Organization of the parietal-frontal network that mediates grasping in monkeys

描述（由申请人提供）：关于人类大脑如何控制最基本的手部动作之一——抓取，存在一个基本的知识缺口。为脑损伤和神经系统疾病引起的肢体损伤制定解决方案取决于缩小这一知识差距。长期目标是确定大脑皮层和皮层下结构如何将感觉信息整合到准确的手部动作中。这一建议的目的是确定调节猴子抓取的顶叶-额叶通路的功能组织，这是迈向长期目标的踏脚石。中心假设是三个顶叶-额叶通路控制着抓取的连续阶段（接近、接触、抬起）。每个路径节点被进一步组织成特定于握持姿势的模块（精确和整个手）。这一假设主要是根据申请人博士后工作期间的研究得出的。提出这项研究的基本原理是，它将填补关于顶叶-额叶网络如何控制最复杂和临床相关的运动功能之一的紧迫知识空白。为了验证这一假设，我们将追求两个具体目标：(1)确定顶叶-额叶通路如何控制抓取的连续阶段；(2)确定顶叶-额叶通路节点内的模块如何编码握力姿势。在第一个目标（K-99阶段）下，光学成像将用于识别在抓取过程中被激活的皮质表面的顶叶和额叶节点。通过光学成像识别的每个节点的电生理记录将用于确定尖峰序列调制和抓取阶段之间的关系。在第二个目标（R-00阶段）下，来自相同网络节点模块的光学成像和电生理记录将显示神经元簇的空间组织，这些神经元簇被调整为特定的握力姿势。在抓取过程中对相同模块的电刺激将用于临时操纵其机制，并进一步测试单个模块对抓取的贡献。单个模块的功能连接将通过并发电刺激和光学成像进行测试，这在申请人手中已经被证明是可行的。这一提议的主要创新之处在于使用了多管齐下的方法，该方法以行为猴子的光学成像为中心，以确定顶叶-额叶网络如何控制抓取。这项研究具有重要意义，因为它有望垂直扩展对灵长类动物大脑中顶叶-额叶网络如何控制抓取的理解。最终，这些知识有可能推动脑机接口的设计，这种接口依靠记录来自大脑的神经元信号来帮助那些由于中枢神经系统损伤或截肢而失去使用双手能力的患者使用手。

DESCRIPTION (provided by applicant): There is a fundamental knowledge gap about how the human brain controls one of the most fundamental hand actions, grasping. Developing solutions for the manual impairments that ensue from brain injuries and neurological diseases hinges on closing this knowledge gap. The long-term goal is to determine how cortical and subcortical structures in the brain integrate sensory information into accurate hand actions. The objective of this proposal, which is a stepping-stone towards the long-term goal, is to determine the functional organizations of the parietal-frontal pathways that mediate grasping in monkeys. The central hypothesis is that three parietal-frontal pathways control successive stages of grasping (approach, contact, lift). Each pathway node is further organized into modules that are specific to grip posture (precision and whole hand). This hypothesis has been formulated primarily from studies conducted during the applicant's postdoctoral work. The rationale for the proposed research is that it will close a pressing knowledge gap about how a parietal-frontal networks controls one of the most sophisticated and clinically relevant motor functions. Two specific aims will be pursued to test this hypothesis: (1) Determine how the parietal-frontal pathways control successive stages of grasping; and (2) Determine how modules within nodes of the parietal-frontal pathways encode grip posture. Under the first aim (K-99 phase), optical imaging will be used to identify the parietal and frontal nodes on the cortical surface that are activated during grasping. Electrophysiological recordings in each node identified with optical imaging will be used to determine the relationships between spike train modulations and grasping stages. Under the second aim (R-00 phase), optical imaging and electrophysiological recordings from modules of the same network nodes will show the spatial organizations of clusters of neurons tuned to specific grip postures. Electrical stimulation of the same modules during grasping will be used to temporarily manipulate its mechanisms and further test the contributions of individual modules to grasping. The functional connections of individual modules will be tested with concurrent electrical stimulation and optical imaging, which has already been proven feasible in the applicant's hands. The chief innovation of this proposal is the use of a multi- pronged approach that centers on optical imaging in behaving monkeys to determine how the parietal-frontal network controls grasping. The proposed research is significant because it is expected to vertically expand the understanding of how the parietal-frontal network in the primate brain controls grasping. Ultimately, such knowledge has the potential to advance the design of brain-machine interfaces that rely on recording neuronal signals from the brain to aid hand use for patients who have lost the ability to use their hands due to central nervous system injury or amputation.