Physiological Analysis Of Voluntary Movement

该项目的目标是更多地了解正常人和自愿运动障碍患者的运动控制，如帕金森氏症、小脑性共济失调、中风偏瘫和肌张力障碍。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(TMS)，以及正电子发射断层扫描和功能磁共振成像(FMRI)的神经成像。目前，该科正在进行的项目包括正常生理学研究、肌张力障碍的病理生理学和治疗、帕金森氏病、S病的运动迟缓、共济失调的治疗以及偏瘫的康复研究。 FMRI被用来研究自动运动的潜在神经关联。我们训练正常受试者进行手指顺序运动，发现与学习前阶段相比，运动自动性与双侧运动前区、顶叶皮质、小脑、对侧感觉运动皮质和SMA的激活程度较低相关。假设存在多模式脑区专门用于刺激触发的运动，我们在右侧颞叶上皮质和右侧背侧运动前皮质显示了这些区域。通过功能磁共振成像，研究了运动想象与运动执行之间的神经基础。结果表明，运动想象与运动相关区域处理感觉信息的功能之一有关。通过功能磁共振成像，我们探索了上面部运动的控制机制，显示了吻侧前扣带回皮质的主要作用，这为临床上常见的中风后上面部运动受限的临床观察提供了另一种解释，涉及大脑中动脉。另一个目标是确定顶叶和额叶皮质区域在复杂运动任务的准备和执行过程中如何参与。使用EEG观察到的一种情况是，大脑对这些动作的准备时间比简单动作早得多。我们提出的假设是，当大脑发出自愿运动的信号时，其他可能的运动会受到积极的抑制，我们用TMS显示，当食指移动时，作用于小指的肌肉的大脑表现被抑制。 我们正在用TMS进行研究，以评估局灶性肌张力障碍和已知遗传来源的全身性肌张力障碍(DYT1肌张力障碍)的皮质内抑制(ICI)，以确定ICI的异常是否可能代表肌张力障碍发展的遗传易感性的标志。为了测试局灶性手部肌张力障碍患者与匹配对照组相比是否存在脑结构异常，我们使用高分辨率解剖MRI和基于体素的形态计量学来测量灰质数量的组间差异。我们还评估了在局灶性肌张力障碍患者运动前和运动期间使用TMS对运动皮质内抑制的调节。运动诱发电位在周围环境中受到显著抑制。在正常受试者的肌肉中，但在局灶性手部肌张力障碍患者中显著增强。这些发现提示局灶性手部肌张力障碍患者运动皮质周围抑制受到干扰。 假设局灶性手部肌张力障碍患者的运动训练可以减少异常共激活，改善肌张力障碍症状，我们监督患者进行为期四周的运动训练计划。应用临床评价量表改善肌张力障碍症状。我们回顾了140例局灶性手部肌张力障碍患者的1100次肉毒毒素注射的临床资料，证明肉毒毒素注射治疗局灶性手部肌张力障碍是安全有效的，治疗时间超过10年。我们已经完成了一项美西律与安慰剂治疗眼睑痉挛和局灶性手部肌张力障碍的临床研究。结果表明，服用美西律的患者总体上没有统计学上的显著改善，但在眼睑痉挛方面有受益的趋势。 利用功能磁共振和行为学实验，我们正在研究如何快速移动和如何快速思考的控制机制。这个问题与帕金森氏病患者潜在的运动减慢(运动迟缓)和可能的认知减慢(迟缓)的病理生理学有关。一项中期分析表明，帕金森患者的运动和对速度的认知控制之间存在部分重叠，明确的运动迟缓伴轻度但严重的迟缓。 我们已经完成了一项针对患有共济失调和抗醇溶蛋白抗体的患者的无麸质饮食的公开试验，并表明这种治疗方法对许多患者来说是有前景的。 在观察到局部麻醉偏瘫手臂上部后，慢性中风患者的手功能有改善后，我们现在正试图在对照研究设计中证实这些发现。

The goal of this project is to learn more about the control of movement in normal humans and in patients with voluntary movement disorders such as Parkinson's disease, cerebellar ataxia, hemiplegia from stroke and dystonia. The tools we use include clinical neurophysiological methods such as electroencephalography, electromyography, and transcranial magnetic stimulation (TMS) and neuroimaging with positron emission tomography and functional magnetic resonance imaging (fMRI). Currently active projects in the Section include studies of normal physiology, the pathophysiology and treatment of dystonia, the bradykinesia in Parkinson?s disease, treatment of ataxia, and studies of recovery from hemiplegia. fMRI was used to investigate the underlying neural correlates of automatic movements. We trained normal subjects to perform sequential finger movements and found that compared to the pre-learning stage, movement automaticity was associated with less activation in bilateral premotor areas, parietal cortex, cerebellum, contralateral sensorimotor cortex and SMA. Pursuing the hypothesis that there are multimodal brain areas devoted to stimulus triggered movements, we showed such regions in right superior temporal cortex and right dorsal premotor cortex. Using functional MRI, neural substrates underlying motor imagination were explored in comparison with motor execution. The results indicate that motor imagination is associated with one of the functions of motor-related areas to process sensory information. Using functional MRI, we explored control mechanisms of upper facial movement and showed a major role of the rostral anterior cingulate cortex; this provides an alternative explanation for the common clinical observation of sparing of upper facial movement after stroke involving the middle cerebral artery. Another goal is to determine how parietal and frontal cortical regions participate during the preparation and execution of complex motor tasks. One observation using EEG is that the brain prepares for such movements much earlier than for simple movements. Pursuing the hypothesis that when there is a brain signal for a voluntary movement, other possible movements are actively inhibited, we showed with TMS that the brain representation of a muscle acting on the little finger was inhibited when the index finger was moved. We are doing studies with TMS to evaluate intracortical inhibition (ICI) in focal dystonia and in generalized dystonia of known genetic origin (DYT1 dystonia) in order to determine whether abnormalities of ICI may represent a marker of genetic predisposition for the development of dystonia. To test the presence of structural abnormalities in the brain of patients with focal hand dystonia compared with that of matched controls, we are using high resolution anatomical MRI and voxel-based morphometry to measure any group differences in the amount of gray matter. We have also evaluated modulation of inhibition within the motor cortex using TMS before and during movement in patients with focal dystonia. Motor evoked potentials were significantly suppressed in a ?surround? muscle in normal subjects, but enhanced significantly in patients with focal hand dystonia. These findings suggest disturbed surround inhibition in the motor cortex of patients with focal hand dystonia. Pursuing the hypothesis that motor training in patients with focal hand dystonia could decrease abnormal co-activation and improve dystonic symptoms, we supervised patients in a motor training program for four weeks. Dystonic symptoms improved using clinical evaluation scales. We conducted a review of clinical data on 1100 botulinum toxin injections in 140 focal hand dystonia patients and demonstrated that botulinum toxin injections are safe and effective treatment for focal hand dystonia over periods of time exceeding 10 years. We have completed a clinical study of mexiletine compared with placebo for the treatment of blepharospasm and focal hand dystonia. Results indicated that there was no statistically significant improvement in the group as a whole with mexiletine, however, there was a trend for benefit in blepharospasm. Using functional MRI and behavioral experiments, we are investigating the control mechanisms of how to move fast as well as how to think fast. This question is addressed with relation to pathophysiology underlying motor slowing (bradykinesia) and possible cognitive slowing (bradyphrenia) in patients with Parkinson's disease. An interim analysis suggests a partial overlap between the movement and cognitive control of speed, and definite bradykinesia with mild but significant bradyphrenia in Parkinson patients. We have completed an open trial of a gluten free diet in patients with ataxia and anti-gliadin antibodies, and showed that this treatment is promising for many patients. Following the observation, that there is an improvement of hand function in chronic stroke after local anesthesia of the upper part of the paretic arm, we are now trying to confirm these findings in a controlled study design.