Dynamic changes in prefrontal cortex involvement during verbal episodic memory formation

During encoding, the neural activity immediately before or during an event can predict whether that event will be later remembered. The contribution of brain activity immediately after an event to memory formation is however less known. Here, we used repetitive Transcranial Magnetic Stimulation (rTMS) to investigate the temporal dynamics of episodic memory encoding with a focus on post-stimulus time intervals. At encoding, rTMS was applied during the online processing of the word, at its offset, or 100, 200, 300 or 400 ms thereafter. rTMS was delivered to the left ventrolateral (VLPFC) or dorsolateral prefrontal cortex (DLPFC). VLPFC rTMS during the first few hundreds of milliseconds after word offset disrupted subsequent recognition accuracy. We did not observe effects of DLPFC rTMS at any time point. These results suggest that encoding-related VLPFC engagement starts at a relatively late processing stage, and may reflect brain processes related to the offset of the stimulus

NIBS as a research tool in studying and enhancing episodic memory in the left prefrontal cortex

In the absence of effective treatments for memory disorders including dementia, NIBS methods are being tested for studying and enhancing memory. Anodal transcranial direct-current stimulation (atDCS) is a safe, non-invasive method of stimulating the brain and modulating neural activity through electrodes placed on the scalp. Controversy has surrounded the implementation of atDCS as a research and clinical tool because of inconsistency in effects and a limited understanding of atDCS parameters and mechanisms. Heterogeneity in atDCS parameters across studies could contribute to the inconsistency in effects. Thus, the current research included a systematic ethodological investigation of atDCS as a potential research and clinical tool. Two meta-analyses and a set of five methodological experiments analysed the efficacy of atDCS given a consistent set of parameters. In younger adults, atDCS led to a weak and volatile effect under certain conditions that fluctuated with modifications to verbal stimuli and sample size. While there was a robust improvement in memory following atDCS over the left PFC in Experiment 1, this effect did not remain consistent in direct and conceptual replications. The metaanalyses provided support to this investigation by demonstrating that when effect sizes were pooled together across all eligible published studies, the average effect size was close to zero. When only the studies in the current investigation were pooled together, the effect size was larger but also non-significant. Thus, the results inform future considerations of atDCS as a research and clinical tool and provide recommendations for the limited applications of atDCS with a framework for applying effective parameters that take into account individual differences. Furthermore, through the course of the investigation of atDCS, novel findings about episodic memory processes and neural correlates were revealed, confirming the importance of activity in the ventrolateral prefrontal cortex (VLPFC) to episodic memory formation. These findings on VLPFC function were further extended with an investigation of the cognitive mechanisms of atDCS effects on VLPFC 3 function in Chapter 6 and an examination of the time window and process in the VLPFC that was most crucial to memory formation with repetitive transcranial magnetic stimulation (rTMS) in Chapter 7. Together, the findings contributed to developing a clearer understanding of atDCS effects on episodic memory and the episodic processes that occur in the VLPFC. This understanding can inform future research in NIBS with other cognitive functions and the development of memory nterventions that can target the VLPFC

Adaptability and reproducibility of a memory disruption rTMS protocol in the PharmaCog IMI European project

Transcranial magnetic stimulation (TMS) can interfere with cognitive processes, such as transiently impairing memory. As part of a multi-center European project, we investigated the adaptability and reproducibility of a previously published TMS memory interfering protocol in two centers using EEG or fMRI scenarios. Participants were invited to attend three experimental sessions on different days, with sham repetitive TMS (rTMS) applied on day 1 and real rTMS on days 2 and 3. Sixty-eight healthy young men were included. On each experimental day, volunteers were instructed to remember visual pictures while receiving neuronavigated rTMS trains (20 Hz, 900 ms) during picture encoding at the left dorsolateral prefrontal cortex (L-DLPFC) and the vertex. Mixed ANOVA model analyses were performed. rTMS to the L-DLPFC significantly disrupted recognition memory on experimental day 2. No differences were found between centers or between fMRI and EEG recordings. Subjects with lower baseline memory performances were more susceptible to TMS disruption. No stability of TMS-induced memory interference could be demonstrated on day 3. Our data suggests that adapted cognitive rTMS protocols can be implemented in multi-center studies incorporating standardized experimental procedures. However, our center and modality effects analyses lacked sufficient statistical power, hence highlighting the need to conduct further studies with larger samples. In addition, inter and intra-subject variability in response to TMS might limit its application in crossover or longitudinal studies

Oscillatory power decreases and long-term memory: the information via desynchronization hypothesis

The traditional belief is that brain oscillations are important for human long-term memory, because they induce synchronized firing between cell assemblies which shapes synaptic plasticity. Therefore, most prior studies focused on the role of synchronization for episodic memory, as reflected in theta (∼5 Hz) and gamma (>40 Hz) power increases. These studies, however, neglect the role that is played by neural desynchronization, which is usually reflected in power decreases in the alpha and beta frequency band (8–30 Hz). In this paper we present a first idea, derived from information theory that gives a mechanistic explanation of how neural desynchronization aids human memory encoding and retrieval. Thereby we will review current studies investigating the role of alpha and beta power decreases during long-term memory tasks and show that alpha and beta power decreases play an important and active role for human memory. Applying mathematical models of information theory, we demonstrate that neural desynchronization is positively related to the richness of information represented in the brain, thereby enabling encoding and retrieval of long-term memories. This information via desynchronization hypothesis makes several predictions, which can be tested in future experiments

Modulating episodic memory formation using non-invasive brain stimulation

Oscillatory activity in the beta frequency range accompanies the formation of long-term memories. Beta power decreases have frequently been shown to correlate with memory formation. However, the causal relationship between beta desynchronization and episodic memory encoding remains unclear. This thesis investigates the causal role beta oscillations play in memory formation and explores ways in which non-invasive brain stimulation can be used to test these causal mechanisms. More specifically, this thesis investigates whether increasing beta power impairs memory formation and whether decreasing beta power improves memory. We used two different non-invasive brain stimulation techniques: tACS was used to increase beta power and impair memory formation, while rTMS was used as a means of decreasing beta power and enhancing memory performance. Chapters 2 and 3 indicate that transient beta tACS does not modulate beta oscillations and does not impair memory formation, while slow rTMS effectively enhanced memory formation by modulating beta power in remote areas, in Chapter 4. This thesis emphasises that negative results are not only important, but necessary to advance our understanding of how non-invasive brain stimulation can help us unravel the causal role that beta oscillatory activity plays in the formation of episodic memories

The effect of interference on reactivation of spatial memories in reconsolidation model by using an innovative experimental paradigm in healthy young adults at the behavioral level

La mémoire déclarative est définie comme notre capacité à acquérir des faits et des événements qui font l'objet d'un souvenir conscient. Après la phase d'encodage, de nouvelles mémoires subissent des transformations hors ligne, qui permettent aux traces initialement labiles de se fixer dans la structure physique du cerveau; un processus appelé consolidation. Il existe également des preuves accumulées qu'une fois qu'une mémoire consolidée est réactivée ou récupérée, cette dernière passe par un processus de reconsolidation au cours duquel elle peut être dégradée, maintenue ou améliorée. Dans la présente étude, nous avons cherché à répondre à la question suivante: Les traces consolidées récupérées sont-elles susceptibles d'être perturbées par le même type d'information? Et quel serait l'effet de l'interférence sur différents tests de reconnaissance comparant les deux groupes. Méthode: Nous avons développé une tâche basée sur le travail de Sonni et al. (Sonni and Spencer 2015), où les sujets devaient apprendre à localiser 36 images d'objets du quotidien situées sur un écran d'ordinateur. 40 sujets en bonne santé (25,03 ± 3,66) ont participé à cette étude. Groupe 1: Interférence (20 sujets); Groupe 2: contrôle (20 sujets). Résultats: Nous avons constaté que l'administration de la matrice B après rappel de la première matrice (Groupe 1) interférait avec la reconsolidation de la mémoire, et augmentait ainsi significativement la quantité d'oubli observée lors de la reprise de la séance le Jour 3. En revanche, nous ne pouvions pas trouver un effet d'interférence dans le groupe de contrôle. Il y avait significativement plus de taux de fausses alarmes dans le groupe d'interférence. Nos résultats confirment l'hypothèse de reconsolidation de la mémoire déclarative, mais des travaux supplémentaires sont nécessaires pour déterminer si les substrats neuronaux et neurophysiologiques qui interviennent dans la reconsolidation sont identiques ou différents de ceux impliqués dans la consolidation.Declarative memory is defined as our capacity to acquire facts and events that are subject to conscious recollection. After the encoding phase, new memories undergo offline transformations, which allow the initially labile traces to become fixed into the physical structure of the brain; a process called consolidation. There is also accumulating evidence that once a consolidated memory is reactivated or retrieved, the latter goes through a reconsolidation process during which it can be degraded, maintained or enhanced. In the present study, we sought to answer the following question: Are retrieved consolidated traces susceptible to disruption by the same type of information? Method: We developed a task based on work by Sonni et al. (Sonni and Spencer 2015), in which subjects were required to learn the location of 36 everyday objects images located on a computer screen. 40 healthy subjects (25.03 ± 3.66) participated in this study. Group 1: Interference (20 subjects); Group 2: control (20 subjects). Results: We found that the administration of the matrix B after recall of the first matrix (Group 1) interfered with reconsolidation of the memory, and thus significantly increase the amount of forgetting seen in the retest session on Day 3. In contrast we could not find any interference effect in the control group. Our results confirm the reconsolidation hypothesis for declarative memory, but further work is needed to identify whether the neural and neurophysiological substrates mediating reconsolidation are the same or different from those involved during consolidation