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

描述（由申请人提供）：在基底神经节-丘脑皮质运动回路中，网络活动被精确定时，以促进自主运动的执行。在帕金森病（PD）中，这种功能网络因过度的神经元同步而受损，从而破坏了整体运动表现所必需的局部振荡。大脑皮层在这种分布式超同步状态中的作用尚不清楚。PD患者的功能影像学研究显示运动准备区如运动前皮层（PreMC）的静息状态代谢活性降低，而其他研究显示初级运动皮层（M1）的静息状态代谢活性增加。在之前的一项研究中（Crowell et al., 2012），我们的研究表明，与对照组相比，PD患者的M1伽马频率功率谱密度在非常宽的频段（30-250 Hz）上增加，表明静息状态活动增加。然而，尚不清楚这种改变是否也与自愿运动有关。这是一个关键的问题，因为PD患者运动能力下降的一个潜在解释是，M1在休息时的病理性过度活动减少了它对涉及执行运动控制的其他额叶区域作出反应的动态范围。另一种解释是，在执行运动任务之前，运动前皮层区域没有被适当地招募来准备运动序列，导致运动执行减弱。第三种解释是基底节区异常的振荡活动阻碍了目标导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测试这些假设在基底神经节功能障碍患者：皮层电图（ECoG）记录PD患者在清醒DBS手术期间执行运动任务的PreMC和M1，并使用弥散张量成像（DTI）对这些患者的皮质-基底神经节通路进行详细的结构映射。这种方法的优点是对皮层活动的高时空分辨率与激活和失活皮层下通路的精确皮质回解剖相匹配。这种方法的新颖性进一步增强了，因为一个运动任务将包括一个Go- no - Go练习，在这个练习中，患者必须激活或抑制对触摸屏设备的提示动作。这将允许在运动前和运动皮质水平上对基底神经节在反应抑制中的作用进行批判性评估。我们假设，与无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）的增加将受到抑制。我们还预测，在PD患者中成功和不成功的No Go试验中，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.