The overall goal of this procedure is to quantitatively assess the manual dexterity of Maca monkeys. This is accomplished by first transferring the monkey to a primate chair without stress to the animal. The next step of the procedure is to measure daily the manual performance for each hand in a reach and grasp task in which the monkey has to collect 50 small objects using the precision grip.
After that, three other manual dexterity tasks are performed to compliment the behavioral assessment. The final step of the procedure is to analyze the performance based on the video sequences collected during the four tests. Ultimately, results can be obtained that show the motor deficits following a lesion of the central nervous system and the extent of the subsequent functional recovery through the time course of changes in the behavioral parameters derived from the quantitative analysis.
The main advantage of this technique of our existing method, such as clinical scoring, which is by the way, subjected to large interrater variability, is that it is truly quantitative and reliable with moderate inter-individual variability. This method can help answer key questions in the behavioral neuroscience field, such as mechanisms underlying plastic reorganization of the central nervous system following a lesion or neurogenerative disease. The implications of this technique extend toward therapy, promoting neural regeneration and or strategies of substitution after lesion of the central nervous system because the non-human primate is often a mandatory step before clinical application of a therapeutic strategy initially developed.
In rodents, The non-human primate is patent testing function specific to primates such as manual dexterity, unsuitable for observing possible detrimental secondary effects. Visual demonstration of this method is critical as the animal training steps are difficult to learn and must be executed very reproducibly. Hello, I am Eric Ye, professor of neurophysiology at University of Fryberg, Switzerland.
The procedure will be demonstrated by several experimenters, Dr.Ab, Dr.Lin, who are both independent investigator Dr.Melanie Keer, a postdoc from my laboratory and three PhD student and doin Zandra, Julie Vidor and Pauline Chatan. Prior to the behavioral tests, prepare the behavioral setup in the laboratory. Fill the wells of the different test boards with the food pellets that serve as reward during the tests.
Next, transfer the monkey from the group housing room into a transfer cage. The monkey is trained to enter a tunnel giving access to the primate chair with subsequent positioning of the head, measure the monkey's weight. Finally transfer the monkey in the primate chair to the laboratory.
The modified brinkman board test is the basic behavioral task of reference to be conducted in every behavioral session. Three digital video cameras are used to record the sequence for offline processing, one above the board, and one on each side of the board. To begin, initiate the video recording with the three cameras.
Place the monkey in front of the brinkman board. Open the right window on the primate chair to give access to the right hand. Using the right hand, the monkey will retrieve the food pellets from the 50 slots after completion of the test.
For the right hand, close the right window and refill the board with pellets. Next, open the left window and repeat the test for the left hand. At the end of the test, reward the animal with a few dried raisins or an almond.
This procedure is repeated at the end of each test to maintain motivation during the whole daily session. The most difficult aspects of this procedure is obtaining the regular and reproducible behavior in the monkeys. This is achieved by adopting a highly standardized and repetitive procedure, such as using the same experimenter for a given monkey and conducting the test session at the same time of the day.
The brinkman box comprises 20 wells, 10 vertical and 10 horizontal. As compared to test one. The monkey has to control the hand in a limited space with reduced degrees of freedom to perform the precision grip movement.
After filling the board with pellets, close the upper facet of the box in order to first conduct the test. In the absence of visual control, thus relying on tactile exploration, turn on the digital camera that is placed below the box. Place the monkey in front of the brinkman box.
Open the left window of the primate chair to test the left hand In the absence of visual control, as the monkey tries to retrieve the 20 pellets, the sequence is recorded by the camera below the box. Next, close the left window of the primate chair. Refill the board with pellets and then open the right window of the primate chair.
The monkey will repeat the test with the right hand. In the absence of visual control, when the tests without visual control are completed, open the top facet of the box to test the ability to grasp pellets. In the brinkman box under visual control, refill the box with pellets and let the monkey perform the test using the right hand.
When the test with the right hand is complete, close the right window of the primate chair. After refilling the box with pellets, open the left window of the primate chair and let the monkey perform the test. Using the left hand, the rotating brinkman board has 32 wells distributed in four concentric rows.
This test is comparable to the modified brinkman board test, except that the board is rotating, forcing the monkey to anticipate the displacement of the board in a clockwise or counterclockwise direction. Fill the board with pellets. The sequence is recorded with the digital camera placed above the setup.
To begin the test, open the right window of the primate chair. The monkey will retrieve the pellets from the 32 wells with its right hand while the board is turning clockwise. To test the left hand, close the right window, refill the board with pellets and open the left window of the primate chair.
The monkey repeats the task with its left hand. Finally, the test for each hand is performed in the same manner as just shown while the board is turning. Counterclockwise wise, the reach and grasp draw task was designed to combine comprehension ability with the capacity to generate force.
A digital camera is placed on top of the drawer to record the trials for offline control of the data. Various other detectors record discrete events such as the hand touching the knob when the finger enters the well and when the pellet is withdrawn from the well. To begin the test, open the right window of the primate chair.
A light beam is interrupted when the hand of the monkey approaches the drawer knob. This soft trigger can be used to synchronize the trial for offline processing. The monkey has to open the drawer by first exerting a grip force on the knob of the drawer, followed by a load force to open the drawer, giving access to a pellet placed inside the drawer.
While the drawer remains open, the pellet is retrieved with the same hand.Again. Using the precision grip, the monkey will perform 10 trials at each of five different levels of resistance. Using the right hand, an analogic button on the setup allows selection of the level of resistance after the test.
For the right hand is complete. Repeat the test with the left hand at the different resistance levels after completion of the tests for seen on that day feed and reward the monkey with food. In addition to the pellets received during the tests, typically the monkey receives cereals and fruits after eating, the monkey is returned to the group housing room.
The four behavioral tests demonstrated in this video are used in studies to investigate the functional recovery from lesion of the cervical spinal cord or of the motor cortex. In the absence or presence of a treatment applied to enhance the spontaneous recovery for test one, the modified brinkman board, the analysis is focused on two parameters. The first parameter is the score given by the number of pellets retrieved by the monkey in 30 seconds, counted separately for the vertical slots and the horizontal slots.
The second parameter is the contact time defined as the time interval between the insertion of the first finger into the slot to touch the pellet and the onset of retrieval of the pellet out of the well. As illustrated in this series of pictures, the leftmost picture shows the hand approaching the slot containing the pellet. The next frame on the right corresponds to the time point of contact.
The rightmost frame corresponds to the time point at which the pellet is taken out of the slot. Hence, the contact time is 240 milliseconds. In this example, representative data derived from the modified brinkman board task performed by monkey subjected to a lesion of the motor cortex are shown Next.
The time is for the consecutive days of the behavioral sessions. The vertical dashed red line is the day at which the lesion was performed. The graph of the score illustrates the initial training phase, the pre lesion plateau, the dramatic drop of score immediately after the lesion, and finally, the progressive functional recovery toward the post lesion plateau.
The functional recovery is the ratio of the median post lesion score at plateau divided by the median pre legion score, which is 59%In this example shown here is the contact time data. In these graphs, each black dot corresponds to the time of contact between the finger and the pellet in one slot. For each session, there were five trials per orientation.
The first five ones attempted by the monkey for each orientation, and the gray bar represents the median value. Since an increase in CT reflects a deficit, the functional recovery is the ratio of the median pre lesion CT divided by the median post lesion CT at plateau, which is about 28%This diagram shows representative data derived from test two, the brinkman box for a monkey performing the task under visual control Here, a more meaningful parameter is the total time defined as the time interval between the picking of the pellet in the first slot and the picking of the pellet. In the last slot, a statistically significant difference was observed between the median total time pre lesion, and the median total time post lesion.
In the last sessions, the functional recovery was calculated to be 89.6%For test three, the rotating brinkman board a sensitive parameter is the contact time measured for the first 10 slots. These two graphs are derived from a monkey subjected to a lesion of the motor cortex. The top graph for a clockwise rotation and the bottom graph for a counterclockwise rotation of the board.
The two vertical gray arrows indicate that the contact time was infinitely long in a few sessions immediately after the lesion, as the monkey was unable to perform the task with the contr lesional hand. This final figure shows representative data derived from a session performed by one monkey on test four, the reach and grasp draw task panel A shows the raw data corresponding to three parameters acquired online during a single trial load force in red, grip force in blue and displacement of the drawer in green. Several markers were also acquired during the task knob touch corresponds to the time point when the animal first touches the knob full open to the full opening of the drawer, and picking time to the time of the reward grasping for the analysis.
Seven cursors were placed at critical time points in the unfolding task, time locked to the touch of the knob by the animal onset of grip force, maximal grip force, onset of load force, maximal load force time locked when the drawer is fully open and time locked to the picking time. Panel B is a representation of the quantitative results for two parameters recorded during the reach and grasp drawer task, the grip force and the load force. The left graph shows the maximal value and the right graph shows the slope value from the onset to the max.
Four out of the five different relative levels of resistance are illustrated here Following this procedure, further analysis can be considered such as qualitative detailed observation of how the grasping with the precision grip can be performed by the monkey in order to answer additional question. For example, the emergence of strategies of substitution to reach the same fin motor goal during the functional recovery from a lesion. After watching this video, you should have a good understanding of how to quantitatively assess manual dexterity in non-human primates based on four behavioral tests addressing a pallet of motor parameters.
Do not forget that working with non-human primates can be extremely as artists and is also ethically sensitive. Therefore, precautions such as preventing direct contact with the monkeys to avoid bites, for instance, and ensuring animal welfare should always be taken while performing this procedure.
