High-frequency stimulation of the subthalamic nucleus selectively decreases central variance of rhythmic finger...

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.