Neurobiological principles applied to the rehabilitation of stroke patients

描述(申请人提供)：我们建议的研究涉及健康受试者和卒中患者完整运动皮质(M1)的可塑性增强机制。M1重组在卒中后运动障碍的恢复中起着重要作用；因此，进一步开发利用这一恢复潜力的康复策略是重要的。我们以前已经证明，运动训练结合d-苯丙胺或M1的经颅磁刺激(IMS)可以增强健康受试者完整M1的使用依赖性可塑性。在这项拟议的研究中，我们将结合电生理学、药理学和运动学技术，进一步研究健康受试者和中风患者受损M1的使用依赖性可塑性的调节。我们的三个具体目标是研究M1的IMS和增强M1中依赖使用的可塑性的药物。在具体目标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-苯丙胺对使用依赖可塑性的有益影响。在特定目标2中，我们将确定IMS刺激M1的参数，这些参数最有效地增强完整健康人M1的使用依赖性可塑性。特定目标3将通过测量M1兴奋性和练习动作的运动学的变化来评估在健康受试者的完整M1中开发的可塑性增强方法在中风患者的损伤M1中的有效性。我们的建议将科学与中风患者的神经康复实践联系起来，将已知的增强完整人类M1对中风患者受伤M1的练习依赖可塑性的原则应用于中风患者的运动恢复。这些新设计的康复策略可能会潜在地降低中风的发病率和残疾，从而显著降低长期门诊和疗养院护理的成本。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.