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).
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