Organisational and neuromodulatory underpinnings of structural-functional connectivity decoupling in patients with Parkinson’s disease

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.

Neurogenetic traits outline vulnerability to cortical disruption in Parkinson’s disease

“…A group of studies tested the hypothesis of Braak staging using standard structural and functional MRI techniques supporting or not the assumed spreading ( Guimaraes et al, 2016 , Kamagata et al, 2013 , Li et al, 2017 , Potgieser et al, 2014 , Tinaz et al, 2011 ). On the other hand, recent studies analysed the utility of connectomics approach applied to structural and functional data to understand the temporo-spatial pattern of accumulation and spreading of misfolded proteins in neurodegenerative diseases ( Yau et al, 2018 , Zarkali et al, 2021 , Zeighami et al, 2015 ). However, to date, there is no agreement about the best method to apply.…”

“…Such findings have been corroborated in more recent studies, suggesting that cortical areas with greater functional or structural connectivity to subcortical pathology reservoirs may present greater cortical impairment ( Yau et al, 2018 ). Finally, graph theory-based approaches may help in understanding the neural correlates of clinical evolution in PD ( Filippi et al, 2020b , Zarkali et al, 2021 ). A recent study has examined changes in structural–functional connectivity coupling in PD patients in relation to underlying different neurotransmitter expression, identifying the organisational patterns that possibly drive cognitive impairment ( Zarkali et al, 2021 ).…”

“…Finally, graph theory-based approaches may help in understanding the neural correlates of clinical evolution in PD ( Filippi et al, 2020b , Zarkali et al, 2021 ). A recent study has examined changes in structural–functional connectivity coupling in PD patients in relation to underlying different neurotransmitter expression, identifying the organisational patterns that possibly drive cognitive impairment ( Zarkali et al, 2021 ).…”

Social isolation, loneliness and all-cause dementia: a longitudinal and imaging-genetic study in the UK Biobank cohort

“…16,17 One recent approach leveraged brain-wide gene expression atlases to link molecular function to macroscale brain organization, 18 which was helpful to understand disease-related brain alterations and has been used in depression 19 and neurodegenerative diseases. 20 The present study utilized the UK Biobank cohort to examine the relative influence of social isolation and loneliness on incident dementia, and to quantity the extent to which these associations were explained by various risk factors such as biological and psychological factors.…”

Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

“…The higher the coupling, the more the structural brain network constrains the functional brain network [ 15 ]. Recent studies have demonstrated that SC-FC coupling is decreased in patients with bipolar disorder [ 16 ], Parkinson’s disease (PD) [ 17 ], multiple sclerosis (MS) [ 18 ], and AD [ 19 ]. The spatial variation in SC-FC coupling was found to be consistent with the functional specialization of the cortex; SC-FC coupling of the rostrolateral prefrontal cortex was correlated with executive function in young adults [ 15 ].…”