This is a proposal requesting five years of support for work concerned with the synaptic and functional organization of frontal lobe cortical areas in the control of forelimb movements in primates. In recent years, our concepts about frontal lobe motor areas and corticospinal output organization have changed dramatically. Information about the synaptic connections of single corticospinal cells has shown clearly that these cells typically influence not just one muscle but combinations of muscles as functional muscle synergies. Moreover, the existence of a remarkable number of discrete premotor areas in the frontal lobe of primates has become clear, each with its own complement of corticospinal neurons. In this application we propose to build upon our previous studies concerning the contribution of the cortical motor areas to forelimb movement in primates. This proposal focuses on two major issues. The first builds upon our recent finding that a large fraction (45%) of corticomotoneuronal (CM) cells engaged in a reach and prehension task simultaneously facilitated or suppressed a combination of both proximal and distal muscles in spike triggered averages of EMG activity (McKiernan et al.,1998). These combinations of CM cell target muscles represent multi-joint, functional muscle synergies underlying basic coactivation patterns observed in proximal and distal muscle during reach and prehension movements of the forelimb. A central remaining question concerns the functional importance of the cell's distal and proximal target muscles. Will such cells only be activated for tasks in which the distal and proximal muscles are coactivated as a synergy? The second issue we wish to address concerns the mounting evidence from mostly anatomical studies favoring the existence of multiple, discrete corticospinal representations of limb muscles within the frontal cortex of primates. In addition to a proposed double representation of distal muscles in primary motor cortex, no less than six premotor areas have been suggested based on anatomical labeling of corticospinal neurons and other anatomical studies. These include two premotor areas in the lateral hemisphere, SMA and three areas buried in the cingulate gyrus. Although the presence of substantial corticospinal projections has prompted speculation that these areas represent parallel channels for direct access to motoneurons and movement control, there have been few physiological studies of the efficacy and characteristics of these corticospinal projections in comparison to those from primary motor cortex. The goal of this proposal will be to apply the techniques of spike and stimulus triggered averaging of EMG activity to map and assess the functional nature of these multiple corticospinal forelimb representations.