Neurobiological principles applied to the rehabilitation of stroke patients

描述（由申请人提供）：我们拟进行的研究涉及健康受试者和M1脑卒中患者完整运动皮质（M1）可塑性增强机制。M1重组在脑卒中后运动缺陷的恢复中起主要作用；因此，必须进一步制定利用这种潜力进行康复的康复战略。我们之前已经证明，运动训练联合d-安非他明或经颅磁刺激（IMS）可以增强健康受试者完整M1的使用依赖性可塑性。在拟议的研究中，我们将使用电生理、药理学和运动学技术的结合，进一步研究健康受试者的完整M1和中风患者的受损M1中使用依赖性可塑性的调节。我们的三个具体目的是研究M1的IMS和药物，以增强M1的使用依赖性可塑性。在Specific Aim 1中，我们将测试与不同神经递质系统特异性相互作用的药物对健康人完整M1中使用依赖可塑性的影响，因为尚不清楚哪些系统介导了d-安非他明对使用依赖可塑性的有益作用。在专项目标2中，我们将确定IMS刺激M1最有效增强健康人Ml使用依赖性可塑性的参数。专项目标3将通过测量M1兴奋性和练习动作的运动学变化，评估在健康人完整M1中开发的可塑性增强方法（专项目标1和2）对中风患者损伤M1的有效性。我们的建议将科学与中风患者的神经康复实践联系起来，将已知的原理应用于增强完整人类M1的练习依赖可塑性，以增强中风患者受伤M1的运动恢复。这些新设计的康复策略可以潜在地降低中风的发病率和致残率，从而大大降低长期门诊和养老院护理的成本。对神经康复领域的积极影响将是相当大的。

DESCRIPTION (provided by applicant): Our proposed research is concerned with plasticity enhancing mechanisms in intact motor cortex (M1) of healthy subjects and lesioned M1 stroke patients.M1 reorganization plays a major-role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. We have shown previously, that motor training combined with d- amphetamine or transcranial magnetic stimulation (IMS) of M1 enhances use-dependent plasticity in intact M1 of healthy subjects. In the proposed study we will further examine modulation of use-dependent plasticity in intact M1 of healthy subjects and lesioned M1 of stroke patients using a combination of electrophysiological, pharmacological and kinematic techniques. Our three specific aims examine IMS of M1 and drugs to enhance use-dependent plasticity in M1. In Specific Aim 1, we will test the effect of drugs that interact specifically with different neurotransmitter systems on use-dependent plasticity in intact M1 of healthy humans as it is not known which systems mediate the beneficial effect of d-amphetamine on use dependent plasticity. In Specific Aim 2, we will identify the parameters, for IMS stimulation of M1 that are most effective to enhance use-dependent plasticity in intact healthy human Ml Specific Aim 3 will assess the efficacy of plasticity enhancing methods developed in intact M1 of healthy subjects (Specific Aims 1 & 2) in lesioned M1 of stroke patients by measuring changes in M1 excitability and kinematics of practiced movements. Our proposal links science to neurorehabilitation practice in stroke patients by applying principles known to enhance practice dependent plasticity in intact human M1 to injured M1 of stroke patients to enhance motor recovery. These newly designed rehabilitation strategies could potentially reduce the morbidity and disability of stroke and, thus, reduce dramatically the costs for long-term ambulatory and nursing home care. The positive impact on the field of neurorehabilitation will be considerable.