Leiker, E. K. | bioRxiv Science

bioRxiv2022

Distinguishing strategic orienting toward memory age from retrieval difficulty: An ERP study

A well-established finding in episodic memory research is that the likelihood of successful retrieval is affected by the age of the targeted memory (i.e. based on the duration of the encoding-retrieval interval). Although such findings are usually interpreted in terms of the memory trace changing in quality or accessibility over time, there is growing evidence that memory performance also depends on preparatory attention and strategic orienting at the time of retrieval. Here, we investigated such readiness to retrieve, as indexed by event-related brain potentials (ERPs), when memory retrieval was aimed toward candidate traces of different ages. As retrieving remote versus recent memories is associated with increased difficulty, the current study was designed to dissociate difficulty from the memory age effects. Subjects encoded two lists of pictures separated by one week, with the items in each list presented once or four times. A series of memory tests targeting pictures from only one week-by-repetition condition at a time were then completed, while new pictures and those from the other conditions were rejected. Consistent with previous results, new-item ERPs were more positive over posterior scalp when recent compared to remote lists were targeted. Importantly, this difference remained when difficulty was matched, and the ERP correlates of difficulty were distinct in both timing and polarity from those of orienting. Together, these findings provide further support for the idea that the age of a targeted memory alone places different demands on readiness and can lead to the differential adoption of retrieval orienting strategies.

neuroscience↗

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↗