Abstract
Parkinson’s dementia is characterised by changes in perception and thought, and preceded by visual dysfunction, making this a useful surrogate for dementia risk. Structural and functional connectivity changes are seen in humans with Parkinson’s disease, but the organisational principles are not known. We used resting-state fMRI and diffusion-weighted imaging to examine changes in structural-functional connectivity coupling in patients with Parkinson’s disease, and those at risk of dementia. We identified two organisational gradients to structural-functional connectivity decoupling: anterior-to-posterior and unimodal-to-transmodal, with stronger structural-functional connectivity coupling in anterior, unimodal areas and weakened towards posterior, transmodal regions. Next, we related spatial patterns of decoupling to expression of neurotransmitter receptors. We found that dopaminergic and serotonergic transmission relates to decoupling in Parkinson’s overall, but instead, serotonergic, cholinergic and noradrenergic transmission relates to decoupling in patients with visual dysfunction. Our findings provide a framework to explain the specific disorders of consciousness in Parkinson’s dementia, and the neurotransmitter systems that underlie these.
Highlights
Parkinson’s dementia is characterised by changes in perception and thought, and preceded by visual dysfunction, making this a useful surrogate for dementia risk
Two weighted, undirected connectivity matrices were derived using the same parcellation[42] comprised of 400 cortical brain regions: a structural connectivity matrix derived from diffusion-weighted imaging and a functional connectivity matrix derived from resting-state functional MRI data
To assess the role that neuromodulatory systems may have in structural–functional connectivity (SC–FC) decoupling in Parkinson’s disease (PD), we investigated the relationship between maps of gene expression for neurotransmitter receptor genes and SC–FC coupling changes in: (1) PD vs controls and (2) PD low vs high visual performers
Summary
Parkinson’s dementia is characterised by changes in perception and thought, and preceded by visual dysfunction, making this a useful surrogate for dementia risk. We hypothesised that the relationship between structural–functional coupling across the brain would be systematically modified in PD and that this pattern of decoupling would occur along with one of two hypothesised directions: (1) across the unimodal–transmodal hierarchical gradient of SC–FC decoupling that is seen in health with more transmodal regions becoming even more decoupled in PD10–12,33; or (2) along the anterior-to-posterior (A–P) axis with decoupling more prominent in posterior regions. This hypothesis was based on the posterior distribution of metabolic and connectivity changes seen in PD 25,30,34–36. We evaluated the specific pattern of decoupling in PD and found that this occurred across both a unimodal–transmodal and anterior–posterior axes
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