title: Modulation of fear extinction processes using transcranial electrical stimulation.
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.
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Abend
authors.affiliation: Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv,Israel.
authors.forename: I
authors.initials: I
authors.lastname: Jalon
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Gurevitch
authors.affiliation: Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Sar-El
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Shechner
authors.affiliation: Section on Developmental Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Pine
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Functional Brain Center, Wohl Institute for Advanced Imaging, Sourasky Medical Center, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv,Israel.|Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Hendler
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv,Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Bar-Haim
mesh_terms: D000328:Adult; D003214:Conditioning, Classical / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D005793:Generalization, Psychological / Q000502:physiology; D006801:Humans; D008297:Male; D017397:Prefrontal Cortex / Q000503:physiopathology*; D065908:Transcranial Direct Current Stimulation; D055815:Young Adult