Technology Research and Development Project 1 (Guiding Beneficial Plasticity)

技术研发项目1（引导有益可塑性）

• 批准号: 10456336
• 负责人: Jonathan Rickel Wolpaw
• 金额: $ 22.16万
• 依托单位: ALBANY RESEARCH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456336
• 关键词: Achievement; Adopted; Adoption; Adult; Animals; Biological; Cerebral Palsy; Chronic; Clinical; Clinical Research; Clinical Trials; Collaborations; Complement; Computer software; Development; Disease; Dose; Electroencephalography; Elements; Feedback; Foundations; Functional Imaging; Functional Magnetic Resonance Imaging; Funding; Genomics; Grant; H-Reflex; Hospitals; Human; Image; Impairment; Implant; Laboratories; Lead; Learning; Life; Locomotion; Longitudinal Studies; Manuals; Measures; Mediation; Medical; Molecular; Molecular Biology; Monkeys; Motor; Motor Neurons; Multiple Sclerosis; Mus; Nervous system structure; Neurologic; Neuromuscular Diseases; Neuronal Plasticity; Neurons; Operant Conditioning; Operative Surgical Procedures; Orthotic Devices; Pathway interactions; Patients; Persons; Probability; Property; Prosthesis; Protocols documentation; RNA Sequences; Rattus; Recovery of Function; Reflex action; Rehabilitation Centers; Rehabilitation therapy; Research Institute; Research Personnel; Rewards; Services; Soleus Muscle; South Carolina; Spinal; Spinal Cord; Spinal cord injury; Stroke; Support System; System; Technology; Telemetry; Testing; Therapeutic; Training; Translating; Universities; Walking; Work; analog; axion; base; classical conditioning; clinical application; clinical development; clinical practice; clinical translation; conditioning; design; efficacy evaluation; equilibrium model; imaging study; improved; improved functioning; mind control; neurotechnology; new therapeutic target; response; skills; spasticity; spinal pathway; spinal reflex; stretch reflex; technology research and development; walking speed; wireless implant

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.

脊髓损伤（SCI）、中风、脑瘫和其他慢性神经肌肉疾病损害重要 目前的治疗方法很少能完全有效，从而实现了强大的新功能。 这些疗法中的第一个是针对关键神经系统通路的有益改变的疗法。 改变特定脊髓反射通路的操作性调节方案引起反射，并且人被激发。 如果反射大小满足标准，则该人学会改变大脑对路径的控制。 增加奖励。这种控制逐渐改变脊髓通路本身。 该途径中的（即可塑性）会导致其他地方更广泛的有益可塑性。 新的脊髓功能协商平衡模型结果是，在患有不完全脊髓损伤的大鼠或人中， 脊髓反射的操作性调节可以提高步行速度并减少跛行。 TR&D1 正在开发并转化为临床使用的操作性调节协议，以诱导有益的可塑性 它包括动物和人类研究揭示了机制和。 指导人类研究的原则，制定治疗方案并将其转化为临床应用。 目标 1 将开发一种完全植入的基于遥测的系统，用于长期 24/7 自由操作调节 通过简化和促进操作条件反射和其他长期研究，这个新的实验室系统 将使许多其他研究人员能够参与这些重要的研究，此外，这一目标将被利用。 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 将开发并验证适用于广泛临床的通用操作条件反射系统 操作性条件反射和相关方案的治疗前景的完全实现需要在临床上进行。 实用的系统，支持广泛的协议并可以改变多种神经系统通路。 新的通用临床系统将由临床合作者进行测试、优化和验证。 与主要康复中心同事的进一步合作将探索反射操作的效率 这项工作将定义改善脑瘫、中风和其他疾病患者功能的调理。 关键功能测量的剂量反应曲线，并将包括功能成像研究来表征 它将描绘潜在的临床应用范围，并有助于改进设计和 这些研究预计将导致更大规模的临床试验的建立。 特定调理方案对于促进特定患者群体功能恢复的价值。 通过创建、验证和传播这些新的动物和人类系统，并通过与 TR&D1 将加速操作性条件反射及相关方案的开发和临床转化 可以补充其他疗法并增强脊髓损伤、中风、 脑瘫和其他破坏性神经肌肉疾病。