Optimization of the Cortical Stimulation Protocol for Motor Recovery

运动恢复皮质刺激方案的优化

• 批准号: 7623967
• 负责人: Jeffrey A Kleim
• 金额: $ 14.72万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7623967
• 关键词: Adverse effects; Affect; Animals; Area; Behavioral; Brain; Cerebral Ischemia; Chemosensitization; Clinical; Clinical Trials; Condition; Data; Development; Educational Intervention; Educational process of instructing; Electric Stimulation; Electrodes; Ensure; Epilepsy; Frequencies; Functional disorder; Goals; Human; Individual; Infarction; Injury; Intervention; Ischemia; Lesion; Limb structure; Measurable; Modeling; Motor; Motor Cortex; Movement; Neurons; Numbers; Outcome Measure; Pattern; Performance; Physiologic pulse; Primates; Protocols documentation; Pulse taking; Range; Rate; Rattus; Recommendation; Recovery; Recovery of Function; Rehabilitation therapy; Relative (related person); Research; Risk; Rodent; Rodent Model; Running; Safety; Seizures; Sentinel; Stroke; Surface; Survivors; Synapses; Techniques; Testing; Therapeutic; Therapeutic Index; Time; Tissues; Training; Translating; Week; Width; behavior measurement; clinical application; day; experience; functional improvement; improved; motor impairment; nonhuman primate; programs; research study; success; therapy duration

The majority of stroke survivors display limb weakness and motor impairments, but will show some measurable recovery of function over time. Regaining some impaired function may be explained by brain plasticity and this holds promise for therapeutic and rehabilitative treatments. A possible strategy for improving functional recovery following cerebral strokes in humans involves augmenting brain plasticity by combining rehabilitative training with mild focal electrical stimulation of peri-infarct cortical areas. The long-term objective is to enhance recovery from stoke by activating and teaching cortical neuronal networks by using cortical stimulation in combination with rehabilitative training. This project has two aims; 1) determine the optimal electrical stimulation parameters (frequency, amplitude, and temporal pattern) on behavioral efficacy, and 2) determine the optimal electrode configuration, duration of therapy and persistence of the enhanced recovery. The effect of the stimulation parameters on movement and seizure thresholds will also be determined in both the lesioned and intact hemisphere. In order to achieve these aims we use a rodent model of stroke. The rats are initially trained on skilled behavioral tasks, undergo a focal ischemic infarct (stroke), receive cortical stimulation with rehabilitative training and are assessed on their recovery. Furthermore, we will determine the stimulation parameters that markedly improve behavioral recovery but minimize unwanted side effects (a maximal therapeutic index). The results from the studies above will then be used to guide the development of clinical applications of the technique in humans that have had strokes.

大多数中风幸存者都表现出肢体弱点和运动障碍，但会显示一些可测量的功能恢复。重新获得一些功能受损的功能可以用大脑可塑性来解释，这具有治疗和康复治疗的希望。人类脑冲程后改善功能恢复的一种可能策略是通过将康复训练与轻度局灶性电刺激对潜在的皮质区域结合起来来增强大脑可塑性。长期目标是通过使用皮质刺激与康复训练结合使用皮质刺激来激活和教授皮质神经元网络，从而增强Stoke的恢复。该项目有两个目标。 1）确定行为上的最佳电刺激参数（频率，振幅和时间模式） 功效和2）确定最佳电极构型，治疗持续时间和增强恢复的持久性。刺激参数对运动和癫痫发作阈值的影响也将在病变和完整半球中确定。为了实现这些目标，我们使用啮齿动物的中风模型。最初，对大鼠进行了熟练的行为任务训练，经历了局灶性缺血性梗塞（中风），通过康复训练接受皮质刺激，并对其恢复进行评估。此外，我们将确定明显改善行为恢复但最小化不良副作用（最大治疗指数）的刺激参数。然后，上述研究的结果将 用于指导该技术在具有中风的人类中的临床应用的发展。