Biomedical Engineering Department, Institute for Computational Medicine, Johns Hopkins University, Baltimore MD, USA.
Front Integr Neurosci. 2012 Jul 26;6:40. doi: 10.3389/fnint.2012.00040. eCollection 2012.
Visual cues open a unique window to the understanding of Parkinson's disease (PD). These cues can temporarily but dramatically improve PD motor symptoms. Although details are unclear, cues are believed to suppress pathological basal ganglia (BG) activity through activation of corticostriatal pathways. In this study, we investigated human BG neurophysiology under different cued conditions. We evaluated bursting, 10-30 Hz oscillations (OSCs), and directional tuning (DT) dynamics in the subthalamic nucleus (STN) activity while seven patients executed a two-step motor task. In the first step (predicted +cue), the patient moved to a target when prompted by a visual go cue that appeared 100% of the time. Here, the timing of the cue is predictable and the cue serves an external trigger to execute a motor plan. In the second step, the cue appeared randomly 50% of the time, and the patient had to move to the same target as in the first step. When it appeared (unpredicted +cue), the motor plan was to be triggered by the cue, but its timing was not predictable. When the cue failed to appear (unpredicted -cue), the motor plan was triggered by the absence of the visual cue. We found that during predicted +cue and unpredicted -cue trials, OSCs significantly decreased and DT significantly increased above baseline, though these modulations occurred an average of 640 ms later in unpredicted -cue trials. Movement and reaction times were comparable in these trials. During unpredicted +cue trials, OSCs, and DT failed to modulate though bursting significantly decreased after movement. Correspondingly, movement performance deteriorated. These findings suggest that during motor planning either a predictably timed external cue or an internally generated cue (generated by the absence of a cue) trigger the execution of a motor plan in premotor cortex, whose increased activation then suppresses pathological activity in STN through direct pathways, leading to motor facilitation in PD.
视觉线索为理解帕金森病 (PD) 打开了一扇独特的窗户。这些线索可以暂时但显著改善 PD 的运动症状。尽管细节尚不清楚，但人们认为这些线索通过激活皮质纹状体通路来抑制病理性基底节 (BG) 活动。在这项研究中，我们在不同提示条件下研究了人类 BG 的神经生理学。我们评估了在七名患者执行两步运动任务时，丘脑底核 (STN) 活动中的爆发、10-30 Hz 振荡 (OSC) 和方向调谐 (DT) 动力学。在第一步 (预测 +提示) 中，当患者看到视觉 GO 提示出现时，患者会移动到目标位置，提示出现的概率为 100%。在这里，提示的时间是可预测的，提示充当执行运动计划的外部触发器。在第二步中，提示随机出现的概率为 50%，患者必须移动到与第一步相同的目标。当提示出现时 (未预测 +提示)，运动计划将由提示触发，但提示的时间不可预测。当提示未出现时 (未预测 -提示)，运动计划将由视觉提示的缺失触发。我们发现，在预测 +提示和未预测 -提示试验中，与基线相比，OSC 显著降低，DT 显著增加，尽管这些调制平均在未预测 -提示试验中延迟 640 毫秒。在这些试验中，运动和反应时间相当。在未预测 +提示试验中，OSC 和 DT 未能调节，尽管在运动后爆发显著减少。相应地，运动性能恶化。这些发现表明，在运动计划中，无论是可预测时间的外部提示还是内部生成的提示（由提示缺失生成）都会触发运动前皮层执行运动计划，其增加的激活随后通过直接通路抑制 STN 的病理性活动，从而导致 PD 中的运动促进。
