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

项目概要 大脑在各种学习和记忆任务以及在学习过程中表现出显着的可塑性 受伤后的恢复。许多人建议通过大脑刺激来利用这种天生的可塑性 治疗神经疾病。实施此类治疗需要先进的工程工具，例如 以及对刺激引起的可塑性如何驱动网络变化的深入理解 大规模和跨多个大脑区域的动态和连接。在此，我提议 使用我们新颖的工程工具精确操纵猕猴感觉运动的神经活动 皮层来研究并诱导有针对性的皮层重组。我假设一个闭环 基于自然功能连接的体感皮层光遗传学刺激 感觉运动系统可以驱动皮质可塑性并诱导功能恢复。的 体感和运动皮质区域的功能连接图将估计为 有针对性的刺激指南。在目标 1 中，意志活动控制的有效性- 将研究依赖性刺激，以加强自然现有的联系和 诱导新的联系。在目标 2 中，对活动依赖性刺激的意志控制将 进行评估以在存在缺血性病变的情况下诱导新的连接。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情况 大脑可塑性和功能恢复机制方面。这些目标的结果将是 概念证明精细刺激模式对于有针对性的康复和 大脑的重新布线不仅可以用于神经康复，还可以帮助理解 这些皮质区域的电路和连接。

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.