Dementia Research Centre, University College London, 8-11 Queen Square, London, WC1N 3AR, UK.
Division of Anaesthesia, School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
Commun Biol. 2022 Sep 8;5(1):928. doi: 10.1038/s42003-022-03903-x.
Hallucinations are a core feature of psychosis and common in Parkinson's. Their transient, unexpected nature suggests a change in dynamic brain states, but underlying causes are unknown. Here, we examine temporal dynamics and underlying structural connectivity in Parkinson's-hallucinations using a combination of functional and structural MRI, network control theory, neurotransmitter density and genetic analyses. We show that Parkinson's-hallucinators spent more time in a predominantly Segregated functional state with fewer between-state transitions. The transition from integrated-to-segregated state had lower energy cost in Parkinson's-hallucinators; and was therefore potentially preferable. The regional energy needed for this transition was correlated with regional neurotransmitter density and gene expression for serotoninergic, GABAergic, noradrenergic and cholinergic, but not dopaminergic, receptors. We show how the combination of neurochemistry and brain structure jointly shape functional brain dynamics leading to hallucinations and highlight potential therapeutic targets by linking these changes to neurotransmitter systems involved in early sensory and complex visual processing.
幻觉是精神病的核心特征，在帕金森病中很常见。它们的短暂、意外性质表明大脑状态发生了变化，但潜在的原因尚不清楚。在这里，我们使用功能和结构磁共振成像、网络控制理论、神经递质密度和遗传分析的组合，研究帕金森病患者幻觉的时间动态和潜在的结构连接。我们发现，帕金森病患者在以分离为主的功能状态下花费了更多的时间，状态之间的转换更少。从整合状态到分离状态的转变在帕金森病患者中需要的能量成本更低，因此可能更可取。这种转变所需的区域能量与区域神经递质密度以及 5-羟色胺能、GABA 能、去甲肾上腺素能和胆碱能受体的基因表达相关，但与多巴胺能受体无关。我们展示了神经化学和大脑结构如何共同塑造导致幻觉的功能性大脑动力学，并通过将这些变化与涉及早期感觉和复杂视觉处理的神经递质系统联系起来，突出潜在的治疗靶点。
