The effect of cortical interactions on motor output by the primary motor cortex

灵长类感觉运动网络由几个专门的皮质区组成，这些皮质区可以与初级运动皮质（M1）相互作用以产生运动。在进化过程中，似乎专门的皮层区域被添加或扩展，以支持手部运动的增加和复杂性。目前，我们对这些专门的皮层区域之间的连接如何在M1内组织以及它们如何参与运动输出的产生的理解有限。我们的长期目标是确定在手臂和手部运动的产生中皮质相互作用的作用。我们以前在卷尾猴（Cebus）的实验表明，运动前区和区5有优先连接，主要是隔离的子区域在手代表的M1。这些结果改变了我们看待M1的方式，并表明它是由几个模块组成的，每个模块都是一个特定的皮层网络的一部分。在这个资助周期中，我们继续研究这些令人兴奋的发现。我们的具体实验是研究1）运动前区和5区与M1的皮质相互作用的地形组织，2）皮质区调节M1输出的不同通路的相对贡献，3）M1与顶叶皮质其他区域的皮质输入和相互作用。** 在AIM 1中，我们将在清醒的猴子中使用慢性电极阵列，以研究配对脉冲刺激方案下M1中皮质相互作用的地形组织。在这些方案中，在M1中的测试刺激之前，在皮层区域中施加条件刺激，并且在EMG信号中量化刺激的效果。我们将研究如何刺激运动前背侧和腹侧皮层（PMd和PMv）和区域5具体影响跨M1的神经元亚群的输出。* 在AIM 2中，在清醒的猴子中使用慢性电极阵列，我们将使用失活技术来研究皮层区域如何使用不同的平行输出通路（皮质、皮质红核和皮质网状）来调节M1的输出并促进手部运动的产生。* 在AIM 3中，我们将使用神经解剖学追踪技术来研究从顶叶皮层的多个躯体感觉区域到M1的皮层输入的特定模式。在急性终端准备，我们将研究这些躯体感觉区的调制效应的一般模式对M1的输出与成对脉冲刺激协议。* 这些项目利用侵入性方法来解决我们对皮质相互作用的知识中的紧迫差距，这些知识无法用非侵入性方法（如经颅磁刺激（TMS））来回答。这些数据将极大地有助于我们理解支持灵长类动物手部运动的复杂皮层网络，并为一个充满活力的研究领域做出独特的贡献。**

The primate sensorimotor network is composed of several specialized cortical areas that can interact with the primary motor cortex (M1) to produce movements. During evolution, it appears that specialized cortical areas were added or expanded to support an increase of the repertoire and complexity of hand movements. We currently have limited understanding of how the connections among these specialized cortical areas are organized within M1 and how they participate in the production of motor outputs. Our LONG-TERM OBJECTIVE is to determine the role of cortical interactions in the generation of arm and hand movements. Our previous experiments in capuchin monkeys (Cebus) have shown that premotor areas and area 5 have preferential connections with largely segregated subregions in the hand representation of M1. These results change the way we view M1 and suggest that it is composed of several modules, each part of a specific cortical network. In this cycle of funding, we pursue our research on these exciting findings. Our SPECIFIC OBJECTIVES are to study 1) the topographic organization of cortical interactions of premotor areas and area 5 with M1, 2) the relative contribution of the different pathways through which cortical areas can modulate M1 outputs and 3) the cortical inputs and interactions of M1 with additional areas of the parietal cortex. *** ***In AIM 1, we will use chronic electrode arrays in awake monkeys to investigate the topographic organization of cortical interactions in M1 with paired-pulse stimulation protocols. In these protocols, a conditioning stimulus is applied in a cortical area prior to a test stimulus in M1 and the effect of the stimulation is quantified in EMG signals. We will study how stimulation of the premotor dorsal and ventral cortex (PMd and PMv) and area 5 specifically affect the outputs of subpopulations of neurons across M1. ***In AIM 2, in awake monkeys with chronic electrode arrays, we will use inactivation techniques to study how cortical areas use different parallel output pathways (corticocortical, corticorubral and corticoreticular) to modulate M1's outputs and contribute to the production of hand movements. ***In AIM 3, we will use neuroanatomical tracing techniques to study the specific pattern of cortical inputs from multiple somatosensory areas of the parietal cortex to M1. In acute terminal preparations, we will study the general pattern of modulatory effects of these somatosensory areas on M1's outputs with paired-pulse stimulation protocols. *** The projects take advantage of invasive approaches to address pressing gaps in our knowledge of cortical interactions that cannot be answered with non-invasive approaches such as transcranial magnetic stimulation (TMS) in humans. The data will greatly contribute to our understanding of the complex cortical network that supports hand movements in primates and uniquely contribute to a vibrant field of research with a wide interest. **