The purpose of this study was to develop a new model of focal ischemia with reperfusion in the non-human primate (M fascicularis) to explore the contributions of both the corticospinal and reticulospinal systems in recovery of reaching following cortical ischemic injury. First, experiments were conducted to improve understanding of electrophysiological techniques used for studying descending motor systems, and ipsilateral corticospinal control of upper limb movements in the intact animal. Single-pulse stimulation and repetitive
stimulation techniques applied at the same pontomedullary reticular formation (PMRF) stimulation site in the same monkey were compared. The type of response (facilitation vs. suppression) was compared between the stimulation methods. The results indicated that for general comparisons of motor outputs, both methods produced comparable responses. This study helped us recognize the possible limitations for our electrophysiological methods for the new cortical injury model. Then, the functional organization of the corticospinal tract (ipsilateral vs. contralateral) was studied to explore ipsilateral corticospinal outputs to muscles of both upper limbs from cortical stimulation applied at sites in the left cerebral cortex spread across the primary motor cortex, dorsal pre-motor cortex and supplementary motor cortex. Ipsilateral effects were evoked from all three cortical motor areas. The percentage of ipsilateral effects was higher than the 10 to 20% expected based on anatomy, with the greatest percentage from pre-motor areas. This study provided valuable insights into ipsilateral corticospinal contributions to upper limb motor control, especially proximal limb muscles.
Next, a vasoconstrictive peptide, Endothelin-1 (ET-1) was used to create a focal ischemic injury in the shoulder/elbow representation of left primary motor cortex (M1). Repetitive microstimulation was used to physiologically map motor outputs from right and left cortical motor areas, and upper limb motor outputs from the PMRF. EMG responses were recorded from shoulder girdle, limb extensor and limb flexor muscles of both upper limbs. Functional deficits were assessed using a behavioral reaching task conducted at set time points before and after the ET-1 induced lesion. MRI scans were used for confirmation of lesion location and quantification of lesion volume. In a subject with a mild lesion, reaching was mildly impaired. Changes were evident in the shoulder/elbow representations of both the affected and contralesional M1. No substantial changes were noted in the pattern of PMRF output. In a subject with a severe lesion, reaching was markedly impaired immediately after the lesion. With intensive rehabilitation, gross reaching recovered in a few weeks, and reaching times were slow but comparable to pre-injury levels by 16 weeks postinjury. Surprisingly, the shoulder/elbow representation in the affected M1 remained completely absent after recovery, and there was little change in the contralesional M1. The novel result was the greater right arm representation from left PMRF sites in this subject. This suggests that there may be increased reliance on PMRF motor outputs associated with upper limb motor recovery after a severe ischemic cortical injury. This opens a new line of investigation to complement cortical plasticity research to understand reticulospinal contributions to functional recovery of reaching after stroke.