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

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.