Impaired sensory filtering as a mechanism of Parkinson's disease

项目总结 帕金森氏病(PD)功能障碍的传统模型没有考虑感觉反馈，这是 两者在基底节均有明显表达，在帕金森病患者中均有明显损害。尽管这一点非常重要 反馈到正常运动，感觉处理受损对帕金森病病理生理学的贡献是 未知。我们的长期目标是阐明感觉反馈在病理性运动产生中的作用。 警察局里的指挥部。这项研究有助于揭示帕金森病的病理和治疗的神经基础， 引导更有效的临床实践，推动新的治疗技术的发展，并帮助 以减轻帕金森病患者和提供者的巨大负担。 在健康人中，运动系统会自动忽略与 目前的行为目标是。在这项建议中，我们试图确定基底节是否参与了这一过程。 目标导向的感觉过滤，以及这一过程在帕金森病中是否受损。这一现象可能会 提供一个框架来解释具有单一潜在原因的帕金森病运动症状：正常的感觉反馈是 没有适当地过滤，这会降低电机系统产生正常命令的能力。 感觉反馈不足会产生过多的跨皮质僵硬反射，破坏大脑的 运动迟缓时的内部模型和干扰运动规划，甚至通过随机产生震颤 共振(一种在非线性神经系统中常见的现象，其中亚阈值振荡被放大 由噪音引起)。 无论我们的具体假设是否得到支持，这项研究的实验范式都将 产生无与伦比的数据和对人类大脑中感觉运动整合的洞察。如果我们的假设是 然而，正确的是，我们将进一步为PD症状的前所未有的机制模型提供一个框架 一代又一代人，并制定了改善治疗的路线图。

PROJECT SUMMARY Conventional models of Parkinson’s disease (PD) dysfunction do not account for sensory feedback, which is both clearly represented in the basal ganglia and clearly impaired in PD. Despite the critical importance of this feedback to normal movement, the contribution of impaired sensory processing to PD pathophysiology is unknown. Our long-term goal is to clarify the role of sensory feedback in the production of pathological motor commands in PD. This research could help reveal the neural basis of both PD pathology and its treatment, leading to more efficient clinical practices, driving the development of novel therapeutic technologies, and helping to alleviate the enormous burdens of PD on patients and providers. In healthy people, the motor system will automatically ignore sensory feedback that is not directly relevant to the current behavioral goal. In this proposal, we seek to determine whether the basal ganglia participate in this goal-directed sensory filtering, and whether this process is impaired in PD. This phenomenon could potentially provide a framework to explain PD motor symptoms with a single underlying cause: normal sensory feedback is not filtered appropriately, which reduces the ability of the motor system to produce normal commands. Underdamped sensory feedback could produce excessive transcortical reflexes in rigidity, corrupt the brain’s internal models and interfere with movement planning in bradykinesia, and even produce tremor via stochastic resonance (a phenomenon common in nonlinear neural systems in which a sub-threshold oscillation is amplified by noise). Whether or not our specific hypotheses are supported, the experimental paradigms of this study will generate unparalleled data and insights into sensorimotor integration in the human brain. If our hypotheses are correct, however, we will further provide a framework for an unprecedented mechanistic model of PD symptom generation and a roadmap towards improved treatment.