Behavioral Assessment of Manual Dexterity in Non-Human Primates

The corticospinal (CS) tract is the anatomical support of the exquisite motor ability to skillfully manipulate small objects, a prerogative mainly of primates1. In case of lesion affecting the CS projection system at its origin (lesion of motor cortical areas) or along its trajectory (cervical cord lesion), there is a dramatic loss of manual dexterity (hand paralysis), as seen in some tetraplegic or hemiplegic patients. Although there is some spontaneous functional recovery after such lesion, it remains very limited in the adult. Various therapeutic strategies are presently proposed (e.g. cell therapy, neutralization of inhibitory axonal growth molecules, application of growth factors, etc), which are mostly developed in rodents. However, before clinical application, it is often recommended to test the feasibility, efficacy, and security of the treatment in non-human primates. This is especially true when the goal is to restore manual dexterity after a lesion of the central nervous system, as the organization of the motor system of rodents is different from that of primates1,2. Macaque monkeys are illustrated here as a suitable behavioral model to quantify manual dexterity in primates, to reflect the deficits resulting from lesion of the motor cortex or cervical cord for instance, measure the extent of spontaneous functional recovery and, when a treatment is applied, evaluate how much it can enhance the functional recovery

Variability of manual dexterity performance in non-human primates (Macaca fascicularis)

The goal of this study was to quantify the inter-individual and intra-individual variability of manual (digits) skill in adult macaque monkeys, over a motor learning phase and, lateron, when motor skills were consolidated. The hypothesis is that several attributes of the stable manual dexterity performance can be predicted from learning characteristics. The behavioral data were collected from 20 adult Macaca fascicularis, derived from their dominant hand, defined as the hand exhibiting a better performance than theother. Two manual dexterity tasks were tested: (i) the modified Brinkman board task, consisting in the retrieval of food pellets placed in 50 slots ina board, using the precision grip (opposition of the thumb and index finger);(ii) the reach and grasp drawer task, in which the grip force and the load force were continuously monitored while the monkey opened a drawer against a resistance, before grasping a pellet inside the drawer. The hypothesis was verified for the performance of manual dexterity after consolidation, correlated with the initial score before learning. Motor habit, reflected by the temporal order of sequential movements executed in the modified Brinkman board task, was established very early during the learning phase. As mostly expected, motor  learning led to an optimization of manual dexterity parameters, such as score, contact time, as well as a decrease in intra-individual variability. Overall,the data demonstrate the substantial inter-individual variability of manual dexterity in non-human primates, to be considered for further pre-clinical applications based on this animal model

Variability of manual dexterity performance in non-human primates ( Macaca fascicularis )

The goal of this study was to quantify the inter-individual and intra-individual variability of manual (digits) skill in adult macaque monkeys, over a motor learning phase and, lateron, when motor skills were consolidated. The hypothesis is that several attributes of the stable manual dexterity performance can be predicted from learning characteristics. The behavioral data were collected from 20 adult Macaca fascicularis, derived from their dominant hand, defined as the hand exhibiting a better performance than theother. Two manual dexterity tasks were tested: (i) the modified Brinkman board task, consisting in the retrieval of food pellets placed in 50 slots ina board, using the precision grip (opposition of the thumb and index finger);(ii) the reach and grasp drawer task, in which the grip force and the load force were continuously monitored while the monkey opened a drawer against a resistance, before grasping a pellet inside the drawer. The hypothesis was verified for the performance of manual dexterity after consolidation, correlated with the initial score before learning. Motor habit, reflected by the temporal order of sequential movements executed in the modified Brinkman board task, was established very early during the learning phase. As mostly expected, motor  learning led to an optimization of manual dexterity parameters, such as score, contact time, as well as a decrease in intra-individual variability. Overall,the data demonstrate the substantial inter-individual variability of manual dexterity in non-human primates, to be considered for further pre-clinical applications based on this animal model

Enhancement of Striatal Dopaminergic Function Following Autologous Neural Cell Ecosystems (ANCE) Transplantation in a Non-Human Primate Model of Parkinson’s Disease

Objective: Previous evidence was provided that parkinsonian monkeys exhibited significant though incomplete behavioral recovery following a cell therapy consisting of auto-transplantation of adult neural progenitor cells. The aim of the present study was to assess for the first time in this parkinsonian non-human primate model the striatal dopaminergic function, in parallel to further behavioral assessment. In other words, is the behavioral recovery associated to a reversal of dopaminergic function despite the auto-transplanted cells are not dopaminergic. Methods: Striatal dopaminergic function and motor behavior (spontaneous motion activities) were monitored in adult parkinsonian macaques in relation to autologous neural cell ecosystem (ANCE) transplantation. In four MPTP intoxicated macaques, adult progenitor cells derived from cortical biopsies were re-implanted in the same animal after a phase of spontaneous functional recovery. The function of the striatal dopaminergic system was assessed using 18F-DOPA positron tomography imaging and the motor function was quantified. Results: Two parkinsonian animals exhibited severe motor symptoms, which were moderate and transient in two other monkeys. 18F-DOPA striatal uptake decreased by 80% in three animals, consistent with losses of dopaminergic neurons in substantia nigra and reduced striatal density of dopaminergic projections. Six months after autologous transplantation, all animals improved their motor functions. This functional recovery was largely consistent with positron emission tomography results showing some recovery of 18F-DOPA striatal uptake toward baseline value following transplantation. Conclusion: The present data confirm that symptoms are variable across individual parkinsonian monkeys and that autologous neural cell ecosystem transplantation indeed attenuates parkinsonian motor symptoms. Yet the present study provides for the first time evidence in favor of an increase in the striatal dopaminergic activity that correlates with motor recovery in this novel therapeutic approach, although the implanted cells are not dopaminergic