The neuropsychological mechanisms of fear learning and memory

Abstract

Soon after experiencing an event, the memory is in an active state until it gets consolidated and encoded into long-term memory. Consolidated memories, once reactivated, become unstable and undergo a re-stabilisation process called reconsolidation, in which they are subject to modification. Interventions applied during the reconsolidation window may modify the original fear memory and prevent the spontaneous recovery and reinstatement of the fear response, leading to a more effective modulation of fear expressions than traditional approaches in which the fear memory is merely inhibited. The four studies reported in this thesis investigates the psychophysiological and neural mechanisms of extinction learning and fear recovery using a reconsolidation-based fear/threat conditioning paradigm. Chapter 1 presents an overview of the thesis and its overarching goal to enhance extinction learning and reduce relapse in anxiety and fear-related disorder. Chapter 2 reviews the literature on threat (or fear) conditioning, awareness and reconsolidation, and their potential to modulate maladaptive fear memories. Chapter 3 presents an experimental study that investigates the extent of attenuation of fear responses, as indexed by pupillometry, during an implicit exposure to conditioned stimuli (N = 59). This study shows that explicit and implicit extinction modulated fear responses and the percentage of fear recovery was higher for implicit than explicit extinction. Chapter 4 assesses the potential of using an implicit reminder cue to reactivate the original fear in a three-day reconsolidation conditioning experiment (N = 61). Although the findings do not support the use of a pre-extinction reminder cue in modulating the reinstatement of fear, the reminded conditioned stimulus (CS) was rated more unpleasant than the non-reminded CS and the safe stimulus following extinction, independent of its perceptual awareness during reactivation. Chapter 5 examines the impact of the reminder-retrieval procedure using an implicit multi-CS conditioning paradigm. In Experiment 3 (N = 36), an unconditioned stimulus reminder cue-induced a distinct pattern of pupil responses for the reminded relative to the non-reminded CS during early extinction. Chapter 6 further investigates the impact of the retrieval-reminder procedure on the neural mechanisms of extinction and the return of fear. In Experiment 4 (N = 22), significant neural activation of the right dorsolateral prefrontal region was observed in the reminded CS relative to the non-reminded CS during early extinction. Importantly, the non-reminded CS evoked stronger neural responses in the right dorsolateral prefrontal cortex and the right hippocampus than the reminded CS following the reinstatement test. Overall, the four experiments provide encouraging physiological and neural evidence for the impact of the retrieval-reminder procedure on extinction learning. Finally, Chapter 7 summarises and integrates the findings into the existing literature, and discusses the clinical implications, limitations and suggestions for future research on modulating maladaptive fear memories.

Date of Award	1 Feb 2021
Original language	English
Awarding Institution	King's College London
Supervisor	Tatia Lee (Supervisor), Jenny Yiend (Supervisor) & Tom Barry (Supervisor)