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Randomized Controlled Trial
. 2016 Oct 11;6(10):e913.
doi: 10.1038/tp.2016.197.

Modulation of fear extinction processes using transcranial electrical stimulation

Affiliations
Randomized Controlled Trial

Modulation of fear extinction processes using transcranial electrical stimulation

R Abend et al. Transl Psychiatry. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) A schematic depiction of the conditioning, extinction and test phases of the paradigm. Face images are from the NimStim set. (b) Alignment of stimulation electrodes; the frontal electrode was the anode. (c) The three stimulation conditions in the study differed in terms of stimulation during Day 2 (extinctions): sham, AC and DC. AC, alternate current; CS, conditioned stimulus; DC, direct current.
Figure 2
Figure 2
The mean skin conductance response (SCR) for each CS+ and CS− in each trial of the (a) conditioning phase (C1–C10, Day 1) and (b) extinction phase (E1–E9, Day 2). CS, conditioned stimulus; P, pre-conditioning phase. Asterisks represent significance of paired-samples t-tests (comparing CS+ and CS− in each trial); +P<0.1; **P<0.01; ***P<0.001. Error bars indicate s.e.m.
Figure 3
Figure 3
Extinction test phase (Day 3). The mean (a) skin conductance response and (b) explicit fear ratings for CS+ and CS− in each stimulation condition (Sham, AC and DC). Note: *P<0.05; ***P<0.001. AC, alternating current; CS, conditioned stimulus; DC, direct current; SCR, skin conductance response. Error bars indicate s.e.m.

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