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

灵长类动物的感觉运动网络由几个专门的皮层区域组成，这些区域可以与初级运动皮层（M1）相互作用以产生运动。在进化过程中，似乎有专门的皮质区域被添加或扩展，以支持手部动作的曲目和复杂性的增加。我们目前对M1内这些特殊皮质区域之间的连接是如何组织的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皮层相互作用在手臂和手部运动产生中的作用。我们之前对卷尾猴（Cebus）的实验表明，运动前区域和5区与M1的手部表征中大部分分离的子区域具有优先连接。这些结果改变了我们对M1的看法，并表明它由几个模块组成，每个模块都是特定皮层网络的一部分。在这个资助周期中，我们继续研究这些令人兴奋的发现。我们的具体目标是研究1)运动前区和皮层5区与M1相互作用的地形组织，2)皮层区域调节M1输出的不同途径的相对贡献，以及3)皮层输入和M1与顶叶皮层其他区域的相互作用。*** ***在AIM 1中，我们将在清醒的猴子中使用慢性电极阵列来研究配对脉冲刺激方案下M1皮层相互作用的地形组织。在这些方案中，在M1的测试刺激之前，在皮质区域施加条件刺激，刺激的效果在肌电图信号中被量化。我们将研究运动前背侧和腹侧皮层（PMd和PMv）和5区的刺激如何具体影响M1神经元亚群的输出。***在AIM 2中，我们将使用失活技术来研究皮质区域如何使用不同的平行输出通路（皮质皮质、皮质和皮质网状）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体感区到M1的皮层输入的具体模式。在急性终末准备中，我们将研究这些体感区域对M1输出的调节作用的一般模式，并采用配对脉冲刺激方案。***这些项目利用侵入性方法来解决我们对皮层相互作用知识的紧迫空白，这些空白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. **