Engineering neuroplasticity using volitional control of activity-dependent optogenetic stimulation in macaque sensorimotor cortex

项目摘要 大脑在各种各样的学习和记忆任务中表现出明显的可塑性， 受伤后的恢复。许多人建议利用大脑刺激来利用这种先天的可塑性 来治疗神经紊乱实施这种治疗需要先进的工程工具， 以及对刺激诱导的可塑性如何驱动网络变化的深刻理解 在大规模和跨多个大脑区域的动态和连通性。在此，我提议 使用我们新颖的工程工具来精确操纵猕猴感觉运动神经活动 皮质，以研究和诱导有针对性的皮质重组。我假设一个闭环 体感皮层的光遗传学刺激，基于 感觉运动系统可以驱动皮层可塑性并诱导功能恢复。的 躯体感觉和运动皮质区的功能连接图将被估计为 有针对性的刺激指南。在目标1中，意志控制活动的有效性- 将研究依赖性刺激，以加强自然存在的联系， 来建立新的联系在目标2中，对活动依赖性刺激的意志控制将 在存在缺血性病变的情况下，评估其诱导新的连接。这些目的是 旨在为我们提供行为和电生理测量，以评估 有针对性的皮层重组这些措施的结合可以揭示不同的 大脑可塑性和功能恢复机制方面。这些目标的结果将是 针对目标康复的精细刺激模式的功效的概念验证， 重新连接大脑，不仅可以用于神经康复， 这些皮层区域的回路和连通性

Project summary The brain shows marked plasticity across a variety of learning and memory tasks as well as during recovery after injury. Many have proposed to leverage this innate plasticity using brain stimulation to treat neural disorders. Implementing such treatments requires advanced engineering tools as well as a solid understanding of how stimulation-induced plasticity drives changes in network dynamics and connectivity at a large scale and across multiple brain areas. Here, I propose to use our novel engineering tools to precisely manipulate neural activity in macaque sensorimotor cortex to investigate and induce targeted cortical reorganization. I hypothesize that a closed-loop optogenetic stimulation of somatosensory cortex based on the natural functional connectivity of the sensorimotor system can drive cortical plasticity and induce functional recovery. The functional connectivity maps of the somatosensory and motor cortical areas will be estimated as a guide for targeted stimulation. In Aim 1 the effectiveness of volitional control of activity- dependent stimulation will be investigated to both strengthen the natural existing connections and to induce new connections. In Aim 2 the volitional control of activity-dependent stimulation will be evaluated to induce new connections in the presence of an ischemic lesion. These aims are designed to provide us with both behavioral and electrophysiological measures to assess the targeted cortical reorganization. The combination of these measures can shed light on different aspects of brain plasticity and functional recovery mechanisms. The results of these aims will be a proof of concept for the power of refined stimulation patterns for targeted rehabilitation and rewiring of the brain that not only can be used for neurorehabilitation but also can help understand the circuits and connectivity in these cortical areas.