The link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson’s disease (PD) where functional up-regulation of postsynaptic D₂ receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level–dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D₂ receptors (using ¹¹C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D₂ binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular–BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional–molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD–molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD.

突触可塑性与健康和疾病中大脑活动重组之间的联系仍然是一个科学挑战。_{我们在帕金森病 (PD) 中检查了这个问题，其中突触后 D 2}的功能上调受体已被记录，但其在神经活动水平上的重要性从未被确定。我们使用动眼神经系统作为模型研究多巴胺能网络的重组，研究了 PD 中的皮质 - 皮质下可塑性。该模型是理想的，因为该系统由于血氧水平依赖 (BOLD) 活动的额叶到顶叶的变化而重组。我们通过结合正电子发射断层扫描/功能磁共振成像来研究多巴胺 D ₂受体的纹状体突触后重组（使用¹¹C-raclopride) 和 PD 中的神经激活。我们使用分子和功能水平的协方差（连接性）统计数据来探测 PD 在开/关药物状态下的纹状体皮质重组，以表明重组的功能和分子形式是相关的。2 _{_}与对照组的额叶区域相比，与对照组的额叶区域相比，PD 中尾状核/壳核和过度活跃的顶叶区域之间的分子连接性增加，这与移位模型一致。关于antisaccades，与额叶区域不同，顶叶-纹状体连接再次在PD中占主导地位。关于分子-BOLD 协方差，观察到显着的符号反转：PD 患者表现出负额-壳核功能-分子关联，与重组转变一致，与对照组中观察到的正相关相反。停药 PD 患者的随访分析证实了负 BOLD-分子相关性。这些结果提供了 PD 中 BOLD 反应、纹状体-皮质突触重组和神经可塑性之间的联系。