Coordinated arm/hand movements are central to primate behavior (e.g. feeding, drinking). Dense projections from primary motor cortex (M1) to spinal cord circuits confer on M1 a critical role in controlling the arm and the hand. M1 zones that control the arm mostly non-overlapping with M1 zones that control the hand. Coordinated arm/hand actions must therefore involve coordinated activity between M1 zones, but the underlying mechanisms are as yet unknown. Our central hypothesis is that neural activity in M1 follows a trajectory that is governed by the spatial organization of the arm and hand representations in M1 and by the local M1 connections. We propose to investigate the spatio-temporal organization of M1 activity during reaching and grasping in macaque monkeys. We also propose to determine the organization of the local connections that support communication within M1. Our rationale for pursuing this proposal is that revealing the functional organization and connectivity of M1 will shed light on how information is processed within M1 in the service of arm/hand control. We have refined an investigative strategy that centers on optical imaging; where signal modulations report on neural activity. Using optical imaging to investigate cortical control of movement in primates is novel. The central advantage of optical imaging for this proposal is the capacity for investigating many millimeters of M1 without spatial interruptions, which is needed for determining how spatial patterns of neural activity evolve across M1 during behavior. In Aim 1, we will determine the spatial and temporal organization of M1 neural activity that support reaching and grasping. To that end, we will optically image M1 and record neurophysiological signals throughout M1 as an animal performs a reach-to-grasp task. Target locations and object dimensions will be systematically varied to motivate a range of reach directions and grip postures. In the same M1 territory, we will map the organization of the corticospinal projections by stimulating discrete points in M1 and determining which arm/hand muscles were activated. By co-registering results from imaging, electrophysiology, and motor mapping, we will learn how spatial patterns of M1 activity evolve across the motor map over the course of arm/hand actions. In Aim 2, we will determine the organization of the connections that support communication within M1. Optical imaging presents a critical advantage here because it would open the possibility of determining the organization of cortical connections for hundreds of sites in M1. In this paradigm, the spatial patterns of cortical activation that results from electrical stimulation of a site, would reflect the connectivity patterns of that site. Next, we test neural interactions between connected zones by electrically stimulating one zone and recording neural activity in the connected zone. By registering the connectivity maps and neural interaction results to the motor map, we expect to shed light on the organization of neural communication within the M1 motor map. The two Aims will collectively close knowledge gaps in our understanding of the organizational principles that confer on M1 the capacity to control movements.

PROJECT NARRATIVE The proposed research is relevant to public health because determining the function-structure relationship in primary motor cortex (M1) is essential to understanding how M1 controls our arms and hands. Knowledge gained from this proposal has the potential to improve brain decoding for the purpose of driving assistive technologies to serve patients with severe loss of manual function. Thus, the proposed research is relevant to the part of NIH’s mission that is concerned with seeking knowledge and applying it to reduce the burden of disability.