The overall aim is to assess whether task specific locomotor training and spinal cord
electrical stimulation (SCES) can induce neural reorganization of the functionally isolated
human spinal cord to improve standing and stepping in individuals with functionally complete
SCI. The investigators propose that locomotor training will result in generation of more
effective standing and stepping efferent patterns by restoring phase dependent modulation of
reflexes and reciprocal inhibition, reducing clonus and mediating interlimb coordination.
The investigators propose that the SCES will optimize the physiological state of the spinal
cord interneuronal circuitry compromised by compensating for loss of supraspinal input for
the retraining of these tasks.
The proposed studies will allow us to gather critical information using commercially
available electrodes to design the more advanced multi-electrode array technique that will
be adaptive and conceivably be effective in a wider range of patient populations. The
current electrodes used in this study will serve two objectives: 1) to improve standing and
stepping with the combination of epidural stimulation and locomotor training in individuals
with functionally complete SCI; and 2) to provide critical information for the development
of more advanced electrodes.
SCREENING: Evaluation Tests and Pre-Training (1st consent)
Dr. Harkema will determine study eligibility based on the inclusion and exclusion criteria
and in accordance with the medical recommendation of Dr. Boakye & Dr. Williams.
Participating in the initial portion of the study does not guarantee their eligibility for
surgical implantation and epidural stimulation.
These individuals will not be enrolled in any other experimental studies unless approved by
the principal investigator.
The investigators will evaluate the research participants for: 1) functional
neurophysiological assessment (FNPA); 2) nerve conduction study (NCS); 3) somatosensory
evoked potentials (SEP); 4) sympathetic skin responses (SSR); 5) efferent motor activity
during standing; 6) efferent motor activity during stepping and 7) reflexes during supine,
prone, sitting and standing; 9) bladder function; 10) CV function. The FNPA, NCS, SEP and
SSR will be performed while the research participant is lying supine on a mat. The efferent
motor assessments will be performed in the body weight support treadmill with the assistance
of trainers at the hip and at each leg.
After completion of these evaluations, participants will undergo 80 sessions of step/stand
training. The investigators will repeat the FNPA, NCS, SEP, SSR, reflexes, bladder function,
CV function and assessment of the efferent motor activity during standing and stepping after
the completion of the 80 training sessions to quantify that no motor pattern changes are
achievable with LT alone. Drs. Harkema, Williams, Park and Boakye will meet to discuss the
results of the preliminary testing and evaluate if the participant is eligible for surgical
implantation for SCES.
FULL ENROLLMENT: Surgery + Epidural Stimulation + Training (2nd consent) If after evaluating
the results, the study investigators determine that the participant is an appropriate
candidate for surgery and epidural stimulation, the participants will be asked to sign an
additional consent form.
The surgery will be performed at University Hospital to insert the epidural stimulating
electrodes. The lead wires will be tunneled subcutaneously to exit 5 centimeters from the
incision site. The implantable neurostimulator will be internalized and the connecting wires
for the implanted electrodes will be tunneled under the skin and connected with the battery
generator that will be placed in the abdominal area. We will repeat the experiments
beginning 2-14 days after the surgery both with and without stimulation for 10 - 14 days.
During the first two weeks after the surgery, the research participants may be hospitalized
at Frazier Rehab Institute to monitor the incision site. We will also identify appropriate
stimulation parameters for inducing stepping and standing in combination with manual
assistance using body weight support on a treadmill (BWST).
Following discharge from inpatient or recovering at home the individuals will be seen at
Frazier Rehab Institute on a daily basis for testing and LT. We will evaluate the
combination of epidural stimulation with manual step/stand training. This stage will be
conducted over six-eight months. During training, the patients will be provided with
epidural stimulation using the parameters defined in Stage 1. Testing (FNPA, MEP, SSR and
efferent motor activity) may be performed weekly.
Locomotor Training: Every research participant will be slowly acclimated to the body weight
support system to make him/her feel comfortable in an upright position. This may help the
research participant avoid experiencing a lowered blood pressure or dizziness. However, if
these conditions should occur, the research participant would immediately be unhooked from
the system, removed from an upright position, the legs elevated, and the blood pressure
monitored. Stepping bouts are relatively short in duration, thus an increase in respiration
as well as an increase in heart rate or blood pressure will generally last for only a couple
of minutes. Each research participant will be closely monitored through each experiment and
training session. Standing or stepping will immediately halt once the research participant
feels tired or winded. Blood pressures & heart rates will be monitored by the PT or trained
staff regularly during each training session. Continuous blood pressure, breathing rate, and
temperature may be monitor with sensors throughout the training sessions and experiments.
Participants may train 2x a day, they will train both to stand and step on the same day. The
sessions will only be counted if the progression criteria are met, for example independence
minutes or weight-bearing minutes.
Before and after every experiment and training session, a physical therapist (PT) or
research staff member will examine the research participant's skin for irritations and
abrasions. If skin irritations or abrasions are caused by the electrodes, harness position
or hand placements of trainers, electrode, the harness and hand placement will be modified
appropriately. Further, the PT will constantly monitor the research participant's skin and
muscle for signs of muscle strain, joint sprain and skin irritation (e.g. temperature and
Dr. Harkema & the PT will continually assess the appropriate BWS & continuously monitor
manual assistance by trainers to avoid joint sprain and fracture. Further, continuous
monitoring of the research participant will be conducted by the staff for potential
injuries. For example, signs of skin redness, swelling of joints, or spasticity can be
indicators of injury when research participants have impaired sensation. Research
participants will also be stretched by the PT or trained staff member before and after each
training session to prevent injury.
If any signs of risks or discomfort are noted, the experiment or training session will be
immediately discontinued. If any complications arise, the stand or step training will
immediately stop and Dr. Williams will immediately be informed. In addition, the research
participant's primary care provider will be notified as necessary. Dr. Williams will be the
medical advisor for the research participants throughout the LT segment of this study. Dr.
Boakye will oversee all surgical related issues for the research participants.
After the training period has ended, patients will be followed by Drs Boakye/Williams and
Harkema every 3-6 months for a total of 3 years following surgery. After 3 years the
patients will be followed up by Drs Boakye/Williams and Harkema every six months for
continued long-term care until the device is explanted or the device is approved for
stepping and standing in spinal cord injury. Follow-up neurological examination for the
purpose of this study will be incorporated into each clinic visit. The decision to continue
to maintain the stimulators or remove them will be made during these follow-up visits.
Dr. Harkema and the research team might ask the participant to return for training in the
laboratory for an extended time (80-100 sessions) during the follow up period. Training
(stand or step) will be designed to optimize parameters and built to improve on previous
training. During this time participants might be asked to functional train with the
combination of our adaptive epidural stimulation strategy with manual LT. During training,
the participants will be provided with ES using the parameters determined using the
computation learning method which is developed during phase 2 described below.
Design including all survey instruments, questionnaires, etc.
Stage 1A: Standing and stepping interventions
FULL ENROLLMENT CONSENT:
Stage 1B: Surgical Procedure Stage 1C: Stimulation with standing and stepping interventions
Stage 2A: Stimulation with standing and stepping assessments Stage 2B: Adaptive
Multielectrode Epidural Stimulation and LT Stage 1A: Standing and stepping interventions
Prior to the initial surgery the participant will undergo 80 sessions of step/stand training
(screening). We will evaluate the research participants for 1) functional neurophysiological
assessment (FNPA), 2) nerve conduction study (NCS); 3) somatosensory evoked potentials
(SEP); 4) sympathetic skin responses (SSR), 5) efferent motor activity during standing, 6)
efferent motor activity during stepping and 7) reflexes during supine, prone, sitting &
standing before the initiation of training, 9) bladder function, 10) CV function, 11) MRI of
the spinal cord. Each of these measurements will take between 1 and 4 hours. We will repeat
these measurements at the end of the initial 80 training sessions.
Body Weight Support on a Treadmill (BWST). The BWST system's primary purpose is to provide
body weight support and control the vertical force exerted on the legs. This also provides
trunk stability and prevents the research participant from falling during standing or
stepping. The BWST is a device used to assist research participants with neurologic injuries
during standing and stepping. Research participants wear a modified parachute harness
connected to a cable, which links to the overhead pneumatic support system. We can input the
desired amount or percentage of support, and the cable will lift the specified weight from
the research participant, leaving less weight to be supported by the research participant.
Our laboratory uses a pneumatic, closed loop force controlled system hoist that provides
weight support and controls ground contact force patterns. If the actual support varies from
the desired support, the system is designed to adjust the pressure in the pneumatic cylinder
to equalize the set and actual support force. Due to the constant feedback, this system
provides safety and allows for the center of mass movement during stepping.
Functional Neurophysiological Assessment (FNPA). Research participants will lie supine on a
mat with legs in an extended position. They will be asked to perform a series of eight
exercises. 1) Relaxation for 5 minutes. 2) Reinforcement maneuvers. 3) Voluntary motor
tasks. 4) Passive movements. 5) Tendon taps.. 6) Manual clonus elicitation. 7) Tonic
vibratory response. 8) Withdrawal suppression. The plantar surface of the foot will be
stimulated as is done to elicit the Babinski sign. The stimulus will be delivered with a
rod. For the initial three trials subjects will be instructed to relax and allow the leg to
jump should it do so. For the subsequent three trials subjects will be instructed to relax
and prevent the leg from jumping.
Nerve Conduction Study (NCS) - Nerve conduction is recorded through surface electrodes to
measure conduction in the peripheral nervesSurface EMG electrodes are placed at a known
distance away from the stimulating electrode over the muscle(s) innervated by the studied
nerve (soleus, tibialis anterior, extensor digitorum longus). Ground straps are placed on
thighs. Repeated single-pulse electrical stimulation is delivered at very low intensities
for the recorded muscles for each of the three nerves evaluated. Stimulation delivery rates
will not exceed 2 per second.
Somatosensory evoked potentials (SEPs) - SEP are recorded through surface electrodes to
measure conduction in the peripheral nerves, cervical and lumbosacral spinal cord, deep
brain structures, and sensory cortex. Surface EMG electrodes are placed over the adductor
pollicis brevis and soleus muscles. Stimulation electrodes are placed over the median nerve
at the wrist and tibial nerve in the popliteal fossa of the right and left upper and lower
limbs. Ground straps are placed on the forearms and thighs. Repeated single-pulse electrical
stimulation is delivered at intensities of 1 and 1.5 times motor threshold for the recorded
muscles for each of the four nerves evaluated. Averaged responses for up to 256 stimuli will
be recorded for each of these two intensities for the right and left median and tibial
nerves. Simultaneous bilateral stimulation will be applied if no recognizable responses are
recorded from the scalp leads. Stimulation delivery rates will not exceed 2 per second.
Sympathetic Skin Response (SSR). The disruption to the spinal autonomic pathways will be
measured by electrophysiological recordings in the supine position, with the room
temperature (21-25 deg C). Subjects will rest supine for at least 10 min before the
beginning of the examination. Self-adhesive electrodes will be applied to the palmar and
dorsal surfaces of the hands and plantar and dorsal surfaces of the feet. The median nerve
will be stimulated (0.2 ms duration, 10-20mA intensity) and 10 SSR samples will be recorded
bilaterally from both hands and feet (band pass of 3Hz to 3 kHz). The average latency (ms)
and amplitude (mV) of the 10 SSRs will be calculated.
Efferent motor activity during standing. During the testing the research participants will
be placed on the treadmill (upright) & suspended in a harness by an overhead cable at the
maximum load at which knee buckling and trunk collapse can be avoided (i.e. BWST). All
participants will stand at their optimized body weight load (BWL) and joint kinematics and
limb load will be consistently maintained by manual assistant by trainers. All trainers are
careful to provide manual assistance only when needed. A trainer positioned behind the
research participant will aid in pelvis and trunk stabilization, by applying anterior forces
at the pelvis and/or posterior forces at the shoulders, ensuring that the trunk and pelvis
are not flexed or hyper-extended. Research participants will take a break and rest at any
time they feel the need to during the session.
Efferent motor activity during stepping. During the testing the research participants will
be placed on the treadmill in an upright position and suspended in a harness by an overhead
cable at the maximum load at which knee buckling and trunk collapse can be avoided (i.e. the
BWST). All trainers are careful to provide manual assistance only when needed. A trainer
positioned behind the research participant will aid in pelvis and trunk stabilization, as
well as appropriate weight shifting and hip rotation during the step cycle. The trainer will
ensure that the trunk and pelvis are not flexed or hyper-extended during stepping, and that
the weight is shifted from the ipsilateral limb to the contralateral limb simultaneous with
ipsilateral swing initiation. Research participants will take a break and rest at any time
they feel the need to during the session. Joint kinematics, limb load and treadmill speed
will be consistently maintained for each phase of the step cycle during these trials.
Reflexes during supine, prone, sitting, and standing. H-reflex elicited at the back or leg
muscle. The H-reflex is analogous to the stretch reflex (muscle spindles activate Ia
afferents that synapse on alpha-motor neurons), but is elicited by an electrical stimulus to
the Ia fibers in the afferent nerve, circumventing the muscle spindle. The H-reflex will be
elicited using electrical stimulation to the tibial nerve using an AgCl cathode in the
popliteal fossa and a 40-mm-diameter anode placed over the patella. The H-reflex can also be
elicited using electrical stimulation from stimulating electrodes placed on the subjects'
back. Concurrently we will record EMG from leg muscles using bipolar surface electrodes
placed on the muscle bellies. The EMG signals propagate through long shielded wires to
custom-built amplifiers (frequency response 20 Hz-10 kHz). The stimulus will be a 1 ms
square wave pulse (0.5 Hz - 200 Hz) delivered by a custom-built computer-controlled constant
current stimulator. This response will be dependent on the stimulus strength. Eliciting a
stimulus with a strength that is just above the threshold for the alpha-motoneurons will
also result in direct stimulation of the leg muscle or back, producing the M-wave. The peak
to peak amplitude of the H-wave will be plotted versus the peak to peak amplitude of the
M-wave. The maximum H-wave amplitude divided by the maximum M-wave amplitude will be
We will use two different reflex protocols to test the long descending propriospinal system.
The long propriospinal system will be tested based on H reflex amplitude in the Soleus
muscle under conditioning stimulation of ulnaris nerve. The ulnaris nerve will be stimulated
via surface electrodes with trains of 3 rectangular pulses (pulse duration: 0.5 ms, pulse
interval: 3 ms). In normal subjects the amplitude of H reflex in the Soleus muscle increases
when the delay between conditioning and testing stimuli is < 40 ms.
A separate protocol will be used to test the reticulospinal connectivity. We will record the
audiospinal startle reaction (ASR) (30 msec tone of 90 dB) based on EMG of multiple leg
muscles. In addition, we will test the H-reflex facilitation of both the tibialis anterior
and Soleus started 50 ms after the sound to peak after 75-125 ms and returned to baseline
values after 250 ms. We will also record evoked responses in leg muscles in response to
epidural stimulation after conditioning with sound stimulation . The delay between sound
stimulation and epidural stimulation will range from 10 - 100 ms.
Bladder Function (cystometrogram). Subjects will undergo a cystometrogram to assess bladder
capacity and pressure. While the subject is supine a catheter will be inserted in the
urethra and advanced into the bladder. The bladder will be filled with saline solution and
the pressure will be recorded. Pressure will also be recorded when the bladder is relieved.
We may use surface electrodes to measure leg muscle activity during bladder filling and
emptying. The test will be performed at an urologist office and does not require sedation or
Cardiovascular (CV) Function (Orthostatic Challenge Test). Prior to orthostatic assessments,
subjects will lie supine in a temperature controlled room for 20 minutes (rest).
Beat-to-beat arterial blood pressure, heart rate, and respiratory rate will be determined in
the supine position, and during a 20 minute passive orthostatic challenge (sit up test).
Indices of stroke volume, cardiac output and peripheral resistance will be calculated from
the blood pressure wave-form. Mean systolic and diastolic arterial blood pressures and heart
rate will be calculated at rest and during orthostatic stress. Catecholamine (adrenaline and
noradrenaline, nm/l) levels will be measured during rest and orthostatic challenge test. A
butterfly catheter (15mm) will be inserted into an antecubital vein before data collection
to draw the blood samples, this will allow the collection of blood without additional stress
to the participant and activation of catecholamine release by venopuncture. The subject will
rest for 20 minutes: a blood sample (10cc) from the antecubital vein will then be taken. A
second blood test (10cc) will be obtained following the passive tilt (sit up test). Serum
level catecholamine levels will be measured. These data will be correlated with the other
indices of CV autonomic function, and severity of injury to spinal autonomic pathways
determined by SSR. Lower extremity EMG will be collected simultaneously to make sure that
stimulation is not regenerating strong muscle contractions that might result in blood
pressure control independent of improvements in CV function.
Magnetic Resonance Imaging (MRI). Subjects will undergo a T1- and T2-weighted MRI scan at
the T10-S2 levels. Standard sagittal and axial T1-weighted images as well as sagittal
T2-weighted turbo inversion recovery spin-echo images will be obtained. The scan will be
performed a few days prior to the surgical procedure to determine incision location for
appropriate placement in more detail. The decision to implant one or two electrodes will be
based on anthropometrical data derived from this scan. If one 16-electrode array does not
span across sufficient number or segments a second array will be implanted.
Quality of Life, cognitive, autonomic function and sexual function questionnaires. Subjects
will be asked to complete a variety of questionnaires focusing on quality of life,
disability, cognitive, autonomic and sexual function. Spinal cord injury CDE standard
questionnaires will be used in addition to standard quality of life questionnaires. These
questionnaires will be administered prior to implantation, at the end of each training
paradigm and at each follow up.
Stage 1B: Surgical Procedure One or two Medtronic Specify 5-6-5, 16-electrode epidural
arrays will be implanted intraoperatively using a single surgery procedure. The surgery will
be conducted at University Hospital under a combined regional and general anesthesic. We do
not anticipate that the patients will experience any pain during this operation. However, if
there is any discomfort, the patients will be administered analgesics by the
anesthesiologist and/or the painful area will be infiltrated with local anesthetic. Patients
will be placed in the prone position with an incision made in the thoracolumbar area of the
spine. We will perform a partial laminectomy at the T11 - T12 interspace providing a site
for electrode insertion. The incision will be approximately 2.0 - 2.5 inches. One electrode
will be threaded upwards to the T11-L1 segmental levels. If necessary the second electrode
will be threaded downward to the S1-S2 segmental levels for placement over the group of
spinal cord nuclei where activation of the muscles occurs. Fluoroscopy and
neurophysiological parameters will be used to determine the optimal lead placement that will
be determined by motor system monitoring.
Following the location of optimal lead(s) placement the participant will be rolled to the
left lateral decubitus position (right side up) and the surgeon will proceed with the
internalization of the implantable neurostimulator into the subcutaneous area of the
abdomen. The wires of the implanted epidural electrodes will be tunneled under the skin and
connected with the battery generator that will be placed in the abdominal area. If
necessary, the same procedure will occur with the participant rolled to the right lateral
decubitus position for the internalization of the second neurostimulator.
We do not anticipate any increased risks other than the well recognized accepted risks of
surgery (infection, bleeding, and anesthesia).
Stage 1C: Stimulation procedures and standing and stepping interventions Prior to the
surgery we will evaluate the research participants for 1) FNPA, 2) nerve conduction study;
3) SEP; 4) sympathetic skin responses (SSR), 5) efferent motor activity during standing, 6)
efferent motor activity during stepping and 7) reflexes during supine, prone, sitting and
standing, 9) bladder function, 10) CV function as described above in the screening. We may
repeat these measurements beginning 2 weeks after the surgery both +/-stimulation for 10 -
14 days. During the two weeks after the surgery, the research participants may be
hospitalized at Frazier Rehab Institute to monitor the incision site. The FNPA, NCS, SEP and
SSR will be performed while the research participant is lying supine on a mat. The efferent
motor assessments will be performed in the body weight support treadmill with the assistance
of trainers at the hip and at each leg.
Optimal configurations will also be tested for bladder and CV function. A specific
stimulation parameter may be used to assess the influence of epidural stimulation on bladder
function and/or CV function. In the case of 9) Bladder function, following its assessment
with stimulation the bladder will be filled with saline solution a second time after a 5
minute break. The optimal stimulation configuration for bladder will be used and the
pressure will be recorded. The individual will be asked to attempt to empty his/her bladder
when the stimulation is ongoing. Pressure will also be recorded when the bladder is relived.
This test will take approximately 60 minutes.
Similarly the CV function might be assessed without & with stimulation. The orthostatic
stress test might be repeated with optimal stimulation for CV control. The butterfly
catheter will remain in place from the initial non stimulation test and blood samples will
be obtained to same time points to assess if any changes in We will also identify
appropriate stimulation parameters for inducing stepping and standing in combination with
manual assistance using body weight support on a treadmill (BWST) or overground in the case
of standing. Each of the sixteen electrodes will be independently stimulated using
subthreshold, tonic, non-patterned epidural stimulation applied at frequencies of 5-50 Hz,
and amplitudes of 1-10 V. The specific stimulation parameters will be optimized for each
individual to achieve the best motor performance for each task. We may monitor continuous
blood pressure, breathing rate and temperature using external sensors pasted over the skins
during training sessions or experiments.
Stage 2A: Stimulation procedures and standing and stepping assessments Following discharge
or following closure of the incision testing and/or training will be conducted 5 times per
week for 160 sessions on an outpatient basis. In Stage 2 the individuals will be seen at
Frazier Rehab Institute on a daily basis for testing and training. They might be asked to
train twice a day (stand and step on the same day) with a 2-4 hour resting period in
between. We will evaluate the combination of epidural stimulation with manual step
(locomotor) training. This stage will be conducted over four months. During training, the
patients will be provided with epidural stimulation using the parameters defined in Stage 1.
The participants may be evaluated weekly for 1) FNPA; 2) NCS; 3) SEP; 4) SSR, 5) efferent
motor activity during standing, 6) efferent motor activity during stepping and 7) reflexes
during supine, prone, sitting and standing, as described above. Following the determination
of optimal parameters for standing or voluntary activity, the participant might be given a
Patient Programmer to translate weight bearing and stand training and/or voluntary movement
with stimulation to the home environment and perform additional training. The programmer
will be optimally programmed by the research team in such a way to restrict configuration
changes by research participant. A very specific protocol for stimulation and training will
be given by the research team and the participant will be required to complete a training
log. The research team will collect the home training log from the participant once a week
and evaluate the need for changes to the home-based training protocol.
Stage 2B: Adaptive Multielectrode Epidural Stimulation and Locomotor Training (LT) Stage 2
will evaluate the combination of our adaptive epidural stimulation strategy with manual step
(locomotor) training. During training, the participants will be provided with ES using the
parameters determined using the computation learning method in Phase 1.
Experimental materials. We will acquire lower extremity & trunk muscles surface EMG activity
& kinematics bilaterally during all experimental conditions. We will also use fine-wire EMG
to acquire activity from the illio-psoas, extensor hallicus longus, extensor digitorum
longus & other deep muscles muscle. We will also record individual limb loading & level of
BWS during standing & stepping conditions. We may acquire continuous blood pressure with a
finger cuff, breathing rate using an elastic band place loosely around their chest &
temperature with 1-3 small sensors taped over their skin above & below their injury level.
Locomotor Training Intervention. Individuals with SCI will participate in 80 sessions of
weight bearing step-training (n=10) for approx 16 - 20 weeks (60-90 min/session, 3-5
sessions/wk) during which the individuals will be placed on the treadmill in an upright
position & suspended by an overhead pulley in a harness. During stepping using BWST & manual
assistance the maximum load will be used that avoids knee-buckling & trunk collapse. A
trainer positioned behind the research participant will aid in pelvis & trunk stabilization,
as well as weight shifting & hip rotation, & trainers positioned at each limb will provide
manual assistance using a customized technique that facilitates knee extension during stance
(by manually stimulating the patellar & Achilles' tendons) & knee flexion & toe clearance
during swing (by manually stimulating the hamstrings & tibialis anterior tendons). Trainers
provide assistance only when needed. Individuals will step at a normal walking speed for
their height & age (0.89 m/s - 1.34 m/s) & at the maximum body weight allowed with minimal
force needed by the trainers to assist during stance. BWS will be continuously reduced over
the course of the 80 sessions as the individuals increase their ability to bear weight on
the legs during stepping.
Participants may also stand train in a stand training device, based on optimal parameters
acquired during the initial phase of training. The participant might be asked to follow a
supine &/or stand training home program (in a standing frame or similar device) once
independence is achieved with the stimulation. The home program will only be used as a
complement to the daily outpatient training sessions, & will be closely monitored by the
research team. The research participants will have to demonstrate independence & safe use of
the patient programmer in the lab prior to initiation of the home program. Parameters loaded
in the patient programmers will only include those that have been used safely and result in
supine movements or independent standing by the research participant in the laboratory
setting. In addition, family members & caregivers will be trained on appropriate techniques
to provided assistance as needed during home-based training. Independent standing &
availability of caregivers to provided assistance in the home environment will be key
factors when developing the home program.
We will collect electromyography (EMG), joint angle, & footswitch data at 1000 Hz using a
24-channel hard-wired analog to digital board & a custom written Labview software
acquisition program during stepping using BWST & manual assistance. EMG data will be sampled
from 0.1 to 1 kHz & AC coupled into a differential amplifier. Following standard skin
preparation, bipolar surface EMG electrodes with a fixed distance between the electrodes
will be placed on the soleus, medial gastrocnemius, tibialis anterior, medial hamstrings,
adductor, vastus lateralis, & rectus femoris bilaterally. Limb kinematics will be digitally
acquired a passive marker high speed motion capture system. Individual limb loads will be
measured with shoe-insole pressure sensors. Data will be processed & synchronized using
Labview software customized by our laboratory. EMG data will be full wave rectified &
filtered using a 4th order bandpass Butterworth filter (40 Hz - 500 Hz). Mean EMG represents
the relative number & frequencies of the motor units recruited per burst. Integrated EMG
assesses the total EMG activity generated per step. EMG mean & integrated amplitudes from
each muscle will be compared before and after LT. Co-activation values of flexors and
extensors will be calculated. The degree of coordination in the stepping-related
oscillations of lower limb segments will be assessed through principal component analysis.
Quantitative measurements and statistical testing have been described in detail in previous
publications listed above. Heart rate will be monitored during training sessions and
- All research participants, irrespective of age or sex, will meet the following
1. stable medical condition without cardiopulmonary disease or dysautonomia that
would contraindicate standing or stepping with BWST;
2. no painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure
sore, or urinary tract infection that might interfere with stand or step
3. no clinically significant depression or ongoing drug abuse;
4. no current anti-spasticity medication regimen;
5. non-progressive SCI above T10;
6. must not have received botox injections in the prior six months;
7. be unable to stand or step independently;
8. at least one-year post injury; and
9. must be at least 18 years of age.
In addition, all subjects must satisfy each of the three conditions of the functional
neurophysiological assessment described below.
Functional Neurophysiological Assessment (FNPA). We will use FNPA to screen potential
research participants based on specific neurophysiological inclusion criteria.
Participants must have no volitional control of movement below the level of the lesion,
but must retain some brain influence on spinal reflexes. Our target population, which will
be identified by FNPA, cannot be identified reliable using traditional assessments: hence
individual subjects may be classified widely as Class A, B, or C on the ASIA SCI scale. We
will include only subjects who fulfill the following three requirements:
1. There is no descending volitional control of movement below the lesion
2. Segmental reflexes remain functional below the lesion
3. Brain influence on spinal reflexes is retained
1. Ventilatory dependent
2. painful musculoskeletal function, unhealed fracture, contracture, or pressure sore
that might interfere with training;
3. clinically significant depression or ongoing drug abuse;
4. cardiovascular, respiratory, bladder or renal disease unrelated to SCI;
5. severe anemia (Hgb<8 g/dL) or hypovolemia; and
6. HIV or AIDS related illness.