How Aging Affects Sleep-Dependent Memory Consolidation?

Memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, termed memory consolidation. Numerous data indicate that sleep plays a major role in this process, notably due to the specific neurochemical environment and the electrophysiological activity observed during the night. Two putative, probably not exclusive, models (“hippocampo-neocortical dialogue” and “synaptic homeostasis hypothesis”) have been proposed to explain the beneficial effect of sleep on memory processes. However, all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults. This review outlines the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging

Etude en imagerie cérébrale fonctionnelle du rôle du sommeil dans la consolidation de souvenirs épisodiques chez le sujet jeune et au cours du vieillissement normal

De nombreux travaux indiquent que le sommeil favorise la consolidation mnésique via une réorganisation des réseaux cérébraux sous-jacents. Jusqu à présent, les études ont été conduites auprès de sujets jeunes et l intérêt pour les liens entre sommeil et mémoire chez les personnes âgées a été négligé. Cette thèse vise à mieux comprendre la façon dont le sommeil module le processus de consolidation au cours du vieillissement normal. Trois études ont été conduites auprès de sujets jeunes ayant dormi ou ayant été privé de sommeil après l apprentissage d images émotionnelles et neutres, et un groupe de sujets âgés ayant dormi sous contrôle polysomnographique. L ensemble des sujets était revu lors d une épreuve de reconnaissance sous IRM, 3 jours et 3 mois après l apprentissage afin de mettre en évidence les réseaux cérébraux impliqués lors de la récupération de souvenirs à moyen et plus long terme. La première étude a précisé l implication de l hippocampe dans la consolidation mnésique en fonction de la nature du souvenir. Les deuxième et troisième études ont évalué l effet du sommeil sur le processus de consolidation de souvenirs émotionnels. Les résultats montrent qu en l absence de différences comportementales notables, ce processus peut être perturbé par la privation de sommeil ou au cours du vieillissement normal. Cette perturbation serait en partie liée à un défaut de connectivité entre l amygdale et le cortex préfrontal ventromédian. Chez les sujets âgés, la réduction de l activité à ondes lentes du sommeil pourrait également compromettre ce processus.Numerous studies indicate that sleep favors episodic memory consolidation, leading to the functional reorganization of cerebral networks supporting this process. If the role of sleep in memory consolidation has been largely investigated in young healthy subjects, little is known about this process in aging. Using fMRI, this thesis aimed at better understanding the effect of sleep on memory consolidation in older adults. Studies were conducted in young and old healthy subjects who slept after learning emotional and neutral pictures and in young subjects who were sleep-deprived after learning. Sleep was recorded in older adults. All these subjects performed an fMRI recognition task 3 days and 3 months after learning to assess mid-term and long-term memory consolidation respectively. The first study demonstrated the role of the hippocampus in memory consolidation according to the episodic or semantic nature of memories. The second and third studies assessed the role of sleep in emotional memory consolidation. Despite the lack of obvious behavioural differences, we showed that sleep deprivation and increasing age are two conditions that may hinder this process. More precisely, we reported that this impairment is associated with decreased coupling between the amygdala and the ventromedial prefrontal cortex. Furthermore, disruption of slow-wave activity disruption in older subjects may also compromise this process.CAEN-BU Droit Lettres (141182101) / SudocSudocFranceF

The hippocampus remains activated over the long term for the retrieval of truly episodic memories.

International audienceThe role of the hippocampus in declarative memory consolidation is a matter of intense debate. We investigated the neural substrates of memory retrieval for recent and remote information using functional magnetic resonance imaging (fMRI). 18 young, healthy participants learned a series of pictures. Then, during two fMRI recognition sessions, 3 days and 3 months later, they had to determine whether they recognized or not each picture using the "Remember/Know" procedure. Presentation of the same learned images at both delays allowed us to track the evolution of memories and distinguish consistently episodic memories from those that were initially episodic and then became familiar or semantic over time and were retrieved without any contextual detail. Hippocampal activation decreased over time for initially episodic, later semantic memories, but remained stable for consistently episodic ones, at least in its posterior part. For both types of memories, neocortical activations were observed at both delays, notably in the ventromedial prefrontal and anterior cingulate cortices. These activations may reflect a gradual reorganization of memory traces within neural networks. Our data indicate maintenance and strengthening of hippocampal and cortico-cortical connections in the consolidation and retrieval of episodic memories over time, in line with the Multiple Trace theory (Nadel and Moscovitch, 1997). At variance, memories becoming semantic over time consolidate through strengthening of cortico-cortical connections and progressive disengagement of the hippocampus

Experimental design.

<p>On day 1, participants were instructed to rate the valence of a series of emotional (positive and negative) and neutral colored pictures and to memorize them. Memory performance was tested on day 4 () and day 90 (±7 days, ) using a recognition task associated with the Remember/Know/Guess paradigm. Functional MRI data were acquired during these recognition sessions. After each session, all pictures that received an R response were presented again outside the scanner during a debriefing interview, to obtain from subjects a justification of their R responses with contextual details. Note that the same learned (“old” pictures) were used for both retrieval sessions allowing to track the fate of memories and their possible qualitative change over time. Thus, we distinguished consistently familiar or semantic memories (KK), consistently episodic memories (RR) and those that were initially episodic and became later semantic (RK). Distracter stimuli were different between the two recognition sessions. The pictures used in the figure are not the original IAPS images, but similar items used for illustrative purposes only.</p

Brain areas commonly activated at 3 months for to the retrieval of consistently episodic memories (RR) and initially episodic, then semantic memories (RK) (inclusive masking at p<0.001).

<p>x, y, z = coordinates in mm in the Montreal Neurological Institute space. For brevity, each region is listed only once; when several peaks were observed in the same region, the coordinates refer to the strongest activation. Minimum cluster size: 10 contiguous voxels.</p

Results of ROI analyses in the hippocampus.

<p>A. Hippocampal activity (mean ± SEM) according to the nature of memories (RR <i>vs</i> RK responses) and delay (3 days <i>v</i>s 3 months). *: p<0.05, ***: p<0.001. B. Hippocampal activity (mean ± SEM) for RR responses according to the delay (3 days <i>vs</i> 3 months) distinguishing the anterior and posterior parts. ***: p<0.001.</p

Brain areas in which activity during the retrieval of initially episodic, later semantic memories (RK) compared to correct rejections is higher after the 3-day than the 3-month delay or conversely.

<p>x, y, z = coordinates in mm in the Montreal Neurological Institute space. All regions listed are statistically significant at p<0.05 (FWE corrected, *) or psvc<0.05 (**), after correction in a small spherical volume (10 mm) around coordinates previously reported in the literature (specified in the last column). For brevity, each region is listed only once; when several peaks were observed in the same region, the coordinates refer to the strongest activation. Minimum cluster size: 10 contiguous voxels.</p

Brain areas associated to the retrieval of initially episodic, later semantic memories (RK responses) compared to correct rejections at the 3-month delay.

<p>x, y, z = coordinates in mm in the Montreal Neurological Institute space. All regions listed are statistically significant at p<0.05 (FWE corrected, *) or psvc<0.05 (**), after correction in a small spherical volume (10 mm) around coordinates previously reported in the literature (specified in the last column). For brevity, each region is listed only once; when several peaks were observed in the same region, the coordinates refer to the strongest activation. Minimum cluster size: 10 contiguous voxels.</p

Brain areas associated to the retrieval of initially episodic, later semantic memories (RK responses) compared to correct rejections at the 3-day delay.

<p>x,y,z = coordinates in mm in the Montreal Neurological Institute space. All regions listed are statistically significant at p<0.05 (FWE corrected, *) or psvc<0.05 (**), after correction in a small spherical volume (10 mm) around coordinates previously reported in the literature (specified in the last column). For brevity, each region is listed only once; when several peaks were observed in the same region, the coordinates refer to the strongest activation. Minimum cluster size: 10 contiguous voxels.</p

Brain areas in which activity during the retrieval of consistently episodic memories (RR) compared to correct rejections is higher after the 3-day than the 3-month delay or conversely.

<p>x, y, z = coordinates in mm in the Montreal Neurological Institute space. All regions listed are statistically significant at p_svc<0.05, after correction in a small spherical volume (10 mm) around coordinates previously reported in the literature (specified in the last column).</p