The authors would like to thank Prof. M.E. Schwab, Dr. P. Freund, Dr. A. Wyss, Dr. S. Bashir, Dr. A. Mir, Dr. J. Bloch, Dr. J.F. Brunet, Dr. J. Aebischer, Dr. A. Meszaros, Dr. V. Goetschman for their contribution to previous experiments and analyses. The experimental set-ups were constructed by Andr&eacute; Gaillard, Bernard Aebischer and Laurent Monney. In the animal facility, the monkeys were placed under the supervision of professional animal caretakers: Josef Corpataux, Laurent Bossy and Jacques Maillard. The behavioral tests and analysis of the data, as well as histology, were conducted with the highly valuable contributions of laboratory technicians: V&eacute;ronique Moret (also web master), Fran&ccedil;oise Tinguely, Christine Roulin, Monica Bennefeld, Christiane Marti and Georgette Fischer. This work was supported by the Swiss National Science Foundation, grants No 31-61857.00, 310000-110005, 31003A-132465 (EMR), 310030-118357, 31003A-104061 (TW), 310030-120411 (ABS), PZ00P3_121646 (ES), Novartis Foundation; The National Centre of Competence in Research (NCCR) on "Neural plasticity and repair".

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No conflicts of interest declared.

Although the present behavioral tasks have been considered so far in our laboratory in the context of studies related to lesion of the cervical cord or to lesion of the motor cortex with the aim to test various treatments (see14,15,17 and <a href="http://www.unifr.ch/neuro/rouiller">http://www.unifr.ch/neuro/rouiller</a> &gt;select "research" in the top bar menu, then &gt; "motor system" &gt; "recovery after lesion"), they may also have a broader application, as manual dexterity is also an aspect to consider in other pathologies, such as Parkinson disease (MPTP monkeys) or in case of sensory de-afferentation affecting proprioception and/or the sense of touch (especially the test 2 in absence of visual control).
The behavioral tests proposed here are suitable to investigate the motor control of distal movements of the forelimb, as involved in manual dexterity. The specificity of the tests is demonstrated by the absence of deficit (except for a couple of days) in case of a lesion which does not impair relevant components of the control system: indeed, in case of a lesion placed more caudal than the motoneurons controlling hand muscles, there was no deficit. The pertinence of the test 1 can be appreciated by comparing on video sequences taken at two time points of the post-lesion recovery curve, which differ by an enhancement of functional recovery of 25%, possibly in relation to a cell therapy treatment17.
In spite of some initial, relatively short training phase at beginning (lasting generally 2-3 months), the behavioral tests proposed here are relatively "natural" and straightforward, as compared to complex (e.g. conditional) tasks for which the training of the monkey may take nearly a year or more. The positive reinforcement is based on solid food, which is less sensitive on the ethical point of view than water deprivation, usually used in more complex tasks23. There is no need to deprive the monkeys from food to obtain stable and consistent results. The pellets received during the tasks represent the first access to the food on the day of the behavioral session (assuming that the monkey does not eat during the preceding night; however additional food may be given until the end of the afternoon of the preceding day). It is crucial that each monkey performs the behavioral session at the same time of the day, as well as respecting the same sequential order between the different monkeys forming a group in the housing room. As the monkeys are sensitive to external disturbing events, the behavioral tasks should be conducted in presence of background music, masking potential disturbing noise coming from neighboring rooms or laboratories. It is crucial that during the whole duration of the experiment (from initial training up to the last daily experimental session, a period of several months if not years), a given monkey is placed daily under the supervision of the same experimenter.
The present behavioral tests, used since several years in our laboratory to quantify manual dexterity, are to some extent comparable to other tests of manual dexterity recently reported in the literature24-28. There is however a crucial need to standardize tests across different laboratories (for better comparison), which is a tentative goal of the present report. On demand, the detailed properties of the set-ups illustrated here for tests 1-4 can be provided by the corresponding author, in order to replicate them. Beyond the issue of regenerative medicine (recovery from lesion of spinal cord or cerebral cortex), the present palette of tests may be suitable to address in normal non-human primates developmental issues (e.g. time course of motor development of dexterous movements), to investigate lateralization aspects (hand preference/dominance) and to decipher evolutionary questions by comparing the motor abilities of different species of primates, including human subjects. Note however that the dimensions of the apparatuses should be adapted according to the digits' size (thickness and length) of the primate species, as it may influence the task performance. In the present study, the tests were conducted on macaca fascicularis monkeys, ranging from 2.5 to 8 years old and weighing between 2.5 and 8 kg. The length of the index finger (used first to manipulate the pellets) ranges from 32 to 35 mm, whereas the circumference of the distal phalanx (tip) of the index finger was between 22 and 25 mm in the monkeys included in our studies. As tested in previous experiments, the same grasping tests are suitable for macaca mulatta as well.
All experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (1996) and approved by local (Swiss) veterinary authorities. All experimental procedures on the monkeys, as well as the detention conditions in the animal facility, were described in detail in recent reports from our laboratory: see references 12-18.

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.
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 diseases2,3.

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Behavioral Assessment of Manual Dexterity in Non-Human Primates

As manual dexterity is a prerogative mainly of primates, behavioral tasks have been developed in macaque monkeys. Four reach and grasp prehension tasks, measuring hand manipulation ability and force, allow to establish functional recovery after a lesion of the central nervous system and to test the effect of a treatment.

The corticospinal (CS) tract is the anatomical support of the exquisite motor ability to skillfully manipulate small objects, a prerogative mainly of ...

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22.1K ビュー.  University of Fribourg. 手先の器用さは、主に霊長類の特権であるため、行動タスクはマカクザルで開発されている。 4つは手の操作能力や力を測定、把握のタスクを達成し、把握、中枢神経系の損傷後の機能回復を確立するために、治療の効果をテストすることができます。