Li Weihua, Lao-Kaim Nicholas P, Li Runtian, Martín-Bastida Antonio, Roussakis Andreas-Antonios, Searle Graham E, Valle-Guzman Natalie, Dayal Viswas, Athauda Dilan, Kefalopoulou Zinovia, Mahlknecht Philipp, Church Alistair, Peall Kathryn J, Widner Håkan, Paul Gesine, Foltynie Tom, Barker Roger A, Piccini Paola
Division of Neurology, Department of Brain Science, Imperial College London, London W12 0NN, UK.
School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing 100876, China.
Brain Commun. 2025 Sep 9;7(5):fcaf308. doi: 10.1093/braincomms/fcaf308. eCollection 2025.
Dopamine and serotonin are two major monoamine neurotransmitters associated with Parkinson's disease (PD), but their spatial distribution and relationship to underlying functional brain architecture are not fully understood. We assessed 30 patients with PD at baseline using structural MRI, resting-state functional MRI (rs-fMRI), C-PE2I and C-DASB PET, along with comprehensive clinical evaluations of motor and non-motor symptoms. Of these, 15 patients with PD who completed the same assessments after 19 months were included in the longitudinal analysis. rs-fMRI was used to assess functional connectivity, while C-PE2I and C-DASB PET were used to evaluate interregional homogeneity of dopamine and serotonin levels, referred to as PET covariance. Functional connectivity and PET covariance were estimated using a region-of-interest (ROI)-based approach with 138 ROIs from the Automated Anatomical Labelling 3 atlas, excluding cerebellar regions. These ROIs were further grouped into eight networks: visual, sensorimotor, attention, limbic, frontoparietal, default mode, subcortical and brainstem. At baseline, linear regression revealed that functional connectivity was positively associated with both C-PE2I PET covariance (-values ranging from 0.575 to 0.790, < 0.001) and C-DASB PET covariance (-values ranging from 0.356 to 0.773, < 0.001) across all networks. Longitudinally, we found positive correlations between baseline functional connectivity and both C-PE2I PET change covariance and C-DASB PET change covariance (-values ranging from 0.166 to 0.576 and 0.312 to 0.671, respectively, < 0.001) across all networks. These correlations remained significant after controlling for the Euclidean distance between ROIs, indicating that the association is independent of spatial proximity. For both tracers, absolute PET uptake across seed ROIs was positively associated with correspondent regression-derived functional connectivity-PET -weights, which represent the relationship between PET uptake in target ROIs and their functional connectivity to the seed. This association between target functional connectivity and PET uptake was correlated with PD motor and non-motor severity across different brain regions in a manner that was dependent on the neurotransmitter system evaluated. Our findings suggest that in patients with PD, dopamine and serotonin levels covary among brain regions that are highly functionally connected. This implies that the spatial distribution of these neurotransmitters follows the organizational principles of the brain's functional connectomes, which are associated with features of the disease.
多巴胺和血清素是与帕金森病（PD）相关的两种主要单胺类神经递质，但其空间分布以及与潜在脑功能结构的关系尚未完全明确。我们在基线时使用结构磁共振成像（MRI）、静息态功能MRI（rs-fMRI）、C-PE2I和C-DASB正电子发射断层扫描（PET）对30例PD患者进行了评估，并对运动和非运动症状进行了全面的临床评估。其中，15例PD患者在19个月后完成了相同的评估，并纳入纵向分析。rs-fMRI用于评估功能连接性，而C-PE2I和C-DASB PET用于评估多巴胺和血清素水平的区域间同质性，即PET协方差。使用基于感兴趣区域（ROI）的方法，从自动解剖标记3图谱中选取138个ROI（不包括小脑区域）来估计功能连接性和PET协方差。这些ROI进一步被分为八个网络：视觉、感觉运动、注意力、边缘系统、额顶叶、默认模式、皮质下和脑干。在基线时，线性回归显示，在所有网络中，功能连接性与C-PE2I PET协方差（-值范围为0.575至0.790，<0.001）和C-DASB PET协方差（-值范围为0.356至0.773，<0.001）均呈正相关。纵向来看，我们发现，在所有网络中，基线功能连接性与C-PE2I PET变化协方差和C-DASB PET变化协方差均呈正相关（-值分别为0.166至0.576和0.312至0.671，<0.001）。在控制ROI之间的欧几里得距离后，这些相关性仍然显著，表明这种关联独立于空间邻近性。对于两种示踪剂，种子ROI的绝对PET摄取与相应回归得出的功能连接性-PET权重呈正相关，该权重代表目标ROI中的PET摄取与其与种子的功能连接性之间的关系。目标功能连接性与PET摄取之间的这种关联，以一种依赖于所评估的神经递质系统的方式，与不同脑区的PD运动和非运动严重程度相关。我们的研究结果表明，在PD患者中，多巴胺和血清素水平在功能高度连接的脑区之间存在共变关系。这意味着这些神经递质的空间分布遵循大脑功能连接组的组织原则，而这与疾病特征相关。
