Technology Research and Development Project 1 (Guiding Beneficial Plasticity)

脊髓损伤（SCI）、中风、脑瘫和其他慢性神经肌肉疾病损害重要的 功能如行走。目前的治疗方法很少完全有效。最新进展使强大的新 针对关键神经系统通路的贝内变化的治疗。这些疗法中的第一种是 操作性条件反射协议，修改一个特定的脊髓反射通路。反应被引出，这个人 如果外汇规模萨蒂斯一个标准，则给予奖励。这个人学会修改大脑对通路的控制， 增加奖励。这种控制逐渐改变脊髓通路本身。此外，贝内的变化 (i.e.,可塑性）在这一途径导致更广泛的贝内的可塑性在其他地方。这种更广泛的影响是由 脊髓功能的新协商平衡模型。结果是，在大鼠或不完全SCI患者中， 脊柱反射的操作性调节增加了行走速度并减少了跛行。 TR&D1正在开发并转化为临床使用操作性条件反射协议，诱导贝内的可塑性 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， 指导人类研究的原则，开发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，用于自由的长期24/7操作性条件反射 移动的老鼠通过简化和促进操作性条件反射和其他长期研究， 将使许多其他研究人员能够从事这些重要的研究。此外，这一目标将使用 这个新系统首次用于脊髓反射调节的分子生物学研究。 目标2将开发和验证一个通用的操作性条件反射系统，适用于广泛的临床 使用.操作性条件反射和相关方案的治疗承诺的充分实现需要临床上的 这是一个实用的系统，支持广泛的协议，可以改变各种神经系统通路。 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进行的其他合作将探索康复操作的有效性。 用于改善脑瘫、中风和其他疾病患者的功能。这项工作将定义 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 潜在的可塑性它将描绘潜在的临床应用范围，并有助于改进设计， 条件协议的实施。这些研究有望导致更大规模的临床试验， 特定的预处理方案对于促进特定患者群体的功能恢复的价值。 通过创建、验证和传播这些新的动物和人类系统，并通过使用 因此，TR&D1将加速操作性条件反射和相关协议的开发和临床转化 它可以补充其他疗法，增强脊髓损伤，中风， 脑瘫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.