Hennings, A. C. | Search bioRxiv

bioRxiv2021

Rewarded extinction increases amygdalar connectivity and stabilizes long-term memory traces in the vmPFC

Neurobiological evidence in rodents indicates that threat extinction incorporates reward neurocircuitry. Consequently, incorporating reward associations with an extinction memory may be an effective strategy to persistently attenuate threat responses. Moreover, while there is considerable research on the short-term effects of extinction strategies in humans, the long-term effects of extinction are rarely considered. In a within-subjects fMRI study, we compared counterconditioning (a form of rewarded-extinction) to standard extinction, at recent (24 hours) and remote ([~]1 month) retrieval tests. Relative to standard extinction, counterconditioning diminished 24-hour relapse of arousal and threat expectancy, and reduced activity in brain regions associated with the appraisal and expression of threat (e.g., thalamus, insula, periaqueductal gray). The retrieval of reward-associated extinction memory was accompanied by functional connectivity between the amygdala and the ventral striatum, whereas the retrieval of standard-extinction memories was associated with connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). One-month later, the retrieval of both standard- and rewarded-extinction was associated with amygdala-vmPFC connectivity. However, only rewarded extinction created a stable memory trace in the vmPFC, identified through overlapping multivariate patterns of fMRI activity from extinction to 24-hour and 1-month retrieval. These findings provide new evidence that reward may generate a more stable and enduring memory trace of attenuated threat in humans. Significance StatementPrevalent treatments for pathological fear and anxiety are based on the principles of Pavlovian extinction. Unfortunately, extinction forms weak memories that only temporarily inhibit the retrieval of threat associations. Thus, to increase the translational relevance of extinction research, it is critical to investigate whether extinction can be augmented to form a more enduring memory, especially after long intervals. Here, we used a multi-day fMRI paradigm in humans to compare the short- and long-term neurobehavioral effects of aversive-to-appetitive counterconditioning, a form of augmented extinction. Our results provide novel evidence that including an appetitive stimulus during extinction can reduce short-term threat relapse and stabilize the memory trace of extinction in the vmPFC, for at least one month after learning.

neuroscience↗

bioRxiv2019

Neural reinstatement guides context-dependent emotional memory retrieval

Reactivating the memory of a context improves retrieval of information learned in that context. But does context reactivation resolve memory competition between related but conflicting emotional experiences? Here, we asked whether spontaneously retrieved episodic context disambiguates competing memories of fear and safety in the healthy brain and in posttraumatic stress disorder. During fMRI, subjects learned that items from an object category were a threat, and then learned that different items from the same category were safe in a unique context. The next day, subjects viewed new threat ambiguous stimuli from the same category and reported their expectation of threat. Multivoxel pattern analysis (MVPA) was used to identify and decode neural patterns unique to the context of safety learning. We show that in healthy adults the degree of neural reinstatement of the safe context predicted activity to threat ambiguous stimuli in the ventromedial prefrontal cortex (vmPFC) and hippocampus, regions important for contextual modulation of emotional memory retrieval. The degree of context reinstatement also disambiguated subjects feelings of threat versus safety. In contrast, context reinstatement did not resolve emotional memory retrieval in subjects with PTSD, indicating a contextual processing deficit in this group. Finally, multivoxel pattern similarity between safe and threat ambiguous stimuli overlapped in the vmPFC in healthy adults but not in PTSD. These findings reveal how neural reinstatement helps resolve context-dependent memory retrieval between opposing sources of emotional information. Understanding how the human brain separately encodes and retrieves competing memories of related events has broad implications for the study of emotional memory, associative learning, and the neuropathophysiology of affective disorders.

neuroscience↗