Mirror Imitation Therapy for Motor Recovery After Stroke

描述(申请人提供)：中枢神经系统(CNS)损伤的急性治疗研究已成为国家优先事项，最近取得了显著进展。不幸的是，这一进展并没有延续到中枢神经系统损伤的不太严重的后遗症，通常包括严重的认知和运动障碍。在所有影响中枢神经系统的疾病中，中风既是成年人最常见的疾病，也是导致严重残疾的主要原因。对中风的长期影响的治疗落后于对这种急性疾病的治疗，通常侧重于发展代偿性神经回路，而不是恢复先前存在的通路。这项建议涉及生理修复，即通过直接重塑恢复行为，旨在恢复原始神经回路。该提案特别侧重于缺血性中风后手运动技能的补救方法。我们的方法是基于功能修复的原则，包括通过重塑先前存在的运动网络来恢复功能。收敛的神经输入是重叠的、分布式神经电路的功能基础，在这些电路中，即使是简单的行为也是高度集成过程的产物。在这个框架内，治疗干预可以涉及操纵特定运动神经回路元素之间相互作用的强度和多样性。运动行为在整合来自感觉、运动和边缘来源的汇聚神经输入的程度上有所不同，因此对中风患者具有不同的治疗潜力。在这项建议中，我们使用了一种基于镜子系统生理学的运动模仿疗法。这里研究的行为任务是熟练的手部动作，在手部运动模仿的背景下使用。这些任务在利用神经回路活动的程度上有所不同，这些活动对应于感觉、运动和联想信息的潜在来源。所有这些都已在手运动修复方面确立了潜力。运动模仿包括使用外部本体感觉和视觉感觉输入的心理练习，可以应用于手运动任务。神经重塑在卒中后有很大的潜在影响。我们调查了专门的晚期基于补救的干预措施所发生的神经重建。我们认为，通过运动观察-模拟系统(镜像神经元系统)的参与，在监督下的练习和手工技能的专门训练，将导致显著的神经回路变化，有利于受损肢体(优势和非优势)的恢复。我们还假设，这些神经回路的改变将伴随着治疗的长期益处。虽然我们通过反映手运动技能的主要结果指标来评估治疗效果，但我们广泛使用神经网络建模程序来表征这一补救过程的生理方面。

DESCRIPTION (provided by applicant): Research into the acute treatment of central nervous system (CNS) injury has become a national priority, and recent progress has been remarkable. Unfortunately this progress has not carried over to the less acute sequelae of CNS injury, which often include serious cognitive and motor disability. Of all diseases affecting the CNS, stroke is both the most prevalent and the primary cause of serious disability among adults. Treatment for the long-term effects of stroke lags behind treatment for the acute illness and typically focuses on developing compensatory neural circuits rather than on reinstatement of pre-existing pathways. This proposal addresses physiological remediation, in which behavior is restored by direct remodeling, aimed at reinstatement of original neural circuits. The proposal specifically focuses on methods for remediation of hand motor skill after ischemic stroke. Our approach is based on principles of functional remediation that involves restoration of function through remodeling of pre-existing motor networks. Convergent neural inputs are the functional basis of overlapping, distributed neural circuits, in which even simple behaviors are the product of a highly integrated process. Within this framework, therapeutic interventions can involve the manipulation of the intensity and diversity of interactions among elements of particular motor circuits. Motor behaviors differ in the degree to which they integrate convergent neural inputs from sensory, motor and limbic sources, and thus have different therapeutic potential for stroke patients. In this proposal we use a motor imitation therapy based on the physiology of the mirror system. The behavioral tasks studied here are skilled hand movements, which are used in the context of hand motor imitation. These tasks differ in the degree to which they harness neural circuit activity corresponding to the potential sources of sensory, motor, and associational information. All have established potential in hand motor remediation. Motor imitation consists of mental practice using external proprioceptive and visual sensory inputs and can be applied with hand motor tasks. Neural remodeling has a large potential impact after stroke. We investigate the neural remodeling that occurs with specialized late remediation-based intervention. We propose that supervised practice and specialized training with manual skill through the involvement of the motor observation-imitation system (mirror neuron system), used in a program of graded incremental complexity, will lead to notable neural circuit changes that favor recovery of impaired limbs (dominant and non-dominant). We also postulate that these neural circuit changes will be accompanied by therapeutic long-term benefits. Although we assess therapeutic benefit with primary outcome measures that reflect hand motor skill, we make extensive use of neural network modeling procedures to characterize the physiological aspects of this remediative process.