Physiological Analysis Of Involuntary Movements

这个项目的目标是了解不同非自愿运动障碍的潜在生理机制。我们使用的工具包括临床神经生理学方法，如脑电(EEG)、肌电(EMG)和经颅磁刺激(TMS)，以及正电子发射断层扫描(PET)和功能磁共振成像(FMRI)的神经成像。目前，该科正在进行的项目包括震颤、抽搐和心因性运动障碍的研究。 治疗特发性震颤需要新药。通过震颤加速计量法和临床震颤试验，我们已经证明，1-辛醇作为单次剂量可以安全地使用(最高可达mg/kg)，并显著减少震颤。我们计划研究辛醇的药代动力学。 我们一直在用几种方法来研究抽搐的生理学。我们对10名抽动症患者进行了事件相关功能磁共振研究，同时自发地表现出各种运动和发声痉挛。这项研究的结果表明，边缘旁和感觉关联区与抽搐的产生密切相关，类似于疼痛或瘙痒等不愉快感觉在内部引发的运动。我们还使用血流正电子发射计算机断层扫描来确定抽动的解剖结构。在这种情况下，我们使用睡眠状态作为基线，这样我们就可以拥有一个基本上没有抽搐和抽搐冲动的状态。数据分析显示，在抽动释放过程中，双侧小脑和脑岛显著激活，同时伴随着已知参与抽动病理的结构的激活，如壳核、辅助运动区(SMA)和前扣带皮质。我们还在用11C配体氟马西尼研究Tourette综合征的PET病理，以评估抑制性GABA A受体的分布和密度的变化。使用BOLD功能磁共振成像，我们正试图描述与非自愿冲动现象相关的大脑激活区域，例如打哈欠的传染性本质。 使用一种范式来评估有意识事件的时间安排和脑电分析，我们试图理解与有意识地意识到运动准备和执行有关的认知过程的时间安排。我们正在调查正常对照组以及两个患者群体--精神分裂症患者和抽动症患者--自愿活动的时间。 我们已经开始探索心因性运动障碍的病理生理学，包括震颤和肌阵挛。我们发现，在心因性肌阵挛之前，脑电焦点频谱功率的变化与自愿运动相似，表明在自愿运动和心因性运动的执行前阶段活跃的神经底物可能是相同的。我们正在开始对这些患者进行全面的精神评估。 不宁腿综合症患者正在通过评估眨眼反射作为多巴胺能功能的探针进行研究。我们感兴趣的是R2成分，以及与对照组相比，听觉和脉冲前抑制对R2成分的影响。 我们对阵发性运动性肌张力障碍患者进行了一项研究，以更好地在临床上描述这种情况。与此同时，一位校外合作者试图找到负责的突变基因。 我们已经开始探索心因性运动障碍的病理生理学，包括震颤和肌阵挛。我们正在进行脑电和神经成像研究，试图确定大脑中负责启动运动的部分。

The goal of this project is to understand the underlying physiological mechanisms of different involuntary movement disorders. The tools we use include clinical neurophysiological methods such as electroencephalography (EEG), electromyography, and transcranial magnetic stimulation (TMS) and neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Currently active projects in the Section include studies of tremor, tic, and psychogenic movement disorders. New drugs are needed for treatment of essential tremor. Using tremor accelerometry and clinical tremor testing we have shown that 1-octanol, as a single dose, can be safely used (up to 64 mg/kg) and that it significantly reduces tremor. We are planning to study the pharmacokinetics of octanol. We have been approaching the physiology of tics in several ways. We conducted an event related fMRI study in 10 patients with Tourette Syndrome while spontaneously exhibiting a variety of motor and vocal tics. The results of this study indicate that paralimbic and sensory association areas are critically implicated in the generation of tics, similarly to movements triggered internally by unpleasant sensations as has been shown for pain or itching. We are also using blood flow PET to try to define the anatomy for tic generation. In this situation, we are using a sleep state for baseline so that we can have a state largely free of both tics and urge to tic. The analysis of data shows significant activation of bilateral cerebellum and insula during tic release accompanied by activation of structures already known to be involved in tic pathology such as the putamen, supplementary motor area (SMA) and anterior cingulate cortex. We are also studying the pathology of Tourette syndrome with PET using ligand 11C flumazenil to evaluate changes in the distribution and density of inhibitory GABA A receptors. Using BOLD fMRI, we are attempting to characterize the areas of brain activation associated with involuntary urge phenomena such as the infectious nature of yawning. Using a paradigm to assess the timing of conscious events and EEG analysis, we are seeking to understand the timing of cognitive processes related to the conscious awareness of movement preparation and execution. We are investigating the timing of voluntary movement in normal controls as well as in two patient populations--schizophrenic patients and patients with Tourette's syndrome. We have begun to explore the pathophysiology of psychogenic movement disorders including tremor and myoclonus. We have found that prior to psychogenic myoclonus electroencephalographic focal spectral power changes occur similarly to that seen with voluntary movements, signaling that neural substrates active during the pre-execution phase of voluntary and psychogenic movements may be shared. We are initiating a comprehensive psychiatric assessment of these patients. Patients with restless legs syndrome are being studied through an evaluation of the blink reflex as a probe of dopaminergic function. We are interested in the R2 component and how it is affected by auditory and prepulse inhibition when compared with controls. We have conducted a study looking at persons with paroxysmal kinesiogenic dystonia to characterize the condition better clinically. Simultaneously, there are attempts by an extramural collaborator to find the responsible mutated gene. We have begun to explore the pathophysiology of psychogenic movement disorders including tremor and myoclonus. We are doing EEG and neuroimaging studies trying to identify the parts of the brain responsible for movement initiation.