Functional Connectivity Signatures Track Progression in Isolated REM Sleep Behaviour Disorder
Poster No:
170
Submission Type:
Abstract Submission
Authors:
Lachlan Churchill1, Anna Ignatavicius1, Ajay Konuri1, Jack Anderson1, Simon Lewis2, Elie Matar3
Institutions:
1University of Sydney, Sydney, New South Wales, 2Macquarie University, Sydney, NSW, 3University of Sydney, Sydney, NSW
First Author:
Co-Author(s):
Introduction:
Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a parasomnia characterized by the loss of skeletal muscle atonia during REM sleep, leading to nocturnal behaviours that mirror dream content (Sateia, 2014). Clinically, iRBD is significant due to its strong association with future α-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) (Boeve et al., 2001; Eisensehr et al., 2001; Palma et al., 2015). Large scale multicentre research has further substantiated this link, revealing that approximately 75% of patients diagnosed with iRBD will transition to PD or DLB within 12 years (Postuma et al., 2019). Subsequently, the prodromal nature of iRBD provides a rare opportunity to study the progression of Lewy body diseases from the earliest stages, enabling the identification of biomarkers and predictive tools that could differentiate between phenotypes and forecast future clinical trajectories.
To address these gaps, neuroimaging has become essential for studying the pathogenesis and progression of early Lewy body diseases. In this study, we used resting-state fMRI to investigate both static and dynamic functional connectivity (FC) in age-matched healthy controls (HC) and iRBD patients. Longitudinally, we examined FC changes within iRBD patients to identify progression patterns. Additionally, we explored longitudinal FC changes in converters and correlated FC alterations with neurotransmitter receptor density to uncover underlying neurobiological mechanisms.
To address these gaps, neuroimaging has become essential for studying the pathogenesis and progression of early Lewy body diseases. In this study, we used resting-state fMRI to investigate both static and dynamic functional connectivity (FC) in age-matched healthy controls (HC) and iRBD patients. Longitudinally, we examined FC changes within iRBD patients to identify progression patterns. Additionally, we explored longitudinal FC changes in converters and correlated FC alterations with neurotransmitter receptor density to uncover underlying neurobiological mechanisms.
Methods:
41 iRBD patients and 38 controls underwent resting state fMRI combined with a battery of clinical testing. Of the iRBD patients, 21 underwent either two (n=17) or three (n=6) scans within 5 years using a 3T GE MRI, with T1 and T2*-weighted functional images parcellated into 400 cortical (Schaefer) and subcortical regions (Tian atlas) (Schaefer et al., 2018; Tian et al., 2020). Static and dynamic FC were analysed across whole brain and Yeo-defined networks. Dynamic measures were calculated using the multiplication of temporal derivates (Shine et al., 2015) and modularity was assessed using Louvain Community Assignment. Key dynamic metrics included modularity, participation coefficient (between-module connectivity), and module degree Z-score (within-module connectivity), extracted using the Brain Connectivity Toolbox (Rubinov & Sporns, 2010). Statistical analyses were conducted with general linear models (cross-sectional) and linear mixed-effects models (longitudinal), with age, sex, and education as covariates.
Results:
iRBD patients exhibited significantly increased whole-brain modularity compared to healthy controls (P<0.05), suggesting a more modular network topology. However, no significant differences were observed in static FC measures between the groups. Longitudinal analyses revealed that iRBD patients displayed increased modularity and a progressive reduction in whole-brain participation coefficient over time, indicating a shift toward network segregation. Participants who converted to dementia exhibited pronounced reductions in FC between the sensorimotor (SMN), dorsal attention (DAN), and ventral attention (VAN) networks and the whole brain (P<0.01). Additionally, patients who converted to any Parkinsonian phenotype, showed worsening module degree Z-scores over time (P<0.05). Importantly, longitudinal changes in participation and average FC, were significantly correlated with increased vesicular acetylcholine transporter density (P<0.05), implicating cholinergic dysfunction as a key neurobiological contributor to these dynamic network disruptions.
·Dynamic Functional Connectivity Signatures in Longitudinal iRBD
·Progression of Static and Dynamic FC measures in Parkinsonian and Dementia Specific Converters
Conclusions:
Disrupted functional dynamics offer insights into the complex cortical changes that occur early and throughout the progression of iRBD. Consequently, these disruptions may serve as valuable markers for understanding the resulting complexities present in symptomology of iRBD and may aid in predicting the phenotypes associated with future disease development.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
Keywords:
Acetylcholine
Degenerative Disease
FUNCTIONAL MRI
Neurological
Sleep
Other - Parkinson's
1|2Indicates the priority used for review
Abstract Information
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Provide references using APA citation style.
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