title: Preventing long-lasting fear recovery using bilateral alternating sensory stimulation: A translational study.
abstract: Posttraumatic stress disorder (PTSD) is a highly debilitating and prevalent psychological disorder. It is characterized by highly distressing intrusive trauma memories that are partly explained by fear conditioning. Despite efficient therapeutic approaches, a subset of PTSD patients displays spontaneous recurrence of traumatic memories after successful treatment. The development of animal behavioral models mimicking the individual variability in treatment outcome for PTSD patients represent therefore an important challenge as it allows for the identification of predicting factors of resilience or susceptibility to relapse. However, to date, only few animal behavioral models of long-lasting fear recovery have been developed and their predictive validity has not been tested directly. The objectives of this study were twofold. First we aimed to develop a simple animal behavioral model of long-lasting fear recovery based on auditory cued fear conditioning and extinction learning, which recapitulates the heterogeneity of fear responses observed in PTSD patients after successful treatment. Second we aimed at testing the predictive validity of our behavioral model and used to this purpose a translational approach based (i) on the demonstration of the efficiency of Eye Movement Desensitization and Reprocessing (EMDR) therapy to reduce conditioned fear responses in PTSD patients and (ii) on the implementation in our behavioral model of an electrical bilateral alternating stimulation of the eyelid which mimics the core feature of EMDR. Our data indicate that electrical bilateral alternating stimulation of the eyelid during extinction learning alleviates long-lasting fear recovery of conditioned fear responses and dramatically reduces inter-individual variability. These results demonstrate the face and predictive validity of our animal behavioral model and provide an interesting tool to understand the neurobiological underpinnings of long-lasting fear recovery.
authors.affiliation: INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, 33077 Bordeaux, France; Univ. Bordeaux, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, 33077 Bordeaux, France.
authors.forename: H
authors.initials: H
authors.lastname: Wurtz
authors.affiliation: Notre Dame University, Faculty of Humanities, Department of Psychology, Zouk Mikael BP 72, Lebanon.
authors.forename: M
authors.initials: M
authors.lastname: El-Khoury-Malhame
authors.affiliation: Division of Clinical Psychology and Psychotherapy and Health Psychology, Department of Psychology, University of Salzburg, Hellbrunnerstrasse 32, A-5020 Salzburg, Austria.
authors.forename: F H
authors.initials: FH
authors.lastname: Wilhelm
authors.affiliation: Division of Clinical Psychology and Psychotherapy, Department of Psychology, Saarland University, Saarbrucken, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Michael
authors.affiliation: Department of Psychiatry and Medical Psychology, Princess Grace Hospital Center, Monaco, France.
authors.forename: E M
authors.initials: EM
authors.lastname: Beetz
authors.affiliation: Center for Treatment of Psychological Trauma, Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Roques
authors.affiliation: Institut de Neurosciences de la Timone, UMR 7289, Marseille, France.
authors.forename: E
authors.initials: E
authors.lastname: Reynaud
authors.affiliation: INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, 33077 Bordeaux, France; Univ. Bordeaux, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, 33077 Bordeaux, France.
authors.forename: J
authors.initials: J
authors.lastname: Courtin
authors.affiliation: Institut de Neurosciences de la Timone, UMR 7289, Marseille, France; Aix-Marseille Université, Marseille, France. Electronic address: stephanie.khalfa@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Khalfa
authors.affiliation: INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, 33077 Bordeaux, France; Univ. Bordeaux, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, 33077 Bordeaux, France. Electronic address: cyril.herry@inserm.fr.
authors.forename: C
authors.initials: C
authors.lastname: Herry
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000818:Animals; D003213:Conditioning, Psychological; D004558:Electric Stimulation; D005108:Extinction, Psychological; D057169:Eye Movement Desensitization Reprocessing; D005143:Eyelids / Q000503:physiopathology; D005239:Fear; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology / Q000523:psychology* / Q000628:therapy
keywords: Eye Movement Desensitization and Reprocessing; PTSD; bilateral alternating stimulation; fear conditioning; fear recovery