PDF(Pubmed)
Abstract：
Parkinson\'s disease (PD) is a circuit-level disorder with clinically-determined motor subtypes. Despite evidence suggesting each subtype may have different pathophysiology, few neuroimaging studies have examined levodopa-induced differences in neural activation between tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtype patients during a motor task. The goal of this functional MRI (fMRI) study was to examine task-induced activation and connectivity in the cortico-striatal-thalamo-cortical motor circuit in healthy controls, TD patients, and PIGD patients before and after levodopa administration. Fourteen TD and 12 PIGD cognitively-intact patients and 21 age- and sex-matched healthy controls completed a right-hand, paced tapping fMRI paradigm. Collectively, PD patients off medication (OFF) showed hypoactivation of the motor cortex relative to healthy controls, even when controlling for performance. After levodopa intake, the PIGD patients had significantly increased activation in the left putamen compared with TD patients and healthy controls. Psychophysiological interaction analysis revealed that levodopa increased effective connectivity between the posterior putamen and other areas of the motor circuit during tapping in TD patients, but not in PIGD patients. This novel, levodopa-induced difference in the neural responses between PD motor subtypes may have significant implications for elucidating the mechanisms underlying the distinct phenotypic manifestations and enabling the classification of motor subtypes objectively using fMRI.
摘要：
帕金森病（PD）是一种具有临床确定的运动亚型的回路级疾病。尽管有证据表明每种亚型可能具有不同的病理生理学，很少有神经影像学研究检查了左旋多巴引起的震颤显性（TD）和姿势不稳定/步态困难（PIGD）亚型患者在运动任务期间的神经激活差异。这项功能MRI（fMRI）研究的目的是检查健康对照中皮质-纹状体-丘脑-皮质运动回路中任务诱导的激活和连通性，TD患者,以及左旋多巴给药前后的PIGD患者。14名TD和12名PIGD认知完整患者以及21名年龄和性别匹配的健康对照者完成了右手，有节奏的轻敲功能磁共振成像范例。总的来说，PD患者停药（OFF）显示相对于健康对照组的运动皮层激活不足，即使在控制性能时。服用左旋多巴后，与TD患者和健康对照组相比,PIGD患者的左壳核激活显著增加.心理生理相互作用分析显示，左旋多巴在TD患者攻丝过程中增加了后壳核与运动回路其他区域之间的有效连通性，但在PIGD患者中没有。这本小说,左旋多巴诱导的PD运动亚型之间神经反应的差异可能对阐明不同表型表现的潜在机制以及使用fMRI客观地对运动亚型进行分类具有重要意义。
