Dementia Research Centre, University College London, 8-11 Queen Square, London, WC1N 3AR, UK.
Huntington's Disease Centre, University College London, Russell Square House, London, WC1B 5EH, UK.
Commun Biol. 2021 Jan 19;4(1):86. doi: 10.1038/s42003-020-01622-9.
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.
帕金森痴呆的特征是感知和思维的改变，且视觉功能障碍在前，这使其成为痴呆风险的一个有用替代指标。在帕金森病患者中可以看到结构和功能连接的变化，但组织原则尚不清楚。我们使用静息态 fMRI 和弥散加权成像来研究帕金森病患者和有痴呆风险的患者的结构-功能连接解耦的变化。我们确定了结构-功能连接解耦的两个组织梯度：从前到后和单模态到跨模态，前侧、单模态区域的结构-功能连接耦合较强，而向后侧、跨模态区域的结构-功能连接耦合减弱。接下来，我们将解耦的空间模式与神经递质受体的表达联系起来。我们发现多巴胺能和 5-羟色胺能递质传递与帕金森病的整体解耦有关，但相反，5-羟色胺能、胆碱能和去甲肾上腺素能递质传递与有视觉功能障碍的患者的解耦有关。我们的发现为解释帕金森痴呆中特定的意识障碍以及这些障碍所依赖的神经递质系统提供了一个框架。
