Lateral asymmetry in the hippocampal response to the remoteness of autobiographical memories

The time scale of hippocampal involvement in retrieving memories, particularly those more remote, is still a matter of debate. Some propose that the hippocampus is not involved in the retrieval of remote memories, whereas others assert that it is necessary for memory retrieval in perpetuity. Functional magnetic resonance imaging was used to examine the effect of remoteness on the neural basis of memory. We used a parametric event-related random-effects design in a large group of subjects to overcome some of the limitations of previous neuroimaging studies. We found that the hippocampi were significantly active during the retrieval of autobiographical memories. Notably, the two hippocampi diverged in their responses to remoteness. The right hippocampus showed a temporal gradient, decreasing in activity the more remote the autobiographical memories. No such effect was apparent in the left hippocampus, suggesting its invariant involvement in remembering autobiographical events throughout the lifespan. The dorsal amygdalas showed a temporal gradient similar to the right hippocampus, but emotional valence and intensity were not directly associated with changes in activity. The current results indicate that consideration of lateral asymmetry may help to broaden the scope of theoretical interpretations concerning hippocampal involvement in remote memory

Shared mechanisms support controlled retrieval from semantic and episodic memory: Evidence from semantic aphasia

Semantic cognition is supported by at least two interactive components: semantic representations and control mechanisms that shape retrieval to suit the circumstances. Semantic and episodic memory draw on largely distinguishable stores, yet it is unclear whether controlled retrieval from these representational systems is supported by shared mechanisms. Patients with semantic aphasia (SA) show heteromodal semantic control deficits following stroke to left inferior frontal gyrus (LIFG), an area implicated in semantic processing plus the control of memory and language. However, episodic memory has not been examined in these patients and although the role of LIFG in semantics is well-established, neuroimaging cannot ascertain whether this area is directly implicated in episodic control or if its activation reflects semantic processing elicited by the stimuli. Neuropsychology can address this question, revealing whether this area is necessary for both domains. We found that: (i) SA patients showed difficulty discarding dominant yet irrelevant semantic links during semantic and episodic decisions. Similarly, recently encoded events promoted interference during retrieval from both domains. (ii) Deficits were multimodal (i.e. equivalent using words and pictures) in both domains and, in the episodic domain, memory was compromised even when semantic processing required by the stimuli was minimal. (iii) In both domains, deficits were ameliorated when cues reduced the need to internally constrain retrieval. These cues could involve semantic information, self-reference or spatial location, representations all thought to be unaffected by IFG lesions. (iv) Training focussed on promoting flexible retrieval of conceptual knowledge showed generalization to untrained semantic and episodic tasks in some individuals; in others repetition of specific associations gave rise to inflexible retrieval and overgeneralization of trained associations during episodic tasks. Although the neuroanatomical specificity of neuropsychology is limited, this thesis provides evidence that shared mechanisms support the controlled retrieval of episodic and semantic memory

Space, time and memory in the medial temporal lobe

This thesis focuses on memory and the representation of space in the medial temporal lobe, their interaction and their temporal structure. Chapter 1 briefly introduces the topic, with emphasis on the open questions that the subsequent chapters aim to address. Chapter 2 is dedicated to the issue of spatial memory in the medial entorhinal cortex. It investigates the possibility to store multiple independent maps in a recurrent network of grid cells, from a theoretical perspective. This work was conducted in collaboration with Remi Monasson, Alexis Dubreuil and Sophie Rosay and is published in (Spalla et al. 2019). Chapter 3 focuses on the problem of the dynamical update of the representation of space during navigation. It presents the results of the analysis of electrophysiological data, previously collected by Charlotte Boccara (Boccara et al., 2010), investigating the encoding of self-movement signals (speed and angular velocity of the head) in the parahippocampal region of rats. Chapter 4 addresses the problem of the temporal dynamics of memory retrieval, again from a computational point of view. A continuous attractor network model is presented, endowed with a mechanism that makes it able to retrieve continuous temporal sequences. The dynamical behaviour of the system is investigated with analytical calculations and numerical simulations, and the storage capacity for dynamical memories is computed. Finally, chapter 4 discusses the meaning and the scope of the results presented, and highlights possible future directions

Telling true from false: cannabis users show increased susceptibility to false memories

Previous studies on the neurocognitive impact of cannabis use have found working and declarative memory deficits that tend to normalize with abstinence. An unexplored aspect of cognitive function in chronic cannabis users is the ability to distinguish between veridical and illusory memories, a crucial aspect of reality monitoring that relies on adequate memory function and cognitive control. Using functional magnetic resonance imaging, we show that abstinent cannabis users have an increased susceptibility to false memories, failing to identify lure stimuli as events that never occurred. In addition to impaired performance, cannabis users display reduced activation in areas associated with memory processing within the lateral and medial temporal lobe (MTL), and in parietal and frontal brain regions involved in attention and performance monitoring. Furthermore, cannabis consumption was inversely correlated with MTL activity, suggesting that the drug is especially detrimental to the episodic aspects of memory. These findings indicate that cannabis users have an increased susceptibility to memory distortions even when abstinent and drug-free, suggesting a long-lasting compromise of memory and cognitive control mechanisms involved in reality monitoring

Event-related brain potential studies of gist-based source memory errors

The experiments presented in this thesis employed a procedure that incorporated two types of memory errors: 'source memory errors' and 'gist-based false recognition', and investigated their underlying mechanisms by recording the ERPs associated with these errors. Subjects studied lists of word pairs formed by pairing one of two, or one of four, associated words with a group of semantically related or unrelated words. At test, subjects differentiated old pairs from 'rearranged pairs', whose initial words had been exchanged, and 'old-new pairs' in which a new second word was paired with an old initial word. The rearranged pairs were either in accordance or not in accordance with the gist of the study pairs. Inaccurate endorsement, or source judgement errors, to these two classes of rearranged pairs were compared. One specific point addressed was whether these memory errors comprise 'recollection' of episodic details, or alternatively, whether these errors solely reflect undifferentiated familiarity. This issue was explored by requesting subjects to report their subjective experiences associated with memory judgments (the Remember/Know procedure) in Experiments One and Three, and by examining the different ERP effects associated with recollection-based recognition memory in Experiments Two, Four, and Five. The first two experiments explored how partial source information derived from gist memories formed at encoding modulates the involvement of recollection processes in source memory errors. Experiments Three and Four explored the necessary conditions for the formation of gist memories that induce recollection-based source judgment errors. The last experiment investigated the relation between brain activity during encoding and subsequent memory judgement accuracy. The results showed that recollection is involved in source judgement errors when the rearranged pairs correspond to the gist of study pairs formed during encoding. Moreover, although correctly classified old pairs and incorrectly classified rearranged pairs appear to engage equivalent processes at the time of retrieval, these two classes of memory judgement appear to depend on qualitatively distinct encoding operations

Mechanisms of Memory Enhancement

The ongoing quest for memory enhancement is one that grows necessary as the global population increasingly ages. The extraordinary progress that has been made in the past few decades elucidating the underlying mechanisms of how long-term memories are formed has provided insight into how memories might also be enhanced. Capitalizing on this knowledge, it has been postulated that targeting many of the same mechanisms, including CREB activation, AMPA/ NMDA receptor trafficking, neuromodulation (e.g. via dopamine, adrenaline, cortisol or acetylcholine) and metabolic processes (e.g. via glucose and insulin) may all lead to the enhancement of memory. These and other mechanisms and/or approaches have been tested via genetic or pharmacological methods in animal models, and several have been investigated in humans as well. In addition, a number of behavioral methods, including exercise and reconsolidation, may also serve to strengthen and enhance memories. By capitalizing on this knowledge and continuing to investigate these promising avenues, memory enhancement may indeed be achieved in the future

Functional specialization and interaction in the amygdala-hippocampus circuit during working memory processing

Both the hippocampus and amygdala are involved in working memory (WM) processing. However, their specific role in WM is still an open question. Here, we simultaneously recorded intracranial EEG from the amygdala and hippocampus of epilepsy patients while performing a WM task, and compared their representation patterns during the encoding and maintenance periods. By combining multivariate representational analysis and connectivity analyses with machine learning methods, our results revealed a functional specialization of the amygdala-hippocampal circuit: The mnemonic representations in the amygdala were highly distinct and decreased from encoding to maintenance. The hippocampal representations, however, were more similar across different items but remained stable in the absence of the stimulus. WM encoding and maintenance were associated with bidirectional information flow between the amygdala and the hippocampus in low-frequency bands (1-40 Hz). Furthermore, the decoding accuracy on WM load was higher by using representational features in the amygdala during encoding and in the hippocampus during maintenance, and by using information flow from the amygdala during encoding and that from the hippocampus during maintenance, respectively. Taken together, our study reveals that WM processing is associated with functional specialization and interaction within the amygdala-hippocampus circuit