Memory updating has been established; however, the mechanism supporting this alteration process is subject to disagreement. Reconsolidation theorists argue that memory updating occurs via an old memory becoming reactivated and returned to a state of susceptibility. In this state, newly presented details can become incorporated into the existing memory. As such, memory updating is an effect of old memory reactivation and new information encoding. In contrast, temporal context theory argues that the temporal context in which the old memory was initially formed is reinstated. Newly presented information becomes tagged to the old context. Therefore, at retrieval, when the old context is reinstated again, the initially bound information and the newer information are simultaneously retrieved. Within this theoretical framework, memory modification is the result of retrieval effects. In contrast, this three-paper dissertation provides evidence that reconsolidation is, at least in part, a combined reactivation and encoding effect. In paper 1, I present neural evidence of both old memory reactivation and new encoding, which demonstrates 1) that strength at reactivation predicts the likelihood that a memory will be modified and 2) that greater brain activation during new encoding predicts the extent of accurate recognition. In paper 2, I show that encoding conditions affect the extent to which new information will be misattributed to the old memory. I demonstrate that learners update explicitly encoded memories but not implicitly coded ones. Lastly, in paper 3, I demonstrate that old memories can be reactivated and altered during sleep. When old-memory reactivation is paired with a forget cue, a subsequent degeneration of the memory and its details ensues. In sum, all three papers provide evidence in support of the reconsolidation theory that memory updating occurs during old-memory reactivation and new encoding.

Emotion is thought to modulate the long-term fate of memories. Experiences that elicit an emotional response tend to be better remembered than comparatively unemotional events, while the emotional charge associated with these memories diminishes over time. Sleep – in particular rapid-eye movement (REM) and slow-wave sleep (SWS) - has been implicated in both the selective strengthening and affective uncharging of emotional memories. According to the sleep to forget, sleep to remember (SFSR) hypothesis, both processes occur in parallel during REM sleep. Although evidence strongly supports a role of REM sleep in the selective consolidation of emotional memories, it is far less clear to what extent sleep is involved in the development of emotional charge. While some studies support a primary role of REM in habituation (i.e. the decrease of emotional charge), others suggest a more central role of SWS. Further, existing literature indicates that the physiological (bottom-up) and cognitive (top-down) components of emotional responses may be differentially processed across sleep. Chapter 2 proposes complementary functions of REM and SWS in emotional memory processes based on a combination of evidence from rodent and human research. The experiments presented in this thesis employed polysomnography (PSG), subjective arousal testing, pupillometry, targeted memory reactivation (TMR), and transcranial alternating current stimulation (tACs) to investigate the respective roles of REM and SWS in the overnight development of subjective and autonomic arousal in response to negative emotional and neutral stimuli. In Chapter 3 I assessed how subjective and autonomic responses to neutral and negative stimuli develop across 12 hours containing either nocturnal sleep or daytime wakefulness. I found that autonomic reactivity – indexed by pupil dilation – decreased across sleep but not wake, while subjective arousal did not change across either interval. In a further experiment, I investigated whether the placement of sleep within a 24 hour interval would affect habituation. Once again, autonomic arousal decreased significantly. Subjective arousal towards negative stimuli was found to decrease more if sleep followed rather than preceded daytime wakefulness within the 24 hour interval. In Chapter 4 I explored the role of REM sleep in emotional habituation by applying 5 Hz tACs in an attempt to entrain endogenous cortical theta (4-7 Hz) activity, which has previously been associated with emotional memory consolidation in humans. Surprisingly, I found that stimulation was associated with a reduction in theta power and no change in subjective or autonomic habituation compared to the sham control night. In Chapters 5 and 6, I addressed the contribution of memory reactivations during SWS and REM sleep, respectively, in emotional habituation using TMR. In Chapter 5, I found that TMR was associated with a decrease and simultaneous increase in autonomic habituation towards negative and neutral stimuli, respectively, without affecting overnight changes in subjective arousal. In contrast, in Chapter 6, TMR during REM sleep was associated with an increase in subjective habituation towards both neutral and negative stimuli without affecting autonomic responses. In conclusion, my results provide new insights to the role of sleep in emotional habituation. I have provided evidence that targeted memory reactivation during REM sleep can modulate the development of cognitive evaluations of emotion, while TMR during SWS may interfere with autonomic habituation. This suggests distinct emotional processing during REM and SWS, as well as a dissociation between subjective and autonomic habituation across sleep. These results are discussed in the light of previous research and the model of sleep-dependent emotional memory processing proposed in Chapter 2.

The method targeted memory reactivation (TMR) uses specific stimulation when subjects are completing tasks and during sleep. The TMR process is known to influence the consolidation of declarative memories. The aim of this thesis is to conduct a systematic review on the effects of TMR on declarative memory consolidation during slow-wave sleep (SWS). The research question is to answer what effect TMR during SWS has on the consolidation of declarative memory in healthy humans when presented with associated cues of the targeted learning experiences. Eighteen studies were included in this review. Four studies found a significant effect of TMR on declarative memory consolidation, and 10 found a non-significant effect. In four studies the effect of TMR depended on different inclusions, analyses, and factors, for example between slow oscillation up-and down-states and between participants that vary in pre-sleep performance in the examined task. In contrast to previous findings, this review does not provide evidence for the effect of TMR on declarative memories during SWS. More research analysing different factors, such as different cues, age of participants, duration of SWS, and specific experimental tasks, needs to be done in the fields of TMR and auditory cues.

Why are some memories easy to retrieve, while others are more difficult to access? Here, we tested whether we could bias memory replay, a process whereby newly learned information is reinforced by reinstating the neuronal patterns of activation that were present during learning, towards particular memory traces. The goal of this biasing is to strengthen some memory traces, making them more easily retrieved. To test this, participants were scanned during interleaved periods of encoding and rest. Throughout the encoding runs, participants learned triplets of images that were paired with semantically related sound cues. During two of the three rest periods, novel, irrelevant sounds were played. During one critical rest period, however, the sound cues learned in the preceding encoding period were played in an effort to preferentially increase reactivation of the associated visual images, a manipulation known as targeted memory reactivation. Representational similarity analyses were used to compare multi-voxel patterns of hippocampal activation across encoding and rest periods. Our index of reactivation was selectively enhanced for memory traces that were targeted for preferential reactivation during offline rest, both compared to information that was not targeted for preferential reactivation and compared to a baseline rest period. Importantly, this neural effect of targeted reactivation was related to the difference in delayed order memory for information that was cued versus uncued, suggesting that preferential replay may be a mechanism by which specific memory traces can be selectively strengthened for enhanced subsequent memory retrieval. We also found partial evidence of discrimination of unique temporal sequences within the hippocampus. Over time, multi-voxel patterns associated with a given triplet sequence became more dissimilar to the patterns associated with the other sequences. Furthermore, this neural marker of sequence preservation was correlated with the difference in delayed order memory for cued versus uncued triplets, signifying that the ability to reactivate particular temporal sequences within the hippocampus may be related to enhanced temporal order memory for the cued information. Taken together, these findings support the claim that awake replay can be biased towards preferential reactivation of particular memory traces and also suggest that this preferential reactivation, as well as representations of reactivated temporal sequences, can be detected within patterns of hippocampal activation. / Psychology

This doctoral thesis aimed at better understanding the contribution of sleep, Targeted Memory Reactivation and transcranial Direct Current Stimulation (tDCS) on the consolidation of neutral and emotional memories. In the first part of this work, we found that REM-enriched naps and more specifically rapid eye movement density is associated with the consolidation of sad stories, suggesting a possible implication of Ponto-Geniculo-Occipital (PGO) waves in the consolidation of sad information. In addition, we observed an increase in emotional reactivity during re-exposure to the sad story following a REM-enriched nap. We postulate that REM sleep favored the consolidation of the emotionalsalience of the sad memories, leading to exacerbated emotional reactivity during re-exposure. We also investigated the impact of TMR during NREM sleep on the consolidation of neutral and negative word pairs leanred with a specific sound. We found an equal benefit of the TMR procedure on neutral and emotional material, suggesting that emotion does not modulate the selective enhancing effect of TMR during NREM sleep. In an additional study, we tested the impact of verbatim presentation of the pairs of words during NREM sleep and did not find the memory benefits of TMR. We ascribed the absence of TMR memory benefit to the detrimental effect of the auditory presntation of the second word which impaired the memory reactivation processes initiated by the presentation of the first word. Together, theseresults indicate the crucial role of a sensitive plastic time window necessary for the successful processes of memory reactivation during sleep. Finally, we evaluated how the combination of tDCS and TMR procedure during a wakeful rest consolidation interval benefits memory consolidation. We found that TMR alone led to selective memory benefits for cued word pairs. When the TMR procedure was combined with either right-anodal or left anodal tDCS, we observed a significant improved global learning, suggesting that tDCS does not potentiate but overshadows the TMRprocedure. Altogether, these studies offer new perspectives in the field of memory consolidation. More specifically, the application of an alternating current during post-learning sleep concomitantly to a TMR procedure might favor the specific brain oscillations involved in successful memory reactivation, and might enhance the associated memory gains. / Doctorat en Sciences psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished