Targeted Motor Learning to Improve Gait for Individuals with Parkinson's Disease

有针对性的运动学习可改善帕金森病患者的步态

• 批准号: 10648097
• 负责人: Eran Dayan
• 金额: $ 21.68万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10648097
• 关键词: Address; Adult; Affect; Attention; Auditory; Basal Ganglia; Behavioral; Biomechanics; Brain; Calibration; Cerebellum; Compensation; Corpus striatum structure; Cues; Data; Deep Brain Stimulation; Dependence; Development; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Educational Intervention; Effectiveness; Evaluation; Exhibits; Freezing; Frequencies; Functional Magnetic Resonance Imaging; Gait; Hippocampus; Impairment; Individual; Intervention; Learning; Length; Long-Term Effects; Magnetic Resonance Imaging; Motor Skills; Movement; Nerve Degeneration; Neural Pathways; Neuroanatomy; Neurodegenerative Disorders; Outcome; Parkinson Disease; Participant; Patients; Periodicity; Persons; Pharmaceutical Preparations; Phase; Physical Rehabilitation; Physical therapy; Positioning Attribute; Process; Psychological reinforcement; Randomized; Rehabilitation therapy; Residual state; Rest; Safety; Speed; Structure; Subconscious; Substantia nigra structure; Testing; Training; Walking; clinical care; dopaminergic neuron; follow-up; gait rehabilitation; improved; insight; motor impairment; motor learning; motor symptom; multimodality; neural; neural circuit; neuroimaging; neurological rehabilitation; pharmacologic; physical therapist; randomized controlled design; walking intervention

Abstract The neurodegeneration in the substantia nigra of the basal ganglia that leads to Parkinson's disease (PD) produces a progressive decline in walking function. A major barrier limiting effective walking interventions in people with PD is the occurrence of insufficient motor learning. In the absence of disease modifying options, dopaminergic medications and deep brain stimulation are often used as the disease progresses. Although effective at improving gait, these solutions are temporary, concealing the concurrent degeneration of dopaminergic neurons. As a result, these solutions become less effective at improving gait as the disease progresses and can wear off later in the day. Physical therapy has the potential to increase walking capacity as well as create long-term improvements through intensive training that focuses on motor learning. In particular, the use of rhythmic auditory cues is a well-established intervention that attempts to overcome the damage to internal cueing mechanisms. Despite consistent benefits observed immediately after training, the long-term (retention) effects are more mixed. We contend that reduced retention is a result of inadequate motor learning. Conventional rhythmic auditory cueing employs strategic (explicit) learning with use-dependent learning. To add implicit learning mechanisms to rhythmic auditory cueing, a subtle error in the tempo can be introduced that requires recalibration (i.e., error-based learning). We propose that the addition of frequent movement recalibrations via subconscious temporal distortions of rhythmic auditory cues will repeatedly engage the early phase of implicit learning for individuals with PD to involve intact neural pathways (i.e., hippocampal driven encoding) for improved motor learning and longer term retention of gait improvements. As this training has the potential to alter neural circuitry, we will assess the neural substrates induced by this intervention through multimodal markers of hippocampal and striatal structure and connectivity. Specifically, we will use a randomized controlled design to perform four weeks of gait training using either no metronome, a metronome with a fixed tempo (strategic learning), or a metronome with a slowly changing tempo (strategic learning + error-based learning). In Aim 1, we will assess the gait behavioral changes post-training and at a 3-month follow-up to determine retention. In Aim 2, we will explore structural and functional neural changes induced by the gait training interventions. Our team is exceptionally well prepared to perform these Aims, consisting of experts in gait neurorehabilitation and biomechanics (Lewek), motor learning and neuroimaging (Dayan), and Parkinson's disease clinical care (Browner). At the conclusion of this project, we will have determined the available mechanisms of motor learning for people with PD, and will have examined the neural substrates that can be targeted to maximize remaining intact neural circuitry. This project has the potential to alter the manner in which rehabilitation is performed with people with PD, using a disease specific motor learning paradigm that makes use of residual neural circuits for long-term retention of functional motor skills.

抽象的 基底神经节黑质的神经变性导致帕金森病 (PD) 导致行走功能逐渐下降。限制有效步行干预的主要障碍 患有PD的人是运动学习不足的发生。在缺乏疾病改变选择的情况下， 随着疾病的进展，经常使用多巴胺能药物和深部脑刺激。虽然 这些解决方案可有效改善步态，但都是暂时的，掩盖了同时发生的退化 多巴胺能神经元。因此，随着疾病的发展，这些解决方案在改善步态方面变得不太有效。 进展并可能在当天晚些时候消失。物理治疗有可能提高步行能力，因为 并通过以运动学习为重点的强化训练来实现长期进步。尤其， 使用有节奏的听觉提示是一种行之有效的干预措施，试图克服对 内部提示机制。尽管训练后立即观察到持续的益处，但长期来看 （保留）效果更为复杂。我们认为记忆力下降是运动学习不足的结果。 传统的节奏听觉提示采用策略（显式）学习和依赖使用的学习。添加 节奏听觉提示的隐式学习机制，可以引入节奏中的微妙错误 需要重新校准（即基于错误的学习）。我们建议增加频繁的运动 通过有节奏的听觉线索的潜意识时间扭曲进行重新校准将反复吸引早期 PD 患者的内隐学习阶段涉及完整的神经通路（即海马驱动 编码）以改善运动学习并长期保留步态改善。由于本次培训有 改变神经回路的潜力，我们将通过以下方式评估这种干预诱导的神经基质 海马和纹状体结构和连接性的多模态标记。具体来说，我们将使用随机 受控设计，使用无节拍器、带固定节拍器的节拍器进行四个星期的步态训练 节奏（策略学习），或节奏缓慢变化的节拍器（策略学习+基于错误的 学习）。在目标 1 中，我们将评估训练后和 3 个月随访时的步态行为变化 确定保留。在目标 2 中，我们将探索步态训练引起的结构和功能神经变化 干预措施。我们的团队由步态专家组成，为实现这些目标做好了充分准备 神经康复和生物力学 (Lewek)、运动学习和神经影像学 (Dayan) 以及帕金森病 疾病临床护理（布朗纳）。在该项目结束时，我们将确定可用的 帕金森病患者的运动学习机制，并将检查可用于治疗的神经基质 旨在最大化剩余完整的神经回路。该项目有可能改变 康复治疗是对帕金森病患者进行的，使用特定于疾病的运动学习范式，使 使用残余神经回路长期保留功能性运动技能。