Re-Examination and Extension of Manual Dexterity Behavioral Data in M1 Lesioned Adult Macaque Monkeys: A Survey of Therapies Induced Enhancement of Functional Recovery.

Abstract

The present report offers a survey, with re-examination and extension of data, of previously published intermediate papers on the functional recovery of manual dexterity in non-human primates following primary motor cortex (M1) lesion, either spontaneous or enhanced with 2 distinct therapies. For each monkey, the M1 lesion volume was derived from histological sections. As a result of data extension, spontaneous recovery is represented here by individual data points derived from 14 monkeys, while data points from 8 monkeys represent therapy enhanced recovery. One therapy consisted of the administration immediately post-lesion of an anti-Nogo-A antibody (n = 4); the other treatment was a delayed autologous cellular therapy (ANCE; n = 4). The manual dexterity performance was longitudinally assessed during several years with the modified Brinkman Board task, testing the ability to grasp small food pellets from horizontal or vertical slots, using the precision grip. After M1 lesion, the grasping score dropped to zero, followed by a spontaneous, incomplete recovery in untreated monkeys, characterized by a unique plateau of recovery. In the majority of treated monkeys (n = 6), there was an additional second plateau of recovery, reflecting the effect of the treatment. Statistical non-parametric comparisons between the 14 untreated versus the 8 treated data points showed a statistically significant difference between the 2 subpopulations, based both on univariate statistics and bivariate statistics taking into account the lesion volume. This was true for recovery expressed as a degree of recuperation expressed in percent (post-lesion score/pre-lesion score × 100) as well as for the post-lesion scores only. The difference between the 2 subpopulations was more pronounced for the most difficult horizontal slots than for the less challenging vertical slots. In conclusion, the treatments appear to be efficient to promote functional motor recovery, even when considering post-lesion behavioral readouts only, as this would be the case in clinical trials.