Abstract
Previous studies have shown that permanent lesions of the hand area of primary motor cortex (M1) in adult macaque monkeys induced a temporary loss of manual dexterity, followed by incomplete, spontaneous functional recovery. Notably, a treatment with anti-Nogo-A antibody or autologous cellular therapy both enhanced the recovery compared to untreated monkeys. An indicator of this improvement in functional recovery is the increased number of small food pellets retrieved from vertical and horizontal slots in a reach-and-grasp task (“modified Brinkman Board” task) which requires the opposition of the thumb and index finger (precision grip) under visual guidance. The horizontal slots proved more challenging than the vertical ones and offered a better discrimination between treated and untreated monkeys.
We hypothesized that further increasing the difficulty of the behavioral readout would better discriminate between the 2 subgroups. Therefore, we developed a novel manual dexterity task performed without visual guidance (“Brinkman Box task without vision”). In this task, the tested hand was inserted into a “blind” box to grasp pellets from hidden slots, relying on motor exploration based on palpation, and executing precision grip without visual guidance. This more challenging blind task required intensive and long training, and additional positive reinforcement. Nevertheless, a successful and stable performance level was achieved in 10 pilot adult macaques which were subsequently subjected to a unilateral permanent lesion of M1. Of these, four monkeys were left untreated (“control”), whereas 4 received the anti-Nogo-A antibody treatment and 2 were treated with cellular therapy.
Immediately post-lesion, the ability to retrieving pellets with the contralesional hand dropped to zero in all monkeys, followed after a few weeks by partial functional recovery, ultimately reaching a plateau of restored manual dexterity. The “treated” monkeys outperformed the control group, corroborating previous behavioral findings from visually guided tests. The greatest discrimination between the 2 subgroups was obtained by combining the results derived from both visually guided and blind tasks. Potential mechanisms underlying functional recovery are discussed in the context of functional and connectional neuroplasticity with emphasis on the involvement of the adjacent intact premotor cortex, in particular with adaptation of its efferent and afferent projections.