Biology subjects

Piguet, O.

Publications and source records attributed to Piguet, O..

3 recordsLinked to original sources

bioRxiv2025

Reorganisation of Cortico-Hippocampal White Matter Pathways in Healthy Ageing: Evidence for Paradoxical Shifts in Structural Connectivity.

The hippocampus plays a central role in episodic memory and has been the focus of extensive research over past decades. A substantial body of work has demonstrated that age-related memory decline is linked to changes in how the hippocampus functionally interacts with distributed brain networks. While functional connectivity changes in ageing are well documented, relatively little is known about alterations in the structural connectivity (SC) of the hippocampus, despite its foundational role in supporting communication across neural systems. In this study, we combined high-quality data from the Human Connectome Project and advanced diffusion-weighted imaging (DWI) methods to investigate age-related changes in hippocampal SC. Using a recently developed tractography pipeline that allows greater anatomical specificity than conventional approaches, we systematically compared connectivity patterns between younger (26-30 years) and older (56-60 years) adults. Results revealed reduced hippocampal SC with the entorhinal cortex and medial parietal cortices in older participants, alongside increased SC with anterior temporal areas. This paradoxical pattern suggests that ageing is associated with both vulnerability and reorganisation of hippocampal networks, with increased hippocampal-temporal connectivity potentially reflecting compensatory plasticity in response to reduced posterior medial connection. These findings provide in vivo evidence of cortico-hippocampal structural reorganisation in late middle age, a critical period when pathological processes such as tau deposition are already detectable in cognitively healthy individuals. More broadly, they demonstrate the power of our anatomically refined tractography pipeline as a proof of concept for detecting subtle, regionally specific changes in hippocampal pathway density. This approach holds promise for charting normative ageing trajectories and identifying early biomarkers of vulnerability and compensation in memory-related networks.

neuroscience↗

bioRxiv2025

Reduced plasma hexosylceramides in frontotemporal dementia are a biomarker of white matter integrity

INTRODUCTIONBlood biomarkers are needed to facilitate new therapeutic trials and improve management of behavioural variant frontotemporal dementia (bvFTD). Since altered white matter integrity is characteristic of bvFTD, this study aimed to determine if plasma levels of myelin-enriched glycolipids are altered in bvFTD and correlate with white matter integrity. METHODSNineteen glycolipids were quantified in bvFTD (n=31) and control (n=26) plasma samples. White matter integrity was assessed using MRI-derived fibre tract density and cross-section (FDC). RESULTSEleven lipids were significantly lower in bvFTD compared to control subjects, seven were inversely correlated with disease duration, and twelve were positively correlated with cognitive performance, with C22:0 hexosylceramide most strongly correlated. FDC was lower in frontotemporal white matter tracts of bvFTD compared to control subjects, and plasma C22:0 hexosylceramide was significantly correlated with FDC in these tracts. DISCUSSIONCirculating glycolipids may be a valuable biomarker of myelin integrity and disease progression in FTD.

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↗