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
Institution: UNIVERSITY OF KANSAS MEDICAL CENTER MSN 1039 KANSAS CITY, KS 66160
Fiscal Year: 2006 Department: MOLECULAR AND INTEGRATIVE PHYSIOLOGY
Project Start: 15-APR-2005 Project End: 31-MAR-2009
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG: SMI
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-Sa�f1, 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-Sa�f 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.
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