Primate Chair, Grant Proposal

November 17, 2005

Jennifer Pryweller

Abstract

A primate chair will be constructed to accommodate fMRI brain scans in awake Rhesus macaques. The chair will be constructed of Delrin or Peek and include adjustable features to accommodate variable monkey size. The neck plate diameter and angle will also be adjustable to account for different monkey sizes. Key features of the chair include a removable waste tray, a reward and reinforcement system, stereotaxic devices and electrophysiological monitoring systems. A juice reward system will be automated so that upon correct visual task performance an air pump will allow the monkey to drink a set amount of juice. In addition, a tone will sound that the monkey is trained to recognize as positive reinforcement. Negative audio tone reinforcement will be used for incorrect visual response. Stereotaxic devices that serve to assist the monkey in holding still (eliminating artifacts in the scan the need for post-processing motion correction) will include perch bars, and a head post and head bar. Electrophysiological measures of interest during an awake monkey scan include monitoring heart rate, blood pressure, body temperature and facial activity. Electrodes will be placed above each eyebrow and on the side of each jaw to monitor muscle twitches in the face. A video camera will be put in place to monitor the monkey's facial and visual responses. A custom circuit will be designed to accommodate electrodes placed in the visual cortex of the brain during scans to identify and monitor individual neurons that are activated in response to specific visual tasks.The entire chair will be design with the monkey's comfort as a forethought. Holes will be drilled in the walls of the chair to allow for air flow. Since the monkey is trained to sit in the sphinx position for the duration of the scan, the chair will be ergonomically designed to accommodate comfort.

Narrative

Project Description

This primate chair will be specially designed to enable researchers to restrain Rhesus macaques effectively for functional MRI brain scanning. The chair will also provide a means of electrophysiological monitoring. Prior to the scan, monkeys are trained to perform functional tasks, namely visual, while sitting in the sphinx position for extended periods of time (see appendix Figure 1). During the scan, the primate chair will allow the monkeys to sit in the same position and perform the same tasks as in training.

The conditions of the MRI scanner itself limit several parameters for the physical design of the monkey chair. The material of the chair will be carefully considered. Most chairs currently on the market are made of polycarbonate because of their strength and heat resistance. This chair will likely be constructed using the metal substitute, Delrin acetal resin. Delrin is an inflexible polymer, synthesized from formaldehyde, that is a lightweight, durable, low wear and low friction plastic. A second potential material for use in any aspect of the chair construction is Peek. Peek, a semi-crystalline material, maintains high mechanical strength, excellent stress cracking resistance and hydrolytic stability in the presence of hot water, steam, solvents and chemicals. The head post will be made of similar material.

Since the monkeys will be awake during the scan several things must be taken into account in the design, including the during-scan monitoring. A removable elimination receptacle will be built into the chair that will allow the monkey the freedom of elimination during the scan and make it easy for the researcher to clean-up afterward. Stereotaxic devices built into the chair will include perch bars and a head bar. Perch bars will be built into the chair that exist for the monkey to hold onto and promote sitting still. The head bar will attach to the crossbar (a part of the chair), and ultimately to the head post implanted on the monkey (see appendix Figure 2). This is the most important feature that allows the researcher to control the movements of the monkey’s head. The neck plate diameter and angle will be adjustable to account for different monkey sizes. Holes will be drilled into the walls of the chair to allow for air flow, providing comfort to the monkey.

Since facial twitches can create undesirable artifacts in the scan, sensors will be used to monitor muscle movement. Four sensors will be placed on the monkey’s face, one above each eyebrow and one on either side of the jaw. Electrical activity will be remotely monitored by the researcher to provide information about monkey response. When the researcher finds that the monkey is properly behaving, shown by a lack of electrical activity in the sensor, the researcher can then provide a juice reward to the monkey. At the request of the primary investigator, the facial sensors may be linked to the reward system to allow for automated rewarding. In this case the researcher would set a specific threshold for the allowed amount of electrical activity read from the sensors.

A juice reward system will be built into the system. Juice will be stored in a small jar and an air pumped feeding straw will run from the jar to the monkey’s mouth. For correct behavior the monkey will be rewarded with a pump of juice, just as in the training sessions. The juice reward system can be remotely monitored allowing the researcher to provide juice at will.

Since the purpose of the research experiment is to map the neuronal circuitry in the visual cortex, a specific device will be built for this task. An electrode will be inserted into the visual cortex of the monkey’s brain through a chamber in the occipital lobe. The electrode will be connected to an electronic amplifier circuit. This circuit will function to identify individual neurons activated during specific visual tasks. The identification of multiple individual neurons in task performance will allow for the mapping of the an entire visual cortex circuit.

Other physiological activity must be monitored to ensure the wellbeing of the monkey. Hear rate, blood pressure and facial expressions are the three best ways to monitor the monkey’s wellbeing. A device to measure blood pressure and heart rate will be developed so that the device will not be distracting or a nuisance to the monkey during the scan and task performance. Also, a video monitoring device, based on video feed technology, to monitor the monkey’s facial expressions and eye movement compliance during task performance will be constructed as an additional piece of the chair unit.

The primate chair will be designed with the parameters of the primary investigator in mind. If the chair proves to be a success the basic construction design can be replicated, taking new design parameters into account. A general chair design would allow for replication across research studies, but most likely the design will function solely to produce a chair specific to the needs of the primary investigator which provides the utmost in competitive advantage.

The social impact of the primate chair is immeasurable. Due to the similarity of human brains to that of the Rhesus macaque, any research involving Rhesus macaques provides for a wide spectrum of impact that is dependent on the research itself. The primate chair provides the ability for the researcher to conduct successful research and meet specific imaging goals.

List of Team Members

Jennifer Pryweller – Team leader, Biomedical Engineering undergraduate, previous exposure to Rhesus macaque research

Dr. Calum Avison – Project advisor; Professor of Radiology and Radiological Sciences, Professor of Pharmacology, Assistant Professor of Neurology; research focus on Rhesus macaques; Vanderbilt University Institute of Imaging Science

Work Plan and Timeline

The primary investigator for the Rhesus macaque research project is out of town. A meeting is set for Monday, November 7 at 1:30p to determine specific time oriented goals, a mode of action, and the identification of equipment and resources. The Institute of Imaging Science does have a work shop, staffed by a professional, that will be available for materials construction.

Literature Review

The following list comprises the initial literary resources for the primate chair design:

Andersen, A. H., Zhang, Z., Barber, T., Rayens, W. S., Zhang, J., Grondin, R., Hardy, P.,

Gerhardt, G. A. Gash, D. M., Functional MRI Studies in Awake Rhesus Monkeys: Methodological and Analytical Strategies. Journal of Neuroscience

Methods 118: 141-152, 2002.

Baker, J. T., Patel, G. H., Corbetta, M., Snyder, L. H., Distribution of Activity Across the

Monkey Cerebral Cortical Surface, Thalamus and Midbrain during Rapid, Visually Guided Saccades. Cerebral Cortex Advance Access. July 1, 2005.

Foeller, P., Tychsen, L., Eye Movement Training and Recording in Alert Rhesus

Macaque Monkeys: 1. Operant Visual Conditioning; 2. Magnetic Search Coil and Head Restraint Surgical Implantation; 3. Calibration and Recording. Strabismus 10(1): 5-22. 2002.

Sawamura, H., Georgieva, S., Vogels, R., Vanduffel, W., Orban, G.A., Using Functional

Magnetic Resonance Imaging to Assess Adaptation and Size Variance of Shape

Processing by Humans and Monkeys. Journal of Neuroscience. 25(17):4294-4306, 2005.

Vanduffel, W., Fize, D., Mandeville, J.B., Nelissen, K., Van Hecke, P., Rosen, B. R.,

Tootell, R. B. H., Orban, G. A., Visual Motion Processing Investigated Using Contrast Agen-Enhanced fMRI in Awake Behaving Monkeys. Neuron. 32: 565-577, 2001.

Appendix

FIGURE 1

FIGURE 2