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: 10654669
• 负责人: Azadeh Yazdan Shahmorad
• 金额: $ 73.38万
• 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 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654669
• 关键词: Area; Behavioral; Brain; Disease; Effectiveness; Electrophysiology (science); Engineering; Foundations; Future; Goals; Human; Injury; Ion Channel; Ischemia; Learning; Lesion; Light; Location; Macaca; Maps; Measures; Memory; Morphologic artifacts; Motor Cortex; Neuronal Plasticity; Neurons; Neurosciences; Pattern; Physiologic pulse; Physiological; Recovery of Function; Rehabilitation therapy; Reporting; Research; Role; Solid; Somatosensory Cortex; Specificity; Stroke; System; Techniques; Testing; Therapeutic Intervention; Time; Transfection; Viral; awake; behavior measurement; brain machine interface; cell type; density; design; experimental study; injured; injury recovery; insight; ischemic lesion; nervous system disorder; neural; neural patterning; neurological rehabilitation; neuroregulation; novel; novel strategies; optogenetics; sensorimotor system; 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, 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.

项目摘要 大脑在各种学习和记忆任务以及期间显示出明显的可塑性 受伤后恢复。许多人建议使用大脑刺激利用这种先天的可塑性 治疗神经障碍。实施此类治疗需要高级工程工具为 以及对刺激诱导的可塑性如何驱动网络变化的深刻理解 大规模和多个大脑区域的动态和连通性。在这里，我建议 使用我们的新型工程工具来精确操纵猕猴感觉运动的神经活动 调查和诱导靶向皮质重组的皮层。我假设闭环 基于自然功能连接的体感皮质的光遗传学刺激 感觉运动系统可以驱动皮质可塑性并诱导功能恢复。这 体感和运动皮质区域的功能连通图估计为 目标刺激指南。在AIM 1中，活动能力控制活动的有效性 - 依赖刺激将被调查以加强自然现有联系和 诱导新连接。在AIM 2中，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措施，以评估 靶向皮质重组。这些措施的结合可以使不同 大脑可塑性和功能恢复机制的各个方面。这些目标的结果将是 有针对性康复的精制刺激模式的概念证明 重新布线大脑，不仅可以用于神经康复，而且可以帮助理解 这些皮质区域的电路和连通性。