Cortical Activation in Parkinson's Disease During a Cued Arm Movement Task

描述(申请人提供)：在基底节-丘脑皮质运动回路中，网络活动被精确地计时，以促进自愿运动的执行。在帕金森氏病(PD)患者中，这一功能网络因过度的神经元同步而受损，这种同步扰乱了整合运动能力所必需的局部振荡。大脑皮层在这种分布式超同步状态中的作用还不是很清楚。帕金森病患者的功能成像研究表明，运动准备区(如运动前皮质(PREMC))的静息状态代谢活动减少，而其他研究表明初级运动皮质(M1)的静息状态代谢活动增加。在之前的一项研究(Crowell等人，2012)中，我们的LA显示PD患者与对照组相比，M1伽马频率功率谱密度在非常宽的频带(30-250赫兹)上增加，表明静息状态活动增加。然而，目前还不清楚这种变化是否也与自愿流动有关。这是一个关键的问题，因为帕金森病患者运动能力下降的一个潜在解释是，静息状态下M1的病理性过度活动降低了它对参与执行运动控制的其他额区做出反应的动态范围。另一种解释是，在运动任务之前，运动前皮质区域没有被适当地招募来准备运动序列，导致运动执行能力减弱。第三种解释是，基底节的异常振荡活动阻碍了目标定向运动所需的运动计划的适当选择。在这里，我们提出了一种新的方法来检验基底节功能障碍患者的这些假说：在清醒的DBS手术中执行运动任务的PD患者的皮层脑电(ECoG)记录的Premc和M1，以及使用弥散张量成像(DTI)绘制这些患者的皮质-基底节通路的详细结构图。这种方法的优点是皮质活动的高空间和时间分辨率，与激活和去激活的皮质下通路的精确的皮质回解剖相匹配。这种方法的新颖性进一步增强，因为一项运动任务将由Go-No Go练习组成，在该练习中，患者必须激活或抑制触摸屏设备的提示到达动作。这将允许在运动前和运动皮质水平上对基底节在反应抑制中的作用进行关键评估。我们假设，与没有运动障碍的患者相比，在GO试验之前和期间，PD患者的Premc和M1中宽带伽马活动(BGA)的增加将被抑制。我们还预测，在PD患者成功和不成功的No Go试验之间，Premc和M1 BGA的模式将保持不变。

DESCRIPTION (provided by applicant): In the basal ganglia-thalamocortical motor circuit, network activity is precisely timed to facilitate execution of voluntary movement. In Parkinson's Disease (PD), this functional network is impaired by excessive neuronal synchronization that disrupts local oscillations necessary for integrated motor performance. The role of the cortex within this distributed hypersynchronous state is not well understood. Functional imaging studies in PD patients suggest decreased resting state metabolic activity in movement preparatory areas such as the premotor cortex (PreMC), while other studies suggest increased resting state metabolic activity in primary motor cortex (M1). In a previous study (Crowell et al., 2012), our la demonstrated an increase in M1 gamma frequency power spectral density over a very broad band (30-250 Hz) in PD patients versus controls, indicative of increased resting state activity. However, it was not clear if this alteration is also associated with voluntary movement. This is a critical question because one potential explanation for diminished motor performance in PD is that pathological overactivity in M1 at rest reduces the dynamic range over which it can respond to other frontal areas involved in executive motor control. An alternative explanation is that, prir to motor tasks, premotor cortical areas are not appropriately recruited to prepare movement sequences, resulting in attenuated motor execution. A third explanation is that abnormal oscillatory activity in the basal ganglia prevents appropriate selection of motor plans required fo goal-directed movement. Here, we propose a novel approach to testing these hypotheses in patients with basal ganglia dysfunction: electrocorticographic (ECoG) recordings of PreMC and M1 in PD patients performing motor tasks during awake DBS surgery along with detailed structural mapping of cortico-basal ganglia pathways in these same patients using diffusion tensor imaging (DTI). The advantage of this approach is high spatial and temporal resolution of cortical activity matched with precise cortical gyral anatomy of activated and deactivated subcortical pathways. The novelty of this approach is further enhanced in that one motor task will consist of a Go-No Go exercise in which the patient must activate or suppress cued reaching movements to a touch-screen device. This will allow the critical evaluation of the basal ganglia's role in response inhibition at the level of the premotor and motor cortices. We hypothesize that increases in broadband gamma activity (BGA) will be suppressed in PreMC and M1 in PD patients before and during Go trials versus patients without a movement disorder. We also predict that the pattern of PreMC and M1 BGA will be unchanged between successful and unsuccessful No Go trials in patients with PD.