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Disruption of reconsolidation erases a fear memory trace in the human amygdala
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
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2012 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 337, no 6101, 1550-1552 p.Article in journal (Refereed) Published
Abstract [en]

Memories become labile when recalled. In humans and rodents alike, reactivated fear memories can be attenuated by disrupting reconsolidation with extinction training. Using functional brain imaging, we found that, after a conditioned fear memory was formed, reactivation and reconsolidation left a memory trace in the basolateral amygdala that predicted subsequent fear expression and was tightly coupled to activity in the fear circuit of the brain. In contrast, reactivation followed by disrupted reconsolidation suppressed fear, abolished the memory trace, and attenuated fear-circuit connectivity. Thus, as previously demonstrated in rodents, fear memory suppression resulting from behavioral disruption of reconsolidation is amygdala-dependent also in humans, which supports an evolutionarily conserved memory-update mechanism.

Place, publisher, year, edition, pages
2012. Vol. 337, no 6101, 1550-1552 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-181451DOI: 10.1126/science.1223006ISI: 000308912900054PubMedID: 22997340OAI: oai:DiVA.org:uu-181451DiVA: diva2:556155
Available from: 2012-09-24 Created: 2012-09-24 Last updated: 2017-12-07Bibliographically approved
In thesis
1. The Amygdala, Fear and Reconsolidation: Neural and Behavioral Effects of Retrieval-Extinction in Fear Conditioning and Spider Phobia
Open this publication in new window or tab >>The Amygdala, Fear and Reconsolidation: Neural and Behavioral Effects of Retrieval-Extinction in Fear Conditioning and Spider Phobia
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
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. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 140
Keyword
Fear conditioning, phobia, memory reconsolidation, retrieval-extinction, exposure therapy, amygdala, fMRI
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:uu:diva-317866 (URN)978-91-554-9863-4 (ISBN)
Public defence
2017-05-12, Gunnar Johansson salen, Blåsenhus, von Kraemers allé 1A, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2017-04-20 Created: 2017-03-20 Last updated: 2017-04-20

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Ågren, ThomasEngman, JonasFrick, AndreasBjörkstrand, JohannesLarsson, Elna-MarieFurmark, TomasFredrikson, Mats

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