Spinal Excitation to Enhance Mobility in Elderly Adults
Phase: PHASE1
Conditions: Aging
Sponsor: VA Office of Research and Development

Coversheet 
 
Protocol 
Spinal excitation to enhance mobility in elderly adults 
NCT03667573 
06/23/2021 

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Protocol 
1. Project Title 
 
Spinal Excitation to Enhance Mobility in Elderly Adults: “The Charge Study” 
 
2. Investigator(s): 
 
David J. Clark, ScD 
Emily J. Fox, PhD PT 
 
3. Abstract: 
 
It is well known that age-related impairments of the brain and peripheral nerves contribute to a 
decline in walking function. Age-related impairment of the spinal cord is also a likely contributing 
factor, as the literature describes a variety of changes in spinal cord structure and function with 
aging. Specifically, the elderly spinal cord is less excitable, conducts signals more slowly, and is 
subject to neural noise. Therefore, we are initiating a new line of research with the goal of 
enhancing walking function in older adults by intervening on age-related neural impairment of 
the spinal cord. The objective of the proposed study is to establish the feasibility, preliminary 
efficacy, and variance of response for using transcutaneous spinal direct current stimulation 
(tsDCS) and textured shoe insoles to excite spinal locomotor circuits and enhance practice-
related performance and retention on an obstacle walking task. Enhanced practice and retention 
effects will support future efforts to translate this approach into a longer term rehabilitation 
intervention. 
Excitatory tsDCS is a non-invasive neuromodulation approach in which a relatively weak 
electrical current is delivered to the desired region of the spinal cord via electrodes placed on 
the skin. The electrical current does not cause discharge of action potentials, but rather is 
designed to bring neurons closer to their discharge threshold by inducing a sub-threshold 
depolarization of membrane potentials. When combined with a behavioral task, tsDCS has the 
potential to upregulate neural circuits in a task-specific manner and promote Hebbian 
neuroplasticity (‘fire together, wire together’). We will use a previously established electrode 
montage to deliver excitatory tsDCS to the lumbosacral spinal cord during practice of a complex 
obstacle walking task. 
We also propose to combine the use of textured shoe insoles with tsDCS. This combinatorial 
approach may be a potent strategy for simultaneously optimizing spinal responsiveness to input 
from both descending and ascending excitatory signals to spinal centers of locomotor control. 
One anticipated benefit of increasing the excitation of spinal locomotor circuits is a reduction in 
the executive demand of walking, as measured by prefrontal cortical activation. Our research 
shows that elderly adults rely heavily on compensatory executive control while walking. This is 
widely considered to be a risk factor for adverse outcomes including falls. 
We propose a parallel groups study design in which 40 older adults who have walking deficits 
and who demonstrate a compensatory executive locomotor control strategy will be randomized 
into one of four groups: 1) active tsDCS with smooth insoles (active/smooth); 2) sham tsDCS 
with smooth insoles (sham/smooth); 3) active tsDCS with textured insoles (active/textured); and 
4) sham tsDCS with textured insole (sham/textured). Participants will be blinded to group 
assignment. While receiving stimulation for up to 30 minutes, participants will engage in walking 
practice over a standardized obstacle course. Practice-related gains in performance will be 
quantified by walking speed and other biomechanical metrics. Retention of performance gains 
will also be assessed at a separate visit 2 days later. tsDCS-induced changes in spinal 
excitability will be assessed by measuring soleus H-reflex. Executive demand of walking will be 
assessed as prefrontal cortical activation, measured with functional near infrared spectroscopy 
(fNIRS). Intervening on age-related impairment of the spinal cord to improve walking function is 

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a promising but untapped area of research. The proposed intervention techniques are low cost 
and translatable to real-world settings, which enhances the potential long term impact of this 
work on the well-being of older adults. 
____________________________________________________________________________ 
4. Background: 
 
People with walking deficits have higher rates of morbidity and mortality, more hospitalizations, 
poorer quality of life, and are less likely to remain independent in the community.1-10 Preserving 
walking function has become a major public health priority as it would drastically reduce health 
care costs and improve quality of life for many older Americans and their families.11 Data from 
the American Community Survey (Profile of Veterans: 2011) shows that over 65% of Veterans 
are age 55 or older. The median age of male Veterans is 64. Therefore, a very large proportion 
of the Veteran population is currently or will soon be at risk for the well-known decline of walking 
function that occurs with aging. Preserving walking function is therefore crucial to the personal 
well-being of aging Veterans and has considerable fiscal and pragmatic implications for the VA 
Health Care System. 
The spinal cord has a critical role in the control of walking. The lumbar spinal cord 
contains complex circuits called central pattern generators (CGPs) that contribute to patterned 
muscle activation needed for intra- and inter-limb coordination of walking.12,13 During complex 
walking tasks such as obstacle crossing, the spinal cord must transmit descending motor 
commands from the brain that are needed to adapt the stepping pattern in order to meet 
environmental demands or task objectives (e.g., clearing the obstacle). These descending 
signals are integrated with ongoing activity of the CPGs, and this process is critical to successful 
stepping adaptations.14 The spinal cord is also crucial for receiving and transmitting 
somatosensory information from the periphery, which is an important source of excitation to 
CPGs15-17 and also important for eliciting reflex responses to unexpected perturbations (e.g., 
striking an obstacle).18,19 Somatosensory information is also a crucial source of feedback for 
motor learning.20,21 In the proposed project we seek to upregulate these spinal control 
mechanisms using tsDCS22-25 in order to enhance performance and retention of walking on a 
complex obstacle course. The obstacle course task was selected because it engages all of the 
aforementioned roles that the spinal cord serves during walking. 
Accumulating evidence has demonstrated that with old age the spinal cord is less 
excitable, conducts signals more slowly, and is subject to neural noise that obscures meaningful 
sensorimotor information. This may reduce the effectiveness of the pattern generating circuitry 
of the spinal cord that is crucial to control of walking. Spinal motor neurons, sensory neurons, 
inter- and projection neurons, axonal pathways, and glial cells are vulnerable to aging.26 Notable 
findings in animal or human research include reduced concentrations of key neurotransmitters27, 
abnormal metabolite levels (consistent with neurodegeneration)28, and decline in spinal white 
matter (myelin) integrity.29-31 There is also a dramatic decrease in the number of central 
terminals at the spinal cord from myelinated primary afferent neurons.32 
Given the importance of the spinal cord to control of walking as well as the prominent 
age-related changes in spinal cord structure and function reported in the literature, we 
hypothesize that interventions targeting the spinal cord are likely to improve walking ability in 
older adults. We propose to test this hypothesis by using tsDCS to enhance practice-related 
performance and retention of an obstacle walking task. tsDCS is a neuromodulatory approach 
that delivers mild non-invasive electrical current via surface electrodes. Evidence suggests that 
tsDCS acts through both synaptic and axonal mechanisms.33 Prior literature indicates that 
tsDCS can induce immediate and lasting changes in spinal cord excitability34-37 and can alter 
reflexive36,38,39 and voluntary25 behaviors in humans and rodents.40 During locomotion, tsDCS 
has been shown to modulate both alpha and gamma motor neuron activity and improve 
rhythmic motor output.40 Human data indicate that tsDCS modulates spinal reflexes including H-

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reflex21,22, increases corticospinal excitability24, and increases motor unit recruitment.41 We 
propose to deliver tsDCS using an electrode montage that targets lumbar spinal excitability, and 
has been validated by modeling of electrical current flow42 and by gains in lower extremity motor 
performance.25 The objective with tsDCS is to bring spinal neurons closer to their discharge 
threshold. When applied during walking, this increased excitability of spinal neurons contributes 
to a physiological environment that is more responsive to task-specific activation by 
descending/motor and afferent/sensory pathways.22 The proposed study is designed to provide 
evidence of short term effects of tsDCS on task practice, which can be translated to longer 
rehabilitation interventions in the future. 
 
____________________________________________________________________________ 
5. Specific Aims: 
 
Specific Aim 1: Acquire preliminary data to assess whether active tsDCS and/or textured 
shoe insoles improve practice-related gains in performance and retention for a complex 
obstacle walking task. 
Hypothesis 1a: Within-session, effect sizes will support the following group differences for 
improved walking speed and reduced prefrontal activity after the practice period: 
[active/textured]   >   [active/smooth = sham/textured]   >   [sham/smooth] 
 
Hypothesis 1b: At the 2-day retention test, effect sizes will support the same findings described 
for Hyp 1a. 
 
Specific Aim 2: Establish evidence of increased spinal excitability following tsDCS. 
 
Hypothesis 2: Spinal excitability post-stimulation (measured by H-reflex) will be significantly 
elevated above pre-stimulation baseline for active tsDCS but not sham tsDCS. 
 
____________________________________________________________________________ 
6. Research Plan: 
 
Study Overview 
All study procedures will be conducted at the Brain Rehabilitation Research Center within the 
Malcom Randall VA Medical Center. Up to forty older men and women will be enrolled in the 
intervention component of this study.  A larger number will be enrolled for onsite screening, 
because some will fail the screening tests and not proceed to the study intervention. 
Participants will undergo the following sequence of events: 
 
Telephone Screening: Volunteers will be screened by telephone to determine if they 
meet basic enrollment criteria including age and general health status. 
 
Informed Consent and Onsite Screening Visit: Volunteers who pass the phone screen 
will be invited to participate in on-site screening.  Informed consent will be obtained.  
Mobility function, cognitive screening, and somatosensory screening will be conducted. 
This visit will last approximately 3 hours. 
 
Study Intervention Visit(s): Qualifying participants will be invited to participate in the full 
study. They will attend either one or two intervention sessions (randomly determined to 
study dosage effects) in which they will practice a “locomotor learning” task comprised of 
a 10m walking course with obstacles and transitions between hard and soft floor 
surfaces. During this task they will receive either active or sham transcutaneous spinal 
direct current stimulation. They will also wear either smooth or textured shoe insoles. 
Biomechanical and neural control of walking will be assessed with various non-invasive 

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modalities. Participants will also undergo H-reflex assessment. This visit will last 
approximately 3 hours. 
 
Follow up Visit: 2 days following the study intervention visit, participants will return to 
perform the “locomotor learning” task again so that we can assess retention of learning. 
This visit will last approximately 2 hours. 
___________________________________________________________________________ 
Telephone Screening 
Participants will be screened by telephone to determine if they meet the following criteria: 
Inclusion criteria 
• 
Age 65 years or older 
• 
Willingness to be randomized to either intervention and to participate in all aspects of 
study assessment and intervention 
 
Exclusion criteria 
• 
Diagnosed neurological disorder or injury of the central nervous system, or observation 
of symptoms consistent with such a condition (spinal cord injury, Alzheimer’s, Parkinson’s, 
stroke, etc.) 
• 
Contraindications to non-invasive spinal stimulation including any prior spinal surgical 
procedure 
• 
Chronic lower back pain 
• 
Obesity, defined as Body Mass Index exceeding 30. This is due to the potential influence 
of body fat on the amplitude of electrical current flow to the spinal cord. 
• 
Use of medications affecting the central nervous system including, but not limited to, 
benzodiazepines, anti-cholinergic medication and GABAergic medication. 
• 
severe arthritis, such as awaiting joint replacement 
• 
current cardiovascular, lung or renal disease; diabetes; terminal illness 
• 
myocardial infarction or major heart surgery in the previous year 
• 
cancer treatment in the past year, except for nonmelanoma skin cancers and cancers 
having an excellent prognosis (e.g., early stage breast or prostate cancer) 
• 
current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder 
• 
difficulty communicating with study personnel (including people who cannot speak 
English) 
• 
uncontrolled hypertension at rest (systolic > 180 mmHg and/or diastolic > 100 mmHg) 
• 
bone fracture or joint replacement in the previous six months 
• 
current participation in physical therapy for lower extremity function or cardiopulmonary 
rehabilitation 
• 
current enrollment in any clinical trial 
• 
clinical judgment of investigative team 
___________________________________________________________________________ 
Informed Consent and Onsite Screening Visit 
 
Upon arriving to the research site, participants will undergo informed consent for screening and 
functional assessments.  As part of screening, we will explain in the detail the full study protocol 
including transcutaneous spinal direct current stimulation. 
All questions from the phone screening will be repeated, and additional health/medical 
screening criteria will be evaluated. This will include: 
 
Resting blood pressure   
 
Basic visual examination with Snellen eye chart 
 
preferred 10m walking speed (inclusion criterion is speed < 1.0 m/s) 
 
Height, weight, age, sex 

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 
Obtain list of medications that the participant is currently using 
 
abdominal skinfold thickness 
 
walking speed during performance of a cognitive task (i.e., dual tasking) 
 
Somatosensory assessments of the foot, including two-point discrimination, vibratory 
perception, and tactile pressure sensation. 
 
Activities Specific Balance Confidence Scale: 16-item questionnaire that gauges 
confidence (on a scale of 0-100%) on various balance and walking tasks relevant to 
household and community ambulation. 
 
Berg Balance Scale: 14-item assessment of balance task performance to assess 
balance ability and fall risk. 
 
Movement-specific Reinvestment Scale: questionnaire that asked about the extent to 
which a person directs conscious attention to control of movement. 
 
Trailmaking Test – paper based test where the person must “connect the dots” between 
numbers or between alternating letters and numbers. 
 
Digit Span Test – paper based test to determine the longest list of numbers that a 
person can remember. 
 
Cognitive Assessment Battery from Cambridge Brain Sciences, which includes up to 12 
cognitive tests.  All are short, simple, computer-based assessment that assess domains 
of cognitive such as spatial working memory, response inhibition, and reasoning. A 
specific example is the visuospatial working memory test, in which participants are 
asked to remember the sequence and location of shapes that appear and disappear 
from the screen.  
 
Following the screening visit, study staff will evaluate performance/responses relative to the 
study enrollment inclusion/exclusion criteria. Medical records may be examined to verify 
absence of exclusion diagnoses, and to obtain complete/accurate medication lists. Individuals 
who meet all criteria will be invited to enroll in the full study. 
 
At the discretion of the Principal Investigator, any individual may be deemed ineligible for further 
participation in this study if there are concerns about the individual’s capability to perform study 
procedures or if it may be unsafe for the volunteer to participate in the study.  Furthermore, 
minor exceptions to the inclusion/exclusion criteria may be permitted at the discretion of the 
Principal Investigator if those exceptions do not influence participant safety. For example, small 
deviations from the target range of walking speed or somatosensory function. This is important 
to ensure that individuals are not excluded for insignificant reasons and to facilitate meeting 
enrollment benchmarks. 
___________________________________________________________________________ 
Walking Practice Visit(s) 
 
Walking practice protocol 
Walking practice will consist of 10-20 passes over a 10-meter complex walking course 
consisting of foam obstacles of various heights and widths, as well as transitioning between 
hard (bare floor) and soft surfaces (exercise mats). Each pass will be separated by a short rest 
period of approximately one minute. Participants will be instructed to walk as fast as safely 
possible. 
 
For most participants, the walking practice protocol will be completed in a single visit. However, 
a subset of participants (up to 20) will perform the walking practice protocol twice so that we can 
study dosage effects (i.e., one session versus two sessions). This subset will be selected 
randomly. 
 

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During the walking practice protocol, participants will receive either active or sham 
transcutaneous spinal direct current stimulation (tsDCS) and will wear either smooth or textures 
shoes insoles. Specifically, participants will be randomized to one of four groups: active tsDCS 
with smooth insoles (active/smooth group); 2) sham tsDCS with smooth insoles (sham/smooth 
group); 3) active tsDCS with textured insoles (active/textured group); and 4) sham tsDCS with 
textured insole (sham/textured group). More detail about tsDCS and insoles are given below. 
 
Transcutaneous spinal direct current stimulation (tsDCS) during walking practice protocol 
tsDCS will be delivered to the posterior lumbar region of the spinal cord during walking using a 
commercially available direct current stimulation unit (Soterix Medical Inc). Each tsDCS 
electrode is comprised of a carbon rubber electrode encased in a saline-soaked sponge. The 
anode electrode will be placed on the skin over the 11th and 12th thoracic vertebrae, and the 
cathode electrode will be placed over the umbilicus. This electrode configuration has been 
shown to appropriately target the lumbosacral spinal cord, as validated by modeling of electrical 
current flow42 and by gains in lower extremity motor performance.25  A standard dosage of up to 
30 continous minutes of 2.5 mA stimulus will be used. This dosage (or similar) has been used in 
numerous prior studies and has been shown to be well-tolerated and to produce measurable 
changes in reflex activity and/or lower extremity motor performance.23-25,38,39,43,44 An identical 
electrode arrangement will be used for the sham condition, except the stimulation will be 
delivered in a brief ramp-like manner for just a few seconds at the beginning and end of the 
stimulation period. This sham approach is widely used in the field of direct current stimulation, 
and has been reported to be indistinguishable from active stimulation.39,45 This is because 
participants quickly habituate to the sensation of active stimulation.  
 
Textured Shoe Insoles during walking practice protocol 
Each participant will be tested using smooth insoles and textured insoles. Both insole types will 
be created with 3D printing technology (SolidWorks software and Makerbot Replicator 2 printer). 
The insole material is a thin flexible plastic called Acrylonitrile Butadiene Styrene. This base 
material is extremely thin (about 1.5 millimeters) and does not substantially alter the fit or feel of 
the shoe. The smooth insole will consist of only this base material. The textured insole will use 
the same base material, but with firm raised cylindrical bumps (approximately 2.5mm height and 
2.0mm diameter) spaced in a grid pattern. The grid of bumps will be located under the big toe, 
the head of the first metatarsal, the heads of 2nd-5th metatarsals, and the heel. On average, the 
typical insole will have 30-50 bumps depending on the size of the individual’s foot. All insoles 
will be custom-sized to fit the participants’ feet. All participants will wear socks (new out of 
package) and appropriately sized sandals (sanitized between study visits) that we provide. The 
sandals will be “walking sandals” with adjustable padded straps across the forefoot and heel. 
 
Dual Task Walking Protocol 
We will also ask participants to perform dual-task walking tests with a verbal phonemic fluency 
task and/or with a serial-7 subtraction task. Dual-task cost will be quantified as decrements in 
performance on either walking (e.g., slowing of walking speed) or cognitive task (e.g., fewer 
correct responses). Participant responses will be captured with a voice recorder and quantified 
as rate of word generation (after accounting for incorrect or repeated words). Participants will be 
instructed to focus equally on both the walking task and the cognitive task, in order to ensure 
divided attention. 
 
Assessments of walking performance and neural control 
Various assessments of walking performance and neural control will be made during the 
walking practice protocol, or during separate periods of walking, or while at rest. 
 

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Biomechanics and movement data 
Performance on walking tests will be assessed using motion analysis instrumentation such as 
force plates, motion capture camera, and/or an electronic walkway. When motion capture 
cameras are used, we will tape small reflective markers to the participant’s body which are 
visible to the camera and allow offline calculation of joint movements.  
 
fNIRS prefrontal activation 
Prefrontal brain activity may be measured with fNIRS during walking and cognitive 
assessments. fNIRS is a safe non-invasive technology for indirectly assessing cortical activation 
based on changes in blood flow and oxygenation. Sensors are placed on the forehead, and 
produce infrared light that is able to pass through the skull and is absorbed or reflected by blood 
and other tissues in the head. Infrared light is considered safe and there is no sensation 
association with this procedure.  Calculations made from the relative amount of light 
absorption/reflection provide an estimate of the metabolic activity level of underlying cortical 
tissue. We will use a commercially available fNIRS monitor (Octamon by Artinis Medical 
Systems). 
 
Muscle activity with surface electromyography (EMG) 
EMG is a non-invasive approach to measuring the timing and amplitude of neuromuscular 
activity by placing recording sensors over the muscles. We may record EMG during walking 
assessments from up to 8 muscles per leg. Adhesives will be used to secure the electrodes to 
the legs. Prior to electrode placement, the recording site will be shaved and cleaned to ensure 
good quality contact. 
 
H-reflex of the soleus muscle to assess spinal excitability 
H-reflex testing involves delivering an electrical stimulus to the peripheral nerve and measuring 
the resultant muscle activity using surface electromyography. H-reflex assessment of the soleus 
muscle may be conducted immediately preceding tsDCS, as well as immediately post-tsDCS 
and at 30 minutes post-tsDCS. H-reflex may also be recorded while the participant rests in a 
semi-reclined positioned with the foot supported in slight ankle dorsiflexion (10 degrees) and the 
knee in 30 degrees of flexion. H-reflex may also be recorded while the participant is walking on 
a treadmill or overground. Stimulation will be delivered via a cathode placed in the popliteal 
fossa and an anode placed above the patella. Electromyography (EMG) will be recorded from 
the soleus with bipolar surface electrodes place 3 cm apart. Electrode placement will be along 
the mid-dorsal line of the leg, 4cm below where the gastrocnemius joins the Achilles tendon. 
 
Sympathetic nervous system activity measured by skin conductance 
Participants may be asked to wear sensors on their fingers that measure skin conductivity, 
which is a measure of sympathetic nervous system arousal. Adhesive electrodes are placed on 
the index and ring fingers. We will use a commercially available data acquisition unit (Flexcomp 
Infiniti by Though Technologies Inc). 
 
Video, photos, and voice recordings 
During this study, videos and/or photos may be taken during to document the functional abilities 
of participants, and for possible use in research presentations or education. We may also use 
voice recordings to capture performance on cognitive assessments such as verbal fluency or 
serial-7 subtraction tests. At the time of consent, participants will choose what their 
videos/photos/recordings can be used for. We will avoid capturing images of the participants’ 
faces, and will obscure or delete any such images. 
 
___________________________________________________________________________ 

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Follow Up Visit 
 
Approximately 2 days after the intervention visit, participants will return to the lab and perform 
several more walking trials on the same course that was used for practice, so that we can 
evaluate retention of walking performance. 
The dual-task walking assessment will also be repeated. 
 
 
 
___________________________________________________________________________ 
Possible Discomforts and Risks: 
As with all physical activity, there is a risk of falling while we test or train walking ability. Falls can 
lead to injuries ranging from minor to serious. When participants are asked to walk on a treadmill 
(e.g., during the H-reflex test described above),  they will wear a safety harness so that they 
cannot fall of the treadmill. The harness will catch the participant, but might still cause injury 
(scrapes or bruises) if there is forceful contact with the straps. It is also possible that participants 
could experience musculoskeletal injury such as an ankle sprain. It is possible that the participant 
may experience fatigue, soreness, and discomfort due to physical activity associated with this 
study. These are unlikely to be worse than what he/she would experience due to increased 
physical activity outside of our study. These are normal responses to exercise and most 
discomfort would generally disappear within a matter of days.  In general, walking exercise is 
strongly recommended for all adults, including elderly adults with medical conditions.  
Transcutaneous spinal direct current stimulation is considered safe but some people might 
experience some side effects.  The most common side effects are itching and tingling or mild 
discomfort at the area of stimulation.  Whenever an electrical stimulation is applied to the body, 
it could possibly have unexpected consequences. tsDCS will be applied and operated by 
research personnel listed in myIRB (with all required training in human subjects research) who 
have been thoroughly trained in the use and safety of tsDCS by the investigative team. 
Furthermore, we will carefully document any potential adverse reactions. We will closely monitor 
any potential discomfort, irritation, redness, muscle spasms, altered sensation, or changes in 
autonomic function due to tsDCS with questionnaires conducted at each session and also with a 
follow-up phone call. 
 
Textured insoles are generally safe, although we will impose exclusion criteria related to foot 
health including prior history of foot ulcer, present signs of broken skin or blisters, and/or 
structural deformity causing major pressure points on the sole of the foot.  If necessary, the 
textured insoles can be trimmed or particular regions can be sanded down to avoid irritating 
sensitive areas on the sole of the foot. The participants’ feet will be visually examined prior to 
and following the assessment, and the participant will be interviewed about any potential 
discomfort. Any noteworthy issues will be recorded. 
fNIRS is considered safe. The infrared light used in assessment is not known to cause any harm 
or to alter the brain in any way.  The sensors are secured to the participant’s head using adhesive 
tape, which may cause minor skin irritation in some people, particularly those who are 
sensitive/allergic to adhesives.  We will check with participants about any known sensitivities to 
adhesives. 
There is a risk that participants may find cognitive and functional tests challenging or 
uncomfortable if they have difficulty succeeding with the tasks.  Participants may skip any 
question that they do not wish to respond do. 
 
8. Possible Benefits: 
 

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There is no direct benefit to the participant. 
 
9. Conflict of Interest: 
 
None. 
 
____________________________________________________________________________ 
Data and Safety Monitoring Plan 
 
Adverse Event Reporting 
Adverse events (including expected, unexpected, serious and non-serious) will be tracked in a 
cumulative table. Adverse events will be reported according to the guidelines of the University of 
Florida Institutional Review.  Specifically, adverse events that are serious and unexpected (see 
definitions below) will be reported to the UF IRB within 5 working days of when study personnel 
learned about it.  Reports of adverse events that are not serious or that are expected (e.g., 
muscle soreness) will be added to the cumulative adverse event table and reported to the UF 
IRB annually. 
A serious adverse event is any adverse event that results in any of the following outcomes:   
• death,  
• a life-threatening adverse event,  
• inpatient hospitalization or prolonging existing hospitalization,  
• a persistent or significant disability/incapacity,  
• or a congenital anomaly/birth defect.   
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse event when the event may jeopardize the 
patient or subject and/or may require medical or surgical intervention to prevent one of the 
outcomes listed in the definition above. 
An unexpected adverse event is any adverse event that is not consistent with the current 
investigator brochure, protocol, consent form, or is not part of the normal disease progression.  
In addition, known adverse events may occur more frequently than expected.  If so, then this 
meets the definition of “unexpected” and must be reported to the IRB. 
Protection Against Risk 
Staff training:  All personnel will be thoroughly trained in the study procedures by the Principal 
Investigator or other appropriate member of the research team, and will complete all required 
trainings concerning human subjects research at the University of Florida. 
Health monitoring and medical response: Volunteers at risk of health problems due to recent 
history of medical conditions (e.g., serious cardiac or pulmonary conditions) will be excluded, as 
noted above in the inclusion/exclusion criteria.  Any adverse events will be recorded and 
monitored as required by our University of Florida Institutional Review Board. In the event o fa 
medical emergency at the VA Hospital (our study site) we will call the hospital emergency 
response line, 6-9-1-1 and alter them to a code blue (medical emergency). Subjects will be able 
to terminate a study session at their request at any time without prejudice. Minimization of risk 
during neurorehabilitation and assessments will be accomplished by monitoring vital signs, with 
prescribed criteria for termination of the testing session.  Vital signs will be monitored before, 
during and after assessment.  Contraindications for participation will include resting heart rate 
>100 bpm or <50 bpm, resting systolic blood pressure >180 mmHg or <100 mm Hg or resting 
diastolic blood pressure >100 mmHg.  Indications to terminate physical activity will include heart 

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rate that exceeds age-predicted maximum (220-age), sudden drop in heart rate exceeding 15 
bpm, systolic blood pressure >220 mmHg or <100 mmHg, or diastolic blood pressure >110 
mmHg.  Other criteria for termination include subject complaints of shortness of breath, light-
headedness, dizziness, confusion, severe headache, dyspnea or onset of angina.  Should the 
session be halted, the subject will be asked to rest while BP and HR are monitored and will 
resume only if BP and HR return to acceptable values. If any of these conditions persist after 
rest, the patient’s primary physician will be called and patient referred for evaluation. If the 
patient complains of angina at rest, loss of consciousness occurs, or cardiac arrest, emergency 
medical services through 911 will be called immediately.  Portable defibrillators are available. 
Confidentiality:  Data will be used only in aggregate and no identifying characteristics of 
individuals will be published or presented. Confidentiality of data will be maintained by using 
research identification numbers that uniquely identify each individual. Safeguards will be 
established to ensure the security and privacy of participants’ study records. Appropriate 
measures will be taken to prevent unauthorized use of study information. Data other than 
demographic information will not use names as an identifier. The research ID number will be 
used. The research records will be kept in a locked room in the study site. The files matching 
participants' names and demographic information with research ID numbers will be kept in a 
locked file that uses a different key from that of all other files. Only trained and certified study 
personnel will have access to these files, and they will be asked to sign a document that they 
agree to maintain the confidentiality of the information.  Electronic records will be stored on 
password protected network server maintained by the university information technology 
department.  In compliance with the Health Insurance Portability and Accountability Act (HIPAA) 
and the Standards for Privacy of Individually Identifiable Health Information of the Department of 
Health and Human Services, we access personal health information and medical records only 
after receiving signed informed consent. 
Safety during walking:  The intensity and duration of walking activity will be carefully monitored 
to ensure that it is appropriate to the participant’s capabilities. Participants will wear a gait belt 
during walking, which will better enable the therapist and/or assistants to provide support in the 
event of a loss of balance.  Falls will be tracked on the therapy log and reported to the PI and 
IRB even if there is no injury associated. 
tsDCS Safety:  Our protocol uses stimulation parameters that are considered standard practice, 
and have been used safely in prior research. The most common side effects of tsDCS are slight 
itching, tingling, and reddening of the skin under the electrode. Participants typically habituate to 
itching or tingling sensations within 60 seconds of stimulation. To minimize risk associated with 
tsDCS, participants will be monitored throughout stimulation sessions and asked to report any 
discomfort. If stimulation sensation is uncomfortable, the stimulation levels will be decreased to 
a comfortable level or will be stopped. 
fNIRS Safety: fNIRS poses no safety risk. Infrared light from the fNIRS device is not harmful and 
elicits no sensation. Sensors may be secured to the skin using adhesive tape, which could lead 
to mild skin irritation in those who are sensitive to adhesives. If a person indicates or displays 
such a sensitivity, we will avoid using adhesive tape and instead use elastic fabric or straps to 
secure the sensors. 
Questionnaire administration: Questionnaire data are collected in secure spaces where the 
interview cannot be overheard. Participants will be informed that they are not required to answer 
questions that they do not wish to answer. 
 
Statistical Analysis Plan: Effect sizes for between-group differences will be calculated for 
improved walking speed after the practice period. For Hypothesis 1b, an analogous comparison 

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will be made for the 2-day retention test. We do not claim that this study is powered to conduct 
statistically significant tests of group differences, although we will examine our data for evidence 
of directional effects: 
 [active/textured]   >   [active/smooth = sham/textured]   >   [sham/smooth]. 
Rather, our goal is to calculate effect sizes and variance of response in order to provide data 
needed for powering a future full scale trial. This study will also provide information on the 
feasibility of our protocol including safety and recruitment. 
 
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