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Stop Animal Exploitation NOW!
S. A. E. N.
"Exposing the truth to wipe out animal experimentation"

Government Grants Promoting Cruelty to Animals

University of Washington, Seattle, WA

EBERHARD E. FETZ - Primate Testing - 2006

Grant Number: 2R37NS012542-32
Project Title: NEURAL CONTROL OF MUSCLE ACTIVITY
PI Information: PROFESSOR EBERHARD E. FETZ, fetz@u.washington.edu 

Abstract: DESCRIPTION (provided by applicant):
We will investigate the neural mechanisms controlling voluntary hand and arm movement in primates. The functional roles of neurons in primary motor cortex and spinal cord will be directly compared. The activity of premotor (PreM) cells (identified by correlational linkages to forelimb motoneurons) and multiple muscles will be documented during multidirectional wrist movements and grip. This repertoire of movements will activate muscles in different synergistic combinations and test the degree to which PreM cells and non-PreM cells are organized in terms of muscles and movement parameters. Spinal interneurons will be identified by their synaptic inputs from different forelimb muscles and from functionally identified cortical sites. The results should reveal significant differences between motor cortex cells and spinal interneurons. We will further investigate the involvement of spinal cord interneurons in preparation and execution of voluntary movements in a two-dimensional (2D) instructed delay task. We will also investigate the movements of arm and hand evoked by electrical stimulation of spinal cord sites; the modulations of these responses during an instructed delay task will reveal the interaction of intraspinally evoked responses with preparation and execution of voluntary movements. To obtain information important for the use of neural activity to control brain-computer interfaces [BCI] we will systematically investigate the volitional control of identified neurons in different cortical areas using biofeedback training. The correlated responses in other cortical cells and muscles will be documented to determine the extent and variability of correlated activity. A novel chronically implanted recurrent BCI will be used to investigate the consequences of directly linking cortical cell activity to stimuli delivered in motor cortex, spinal cord and muscles. .An implanted computer chip will allow long-term monitoring of cell and muscle activity during unrestrained behavior and will test the monkeys' adaptation to continuous operation of recurrent circuits. The recurrent BCI will be used to test the feasibility of directly controlling functional electrical stimulation of muscles with activity of motor cortex cells. These studies of the primate motor system will provide unique information essential to understanding and effectively treating clinical motor disorders, like cerebral palsy, stroke and spinal cord injury. Results with the implanted recurrent BCI will have significant consequences for development of prosthetic applications.

Thesaurus Terms:
interneuron, limb movement, motor cortex, motor neuron, neuromuscular function, neuromuscular system, neuroregulation, spinal cord action potential, afferent nerve, arm, central neural pathway /tract, computational neuroscience, hand, membrane potential, neural facilitation, neuromuscular transmission, sensorimotor system, synapse
Macaca mulatta, electrode, electromyography, single cell analysis

Institution: UNIVERSITY OF WASHINGTON
Office of Sponsored Programs, SEATTLE, WA 98105
Fiscal Year: 2006
Department: PHYSIOLOGY AND BIOPHYSICS
Project Start: 30-SEP-1978
Project End: 31-MAY-2010
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG: SMI

Correlations Between the Same Motor Cortex Cells and Arm Muscles During a Trained Task, Free Behavior, and Natural Sleep in the Macaque Monkey

Andrew Jackson1, Jaideep Mavoori2 and Eberhard E. Fetz1

1 Department of Physiology and Biophysics and Washington National Primate Research Center and 2Electrical Engineering, University of Washington, Seattle, Washington
 
J Neurophysiol 97: 360-374, 2007. First published October 4, 2006; doi:10.1152

Behavioral training
Two male Macacca nemestrina monkeys (monkey Y: 3 yr, weight: 4.3 kg, and monkey K: 3 yr, weight: 4.6 kg) were trained to perform a two-dimensional torque-tracking task with the right wrist. The monkeys sat in a chair with the elbow and hand immobilized by padded restraints.

A six-axis force transducer (model FS6, AMTI, Watertown, MA) measured the isometric torque exerted by the monkeys around the wrist joint, and the flexion-extension and radial-ulnar components of this torque controlled the horizontal and vertical position of a cursor on a screen.

The monkey's task was to hold the cursor inside targets which appeared on the screen. One complete trial required the monkey to move the cursor from a central target to one of eight peripheral targets and hold for 1 s before returning to the center to receive a fruit sauce reward.

Surgical implants
Before surgery, an array incorporating 12 microwire electrodes was assembled under sterile conditions using 50-µm-diam, Teflon-insulated tungsten wire (No. 795500, A-M Systems, Carlsborg, WA) cut flush with sharp scissors, yielding a tip impedance of around 0.5 M at 1 kHz. The wires ran from a crimp-connector (Centi-Loc, ITT Canon, Santa Ana, CA) into polyamide guide-tubes 20 mm in length which funneled into a 6 x 2 array (inter-electrode spacing: 500 µm). Each guide tube was filled with ophthalmic antibiotic ointment (Gentak, Akorn, Buffalo Grove, IL) and sealed at both ends with silastic (Kwik-Sil, WPI, Sarasota, FL).

The monkeys received pre- and postoperative corticosteroids (dexamethasone: 1 mg/kg po) to reduce cerebral edema. During a surgery performed under inhalation anesthesia (isoflurane: 2–2.5% in 50:50 O2:N2O) and aseptic conditions, the scalp was resected and a craniotomy made over left M1 (A: 13 mm, L: 18 mm). The dura mater was removed, and the pia mater was bonded to the edge of the craniotomy with cyano-acrylate glue to prevent cerebrospinal fluid leakage and to stabilize recordings (Kralik et al. 2001 ). The central sulcus was visualized, and the precentral cortex was stimulated with a silver ball electrode to locate the lowest threshold site for eliciting wrist and hand movements. The microwire assembly was positioned at this location with the long axis of the array running parallel to the central sulcus, and the connector was anchored with dental acrylic to several titanium skull screws. Because the Teflon-insulated microwires slide freely through the silastic seal, our design allowed each wire to be lowered individually into the cortex during surgery and adjusted at any time subsequent to implantation.

A 6-cm-diam cylindrical titanium chamber to protect the microwire assembly and house the electronics was anchored with additional skull-screws. Wires were wrapped around two of the screws to serve as ground connections. Any remaining space inside the craniotomy was filled with gelfoam, and the exposed skull was coated with dental varnish (Copaliner, Bosworth, East Providence, RI). The inside of the implant was sealed with a thin layer of dental acrylic covering the skull and craniotomy. The casing was closed with a removable Plexiglas lid, and the skin was drawn around the implant with sutures. Twisted pairs of stainless steel wires were tunneled subcutaneously from the inside of the casing to a connector on the monkey’s back for attaching EMG electrodes. Surgery was followed by a full program of analgesic (buprenorphine: 0.15 mg/kg im and ketoprofen: 5 mg/kg po) and antibiotic (cephalexin: 25 mg/kg po) treatment.

During the course of the experiment, the monkeys were lightly sedated with ketamine (10 mg/kg im) on a weekly basis to sterilize the inside of the head casing (with dilute chlorohexadine solution followed by alcohol). With the monkeys sedated, the cortical microwires could be moved to sample new cells. This was usually performed every 2–3 wk and always after the interior of the casing had been sterilized. The microwires were moved by grasping the loop of exposed wire between the connector and guide-tube with sterile forceps. Typically, four to eight wires were adjusted sequentially while monitoring the recorded signal for action potentials. We concentrated on moving the wires into the approximate vicinity of cell activity rather than trying to optimize for specific units because cells obtained immediately after moving the wires proved to be unstable as the tissue settled. Often different units appeared over the course of the next day, including on wires which had been initially quiet. Typically this procedure resulted in 1 to 5 securely isolated single units 1 day after moving the wires; these units could then be recorded stably for several days to weeks.

While the monkeys were sedated, EMG electrodes made from pairs of braided steel wire (No. A5637, Cooner Wire, Chatsworth, CA) with 2–3 mm of insulation stripped from the end were inserted transcutaneously into various arm and wrist muscles using a 22-gauge needle. Electrode pairs were spaced 1 cm apart. The leads were fixed to the skin with a drop of cyano-acrylate glue, covered with surgical tape and plugged into the back connector. Throughout the experiment the monkeys wore loose-fitting, long-sleeved jackets to protect the wires and back connector.

Video recording revealed that nighttime muscle activity corresponded with episodes of limb twitching, scratching, postural adjustments, and apparent waking behavior. However, unlike during the daytime, correlations between cells and muscles were always positive during these episodes. Even CCFs compiled with ipsilateral muscles exhibited correlation peaks. Figure 6, E and F, shows CCFs between a cell in left M1 and EMG recorded from muscle FCR of the right (contralateral) and left (ipsilateral) arm. During the daytime (Fig. 6E), there was a strong correlation peak with the contralateral muscle but a flat CCF with the ipsilateral muscle. By contrast, during the night CCFs with both contra- and ipsilateral muscles displayed positive peaks (Fig. 6F).

Please email:  EBERHARD E. FETZ, fetz@u.washington.edu to protest the inhumane use of animals in this experiment. We would also love to know about your efforts with this cause: saen@saenonline.org

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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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