Mechanisms of Movement Facilitation and Release by Cueing in Parkinson's disease

帕金森病中提示的运动促进和释放机制

• 批准号: 8325009
• 负责人: COLUM D MACKINNON
• 金额: $ 28.81万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325009
• 关键词: Acoustics; Adult; Area; Clinic; Clinical; Clinical Trials; Consensus; Cues; Data; Deep Brain Stimulation; Development; Devices; Disease; Disease Progression; Effectiveness; Electroencephalography; Freezing; Functional Magnetic Resonance Imaging; Gait; Goals; Home environment; Impairment; Kinetics; Levodopa; Measures; Mediating; Modality; Motor; Motor output; Movement; Parkinson Disease; Pathway interactions; Patients; Pharmaceutical Preparations; Play; Poverty; Preparation; Protocols documentation; Quality of life; Reaction Time; Refractory; Relative (related person); Resolution; Reticular Formation; Role; Sensory; Signal Transduction; Staging; Stimulus; Structure; Symptoms; Syndrome; Testing; Time; Upper limb movement; Visual; Work; analog; blood oxygen level dependent; density; effective therapy; improved; insight; kinematics; neuroregulation; novel; novel therapeutic intervention; research study; somatosensory; success

DESCRIPTION (provided by applicant): In advanced stages of Parkinson's disease (PD), the absence of spontaneous volitional movements (akinesia) often becomes the most debilitating aspect of the disease. In a subset of patients, akinesia manifests as an episodic impairment in the initiation of gait (start hesitation) in conjunction with freezing of gait (FOG). With disease progression, akinesia, start hesitation and FOG often becomes refractory to current treatments such as levodopa and deep brain stimulation. Currently there are no effective treatments for these symptoms. Yet, one of the paradoxes of PD is it that, under certain contexts, the provision of external cues can markedly facilitate movement initiation, even in those with profound akinesia in the off medication state. This observation demonstrates that patients with PD retain the capacity to initiate movement, but for reasons that are not understood, are unable to reliably access these pathways, particularly in self-initiated (non-cued) conditions. Despite the consensus that external cues can facilitate movement initiation in PD, clinical trials examining the efficacy of using external cues in the home environment have been disappointing. We propose that the utility of using external cues in clinical and home environments is currently limited by our lack of understanding of the conditions required to reliably facilitate initiation with cues and the mechanisms mediating the release of movement. The first Specific Aim of this project will examine the effects of cueing modality (acoustic, visual or somatosensory) and cue timing on the preparation and initiation of gait in patients with start hesitation. Information derived from these experiments can be used to establish stimulus presentation protocols that can be implemented in the clinical or home environments or via portable devices. Specific Aim 2 will use high- resolution EEG recordings and functional magnetic resonance imaging (fMRI) to examine the cortical and subcortical structures that mediate the preparation and release of movements by external cues. Specific Aim 3 will use transcranial direct current stimulation (tDCS) to examine the effects of transient suppression or facilitation of frontal cortical structures that are considered to a play role in the planning, preparation and initiation of gait and upper limb movements. These experiments will provide insight into the mechanisms and pathways that enable external cues to circumvent the impaired initiation of voluntary movements in patients with PD, such as start hesitation, and will provide an empirical rationale for the development of novel therapeutic interventions that facilitate these pathways.

描述（由申请人提供）：在帕金森病 (PD) 的晚期阶段，自发意志运动的缺乏（运动不能）往往成为该疾病最令人衰弱的方面。在一部分患者中，运动不能表现为步态开始时的间歇性障碍（开始犹豫）以及步态冻结（FOG）。随着疾病进展，运动不能、开始犹豫和 FOG 通常对左旋多巴和深部脑刺激等当前治疗无效。目前没有针对这些症状的有效治疗方法。然而，PD 的悖论之一是，在某些情况下，提供外部线索可以显着促进运动启动，即使对于那些在停药状态下患有严重运动不能的患者也是如此。这一观察结果表明，PD 患者保留了启动运动的能力，但由于未知的原因，无法可靠地访问这些路径，特别是在自我启动（非提示）的情况下。尽管人们一致认为外部线索可以促进帕金森病的运动启动，但检验在家庭环境中使用外部线索的功效的临床试验却令人失望。我们认为，目前在临床和家庭环境中使用外部线索的效用受到限制，因为我们对可靠地促进线索启动所需的条件和介导运动释放的机制缺乏了解。该项目的第一个具体目标将检查提示方式（听觉、视觉或体感）和提示时间对开始犹豫的患者准备和开始步态的影响。从这些实验中获得的信息可用于建立可在临床或家庭环境中或通过便携式设备实施的刺激呈现协议。具体目标 2 将使用高分辨率脑电图记录和功能磁共振成像 (fMRI) 来检查通过外部线索介导运动准备和释放的皮质和皮质下结构。具体目标 3 将使用经颅直流电刺激 (tDCS) 来检查瞬时抑制或促进额叶皮层结构的效果，这些结构被认为在步态和上肢运动的规划、准备和启动中发挥着作用。这些实验将深入了解使外部线索能够避免帕金森病患者自主运动启动受损（例如开始犹豫）的机制和途径，并将为开发促进这些途径的新型治疗干预措施提供经验依据。