Neural dynamics of somatosensory guidance of dexterous movement in intact and stroke-injured networks

项目摘要 在未来15年内，全球范围内导致中风的疾病、残疾和过早死亡的人数将增加一倍。尽管 物理治疗，约50%的中风幸存者有受损的手功能，这强烈影响活动 日常生活和独立性;迫切需要新的治疗方法。虽然大多数临床前研究 解决中风恢复和康复集中于恢复受损的下行运动路径， 灵巧手的功能也依赖于大脑接收上行体感输入， 用它来引导运动。在临床和动物模型中，躯体感觉皮层的缺陷预示着更糟的情况。 中风后手功能的恢复，虽然躯体感觉信号的功能机制， 支撑手功能仍然没有得到很好的表征。在这项提案中，我们的目标是揭示体感如何 信号驱动运动活动过程中的收购和表现灵巧的操作行为，在完整的 和中风后的非人类灵长类动物。 该方案的主要实验途径包括同时高密度、高通道数 来自躯体感觉丘脑、初级躯体感觉皮层的急性电生理记录， 在完整的和中风后的非人类灵长类动物执行复杂的操作任务的初级运动皮层。的 主要的分析方法包括将运动活动演变建模为内在运动皮层 来自躯体感觉丘脑和躯体感觉皮层的动力学和输入。这个提议的假设 躯体感觉输入信号引导有效运动活动轨迹的识别， 频繁使用，输入依赖性较低，操作技能得到提高。因此，体感信号是 对脑卒中后手法技能的提高和灵巧度的恢复至关重要。完成本提案 将确定节点和功能的相互作用，在感觉运动系统，可以有针对性的新的 用于改善中风后手功能恢复的疗法。 我将在Karunesh博士领导的优秀指导团队的指导下完成这些目标 甘古利和包括乔尼沃利斯博士，罗伯特莫克拉夫特博士，和亚伦苏明斯基博士。在辅导阶段 在加州大学旧金山分校的奖项，我将开发一个国家的最先进的高通道计数，多区域电生理 监测感觉运动网络的方法。我还将在动物身上进行拟议的实验 执行对象操作任务，驾驶触觉脑机接口任务，并专注于专业 发展，以促进成功过渡到一个独立的教师职位在学术 机构。

PROJECT SUMMARY Stroke-causing illness, disability, and early death is set to double worldwide within the next 15 years. Despite physical therapy, about 50% of stroke survivors have impaired hand function, which strongly impacts activities of daily living and independence; novel treatment methods are urgently required. While most pre-clinical research addressing stroke recovery and rehabilitation focuses on restoring damaged descending movement pathways, dexterous hand function is also reliant on the brain receiving ascending somatosensory input and being able to use it to guide movements. Clinically and in animal models, deficits in somatosensory cortices predict worse recovery of hand function following stroke, though the functional mechanisms by which somatosensory signals support hand function remain poorly characterized. In this proposal, we aim to uncover how somatosensory signals drive motor activity during the acquisition and performance of dexterous manipulation behaviors in intact and post-stroke non-human primates. The main experimental approach of this proposal includes simultaneous high-density, high channel-count acute electrophysiological recordings from the somatosensory thalamus, primary somatosensory cortex, and primary motor cortex in intact and post-stroke non-human primates performing complex manipulation tasks. The main analytical approach includes modeling motor activity evolution as a combination of intrinsic motor cortical dynamics and inputs from somatosensory thalamic and somatosensory cortex. The hypothesis of this proposal is that somatosensory input signals guide the identification of effective motor activity trajectories that become frequently used and less input-dependent with improved manipulation skill. Thus, somatosensory signals are critical for improvement of manipulation skill and recovery of dexterity post-stroke. Completion of this proposal will identify nodes and functional interactions within the sensorimotor system that could be targeted with novel therapies for improving recovery of hand function following stroke. I will complete these aims with the guidance of an exceptional mentoring team led by Dr. Karunesh Ganguly and including Dr. Joni Wallis, Dr. Robert Morecraft, and Dr. Aaron Suminski. During the mentored phase of the award at UCSF, I will develop a state-of-the-art high channel-count, multi-area electrophysiological approach for monitoring the sensorimotor network. I will also conduct the proposed experiments in animals performing object manipulation tasks, pilot a haptic brain-machine-interface task, and focus on professional development in order to facilitate a successful transition into an independent faculty position at an academic institution.