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

利用意志控制猕猴感觉运动皮层活动依赖性光遗传学刺激来工程神经可塑性

• 批准号: 10523649
• 负责人: Azadeh Yazdan Shahmorad
• 金额: $ 5.43万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10523649
• 关键词: Area; Behavioral; Brain; Disease; Effectiveness; Electrophysiology (science); Engineering; Learning; Light; Macaca; Maps; Measures; Memory; Motor; Neuronal Plasticity; Neurons; Parents; Pattern; Physiological; Recovery of Function; Rehabilitation therapy; Role; Solid; Somatosensory Cortex; Stroke; Structure; Volition; awake; base; design; injury recovery; insight; ischemic lesion; nervous system disorder; neurological rehabilitation; novel; optogenetics; relating to nervous system; sensorimotor system; somatosensory; tool

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, we 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 activity-dependent stimulation informed by the brain state and structure will be investigated to both strengthen the natural existing connections and to induce new connections. In Aim 2 the same activity-dependent stimulation as aim 1 will be evaluated to induce new connections in the presence of an ischemic lesion. The results of these aims will be compared with the three stimulation paradigms proposed in the parent R01 to evaluate the role of brain state and structure in stimulation-induced plasticity. 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.

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，我们建议 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，活动依赖性刺激的有效性 由大脑的状态和结构通知将被调查，以加强自然 现有的连接和诱导新的连接。在目标2中，相同的活动依赖性 将评估作为目标1的刺激以在缺血性脑损伤存在的情况下诱导新的连接。 损伤。这些目标的结果将与提出的三种刺激范式进行比较 在亲本R01中评估大脑状态和结构在刺激诱导的可塑性中的作用。 这些目标旨在为我们提供行为和电生理测量 来评估目标皮层重组这些措施的结合可以揭示 大脑可塑性和功能恢复机制的不同方面。的结果予以 目标将是一个概念的证明，为有针对性的细化刺激模式的力量， 大脑的康复和重新布线，不仅可以用于神经康复， 可以帮助理解这些皮层区域的电路和连接。