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域组成，这些区域可以与初级运动皮质(M1)相互作用，产生运动。在进化过程中，专门的皮质区域似乎被增加或扩大，以支持手部运动的曲目和复杂性的增加。我们目前对M1中这些专门的皮质区域之间的联系是如何组织的，以及它们如何参与产生运动输出的了解有限。我们的长期目标是确定大脑皮层相互作用在手臂和手的运动产生中的作用。我们之前在卷尾猴(Cebus)上的实验表明，运动前区和第5区与M1手部表征中的大部分分离亚区有优先联系。这些结果改变了我们看待M1的方式，并表明它由几个模块组成，每个模块都是特定皮质网络的一部分。在这个资金周期中，我们继续对这些令人兴奋的发现进行研究。我们的具体目标是研究1)运动前区和5区与M1的皮质相互作用的地形图组织，2)皮质区域调节M1输出的不同途径的相对贡献，3)M1与顶叶皮质的额外区域的皮质输入和相互作用。*在目标1中，我们将使用清醒猴子的慢性电极阵列来研究配对脉冲刺激方案下M1区皮质相互作用的地形图组织。在这些方案中，在M1中的测试刺激之前，在皮质区域施加条件刺激，并且刺激的效果在EMG信号中被量化。我们将研究刺激运动前、背侧和腹侧皮质(PMD和PMV)以及第5区如何特异性地影响M1上神经元亚群的输出。*在AIM 2中，在有慢性电极阵列的清醒猴子中，我们将使用失活技术来研究大脑皮层如何使用不同的平行输出通路(皮质、皮质和皮质)来调节M1‘S的输出，并参与手部运动的产生。*在AIM 3中，我们将使用神经解剖学跟踪技术来研究从顶叶皮质的多个体感区域到M1的皮质输入的特定模式。在急性末梢准备中，我们将用双脉冲刺激方案研究这些体感区域对M1‘S输出的调制作用的一般规律。*这些项目利用侵入性方法来解决我们在皮质相互作用方面知识中的紧迫差距，这些差距无法用非侵入性方法(如人体经颅磁刺激(TMS))来解决。这些数据将极大地帮助我们理解支持灵长类动物手部运动的复杂的皮质网络，并为具有广泛兴趣的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. **