OUTPUT FROM MOTOR CORTEX TO CONTRALATERAL AND IPSILATERAL HINDLIMB MUSCLES IN THE PRIMATE

Abstract

Although corticospinal control of the forelimb has been heavily studied for several decades, relatively little is known about corticospinal control of the hindlimb despite its importance. The overall goal of this project is to investigate hindlimb corticospinal organization and function using methods that have been successfully used to investigate the forelimb. The first two specific aims are designed to evaluate the organization and characteristics of output from primary motor cortex (M1) to hindlimb muscles using spike triggered averaging (SpTA) of electromyography (EMG) recordings. Aim one is to determine whether postspike effects can be detected in averages of EMG activity of distal and proximal hindlimb muscles. This was done by isolating single neurons in the hindlimb representation of M1 and generating averages of EMG segments associated with the individual action potentials (spikes) of each cell. The second aim is to compare the properties of hindlimb postspike effects to forelimb postspike effects collected previously in the laboratory. The third aim is to determine the extent to which poststimulus effects, elicited by stimulus triggered averaging (StTA) in distal and proximal muscles match the postspike effects from a single cell recorded at the same cortical site. Aim four is to evaluate the organization and characteristics of output from the ipsilateral M1 to hindlimb muscles using StTA of EMG activity. In this aim, we will document the properties of poststimulus effects in hindlimb muscles from ipsilateral cortex compared to those from the contralateral cortex. Aim five is to evaluate the function of hindlimb M1 in voluntary movement by reversibly inactivating large portions of the M1 hindlimb representation using injections of the GABA-A agonist, muscimol. Three-hundred-seventy-one neurons in the hindlimb representation of M1 were isolated and tested with spike triggered averaging of EMG activity from twenty-two hindlimb muscles including hip, knee, ankle, digit and intrinsic foot muscles. Despite the presence of monosynaptic connections from corticospinal neurons to hindlimb motoneurons and the fact that the density of corticospinal neurons in hindlimb M1 is similar to that of forelimb M1 (Cheney et al. 2004), the effects in hindlimb muscles from M1 differed substantially from those of forelimb M1. Although the fraction of cells producing a significant postspike effect was similar for forelimb and hindlimb M1, the number of muscles with postspike effects (muscle field) per cell was markedly lower for hindlimb. Another striking difference was the much higher incidence of synchronous and complex effects, compared to true postspike effects, from hindlimb neurons compared to forelimb. To evaluate the strength of motor output from ipsilateral M1 cortex (Aim 4), microstimuli (120 μA) were applied a low rate (5 Hz) and served as triggers to construct stimulus triggered averages of EMG activity. Post-stimulus effects from ipsilateral M1 cortex were then compared to those from contralateral cortex obtained under the same conditions. The magnitudes of contralateral effects were far greater than the magnitudes of ipsilateral effects. In addition, there were fewer effects from ipsilateral cortex obtained at the same stimulus intensity. The organization of neurons was also quite different. For all muscles, the location of maximal output from M1 was shifted anterior and laterally in the ipsilateral cortex compared to contralateral M1. Surprisingly, the minimal onset latencies of effects from ipsilateral cortex were similar to those from contralateral cortex. In conclusion, we were able to detect clear effects in spike triggered averages of EMG activity. The output effects from single neurons in hindlimb M1 differ from those from forelimb M1 neurons in the number and strength of effects as well as the incidence of strong synchrony effects. We used stimulus triggered averaging of EMG activity to evaluate the ipsilateral connections from M1 to motoneurons. Effects from ipsilateral cortex are distinctly weaker than those from contralateral cortex. However, the onset latency of the shortest latency effects from ipsilateral cortex were similar to those from contralateral cortex suggesting that ipsilateral cortex has a minimal linkage that is as direct as that from contralateral cortex. This result suggests that at least some corticospinal neurons in ipsilateral cortex make monosynaptic connections with motoneurons in the spinal cord. We used stimulus triggered averaging data to construct maps of cortical output to different muscle groups. Comparing ipsilateral and contralateral maps revealed that the spatial distribution of neurons producing maximal output effects from ipsilateral cortex is not a mirror image of those in contralateral cortex. Rather, the best location for producing output to a particular muscle from ipsilateral cortex is substantially displaced relative to its position in contralateral cortex. This dissertation provides foundational data on the output properties of ipsilateral cortex in healthy, intact subjects. How these properties may change in relation to recovery of function following damage to contralateral M1 cortex is a question that remains for future studies.