A Successful Approach to Reduce Phobic Behavior

Investigators used fMRI to examine whether disruption of long-term fear memory reconsolidation can attenuate the activity in the amygdala at re-exposure to fear cues.
Investigators used fMRI to examine whether disruption of long-term fear memory reconsolidation can attenuate the activity in the amygdala at re-exposure to fear cues.

In a new study published in Current Biology, researchers at the Karolinska Institutet and Uppsala University in Sweden explored whether disrupting the process of memory reconsolidation can attenuate “naturally occurring” long-term fears in humans. Previous findings indicate that disrupting reconsolidation can attenuate experimental, conditioned fear memories, but this had yet to be shown for natural, decades-old memories of fear.

It is well established that once consolidated, long-term memory is in a highly labile phase in which it is susceptible to disruption upon its reactivation, and must be stabilized through a process termed reconsolidation. Reconsolidation of memory occurs in a broad range of learning paradigms and species, and the instable period (ie, labile phase) of the memory reconsolidation process persists for several hours after memory retrieval.

Additionally, it is has been shown that both memory consolidation and memory reconsolidation require de novo protein synthesis for the memory to persist further. However, the molecular mechanisms underlying these 2 processes are different. More specifically, brain-derived neurotrophic factor (BDNF) is selectively required for memory consolidation in the hippocampus or the amygdala, whereas the transcription factor zinc finger-268 (Zif-268) is selectively required for reconsolidation of memory, but BDNF is not.

In the current study, investigators recruited individuals [n=45; 33 women; mean age=26.2 (SD=7.57)] with a lifelong fear of spiders. They used functional brain imaging (fMRI) to examine whether disruption of reconsolidation, by repeated exposure to feared cues (ie, images of spiders) at 10 minutes post-fear memory activation, can attenuate the activity in the basolateral amygdala at re-exposure to cues 24 hours later. They compared the activity in the amygdala [at re-exposure to cues 24 hours later] in this group of participants with the amygdala activity in the group of individuals who were repeatedly exposed to fear cues at 6 hours after the initial fear memory activation. “Thus, one slide used to activate the long-term fear memory was followed by repeated exposure when the fear memory representation was [unstable] in the 10 minute group, but [stable] in the 6 hour group,” the authors wrote in their publication.

In line with previous reports, images of spiders during first exposure enhanced the reactivity of the amygdala in both groups of participants (ie, 10 minute and 6 hour group), when compared with activity in the amygdala when neutral images (ie, images of mushrooms) were presented on the screen. The activity in the amygdala of both groups was reduced after the repeated exposure to images of spiders (ie, this procedure is equivalent to fear extinction training in experimental, fear conditioning procedures).

Next, investigators compared the change in BOLD reactivity within the amygdala during repeated exposure on day 1 (ie, 10 minutes after the initial exposure to fear cues in group 1, or 6 hours after the initial exposure to fear cues in group 2) to re-exposure on day 2 (ie, 24 hours post-initial fear cue exposure). “We found support for the central hypothesis that repeated exposure within, but not outside, the reconsolidation interval affects the neural fear representation because amygdala reactivity to the activated and exposed stimulus was attenuated in the 10 minute group [group 1] but significantly enhanced in the 6 hour group [group 2] on day 2 as compared to day 1,” investigators wrote.

With regard to the behavioral findings, investigators used a validated behavioral approach-avoidance task to show that group 1 participants (ie, 10 minute group) were significantly more likely, compared with group 2 participants (ie, 6 hour group), to choose to watch the images of spiders when given a choice between spider images or neutral images. However, these between-group differences were observed only when the participants were offered higher-end (2 or 5 Swedish Krona), rather than lower-end (0.1, 0.5, or 1 Swedish Krona), monetary rewards for viewing the images of spiders. Also, the amygdala reactivity significantly predicted the approach or avoidant behavior in the behavioral task.

The above neural and behavioral findings hold great clinical significance, as “decades-old fear memories are…. sensitive to behavioral disruption, and the amygdala seems to hold a key brain representation not only of experimentally induced fear associations, but also of long-term fears acquired in natural settings outside of the laboratory,” the authors concluded.

Reference

Björkstrand J, Agren T, Åhs F, et al. Disrupting reconsolidation attenuates long-term fear memory in the human amygdala and facilitates approach behavior. Curr Biol. 2016. doi: 10.1016/j.cub.2016.08.022.

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