Prefrontal-hippocampal interactions supporting the extinction of emotional memories: the retrieval stopping model

Abstract

Neuroimaging has revealed robust interactions between the prefrontal cortex and the hippocampus when people stop memory retrieval. Efforts to stop retrieval can arise when people encounter reminders to unpleasant thoughts they prefer not to think about. Retrieval stopping suppresses hippocampal and amygdala activity, especially when cues elicit aversive memory intrusions, via a broad inhibitory control capacity enabling prepotent response suppression. Repeated retrieval stopping reduces intrusions of unpleasant memories and diminishes their affective tone, outcomes resembling those achieved by the extinction of conditioned emotional responses. Despite this resemblance, the role of inhibitory fronto-hippocampal interactions and retrieval stopping broadly in extinction has received little attention. Here we integrate human and animal research on extinction and retrieval stopping. We argue that reconceptualising extinction to integrate mnemonic inhibitory control with learning would yield a greater understanding of extinction’s relevance to mental health. We hypothesize that fear extinction spontaneously engages retrieval stopping across species, and that controlled suppression of hippocampal and amygdala activity by the prefrontal cortex reduces fearful thoughts. Moreover, we argue that retrieval stopping recruits extinction circuitry to achieve affect regulation, linking extinction to how humans cope with intrusive thoughts. We discuss novel hypotheses derived from this theoretical synthesis.

Time-dependent emotional memory transformation: Divergent pathways of item memory and contextual dependency.

“…One of the proposed explanations for these null findings is that the formation and processing of memories may be highly heterogenous across participants (Hirst et al, 2009). For instance, some participants may rehearse or reactivate their memories in between encoding and testing, which is known to modulate (autobiographical) memory accessibility (Nadel et al, 2007) or, in contrast, try to stop any retrieval of unpleasant memories (Anderson & Floresco, 2022). Our findings underscore that it is additionally important to consider what components of memory are being assessed, as central memories can be enhanced but contextual elements may be impaired for emotional events (e.g., Brewin et al, 2010; Elzinga & Bremner, 2002).…”

Lipopolysaccharide Exposure Differentially Alters Plasma and Brain Inflammatory Markers in Adult Male and Female Rats

“…Neonatal LPS exposure produces profound alterations in microglial morphology in the PFC in middle-aged male and female rats, indicating an activated state, and an effect that was evident months after challenge. In adult male rats, studies show that 24 h after exposure to a low to moderate dose, LPS increases microglial activity in the PFC [ 19 , 34 ], a brain region that plays a significant role in cognitive performance [ 35 , 36 ]. Notably, activated microglia, specifically in the cortex, associated with inflammatory insult during early postnatal development in rodents, is influenced by CXCL1 signaling [ 37 ], suggesting a role for brain chemokines in microglial activation.…”

Hippocampal-Prefrontal cortex network dynamics predict performance during retrieval in a context-guided object memory task

“…Human studies have shown that prefrontal regions are engaged during retrieval inhibition and that they modulate the activity of downstream areas (Anderson and Floresco, 2021). Interestingly, functional homologous regions in rodents, like the mPFC, have also been associated with retrieval inhibition (Bekinschtein et al, 2018).…”