Behavioral Assessment of Manual Dexterity in Non-Human Primates

Abstract

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 . Video LinkThe video component of this article can be found at https://www.jove.com/video/3258/ ProtocolThe overall scheme of the experiment is depicted in Figure 1. Animal preparation and transfer to the behavioral laboratory1. In the laboratory, prepare the behavioral set-up: fill the wells of the different test boards (tests 1 to 3 below) with the pellets, which serve as reward during the behavioral tests. 2. Transfer the monkey from...

Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: Evidence for a contribution of the dorsolateral prefrontal cortex

“…To address this issue, adult monkeys were trained to perform repetitive manual dexterity tasks (derived from previous versions: see Brinkman and Kuypers, 1973;Brinkman, 1984), comprising a spatial component and a temporal sequence, thus possibly implicating dlPFC, at least during the training phase (Shima et al, 2007). Nevertheless, contrarily to most, if not all, studies on dlPFC (e.g., Barone and Joseph, 1989;Ninokura et al, 2004;Shima et al, 2007), which are built on conditional tasks with delay and emphasize on the retention of a pertinent information (spatial) used to execute the sequential task correctly, the present results are based on "free-will" manual dexterity tasks (see Schmidlin et al, 2011). The manual tasks require a sequence of repetitive movements aimed at different locations, in absence of any constraint of success, temporal order or pace.…”

“…For the present investigation, the motor performances at the modified Brinkman board task e static e and the rotating Brinkman board task e moving either clockwise or counterclockwise e were analysed. These two tasks were described in more detail in previous studies (Brinkman and Kuypers, 1973;Brinkman, 1984;Liu and Rouiller, 1999;Freund et al, 2009;Kaeser et al, 2010Kaeser et al, , 2011Schmidlin et al, 2011) and can be seen on the following web page: http://www.unifr.ch/neuro/rouiller/ research/brink.php. For each monkey, the performance of the left hand and the right hand were analysed separately.…”

“…All the behavioural and surgical procedures were approved by the local ethical committee, in accordance with the Guidelines for the Care and Use of Laboratory Animals and approved by Swiss veterinary authorities (see e.g., Kaeser et al, 2010Kaeser et al, , 2011Bashir et al, 2012;Schmidlin et al, 2011). Briefly, the monkeys were trained to enter and sit into a Plexiglas primate chair (Schmidlin et al, 2011). On the front panel of the primate chair, two sliding doors allowed testing separately the left hand or the right hand in various manual dexterity tasks (Schmidlin et al, 2011).…”

“…Briefly, the monkeys were trained to enter and sit into a Plexiglas primate chair (Schmidlin et al, 2011). On the front panel of the primate chair, two sliding doors allowed testing separately the left hand or the right hand in various manual dexterity tasks (Schmidlin et al, 2011). The monkeys were not food deprived and had free access to water, but they did not eat before the training sessions on that day.…”

“…The monkeys ranged from 2.5 to 5.5 years old at the time of initiation of behavioural training sessions. All the behavioural and surgical procedures were approved by the local ethical committee, in accordance with the Guidelines for the Care and Use of Laboratory Animals and approved by Swiss veterinary authorities (see e.g., Kaeser et al, 2010Kaeser et al, , 2011Bashir et al, 2012;Schmidlin et al, 2011). Briefly, the monkeys were trained to enter and sit into a Plexiglas primate chair (Schmidlin et al, 2011).…”