Technology Research and Development Project 1 (Guiding Beneficial Plasticity)

脊髓损伤(SCI)、中风、脑瘫等慢性神经肌肉疾病损害重要 步行等功能。目前的治疗方法很少完全有效。最新进展使强大的新技术成为可能 针对关键神经系统通路的有益改变的治疗方法。在这些疗法中，最早的fi是 修改特定fic脊髓Reflex通路的可操作性条件调节方案。Refl前任被引诱，而此人是 如果Reflex Size满足fi标准，则会得到奖励。这个人学会修改大脑对通路的控制，以 增加奖励。这种控制逐渐改变了脊髓通路本身。此外，fi带来的好处是 (即可塑性)在这一途径导致更广泛的有利fi其他地方的可塑性。这种更广泛的影响是由 新的脊髓功能协商平衡模型。结果是，在老鼠或患有不完全性脊髓损伤的人中， 脊柱ReflEX的可操作性调节提高了行走速度，减少了跛行。 Tr&d1正在开发并转化为临床使用的操作条件调节方案，以诱导良好的fi神经可塑性 在神经系统中。它包括动物和人类研究。动物研究揭示了机制和 指导人体研究的原则，制定治疗方案并将其转化为临床应用。 Aim 1将开发一种完全植入的基于遥测的系统，用于长期24/7操作条件调节 移动的老鼠。通过简化和促进操作性条件作用和其他长期研究，这一新的实验室系统 将使许多其他研究人员有可能从事这些重要的研究。此外，这一目标将使用 这一新的fi系统首次研究了脊髓Refl预适应的分子生物学。 目标2将开发和验证一种适用于广泛临床的通用操作性调节系统 使用。完全实现操作性条件反射和相关方案的治疗承诺需要临床上 支持多种协议并可改变多种神经系统通路的实用系统。 新的通用临床系统将与临床合作者一起进行测试、优化和验证。 与主要康复中心的同事的更多合作将探索refiex OPERANT的efflcacy 用于改善脑瘫、中风和其他疾病患者的功能的条件作用。这项工作将使fiNe 关键功能测量的剂量-反应曲线，并将包括功能成像研究，以表征 潜在的可塑性。它将勾勒出潜在的临床应用范围，并有助于改进设计和 条件化协议的实施。这些研究有望导致更大规模的临床试验，以建立 SPECIfic条件反射方案对促进SPECIfic组患者功能恢复的价值。 通过创建、验证和传播这些新的动物和人类系统，并通过与 其中，tr&d1将加速操作性条件反射和相关方案的开发和临床翻译 这可以作为其他疗法的补充，促进脊髓损伤、中风、 脑性瘫痪和其他毁灭性的神经肌肉疾病。

Spinal cord injury (SCI), stroke, cerebral palsy and other chronic neuromuscular disorders impair important functions such as walking. Current therapies are seldom fully effective. Recent advances enable powerful new therapies that target beneficial change to key nervous system pathways. Among the first of these therapies are operant conditioning protocols that modify a specific spinal reflex pathway. The reflex is elicited, and the person is rewarded if reflex size satisfies a criterion. The person learns to modify the brain's control over the pathway to increase rewards. This control gradually changes the spinal pathway itself. Furthermore, the beneficial change (i.e., plasticity) in this pathway leads to wider beneficial plasticity elsewhere. This wider effect is predicted by the new negotiated equilibrium model of spinal cord function. The result is that, in rats or people with incomplete SCI, operant conditioning of a spinal reflex increases walking speed and reduces limping. TR&D1 is developing and translating into clinical use operant conditioning protocols that induce beneficial plasticity in the nervous system. It includes animal and human studies. The animal studies reveal mechanisms and principles that guide the human studies, which develop therapeutic protocols and translate them into clinical use. Aim 1 will develop a fully implanted telemetry-based system for long-term 24/7 operant conditioning in freely moving rats. By simplifying and facilitating operant conditioning and other long-term studies, this new lab system will make it possible for many other researchers to engage in these important studies. In addition, this aim will use this new system for the first studies of the molecular biology of spinal reflex conditioning. Aim 2 will develop and validate a general-purpose operant conditioning system suitable for widespread clinical use. Full achievement of the therapeutic promise of operant conditioning and related protocols requires a clinically practical system that supports a broad range of protocols and can change a variety of nervous system pathways. The new general-purpose clinical system will be tested, optimized, and validated with clinical collaborators. Additional collaborations with colleagues at major rehabilitation centers will explore the efficacy of reflex operant conditioning for improving function in people with cerebral palsy, stroke, and other disorders. This work will define dose-response curves for key functional measures and will include functional imaging studies to characterize the underlying plasticity. It will delineate the range of potential clinical applications and help improve the design and implementation of conditioning protocols. These studies are expected to lead to larger clinical trials to establish the value of specific conditioning protocols for enhancing recovery of function for specific groups of patients. By creating, validating, and disseminating these new animal and human systems, and by conducting studies with them, TR&D1 will accelerate development and clinical translation of operant conditioning and related protocols that can complement other therapies and enhance functional recovery for people with spinal cord injury, stroke, cerebral palsy, and other devastating neuromuscular disorders.