Charité - Universitätsmedizin Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Campus Virchow Klinikum and Campus Mitte, Charitéplatz 1, 10119, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Campus Virchow Klinikum and Campus Mitte, Charitéplatz 1, 10119, Berlin, Germany; Artificial Intelligence, Department of Computer Science, Chemnitz University of Technology, Strasse der Nationen 62, 09107, Chemnitz, Germany.
Parkinsonism Relat Disord. 2019 Jun;63:185-190. doi: 10.1016/j.parkreldis.2019.02.003. Epub 2019 Feb 5.
Motor but also non-motor effects are modulated by dopamine (DA) in Parkinson's disease (PD). Impaired inhibition has been related to dopamine overdosing of the associative striatum. We compared effects of dopaminergic medication on inhibitory control in patients with young (age at onset <50 years, YOPD) and late onset PD (LOPD) and related them to nigrostriatal degeneration.
27 patients (10 YOPD, 17 LOPD) underwent a Go/NoGo paradigm comprising a global and specific NoGo condition ON and OFF DA. The ratio of dopamine transporter availability (DAT) in the associative relative to the sensorimotor striatum according to [I]FP-CIT SPECT was compared between YOPD and LOPD (n = 8/12). Neuro-computational modeling was used to identify pathway activation during Go/NoGo performance.
Patients made more errors ON compared to OFF in the global NoGo. This DA effect on global NoGo errors correlated with disease duration (r = 0.489, p = 0.010). YOPD made more errors in the specific NoGo ON-OFF compared to LOPD (p = 0.015). YOPD showed higher associative-to-sensorimotor DAT ratios compared to LOPD (p < 0.001). Neuro-computational modeling revealed DA overdosing of the associative striatum in YOPD resulting in excess activation of the direct basal ganglia pathway triggering incorrect responses.
Depending on the age of symptom onset, DA differentially modulated inhibition in PD with detrimental effects on specific NoGo performance in YOPD but increased performance in LOPD. YOPD showed relatively less degeneration in the associative striatum suggesting DA overdosing that is supported by our neuro-computational model. Reduced inhibition in the global NoGo condition suggests different pathway activation.
多巴胺（DA）可调节帕金森病（PD）中的运动和非运动效应。已发现抑制受损与联合纹状体中的多巴胺过量有关。我们比较了年轻起病（发病年龄<50 岁，YOPD）和晚发型 PD（LOPD）患者的多巴胺药物治疗对抑制控制的影响，并将其与黑质纹状体变性相关联。
27 名患者（10 名 YOPD，17 名 LOPD）接受了 Go/NoGo 范式测试，该范式包括全局和特定 NoGo 条件的 DA 开启和关闭。根据 [I]FP-CIT SPECT 比较了 YOPD 和 LOPD 中联合纹状体与感觉运动纹状体之间的多巴胺转运体可利用性（DAT）比值（n=8/12）。神经计算模型用于确定 Go/NoGo 表现期间的途径激活。
与 DA 关闭相比，患者在全局 NoGo 时ON 时的错误更多。该 DA 对全局 NoGo 错误的影响与疾病持续时间相关（r=0.489，p=0.010）。与 LOPD 相比，YOPD 在特定 NoGo ON-OFF 时的错误更多（p=0.015）。与 LOPD 相比，YOPD 的联合纹状体到感觉运动纹状体的 DAT 比值更高（p<0.001）。神经计算模型表明，YOPD 中的联合纹状体存在多巴胺过量，导致直接基底节途径过度激活，从而引发错误反应。
根据症状发作的年龄，DA 可调节 PD 中的抑制作用，对 YOPD 的特定 NoGo 表现产生不利影响，但对 LOPD 的表现有改善作用。YOPD 中的联合纹状体相对较少变性，表明存在多巴胺过量，这得到了我们的神经计算模型的支持。全局 NoGo 条件下的抑制减少表明不同途径的激活。
