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

项目总结 大脑在各种学习和记忆任务中表现出显著的可塑性，在 受伤后的恢复。许多人建议通过脑刺激来利用这种天生的可塑性。 用来治疗神经紊乱。实施这类治疗需要先进的工程工具，如 以及对刺激诱导的可塑性如何驱动网络变化的深入理解 大范围和跨多个大脑区域的动态和连接。在此，我建议 使用我们的新型工程工具精确操纵猕猴感觉运动的神经活动 以研究和诱导有针对性的皮质重组。我假设一个闭合环路 基于自然功能连接的躯体感觉皮层的光遗传刺激 感觉运动系统可以驱动皮质可塑性和诱导功能恢复。这个 躯体感觉和运动皮质区域的功能连接图将被估计为 靶向刺激指南。在目标1中，活动的意志控制的有效性- 将对依赖刺激进行调查，以加强自然存在的联系和 来建立新的联系。在目标2中，依赖活动的刺激的意志控制将 在存在缺血损伤的情况下进行评估以诱导新的连接。这些目标是 旨在为我们提供行为和电生理测量来评估 有针对性的皮质重组。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的方面。这些目标的结果将是 对精细化刺激模式用于定向康复的力量的概念证明 大脑的重新布线，不仅可以用于神经康复，还可以帮助理解 这些大脑皮层区域的回路和连接。

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.