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Think twice, it's all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.ORCID-id: 0000-0002-6355-660X
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.ORCID-id: 0000-0003-2516-9075
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2017 (Engelska)Ingår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 324, s. 125-129Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.

Ort, förlag, år, upplaga, sidor
2017. Vol. 324, s. 125-129
Nyckelord [en]
Reconsolidation disruption, Extinction, Exposure therapy, Amygdala, Approach behavior, Spider fear
Nationell ämneskategori
Neurologi
Identifikatorer
URN: urn:nbn:se:uu:diva-315854DOI: 10.1016/j.bbr.2017.02.016ISI: 000397691100016PubMedID: 28214541OAI: oai:DiVA.org:uu-315854DiVA, id: diva2:1075999
Forskningsfinansiär
Vetenskapsrådet, 2013-2825, 2012-00804Hjärnfonden, F02014-0151Tillgänglig från: 2017-02-21 Skapad: 2017-02-21 Senast uppdaterad: 2018-06-26Bibliografiskt granskad
Ingår i avhandling
1. The Amygdala, Fear and Reconsolidation: Neural and Behavioral Effects of Retrieval-Extinction in Fear Conditioning and Spider Phobia
Öppna denna publikation i ny flik eller fönster >>The Amygdala, Fear and Reconsolidation: Neural and Behavioral Effects of Retrieval-Extinction in Fear Conditioning and Spider Phobia
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The amygdala is crucially involved in the acquisition and retention of fear memories. Experimental research on fear conditioning has shown that memory retrieval shortly followed by pharmacological manipulations or extinction, thereby interfering with memory reconsolidation, decreases later fear expression. Fear memory reconsolidation depends on synaptic plasticity in the amygdala, which has been demonstrated in rodents using both pharmacological manipulations and retrieval-extinction procedures. The retrieval-extinction procedure decreases fear expression also in humans, but the underlying neural mechanism have not been studied. Interfering with reconsolidation is held to alter the original fear memory representation, resulting in long-term reductions in fear responses, and might therefore be used in the treatment of anxiety disorders, but few studies have directly investigated this question.

The aim of this thesis was to examine the effects of the retrieval-extinction procedure on amygdala activity and behavioral fear expression in humans. The work presented here also investigated whether findings from studies on recent fear memories, established through fear conditioning, extends to naturally occurring long-term phobic fears.

Study I, combining fear conditioning and a retrieval-extinction procedure with functional magnetic resonance imaging (fMRI), demonstrated that memory retrieval shortly followed by extinction reduces later amygdala activity and fear expression in healthy subjects. In Study II, these subjects were re-tested 18 months later. The results showed that the effects on fear expression were still present and that initial amygdala activity predicted long-term fear expression. Using an adapted version of the retrieval-extinction procedure, Study III showed that memory retrieval shortly followed by exposure to spider pictures, attenuates subsequent amygdala activity and increases approach behavior in subjects with life-long fear of spiders. In Study IV, these subjects were re-tested 6 months later, and the results showed that effects on amygdala activity as well as approach behavior were maintained.

In summation, retrieval-extinction leads to long-lasting reductions in amygdala activity and fear expression. These findings are consistent with the hypothesis that retrieval-extinction alters an amygdala dependent fear memory. Retrieval-extinction can also attenuate long-term phobic fears, indicating that this manipulation could be used to enhance exposure-based treatments for anxiety disorders. 

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2017. s. 72
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 140
Nyckelord
Fear conditioning, phobia, memory reconsolidation, retrieval-extinction, exposure therapy, amygdala, fMRI
Nationell ämneskategori
Psykologi
Forskningsämne
Psykologi
Identifikatorer
urn:nbn:se:uu:diva-317866 (URN)978-91-554-9863-4 (ISBN)
Disputation
2017-05-12, Gunnar Johansson salen, Blåsenhus, von Kraemers allé 1A, Uppsala, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2017-04-20 Skapad: 2017-03-20 Senast uppdaterad: 2017-04-20

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Björkstrand, JohannesÅgren, ThomasÅhs, FredrikFrick, AndreasLarsson, Elna-MarieHjorth, OlofFurmark, TomasFredrikson, Mats

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Björkstrand, JohannesÅgren, ThomasÅhs, FredrikFrick, AndreasLarsson, Elna-MarieHjorth, OlofFurmark, TomasFredrikson, Mats
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