Roquet, D. | Search bioRxiv

bioRxiv2024

Resting-state functional connectivity and fast spindle temporal organization contribute to episodic memory consolidation in healthy aging

Episodic memory consolidation relies on the functional specialization of brain networks and sleep quality, both of which are affected by aging. Functional connectivity during wakefulness is crucial to support the integration of newly acquired information into memory networks. Additionally, the temporal dynamics of sleep spindles facilitates overnight memory consolidation by promoting hippocampal replay and integration of memories within neocortical structures. This study aimed at exploring how resting-state functional connectivity during wakefulness contributes to sleep-dependent memory consolidation in aging, and whether spindles clustered in trains modulates this relationship. Forty-two healthy older adults (68.82 {+/-} 3.03 years), enrolled in the Age-Well clinical trial, were included. Sleep-dependent memory consolidation was assessed using a visuo-spatial memory task performed before and after a polysomnography night. Resting-state functional connectivity data were analyzed using graph theory applied to the whole brain, specific brain networks and the hippocampus. Lower limbic network integration and higher centrality of the anterior hippocampus were associated with better memory consolidation. Spindle trains modulated these effects, such that older participants with longer spindle trains exhibited a stronger negative association between limbic network integration and memory consolidation. These results indicate that lower functional specialization at rest is associated with weaker memory consolidation during sleep. This aligns with the dedifferentiation hypothesis, which posits that aging is associated with reduced brain specificity, leading to less efficient cognitive functioning. These findings reveal a novel mechanism linking daytime brain network organization and sleep-dependent memory consolidation, and suggest that targeting spindle dynamics could help preserve cognitive functioning in aging.

neuroscience↗

bioRxiv2019

Establishing two principal dimensions of cognitive variation in Logopenic Progressive Aphasia

Logopenic Progressive Aphasia (LPA) is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal atrophy. Clinical descriptions of LPA largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits, even on tasks with minimal language demands. Although non-linguistic cognitive deficits in LPA are thought to scale with disease severity, patients at discrete stages of language dysfunction display overlapping cognitive profiles, suggesting individual-level variation in cognitive performance, independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose individual-level variation in cognitive performance in 43 well-characterised LPA patients who underwent multi-domain neuropsychological assessments and structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected speech production and verbal memory deficits which typify LPA. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable Factor 1 scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inter-individual variability in cognitive profiles in comparably logopenic patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralised temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, LPA patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralised temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in cognitive performance at an individual- and group-level in LPA, suggesting the presence of a genuine co-occurring cognitive impairment that is independent of language function and disease severity.

neuroscience↗