PHYSIOLOGICAL ANALYSIS OF INVOLUNTARY MOVEMENTS

不自主运动的生理分析

• 批准号: 6432895
• 负责人: MARK A HALLETT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432895
• 关键词: Gaucher's disease; abnormal involuntary movement; botulinum toxins; clinical research; disease /disorder classification; electromyography; evoked potentials; gamma aminobutyrate; glycine receptors; human subject; myoclonus; neuromuscular disorder diagnosis; neurophysiology; partial seizure; pathology; positron emission tomography; reflex; sleep; sleep disorders; spinal cord; tremor

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, electromyography, and transcranial magnetic stimulation and neuroimaging with positron emission tomography and functional magnetic resonance imaging. Currently active projects in the Section include studies of tremor, tic, and periodic movements in sleep. We are using physiological methods to see if criteria can be defined to make the diagnosis of psychogenic tremor. One test that looks promising is measuring the frequency spectrum of the tremor in one extremity while asking the patient to make movements with specified frequencies in the opposite extremity. We are also collecting information regarding patterns of muscle recruitment, sensory modulation and cortical activity (using EEG) associated with psychogenic movements. Analysis reveals that the preparatory cortical activity (measured by pre-movement potentials) is similar to that preceding voluntary movements. The pattern of stimulus-response was found to be highly variable and inconsistent in patients who had stimulus sensitive myoclonus. We have shown that somatosensory evoked potentials are a sensitive measure of disease burden in all type 3 neuronopathic Gaucher disease (GD3) patients. The mean potential amplitude in patients differed significantly from controls and from type 1 Gaucher patients. Amplitude and the IQ of patients also was significantly correlated. Somatosensory evoked potentials were also evaluated in patients with restless legs syndrome. The study was done to test the hypothesis that excitability of the sensory system is increased in these patients. Compared to controls, a significant increase in the amplitude of the posterior tibial nerve somatosensory evoked potential was seen in patients. Preliminary analysis of parkinsonian tremor showed coherence between the motor cortex and muscle at the tremor frequency. In contrast, cortico-muscular coherence at the tremor frequency was not observed at the tremor frequency in normal (physiologic tremor) and essential tremor patients. These findings suggest an important role of the motor cortex in parkinsonian tremor. In the future, this method might be a useful tool to the early stage of Parkinson?s disease from other disorders. We treated a patient with Lafora Body Disease with a ketogenic diet attempting to control his epilepsy. Additionally his myoclonus and mental state have improved. Concomitantly, significant insulin resistance and marked hyperinsulinemia despite ketosis was noticed, a new finding in Lafora disease which suggests a possible role of Laforin (a novel tyrosine phosphatase) in insulin signaling.

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、肌电和经颅磁刺激，以及正电子发射断层扫描和功能磁共振成像的神经成像。目前，该科正在进行的项目包括研究睡眠中的震颤、抽搐和周期性运动。我们正在使用生理学方法，看看是否可以定义标准来诊断心因性震颤。一种看起来很有希望的测试是测量一端震颤的频谱，同时要求患者在另一端以指定的频率进行运动。我们还在收集与心理运动相关的肌肉招募、感觉调节和皮质活动(使用脑电)模式的信息。分析表明，预备性皮质活动(由运动前电位测量)与之前的自愿运动相似。在有刺激敏感型肌阵挛的患者中，刺激反应模式被发现是高度可变和不一致的。我们已经证明，体感诱发电位是衡量所有3型神经病变高谢病(GD3)患者疾病负担的灵敏指标。患者的平均电位波幅与对照组和1型高雪病患者有显著差异。波幅与患者的智商也显著相关。对不宁腿综合征患者的体感诱发电位也进行了评估。这项研究是为了检验这些患者感觉系统的兴奋性增加的假设。与对照组相比，患者的胫后神经体感诱发电位的波幅显著增加。对帕金森氏症震颤的初步分析表明，运动皮质和肌肉在震颤频率上是一致的。相反，在正常震颤(生理性震颤)和特发性震颤患者中，没有观察到震颤频率下的皮质-肌肉一致性。这些发现表明运动皮质在帕金森氏震颤中起着重要作用。在未来，这种方法可能是一种有用的工具，以早期帕金森？S病从其他障碍。我们用生酮饮食治疗了一名患有拉福拉体病的患者，试图控制他的癫痫。此外，他的肌阵挛和精神状态也有所改善。随之而来的是显著的胰岛素抵抗和明显的高胰岛素血症，这是在Lafora病中的一个新发现，表明Laforin(一种新的酪氨酸磷酸酶)可能在胰岛素信号转导中发挥作用。