title: Renewal of conditioned fear in a novel context is associated with hippocampal activation and connectivity.
abstract: Return of fear is a serious problem in exposure-based treatments of anxiety disorders. Renewal of the fear response may occur when re-encountering the conditioned stimulus within a novel context. Findings in rodents underpin the hippocampus' role in conditioned fear renewal in novel contexts, but it has yet to be investigated in humans. Forty-six healthy men took part in a 2-day, context-dependent, cued fear conditioning paradigm with fear acquisition, extinction learning (day 1) and extinction recall in the acquisition, extinction and a novel context one day later. Conditioned evaluative, skin conductance responses (SCRs) and blood-oxygen-level-dependent responses served as dependent variables. Context-dependent fear renewal was reflected in stronger conditioned SCRs. In the acquisition context, individuals with a higher renewal of conditioned SCRs showed stronger activation of the fear circuit. Hippocampal activation distinguished conditioned responding in the novel compared with the extinction context. Individuals with a stronger renewal of conditioned SCRs in the novel context showed increased effective connectivity of hippocampal activation foci with structures in the fear and extinction network. These results outline the pivotal role of the hippocampus and its connectivity in conditioned fear renewal in a novel context in humans and might have important implications for exposure therapy in anxiety disorders.
authors.affiliation: Department of Psychotherapy and Systems Neuroscience and Bender Institute of Neuroimaging, Justus Liebig University Giessen, Germany andrea.hermann@psychol.uni-giessen.de.
authors.forename: A
authors.initials: A
authors.lastname: Hermann
authors.affiliation: Department of Psychotherapy and Systems Neuroscience and Bender Institute of Neuroimaging, Justus Liebig University Giessen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Stark
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Milad
authors.affiliation: Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr-University Bochum, Germany Department of Biological and Clinical Psychology, University of Trier, Germany.
authors.forename: C J
authors.initials: CJ
authors.lastname: Merz
mesh_terms: D000328:Adult; D003213:Conditioning, Psychological / Q000502:physiology*; D003463:Cues; D005108:Extinction, Psychological; D005239:Fear / Q000502:physiology*; D005712:Galvanic Skin Response / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: amygdala; extinction; fMRI; fear conditioning; hippocampus