Fine Manual Dexterity Assessment After Autologous Neural Cell Ecosystem (ANCE) Transplantation in a Non-human Primate Model of Parkinson's Disease.

Background. Autologous neural cell ecosystem (ANCE) transplantation improves motor recovery in MPTP monkeys. These motor symptoms were assessed using semi-quantitative clinical rating scales, widely used in many studies. However, limitations in terms of sensitivity, combined with relatively subjective assessment of their different items, make inter-study comparisons difficult to achieve. Objective. The aim of this study was to quantify the impact of MPTP intoxication in macaque monkeys on manual dexterity and assess whether ANCE can contribute to functional recovery. Methods. Four animals were trained to perform 2 manual dexterity tasks. After reaching a motor performance plateau, the animals were subjected to an MPTP lesion. After the occurrence of a spontaneous functional recovery plateau, all 4 animals were subjected to ANCE transplantation. Results. Two of 4 animals underwent a full spontaneous recovery before the ANCE transplantation, whereas the 2 other animals (symptomatic) presented moderate to severe Parkinson's disease (PD)-like symptoms affecting manual dexterity. The time to grasp small objects using the precision grip increased in these 2 animals. After ANCE transplantation, the 2 symptomatic animals underwent a significant functional recovery, reflected by a decrease in time to execute the different tasks, as compared with the post-lesion phase. Conclusions. Manual dexterity is affected in symptomatic MPTP monkeys. The 2 manual dexterity tasks reported here as pilot are pertinent to quantify PD symptoms and reliably assess a treatment in MPTP monkeys, such as the present ANCE transplantation, to be confirmed in a larger cohort of animals before future clinical applications.

Distinction between hand dominance and hand preference in primates: a behavioral investigation of manual dexterity in nonhuman primates (macaques) and human subjects.

Background The present study aimed to determine and confront hand preference (hand chosen in priority to perform a manual dexterity task) and hand dominance (hand with best motor performance) in eight macaques (Macaca fascicularis) and in 20 human subjects (10 left-handers and 10 right-handers). Methods Four manual dexterity tests have been executed by the monkeys, over several weeks during learning and stable performance phases (in controlled body position): the modified Brinkman board, the reach and grasp drawer, the tube and the bimanual board tasks. Three behavioral tests, adapted versions from the monkeys tasks (modified Brinkman board, tube and bimanual board tasks), as well as a handedness questionnaire, have been conducted in human subjects. Results In monkeys, there was a large disparity across individuals and motor tasks. For hand dominance, two monkeys were rather right lateralized, three monkeys rather left lateralized, whereas in three monkeys, the different parameters measured were not consistent. For hand preference, none of the eight monkeys exhibited a homogeneous lateralization across the four motor tasks. Macaca fascicularis do not exhibit a clear hand preference. Furthermore, hand preference often changed with task repetition, both during training and plateau phases. For human subjects, the hand preference mostly followed the self-assessment of lateralization by the subjects and the questionnaire (in the latter, right-handers were more lateralized than left-handers), except a few discrepancies based on the tube task. There was no hand dominance in seven right-handers (the other three performed better with the right hand) and in four left-handers. Five left-handers showed left-hand dominance, whereas surprisingly, one left-hander performed better with the right hand. In the modified Brinkman board task, females performed better than males, right-handers better than left-handers. Conclusions The present study argues for a distinction between hand preference and hand dominance, especially in macaque monkeys.

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 primates(1). 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 primates(1,2). 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. The behavioral assessment of manual dexterity is based on four distinct, complementary, reach and grasp manual tasks (use of precision grip to grasp pellets), requiring an initial training of adult macaque monkeys. The preparation of the animals is demonstrated, as well as the positioning with respect to the behavioral set-up. The performance of a typical monkey is illustrated for each task. The collection and analysis of relevant parameters reflecting precise hand manipulation, as well as the control of force, are explained and demonstrated with representative results. These data are placed then in a broader context, showing how the behavioral data can be exploited to investigate the impact of a spinal cord lesion or of a lesion of the motor cortex and to what extent a treatment may enhance the spontaneous functional recovery, by comparing different groups of monkeys (treated versus sham treated for instance). Advantages and limitations of the behavioral tests are discussed. The present behavioral approach is in line with previous reports emphasizing the pertinence of the non-human primate model in the context of nervous system diseases(2,3).