Department of Physical Medicine and Rehabilitation, University of Michigan, 325 East Eisenhower Parkway, Ann Arbor, MI 48109-1109, United States; School of Kinesiology, University of Michigan, 1402 Washington Heights, Ann Arbor, MI 48109-2013, United States.
Behav Brain Res. 2013 Nov 15;257:100-10. doi: 10.1016/j.bbr.2013.09.032. Epub 2013 Sep 25.
The basal ganglia are thought to play a critical role in duration perception and production. However, experimental evidence for impaired temporal processing in Parkinson's disease (PD) patients is mixed. This study examined the association between striatal dopaminergic denervation in PD patients and sensorimotor synchronization. Twenty-eight mild-to-moderate stage PD patients synchronized finger taps to tone sequences of either 500 ms, 1000 ms or 1500 ms time intervals while ON levodopa (l-DOPA) or placebo pill (on separate test days) with the index finger of their more and less affected hands. We measured the accuracy and variability of synchronization. In a separate session, patients underwent (11)C-dihydrotetrabenazine ((11)C-DTBZ) PET scanning to measure in vivo striatal dopaminergic denervation. Patients were less accurate synchronizing to the 500 ms target time interval, compared to the 1000 ms and 1500 ms time intervals, but neither medication state nor hand affected accuracy; medication state, hand nor the target time interval affected synchronization variability. Regression analyses revealed no strong relationships between synchronization accuracy or variability and striatal dopaminergic denervation. We performed a cluster analysis on the degree of dopaminergic denervation to determine whether patient subgroup differences underlie our results. Three patient subgroups showed behavioral differences in synchronization accuracy, but not variability, paralleling their pattern of denervation. These findings provide further evidence for the role of the basal ganglia and dopamine in duration production and suggest that the degree of striatal dopaminergic denervation may explain the heterogeneity of performance between PD patients on the sensorimotor synchronization task.
基底神经节被认为在时间感知和产生中起着关键作用。然而,帕金森病(PD)患者在时间处理方面受损的实验证据存在差异。本研究考察了 PD 患者纹状体多巴胺能神经变性与感觉运动同步之间的关联。28 名轻度至中度 PD 患者在服用左旋多巴(l-DOPA)或安慰剂(在单独的测试日)时,用更受影响和较不受影响的手的食指,同步敲击与 500ms、1000ms 或 1500ms 时间间隔的音调序列。我们测量了同步的准确性和可变性。在单独的会议中,患者接受了(11)C-二氢四苯并嗪((11)C-DTBZ)PET 扫描,以测量体内纹状体多巴胺能神经变性。与 1000ms 和 1500ms 时间间隔相比,患者在同步 500ms 目标时间间隔时准确性较差,但药物状态和手均不影响准确性;药物状态、手或目标时间间隔均不影响同步可变性。回归分析显示,同步准确性或可变性与纹状体多巴胺能神经变性之间没有很强的关系。我们对多巴胺能神经变性的程度进行了聚类分析,以确定患者亚组差异是否是我们结果的基础。三个患者亚组在同步准确性方面表现出行为差异,但可变性没有差异,这与他们的神经变性模式一致。这些发现为基底神经节和多巴胺在时间产生中的作用提供了进一步的证据,并表明纹状体多巴胺能神经变性的程度可能解释了 PD 患者在感觉运动同步任务中的表现异质性。