Publication
Title
Early altered directionality of resting brain network state transitions in the TgF344-AD rat model of Alzheimer's disease
Author
Abstract
Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disease resulting in memory loss and cognitive decline. Synaptic dysfunction is an early hallmark of the disease whose effects on whole-brain functional architecture can be identified using resting-state functional MRI (rsfMRI). Insights into mechanisms of early, whole-brain network alterations can help our understanding of the functional impact of AD's pathophysiology.Methods Here, we obtained rsfMRI data in the TgF344-AD rat model at the pre- and early-plaque stages. This model recapitulates the major pathological and behavioral hallmarks of AD. We used co-activation pattern (CAP) analysis to investigate if and how the dynamic organization of intrinsic brain functional networks states, undetectable by earlier methods, is altered at these early stages.Results We identified and characterized six intrinsic brain states as CAPs, their spatial and temporal features, and the transitions between the different states. At the pre-plaque stage, the TgF344-AD rats showed reduced co-activation of hub regions in the CAPs corresponding to the default mode-like and lateral cortical network. Default mode-like network activity segregated into two distinct brain states, with one state characterized by high co-activation of the basal forebrain. This basal forebrain co-activation was reduced in TgF344-AD animals mainly at the pre-plaque stage. Brain state transition probabilities were altered at the pre-plaque stage between states involving the default mode-like network, lateral cortical network, and basal forebrain regions. Additionally, while the directionality preference in the network-state transitions observed in the wild-type animals at the pre-plaque stage had diminished at the early-plaque stage, TgF344-AD animals continued to show directionality preference at both stages.Discussion Our study enhances the understanding of intrinsic brain state dynamics and how they are impacted at the early stages of AD, providing a nuanced characterization of the early, functional impact of the disease's neurodegenerative process.
Language
English
Source (journal)
Frontiers in human neuroscience
Publication
2024
ISSN
1662-5161
DOI
10.3389/FNHUM.2024.1379923
Volume/pages
18 (2024) , p. 1-17
Article Reference
1379923
ISI
001205084900001
Pubmed ID
38646161
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Multimodal Imaging of cholinergic neuromodulation during specific memory phases in the rodent brain.
Improved classification of Alzheimer's disease assessed from the slowly propagating waves of BOLD intensity, the Quasi-Periodic patterns, observed in dynamic resting-state fMRI in a AD rat model at rest and upon sensory stimulation.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 02.05.2024
Last edited 28.05.2024
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