Abstract

Recently, it has been shown in animals that reactivation of previously consolidated memory trace works to destabilize the trace, thereby rendering it once again labile and sensitive to disruptive treatments. While in this labile state (due to retrieval or reinstantiation of the learning context), the trace may be updated, altered, strengthened or eradicated. This effect, termed ‘reconsolidation’ sheds light on possible treatment options for some patient populations (e.g. PTSD and drug addiction). Many studies have demonstrated that a variety of pharmacological agents can disrupt fear memory reconsolidation if applied immediately after memory reactivation, thereby suggesting that it might be possible to identify pharmacotherapies to be used in tandem with exposure-based therapies to weaken pathogenic memories that are responsible for perpetuating the strength of traumatic or drug paired contextual cues. Investigating the behavioural and electrophysiological sequelae of context and stress in human episodic memory in terms of reconsolidation processing, the experiments reported here represent an important first step in isolating the factors which could allow for strides to be made within this therapeutic realm in humans. Firstly we demonstrated, using visual paired-associates, that episodic processing takes place behaviourally on a conscious, item-familiarity based level. Further, we found that context facilitates episodic stimulus recognition in the same way that it influences episodic word recognition and semantic object identification. Further, we isolated the neural correlates of implicit local context processing, showing that implicit local context interacted to affect learning of paired-associates at a relatively early stage in the information-processing stream and that item-context pairings were processed as a unitary percept rather than as a set of linked elements. The electrophysiological findings suggested that the association between context and stimulus pair occurs unconsciously and somewhat separate from later processing. We ultimately contend, in line with Multiple Trace Theory, that implicit contextual processing of episodic memory remains within the remit of MTL regions, whereas explicit item-based processing no longer relies upon MTL regions at this juncture. We subsequently found that reactivation of a pre-consolidated episodic memory trace allows for the integration of new information into the trace, and that reactivation of an episodic memory trace exerts an immediate effect on memory for that trace. Finally, we attempted to induce reconsolidation-based amnesic effects on episodic memory by disrupting protein synthesis while traces were labile; data showed that stressed participants appear to lose the ability to distinguish “true” and “false” memories when stressed, possibly reflective of the role of both the hippocampal and prefrontal systems in contextual remembering, and the modulation of these systems by stress. These findings have implications for treatment of patient groups wherein stress is often a precipitating factor in terms of relapse. Overall, the results emanating from the present thesis have numerous widespread implications for the attenuation of implicit pathological memory traces through reconsolidation of consciously-mediated episodic memory.