Compensatory mechanisms in Parkinson’s disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson’s disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson’s disease, the underlying pathophysiology is unclear. Here, we investigate motor compensation in Parkinson’s disease by investigating the relationship between clinical signs, dopamine transporter imaging data and neurophysiological measures of the primary motor cortex (M1), using transcranial magnetic stimulation in presymptomatic and symptomatic hemispheres of patients. In this cross-sectional, multicentre study, we screened 82 individuals with Parkinson’s disease. Patients were evaluated clinically in their medication OFF state using standardized scales. Sixteen Parkinson’s disease patients with bilateral dopamine transporter deficit in the putamina but unilateral symptoms were included. Twenty-eight sex- and age-matched healthy controls were also investigated. In all participants, we tested cortical excitability using single- and paired-pulse techniques, interhemispheric inhibition and cortical plasticity with paired associative stimulation. Data were analysed with ANOVAs, multiple linear regression and logistic regression models. Individual coefficients of motor compensation were defined in patients based on clinical and imaging data, i.e. the motor compensation coefficient. The motor compensation coefficient includes an asymmetry score to balance motor and dopamine transporter data between the two hemispheres, in addition to a hemispheric ratio accounting for the relative mismatch between the magnitude of motor signs and dopaminergic deficit. In patients, corticospinal excitability and plasticity were higher in the presymptomatic compared with the symptomatic M1. Also, interhemispheric inhibition from the presymptomatic to the symptomatic M1 was reduced. Lower putamen binding was associated with higher plasticity and reduced interhemispheric inhibition in the presymptomatic hemisphere. The motor compensation coefficient distinguished the presymptomatic from the symptomatic hemisphere. Finally, in the presymptomatic hemisphere, a higher motor compensation coefficient was associated with lower corticospinal excitability and interhemispheric inhibition and with higher plasticity. In conclusion, the present study suggests that motor compensation involves M1–striatal networks and intercortical connections becoming more effective with progressive loss of dopaminergic terminals in the putamen. The balance between these motor networks seems to be driven by cortical plasticity.

中文翻译：

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早期帕金森病运动代偿机制的神经生理标志物


帕金森病的代偿机制被定义为大脑用来适应神经退行性和进行性多巴胺减少的变化。尽管存在双侧黑质纹状体变性，但早期帕金森病的运动代偿可能部分导致临床运动体征的单侧发作。尽管已经提出了几种用于帕金森病代偿适应的机制，但潜在的病理生理学尚不清楚。在这里，我们通过在患者的症状前和症状半球使用经颅磁刺激来研究临床体征、多巴胺转运蛋白成像数据和初级运动皮层 （M1） 的神经生理学测量之间的关系，从而研究帕金森病的运动代偿。在这项横断面、多中心研究中，我们筛选了 82 名帕金森病患者。使用标准化量表对患者在药物关闭状态下进行临床评估。包括 16 例帕金森病患者，壳中双侧多巴胺转运蛋白缺乏但有单侧症状。还调查了 28 个性别和年龄匹配的健康对照。在所有参与者中，我们使用单脉冲和配对脉冲技术测试了皮质兴奋性、半球间抑制和皮质可塑性与配对联想刺激。使用方差分析、多元线性回归和 logistic 回归模型分析数据。根据临床和影像学数据定义患者的个体运动代偿系数，即运动代偿系数。 运动补偿系数包括一个不对称评分，用于平衡两个半球之间的运动和多巴胺转运蛋白数据，此外还包括一个半球比率，用于解释运动体征幅度和多巴胺能缺陷之间的相对不匹配。在患者中，与症状性 M1 相比，症状前患者的皮质脊髓兴奋性和可塑性更高。此外，从症状前到症状性 M1 的半球间抑制降低。较低的壳核结合与较高的可塑性和症状前半球的半球间抑制降低有关。运动补偿系数区分症状前半球和症状半球。最后，在症状前半球，较高的运动补偿系数与较低的皮质脊髓兴奋性和半球间抑制以及较高的可塑性相关。总之，本研究表明，运动代偿涉及 M1-纹状体网络，随着壳核中多巴胺能末端的进行性丧失，皮层间连接变得更加有效。这些运动网络之间的平衡似乎是由皮质可塑性驱动的。