Pattern separation of fear extinction memory

Abstract

While fear generalizes widely, extinction is stimulus-specific. Using a hybrid conditioning/episodic memory paradigm, subjects encoded nonrepeating category exemplars during fear conditioning and extinction. Twenty-four hours later, a surprise memory test included old, similar, and novel category exemplars. Results showed strong dissociation between pattern completion (generalization) and pattern separation (discrimination) in episodic memory for items encoded during fear conditioning versus extinction, respectively. These data suggest that directly threat-conditioned stimuli are better recognized at the expense of mnemonic precision, whereas discrimination is enhanced for extinguished stimuli. Overly precise extinction memory may be a contributing factor to fear relapse.

Integrating and fragmenting memories under stress and alcohol

“…Nevertheless, further empirical evidence supports the idea of greater integration , rather than fragmentation, with a single . For example, recent evidence indicates that healthy participants misattributed cues presented during extinction as having been presented during conditioning (particularly for exemplars from the shock-paired category), perhaps reflecting broad integration with the same underlying LC ( Hennings et al, 2021 ; Laing and Dunsmoor, 2023 ). A study of patients with PTSD also found that these individuals were impaired at differentiating their expectation of shock between contexts that were and were not paired with shock, and this impoverished differentiation was associated with more severe PTSD symptoms ( Steiger et al, 2015 ).…”

Resetting the Hippocampal Buffer: A Neurocognitive Account of Psychedelic Therapy for Anxiety-Related Psychopathology

“…The postacute period of heightened cortical plasticity may facilitate the re-balancing of cortical network interactions (i.e., more balanced deployment of the DMN/ECN via the SN; Daws et al, 2022;Pasquini et al, 2020;Sampedro et al, 2017). The potential for psychedelics to drive hippocampal neurogenesis could also aid in differentiating aversive from non-aversive cues via pattern separation (the differentiation of similar inputs to minimize mnemonic interference; Laing & Dunsmoor, 2023;Yassa & Stark, 2011). This "resetting of the hippocampal buffer" may be in contrast to SSRIs that may dampen symptoms of anxiety but can also attenuate new learning that could otherwise provide long-term relief in anxiety-related psychopathology following cessation of SSRI treatment (Burghardt & Bauer, 2013).…”

“…Given that psychedelics can post-acutely enhance extinction learning (Cameron et al, 2019;de la Fuente Revenga et al, 2021), exposure therapy (Hamlett et al, 2023;Pittig et al, 2016) may be facilitated. However, if hippocampal function, particularly pattern separation, is enhanced (Hibicke et al, 2023;Morales-Garcia et al, 2020;Wießner et al, 2022), this could lead to extinction that fails to generalize to new contexts (Laing & Dunsmoor, 2023). The heightened period of cortical plasticity may be opportune for other forms of cognitive behavioral therapy, which includes techniques for revising maladaptive beliefs (Hofmann et al, 2012).…”

Pavlovian safety learning: an integrative theoretical review

“…When tested ~24hrs after conditioning, items resembling CS+ from fear conditioning are rated 'old' (generalized) whereas those resembling items encoding during extinction were discriminated as 'new' (Laing & Dunsmoor, 2023Starita et al, 2019). In other words, despite showing equivalent overall memory accuracy, fear-and safety-associated stimuli diverge markedly in how memories are generalized (fear) or discriminated (safety).…”