Biology subjects

Dunsmoor, J. E.

Publications and source records attributed to Dunsmoor, J. E..

5 recordsLinked to original sources

bioRxiv2025

Enhanced Episodic Memory Following Putative Inhibition of the Amygdala via Transcranial Low-Intensity Focused Ultrasound

The amygdala is considered crucial to the formation of emotional episodic memories, but causal evidence in humans is limited due to challenges in non-invasive neuromodulation of deep brain structures. In a double-blind, sham-controlled, repeated measures study, we examined whether transcranial low-intensity focused ultrasound (tFUS) targeting the left amygdala prior to the encoding of emotional and neutral pictures impacted memory for these pictures 24 hours later. We used a putative inhibitory tFUS protocol shown to attenuate amygdala blood-oxygenation- level-dependent signal, thus testing the hypothesis that pre-encoding amygdala inhibition diminishes emotional memory. Surprisingly, active vs. sham sonication enhanced multiple measures of neutral and emotional memory across two memory tests. A secondary test of amygdala function found that active sonication enhanced fear recognition in faces. Computational modeling further supported these results. These findings motivate a novel conceptualization of the amygdalas role in emotional episodic memory. Rather than enhancing memory via amplification of salient stimuli, the amygdala may instead act as a filter that attenuates the maintenance of non-salient stimuli in long-term memory. Finally, the potential to enhance memory serves as an impetus to test tFUS of the amygdala in disorders such as depression and posttraumatic disorder that exhibit comorbid hyperreactive amygdalae and memory impairments.

neuroscience↗

bioRxiv2024

Unravelling the neurocognitive mechanisms underlying counterconditioning in humans

Counterconditioning (CC) aims to enhance extinction of threat memories by establishing new associations of opposite valence. While its underlying neurocognitive mechanisms remain largely unexplored, previous studies suggest qualitatively different mechanisms from regular extinction. In this functional MRI study, participants underwent categorical threat conditioning (CS+/CS-: images of animals/tools), followed by either CC (CS+ images reinforced with monetary rewards, n=24) or regular extinction (n=24). The following day, we assessed spontaneous recovery of threat responses and episodic memory for CS+ and CS-category exemplars. While the ventromedial prefrontal cortex (vmPFC) was activated during regular extinction, participants undergoing CC showed persistent CS+-specific deactivation of the vmPFC and hippocampus, and CS+-specific activation of the nucleus accumbens (NAcc). The following day, physiological threat responses returned in the regular extinction group, but not in the CC group. Counterconditioning furthermore strengthened episodic memory for CS+ exemplars presented during CC, and retroactively also for CS+ exemplars presented during the threat conditioning phase. Our findings confirm that CC leads to more persistent extinction of threat memories, as well as altered consolidation of the threat conditioning episode. Crucially, we show a qualitatively different activation pattern during CC versus regular extinction, with a shift away from the vmPFC and towards the NAcc.

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↗

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↗

bioRxiv2018

Effects of post-training novelty exposure on contextual fear memory: An attempt to translate behavioral tagging to humans

In rodents, poorly formed hippocampal memories can be improved by novelty exploration within a critical time window, in line with the \"behavioral tagging\" hypothesis. Here, we sought to establish an analogue protocol to investigate if novelty exploration similarly operates to rescue weak hippocampal-dependent memories in humans. Adult humans underwent suboptimal contextual fear conditioning, followed 10 minutes later by open field novelty exploration in immersive 3D virtual reality. Novelty exploration did not improve long-term contextual fear memory, contrary to a behavioral tagging hypothesis. Despite this null result, we suggest further attempts to translate behavioral tagging from rodents to humans is warranted.

neuroscience↗