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Government Grants Promoting Cruelty to Animals

University of Kansas Medical Center, Kansas City, KS

PAUL D. CHENEY - Primate Testing - 2006

Grant Number: 5R01NS051825-02
Project Title: Electrical Stimulation of Cortical Motor Output
PI Information: DIRECTOR PAUL D. CHENEY, [email protected]

Abstract: DESCRIPTION (provided by applicant):
Graziano et al. (2002a) recently demonstrated that applying repetitive intracranial microstimulation (RL-ICMS) to cortical motor areas for long durations (500 ms), matching the duration of normal movements, produces natural appearing arm movements ending with the hand positioned in different parts of extrapersonal space, depending on the cortical subregion stimulated. Three subregions were identified as producing movements with different characteristics. RL-ICMS of primary motor cortex (M1) evoked movements ending with the hand positioned in central space immediately in front of the monkey's chest and the formation of various postures of the digits appropriate for object manipulation. It was also reported that the pattern of EMG activity from stimulation was arm posture dependent and could switch from excitation to inhibition depending on initial posture. These findings were viewed as consistent with the hand reaching the same final position independent of the initial starting position. More recently, Graziano et al. (2004), reported that stimulus evoked output effects were also highly joint angle dependent. These results are remarkable and suggest a novel view of frontal lobe motor function. RL-ICMS was viewed as engaging functional neural substrates for natural, purposeful movements. In this application we will use stimulus triggered averaging of EMG and focus on M1 cortex to investigate some of the findings from RL-ICMS and to test possible alternative explanations for the findings observed. Four specific aims are proposed to rigorously test: 1) the extent to which EMG responses are limb posture and joint angle dependent, 2) the possibility that natural appearing responses observed with RL-ICMS can be explained by sustained, tonic coactivation of a particular set of muscles at each joint that simply achieve a final equilibrium position, and 3) the extent to which muscles activated with RL-ICMS can be explained based on detailed knowledge of M1 muscle maps and the pattern of spread of excitation through these muscle representations associated with ICMS.

Thesaurus Terms:
brain electronic stimulator, electrostimulus, limb movement, neural information processing, neuromuscular transmission
brain mapping, motor cortex, muscle function
Macaca mulatta, behavioral /social science research tag, electromyography

MSN 1039
Fiscal Year: 2006
Project Start: 15-APR-2005
Project End: 31-MAR-2009

The Journal of Neuroscience, April 15, 2001, 21(8):2784-2792

Consistent Features in the Forelimb Representation of Primary Motor Cortex in Rhesus Macaques
Michael C. Park1, Abderraouf Belhaj-Saf1, Michael Gordon2, and Paul D. Cheney1

1 Department of Molecular and Integrative Physiology and Mental Retardation Research Center, and 2 Departments of Pharmacology and Surgery, University of Kansas Medical Center, Kansas City, Kansas 66160

Behavioral task.
Data were collected from two male rhesus monkeys (Macaca mulatta; ~9 kg, 6 years old). The monkeys were trained to perform a reach and prehension task requiring coactivation of multiple proximal and distal forelimb muscles in natural, functional synergies. Training procedures and the behavioral task have been described in detail previously (Belhaj-Saf et al., 1998 ; McKiernan et al., 1998 ). Briefly, during each data collection session, the monkey was seated in a custom primate chair and placed in a sound-attenuating chamber. The left forelimb of the monkey was restrained during task performance, whereas the right forelimb had freedom of movement. The monkey was guided in performance of the task by audio and video cues provided by an IBM-compatible computer. The monkey initiated the task by placing its right hand on a pressure plate located at waist height directly in front of him. Having the hand on the plate for a preprogrammed length of time triggered the release of a food reward and a "go" signal. The monkey then reached out to a small food well located at shoulder level, a little less than one arm length away and oriented ~20 from vertical. The monkey used a precision grip to extract a food pellet from the well and bring the pellet to its mouth. The task was completed by returning the hand to the pressure plate.
Surgical procedures.
On completion of training, each monkey was implanted with a cortical recording chamber and EMG electrodes. For all implant surgeries, the monkeys were tranquilized initially with ketamine, administered atropine, and subsequently anesthetized with isoflurane gas. Both monkeys received prophylactic antibiotic before and after surgery and analgesic medication postoperatively (Park et al., 2000 ). All surgeries were performed in a facility accredited by the Association for Assessment and Accreditation of Laboratory Animal Care using full sterile procedures. All procedures conformed to the Guide for the Care and Use of Laboratory Animals, published by the United States Department of Health and Human Services and the National Institutes of Health.
A magnetic resonance imaging (MRI)-compatible plastic chamber allowing exploration of a 30-mm-diameter area (see Fig. 3A,B) was stereotaxically implanted over the forelimb area on the left hemisphere of each monkey as described previously (Kasser and Cheney, 1985 ; Mewes and Cheney, 1991 ; McKiernan et al., 1998 ). The chambers were centered at anterior 21.6 mm, lateral 11.4 mm (monkey M), and anterior 16.0 mm, lateral 7.4 mm (monkey D), at a 30 angle to the midsagittal plane. For MRI compatibility, titanium screws (Bioplate, Los Angeles, CA) and titanium restraining nuts (McMaster-Carr, Chicago, IL) were used. In addition, a titanium screw (Synthes, Monument, CO) in contact with the dura served as a reference ground for electrophysiology.
EMG activity from 24 muscles of the forelimb was recorded using pairs of multistranded stainless steel wires (Cooner Wire, Chatsworth, CA) implanted during a sterile surgical operation. One monkey was implanted using a modular subcutaneous implant technique, and the other was implanted using a cranial subcutaneous implant technique. These procedures were described in detail previously by Park et al. (2000) . Briefly, for both techniques, pairs of wires for each muscle were tunneled subcutaneously to their target muscles. The modular subcutaneous implant technique used four connector (ITT Canon, New Britain, CT) modules, two placed above and two below the elbow. The cranial subcutaneous implant technique used one circular connector (Wire Pro Inc., Salem, NJ) module placed near the cortical recording chamber. The wire insertion points for specific muscles were identified on the basis of external landmarks and palpation of the muscle belly. The wires of each pair were bared of insulation for ~2 mm at the tip and inserted into the muscle with a separation of ~5 mm. We tested proper placement by stimulating electrically through the wires with short trains or single pulses while observing the evoked movements. The wires were removed and reinserted if necessary.   

Please email:  PAUL D. CHENEY, [email protected] to protest the inhumane use of animals in this experiment. We would also love to know about your efforts with this cause: [email protected]

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Rats, mice, birds, amphibians and other animals have been excluded from coverage by the Animal Welfare Act. Therefore research facility reports do not include these animals. As a result of this situation, a blank report, or one with few animals listed, does not mean that a facility has not performed experiments on non-reportable animals. A blank form does mean that the facility in question has not used covered animals (primates, dogs, cats, rabbits, guinea pigs, hamsters, pigs, sheep, goats, etc.). Rats and mice alone are believed to comprise over 90% of the animals used in experimentation. Therefore the majority of animals used at research facilities are not even counted.

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