parameters tested here yielded effects opposite to those anticipated and could be clinically detrimental. These results highlight the potential capacity of stimulation to manipulate processes relevant for treatment of anxiety and stress-related disorders, but also emphasize the need for additional research to identify delivery parameters to enable its translation into clinical practice. Clinical trial identifiers: Modulation of Fear Extinction Processes Using Transcranial Electrical Stimulation; https://clinicaltrials.gov/show/NCT02723188; NCT02723188 NCT02723188.

Highlights

Research links the processes of fear conditioning and extinction to the treatment of anxiety and stress-related disorders.[1,2,3] considerable translational research examines the neural correlates of these processes.[4,5,6] research manipulating neural correlates of these processes in humans is still scarce,[7] which limits basic clinical integration
The results of the current study demonstrate that Transcranial electrical stimulation (tES) applied during extinction learning modulated fear response during a subsequent test phase
AC stimulation potentiated the expression of fear response following extinction, whereas DC stimulation led to overgeneralization of the fear response to non-reinforced stimuli

Summary

Introduction

Research links the processes of fear conditioning and extinction to the treatment of anxiety and stress-related disorders.[1,2,3] considerable translational research examines the neural correlates of these processes.[4,5,6] research manipulating neural correlates of these processes in humans is still scarce,[7] which limits basic clinical integration. Exposure therapy, involving gradual extinction of maladaptive fear associations, represents one of the most effective treatments for anxiety and stress-related disorders.[8,9,10] In this treatment approach, stimuli associated with a fear response are evoked in a safe context, leading to the formation of new safety associations.[11]

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