Functional Neurosurgery and Experimental Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Neuropsychologia. 2012 Aug;50(10):2460-6. doi: 10.1016/j.neuropsychologia.2012.06.017. Epub 2012 Jun 29.
Timing is central to all motor behavior, especially repetitive or rhythmic movements. Such complex programs are underpinned by a network of motor structures, including the cerebellum, motor cortex, and basal ganglia. Patients with Parkinson's disease (PD) are impaired in some aspects of timing behavior, presumably as a result of the disruption to basal ganglia function. However, direct evidence that this deficit is specifically due to basal ganglia dysfunction is limited. Here, we sought to further understand the role of the basal ganglia in motor timing by studying PD patients with implanted subthalamic nucleus (STN) electrodes. Patients performed a synchronization-continuation tapping task at 500 ms and 2000 ms intervals both off and on therapeutic high frequency stimulation of the STN. Our results show that the mean tap interval was not affected by STN stimulation. However, in the un-stimulated state variability of tapping was abnormally high relative to controls, and this deficit was significantly improved, even normalized, with stimulation. Moreover, when partitioning the variance into central and peripheral motor components according to the Wing and Kristofferson model (1973), a selective reduction of central, but not motor, variance was revealed. The effect of stimulation on central variance was dependent on off-stimulation performance. These results demonstrate that STN stimulation can improve rhythmic movement performance in PD through an effect on central timing. Our experimental approach strongly implicates the STN, and more generally the basal ganglia, in the control of timing stability.
时间对于所有运动行为至关重要，尤其是重复或有节奏的运动。这种复杂的程序由运动结构网络支撑，包括小脑、运动皮层和基底神经节。帕金森病（PD）患者在某些时间行为方面存在障碍，推测是基底神经节功能障碍所致。然而，直接证据表明这种缺陷是由于基底神经节功能障碍导致的是有限的。在这里，我们通过研究植入丘脑底核（STN）电极的 PD 患者，进一步了解基底神经节在运动计时中的作用。患者在 STN 治疗性高频刺激开/关状态下，以 500ms 和 2000ms 的间隔执行同步-连续敲击任务。我们的结果表明，STN 刺激不会影响平均敲击间隔。然而，在未刺激状态下，相对于对照组，敲击的变异性异常高，且刺激可显著改善甚至正常化该缺陷。此外，根据 Wing 和 Kristofferson 模型（1973）将方差分为中央和外周运动分量时，揭示了中央但不是运动分量的选择性减少。刺激对中央方差的影响取决于刺激前的表现。这些结果表明，STN 刺激可通过对中央计时的影响改善 PD 患者的节律运动表现。我们的实验方法强烈表明，STN 更普遍地说，基底神经节在计时稳定性的控制中发挥作用。
