Reorganizing motor cortex in stroke patient through Hebbian-type stimulation

描述(由申请人提供)：中风是美国发病率的主要原因，但由于对康复机制的不完全了解，确定改善结果的治疗策略受到限制。受损大脑半球的运动皮质重组在卒中后运动功能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具有重要意义。非侵入性皮质刺激可增强运动训练对运动皮质功能可塑性和运动能力的有益影响。在这些研究中使用的不同方法中，Hebbian型M1刺激特别耐人寻味，因为与随机M1刺激相比，它似乎更有效。有新的证据表明，运动训练或皮质刺激相关的功能改善与目标大脑区域灰质的增加有关。因此，虽然有一些证据支持人类M1对运动学习和皮质刺激的反应进行结构重组，但这些变化背后的机制及其与功能可塑性的关系尚不清楚。更好地了解事件的顺序对于开发最佳的治疗干预措施以改善中风后的康复至关重要。在具体目标1中，我们将确定反复暴露于训练结合Hebbian型M1刺激是否能促进中风患者受损M1的功能重组。在具体目标2中，我们将确定反复暴露于训练结合Hebbian型M1刺激是否会增强中风患者受损M1的结构重组。然后，我们将探索训练相关的功能性皮质重组和结构性皮质重组之间的关系。在这个项目完成后，我们期望我们将确定Hebbian型刺激对脑功能和结构重组的影响，从而获得与训练相关的改善和维持中风患者运动功能的神经底物的间接证据。这一知识有望对中风患者的治疗产生实质性的积极影响，这将显著改善康复，并将推动神经康复领域的发展。

DESCRIPTION (provided by applicant): Stroke is a leading cause of morbidity in the U.S. but identification of treatment strategies to improve outcome is limited by the incomplete understanding of the mechanisms of recovery. Motor cortex reorganization of the lesioned hemisphere (lesioned M1) plays a major role in post-stroke recovery of motor function; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. Non-invasive cortical stimulation can enhance the beneficial effects of motor training on performance and functional plasticity of motor cortex. Among the different approaches used in these studies, Hebbian-type M1 stimulation is particularly intriguing, as it seems to be more effective when compared to random M1 stimulation. There is emerging evidence that motor training or cortical stimulation related improvement of function are associated with increases in the grey matter of targeted brain areas. While there is therefore some evidence supporting structural reorganization in human M1 in response to motor learning and cortical stimulation, the mechanisms underlying these changes and their relationship to functional plasticity are not known. A better understanding of the sequences of events is critical to development of optimal therapeutic interventions to improve recovery following stroke. In Specific Aim 1, we will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances functional reorganization in lesioned M1 of stroke patients. In Specific Aim 2, we will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances structural reorganization in lesioned M1 of stroke patients. We will then explore the relationship between training related functional and structural cortical reorganization. At the completion of this project, it is our expectation that we will have determined the effect of Hebbian-type stimulation on both, functional and structural brain reorganization, thereby obtaining indirect evidence for the neuronal substrate underlying training related improvement and maintenance of motor function in stroke patients. This knowledge would be expected to have a substantial positive impact on treatment for stroke patients that will significantly improve recovery and would move the field of neurorehabilitation forward.