title: Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior.
abstract: Memories become labile and malleable to modification when recalled [1]. Fear-conditioning experiments in both rodents and humans indicate that amygdala-localized short-term fear memories can be attenuated by disruption of their reconsolidation with extinction training soon after memory activation [2-7]. However, this may not be true for natural long-term fears. Studies in rodents indicate that although it is possible to disrupt the reconsolidation of older memories [8-11], they appear to be more resistant [1, 3, 9, 12, 13]. In humans, 1-week-old conditioned fear memories have been attenuated by behaviorally induced disruption of reconsolidation [14], but it remains to be seen whether this is possible for naturally occurring long-term fears and whether the underlying neural mechanisms are similar to those found in experimental fear-conditioning paradigms. Using functional brain imaging in individuals with a lifelong fear of spiders, we show that fear memory activation followed by repeated exposure to feared cues after 10 min, which disrupts reconsolidation, attenuates activity in the basolateral amygdala at re-exposure 24 hr later. In contrast, repeated exposure 6 hr after fear memory activation, which allows for reconsolidation, did not attenuate amygdala activity. Disrupted, but not undisrupted, reconsolidation facilitated approach behavior to feared cues, and approach behavior was inversely related to amygdala activity during re-exposure. We conclude that memory activation immediately preceding exposure attenuates the neural and behavioral expression of decades-old fear memories and that, similar to experimentally induced fear memories, the basolateral amygdala is crucially involved in this process.
authors: Department of Psychology, Uppsala University, Uppsala 752 37, Sweden. Electronic address: johannes.bjorkstrand@psyk.uu.se.
authors: Johannes
authors: J
authors: Björkstrand
authors: Department of Psychology, Uppsala University, Uppsala 752 37, Sweden.
authors: Thomas
authors: T
authors: Agren
authors: Department of Psychology, Uppsala University, Uppsala 752 37, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm 171 76, Sweden.
authors: Fredrik
authors: F
authors: Åhs
authors: Department of Psychology, Uppsala University, Uppsala 752 37, Sweden.
authors: Andreas
authors: A
authors: Frick
authors: Department of Surgical Sciences/Radiology, Uppsala University, Uppsala 751 85, Sweden.
authors: Elna-Marie
authors: EM
authors: Larsson
authors: Department of Psychology, Uppsala University, Uppsala 752 37, Sweden.
authors: Olof
authors: O
authors: Hjorth
authors: Department of Psychology, Uppsala University, Uppsala 752 37, Sweden.
authors: Tomas
authors: T
authors: Furmark
authors: Department of Psychology, Uppsala University, Uppsala 752 37, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm 171 76, Sweden.
authors: Mats
authors: M
authors: Fredrikson
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D002755:Choice Behavior; D005239:Fear / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D000069077:Memory Consolidation; D013112:Spiders; D055815:Young Adult