Transcutaneous Spinal Direct Current Stimulation to Enhance Locomotion After Spinal Cord Injury
Phase: NA
Conditions: SCI - Spinal Cord Injury, Incomplete Spinal Cord Injury
Sponsor: University of Florida

 
 
 
 
 
 
 
 
 
 
Transcutaneous Stimulation to Enhance Walking after Spinal Cord Injury 
 
ClinicalTrials.gov# NCT 03702842 
 
 
Principal Investigator 
Emily J Fox, DPT, MHS, PhD 
ejfox@phhp.ufl.edu 
 
 
 
 
 
 
 
 
Document History: Original IRB-approved protocol, version 4.25.2019 
IRB protocol 2018-1582 
 
 
This document contains proprietary information.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
1. 
Title: Transcutaneous spinal direct current stimulation to enhance locomotion after 
spinal cord injury 
 
2. 
Investigators: 
 
Principal Investigator: 
 Emily Fox, DPT, PhD, NCS 
 
Co-Investigators and study staff: 
 David Clark, ScD 
 Geneva Jacobs (Tonuzi), MD 
 Lou DeMark, DPT, NCS 
 Arian Vistamehr, PhD 
 Kathryn Doughty (Cavka), DPT, NCS 
 Kelly Hawkins, DPT, NCS 
 Christy Conroy, MSPT 
 Gina Brunetti, DPT, NCS 
 Kayla Blunt, BS 
 Paul Freeborn, BS 
 
3. 
Abstract:  
 
Locomotor training is a well-established rehabilitation strategy that promotes 
walking recovery after ISCI.1-4 A primary objective of this approach is to promote recovery 
of spinal locomotor circuitry through excitation from descending motor signals and 
afferent somatosensory inputs to the spinal cord.5,6 Following locomotor training, 
individuals with ISCI often demonstrate improved walking function.1,3,7,8 However, most 
people with ISCI continue to have serious walking impairments that limit mobility, 
community participation and quality of life.2,7,9 A key limitation of current rehabilitation 
approaches, including locomotor training, is insufficient excitation of spinal locomotor 
circuitries.6,10,11 Excitation is needed to drive neuroplastic recovery. Since the majority of 
SCIs are incomplete, a promising strategy to promote spinal excitation is to use adjuvant 
approaches that leverage spared pathways and the intact afferent pathways below the 
level of the lesion.5,12,13 Transcutaneous spinal direct current stimulation (tsDCS) is a 
neuromodulatory approach that uses mild and non-invasive electrical stimulation.14,15 
tsDCS induces immediate and lasting changes in spinal cord excitability14,16-18 and alters 
reflexive and voluntary behaviors in rodents.19 Likewise, in humans, tsDCS modulates 
spinal reflexes,20 increases corticospinal excitability,21 and increases motor unit 
recruitment.22 Although ample mechanistic evidence suggests that tsDCS could 
substantially enhance the therapeutic effect of locomotor rehabilitation, this combinatorial 
approach has not been evaluated in humans with SCI. We propose a proof-of-concept 
study to investigate the effects of tsDCS on locomotor function and rehabilitation 
outcomes in individuals with ISCI. The immediate effects of tsDCS will be examined by 
testing changes in muscle activation, walking kinematics and spinal reflex excitability after 
a single period of tsDCS application. Furthermore, we will test the hypothesis that tsDCS 
applied during a regimen of locomotor training will improve the functional walking 

outcomes achieved. Results of this pilot project may contribute to the development of a 
combinatorial rehabilitation strategy that leverages current best practice and a novel non-
invasive neuromodulation approach to enhance recovery of walking after ISCI. 
 
4. 
Background: 
 
Locomotor training is a well-established rehabilitation strategy that promotes 
walking recovery after ISCI.1-3,7-9,23-27 Locomotor training emphasizes repetitive and task-
specific practice of coordinated walking, often with therapist assistance or cueing to 
promote high quality movement patterns. A primary objective of this therapy is to promote 
neuroplastic recovery of spinal locomotor circuitry through excitation from descending 
motor signals and afferent somatosensory inputs to the spinal cord.5,28 Somatosensory 
inputs include limb loading and hip extension, which are known to elicit afferent volleys 
that are important for facilitating propulsion and swing initiation, respectively.29-34 
Following locomotor training, individuals with ISCI often demonstrate improved walking 
function.1-3,7-9,23-27 However, most people with ISCI continue to have serious walking 
impairments that limit mobility, community participation and quality of life.1-3,7,9 Adjuvants 
that increase spinal excitation during locomotor training may enhance the effectiveness 
of this therapy.6,35  
A key limitation of current rehabilitation approaches is insufficient excitation of 
spinal locomotor circuitries.6 Excitation is necessary to drive Hebbian learning and 
activity-dependent neuroplasticity. Since the majority of spinal cord injuries are 
incomplete, a promising strategy for promoting excitation of the spinal cord is to use 
adjuvant/combinatorial approaches that leverage spared pathways and the intact afferent 
pathways below the level of the lesion.13,28,35 Here we propose to combine 
transcutaneous spinal direct current stimulation (tsDCS) with locomotor training to 
increase spinal excitation and thereby increase the effectiveness of locomotor 
rehabilitation. tsDCS is a neuromodulation approach that uses a mild electrical current to 
alter the membrane potential of spinal neurons.18,36 We propose to use an electrode 
montage that has been shown to induce a net depolarization, thereby bringing neurons 
closer to their discharge threshold.21,22 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/somatosensory 
pathways.37 This combinatorial strategy is particularly promising because tsDCS is a 
relatively simple, non-invasive approach that realistically could be implemented in clinical 
settings. Overall, accumulating evidence indicates that a combined tsDCS strategy is 
likely to be effective and is a critical next step in advancing neuromodulation for locomotor 
rehabilitation.  
 
tsDCS modulates spinal reflexes and locomotor circuits. tsDCS involves the 
delivery of a mild constant direct current over the spinal cord through surface electrodes. 
This approach is noninvasive, relatively simple and well tolerated. tsDCS can induce 
immediate and lasting changes in spinal cord excitability16,38,39 and can alter reflexive and 
voluntary behaviors in rodents.19 During locomotion, tsDCS has been shown to modulate 
both alpha and gamma motor neuron activity and improve rhythmic motor output.19 
Specifically, tsDCS has been reported to modulate somatosensory input and improve the 
coordination and amplitude of muscle activation during treadmill locomotion.19 Human 

data indicate that tsDCS increases corticospinal excitability21 and motor unit 
recruitment.22  
 
tsDCS also modulates spinal reflexes in humans18,36,40,41 which may be beneficial 
for improving walking function after ISCI.15 After ISCI, spinal reflexes are altered and poor 
reflex modulation contributes to walking impairments.42,43 For instance, reflex hyper-
excitability and reduced post-activation depression of the Hoffman reflex (H-reflex) 
contributes to over-activation of the ankle plantarflexors during walking.44-46 tsDCS has 
been shown to increase post-activation depression in heathy individuals,47 suggesting 
tsDCS could have a beneficial effect on walking function in adults post SCI. These effects 
may be even greater when combined with walking rehabilitation since walking 
rehabilitation is also known to modulate spinal reflexes by increasing post-activation 
depression48,49 and improving reflex modulation during walking.6,46,50  
Overall, studies of tsDCS support its use as a neuromodulatory approach. The 
next important step is to test whether this approach can substantially augment the 
effectiveness of locomotor rehabilitation and improve the neuromuscular control of 
walking in individuals with ISCI and other neurological conditions.51 Also noteworthy is 
that the potential efficacy of tsDCS is supported by a parallel body of evidence from direct 
current brain stimulation, which shows gains in motor and cognitive function for 
neurologically-impaired populations such as adults post-stroke.51-54  
 
5. 
Specific Aims: 
 
Specific Aim 1 (Cross-sectional): To test the hypothesis that tsDCS applied during walking 
will improve muscle activation and lower limb kinematics in adults with chronic ISCI. A 
random order, double blind cross-over study will be conducted across two test sessions 
to compare the immediate effects of two dosages of tsDCS during walking. The higher 
dosage of tsDCS aligns with previous research protocols, while the lower dosage can be 
effectively be viewed as sham stimulation. Bilateral lower extremity surface 
electromyograms and 3-dimensional kinematics will be recorded. Outcomes will be 
changes in muscle activation amplitude and timing, and hip joint excursion during walking. 
tsDCS induced changes in spinal excitability, as measured by tests of the Hoffman reflex 
(H-reflex), also will be assessed.  
 
Specific Aim 2 (Interventional): To test the hypothesis that tsDCS applied during 16 
sessions of locomotor training will improve functional walking outcomes. Participants will 
be randomized to receive 16 sessions of tsDCS at one of the two dosages with locomotor 
training. Primary functional outcomes will include standardized clinical tests of walking 
speed and endurance. Secondary outcomes will include quantifying changes in muscle 
activation amplitude and timing, lower limb kinematics and the cortical control of walking 
during over ground walking.  
 
6. 
Research Plan: 
 
Recruitment 
 
A minimum of eight individuals are required to complete this pilot study. We aim to 
screen 30 individuals and enroll 20 subjects in this study. The target population will be 

individuals with SCI. Study procedures will take place at Brooks Rehabilitation, which 
includes a clinical research facility directed by Dr. Emily Fox (Principal Investigator). 
Potential participants will learn about the study and be recruited in the following primary 
ways: 
 
1.  Local advertisements or study flyers (see Recruitment Methods attachments 
for study flyer and email script for potential participants). Individuals may 
contact study personnel at Brooks Rehabilitation. Study staff will be available 
to answer any questions and if the potential participant is interested, the 
individual will be screened for eligibility (screening process detailed below). 
 
2.  Health care providers at Brooks Rehabilitation or other clinics in the north 
Florida area (e.g. physicians, physical therapists, or occupational therapists) 
(see Recruitment Methods attachments for email script for healthcare 
providers). Health care providers may ask potential participants if they would 
like to learn more about a current research study. If interested, the potential 
participants will be provided with a flyer, which will contain instructions for 
contacting the study staff at the Brooks Rehabilitation Motion Analysis Center. 
Study staff will be available to answer any questions and if the potential 
participant is interested, the individual will be screened for eligibility. 
 
3.  Additionally, the health care provider may ask the potential participant if they 
are interested in being contacted by a study staff member regarding this 
research study (see Recruitment Methods attachments for authorization to 
release patient information form). If written authorization is provided by the 
potential participant, the health care provider will request his/her name, 
telephone number, and email address in order to be contacted by the study 
staff directly. This recruitment strategy will be necessary to help facilitate 
communication between the potential participant and the study staff. Study 
staff will contact the potential participant and answer any questions. If the 
potential participant is interested, the individual will be screened for eligibility.  
 
4. Individuals admitted to Brooks Health System. All individuals admitted to 
Brooks Health System sign a Brooks Notice of Privacy Practices upon 
admission which indicates their information may be used for research (see 
Recruitment Methods section attachments for Brooks Notice of Privacy 
Practices). This is a standard practice for the Brooks Health System facilities. 
We have attached this form to the Recruitment Methods section. For 
individuals who sign this form, Brooks Research Recruitment personnel have 
permission to access their medical records for research-related purposes. 
Therefore, Brooks Research Recruitment personnel would be aware of our 
study (as it is being conducted at a Brooks facility) and would include this as 
one of several potential research study opportunities when contacting Brooks 
patients. This procedure is independent of our research study procedures and 
is carried out by Brooks Research Recruitment personnel; potential 
participants will only be contacted for screening for this specific study if they 
indicate to Brooks Research Recruitment personnel that they want to learn 
more about our study.  

Screening and Enrollment 
Individuals who are interested in participating in the study will be asked to complete a 
three-step screening process to determine if they are eligible to participate. Informed 
consent will be obtained twice- once during screening and, if enrolled for the full 
study, a second time for the study procedures. Individuals will have ample opportunities 
to ask questions about the study prior to enrollment. 
 
The screening procedures will verify the participant meets the following inclusion and 
exclusion criteria: 
 
Inclusion criteria 
1) Male or female, ages 18-65 
2) Single spinal cord injury (duration >1 year) classified as neurologic level T12 or 
above based on the International Standards for the Neurologic Classification of 
Spinal Cord Injury, and classified on the American Spinal Cord Injury Association 
(ASIA) Impairment Scale (AIS) as ‘C’ or ‘D’ motor incomplete 
3) Capable of ambulating 10 feet with or without the use of gait devices, braces, or 
the assistance of one person 
4) Medically stable with no acute illness or infection 
5) Able to provide informed consent 
Exclusion criteria 
1) Current diagnosis of an additional neurologic condition such as multiple sclerosis, 
Parkinson’s disease, stroke, or brain injury 
2) Presence of unstable or uncontrolled medical conditions such as cardiovascular 
disease, myocardial infarction (<1 year), pulmonary infection or illness, renal 
disease, autonomic dysreflexia, infections, pain, heterotopic ossification 
3) Cognitive or communication impairments limiting communication with study staff 
or ability to provide informed consent 
4) Lower extremity joint contractures limiting the ability to stand upright and practice 
walking  
5) Skin lesions or wounds affecting participation in walking rehabilitation  
6) Acute or unstable fracture, diagnosis of osteoarthritis or bone impairments 
affecting safe participation in walking rehabilitation 
7) Severe spasticity or uncontrolled movements limiting participation in walking 
rehabilitation  
8) Body weight or height that is incompatible with safe use of a support harness and 
body weight support system  
9) Pain that limits walking or participation in walking rehabilitation 
10) Current participation in rehabilitation to address walking function 
11) Botox injections in lower extremity muscles affecting walking function within 4 
months of study enrollment 
12) Legal blindness or severe visual impairment 
13) Known pregnancy 
14) Implanted metal hardware of the spine below the 8th thoracic vertebrae 
 

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, a small deviation from the requirement for 
the participant to walking 10 feet with minimal assistance (i.e. able to walk 8 feet) may 
be permitted if they demonstrate the capacity to complete the testing and training. This 
is important to ensure that individuals are not excluded for insignificant reasons and to 
facilitate meeting enrollment benchmarks. 
 
Step one- phone screening 
Once a potential participant makes contact with study staff through one of the above-
mentioned means, an IRB-approved phone script and screening form will be used to 
guide the phone screening process (see Recruitment Attachments for phone screening 
script). Depending on preference, we can also conduct this screening in person. The 
screening form, designed to avoid collection of protected health information, will ask 
subjects general information about their eligibility. This information may include health 
status, physical functioning, history of neurologic impairments, the date of their SCI, 
movement and sensory impairments, other secondary medical conditions and other 
information pertaining to inclusion/exclusion criteria. If any potential participant is 
deemed ineligible for the study during this or a later step of the screening process, all 
study documentation that had been collected regarding the individual will be destroyed. 
If an individual passes step one of the screening process and would like to continue with 
the screening process, participants will be informed of the on-site screening (step two) 
and medical screening (step three) processes. 
 
Step two- on-site screening 
Participants will be asked to come to Brooks Rehabilitation for the on-site screening. At 
the beginning of this visit, informed consent will be obtained, using the ICF-Screening 
form for guidance, to inform the individual of the purpose, procedures, possible 
benefits/risks, alternative to the screening process, and how the individual’s protected 
health information will be collected, used, and shared with others. The potential 
participant will have the opportunity to review the ICF-Screening and a study staff 
member will be available to answer questions. We anticipate that some potential 
participants may want to meet with study staff ahead of time to discuss the screening 
and study procedures. If so, the informed consent process for the screening may occur 
on a separate day based on the preference of the potential participant. 
 
The screening will involve clinical tests of motor function (i.e. clinical tests of strength) 
and functional mobility tasks such as standing and walking. The potential participant will 
be asked about any conditions of pain and we will confirm any details pertaining to their 
health and functioning to verify their ability to perform locomotor training (condition of 
skin, range of motion, spasticity). The following tests, or portions of them, may be used 
to objectively measure the participant’s status and confirm eligibility for enrollment: 

 International Standards for the Neurological Classification of Spinal Cord 
Injury (INSCI) examination- The ISNCSCI is a standardized assessment used 
to determine the motor and sensory impairment  and severity of a spinal cord 
injury (previously known as the ASIA examination based on the American 
Spinal Injury Association).55 
 Spinal Cord Assessment Tool for Spastic Reflexes (SCATS)- The SCATS is 
a reliable and valid tool for assessing spasm activity of flexor and extensor 
muscle groups as well as spastic hypertonia in patients with spinal cord 
injury.56  
 Brief Pain Inventory (BPI)- This validated self-report questionnaire assesses 
pain severity and its impact on function.57 The BPI items are a more 
comprehensive measure of pain interference compared to some other 
measures in the SCI population.58 
 10-Meter Walk Test (10MWT)- This validated measures assesses forward 
walking speed.59,60 
 Vital signs- To assess participant safety and responses to study procedures, 
we will monitor blood pressure, heart rate, respiratory rate and pulse oximetry 
during study procedures. Establishment of baseline readings and monitoring 
of cardiopulmonary responses will allow for assessment of abnormal 
responses such as autonomic dysreflexia.61 
 
Female subjects of potential childbearing age will be asked to take a pregnancy 
test. Furthermore, participants will be instructed that they should take precautions 
against becoming pregnant during the study because the fetal risks associated with 
tsDCS are unknown. If a participant learns that she is pregnant, she must withdraw from 
the study immediately. All test outcomes will be recorded on the On-Site Screening 
Form (see Information Sources and Identifier attachments). If participants complete the 
on-site screening, are deemed eligible and wish to pursue enrollment in the study, the 
participant will proceed to the medical screening step. They will also be provided with 
the informed consent form for the full study (ICF- Intervention) so that they may review 
this information ahead of time. 
 
Step three- medical screening and physician approval 
Medical records will be obtained using the Medical Record Authorization form (see 
Information Sources and Identifier attachments). This form will be provided to the 
potential participant requesting their date of birth and signature to allow release of their 
medical records. Once the records are received, study staff will perform a medical 
record screen using the Medical Record Screening Form (see Information Sources and 
Identifier attachments) to verify the potential participant meets enrollment criteria. The 
study physician will oversee this process. In addition to the medical record screen, a 
written confirmation of medical approval by a physician, using the IRB-approved 
Physician Approval Letter/Form (see Information Sources and Identifier attachments), 
also will be required to indicate the potential participant is medically safe to participate in 
study procedures and does not have known medical conditions that violate the 
enrollment criteria. 
 

If an individual completes and passes all three steps of the screening process, the 
participant can then choose to enroll in the full study. The informed consent form (ICF-
Intervention) will be provided at the completion of the screening visit to allow potential 
participants to time to review the document in advance. Generally, the individual will be 
informed of the study purpose, procedures, possible benefits/risks, the alternatives to 
being in the study and how the individual’s protected health information will be collected, 
used, and shared with others using the ICF-Intervention as a guide. Participants can 
either complete the informed consent and begin study procedures on the same day or 
study staff will schedule a separate time for the individual to complete the informed 
consent and enroll in the study. 
 
Study Procedures Overview 
For Aim 1 (immediate effects of tsDCS), participants will complete two separate testing 
sessions, presented in random order, that involve up to 30 minutes of tsDCS at one of 
the two dosages while walking. We will assess changes in muscle activity, kinematics and 
spinal excitability before and at the end of the period of walking. The two sessions will last 
about 3 hours and no longer than 6 hours and will take place at least 48 hours apart to 
allow for wash-out of stimulation effects. 
 
For Aim 2 (effects of tsDCS applied with locomotor training), participants will be 
randomized to receive 16 sessions of locomotor training with tsDCS at one of the two 
dosages. Each intervention session will last about 1 hour and no longer than 2.5 hours. 
Before and after the 16-session intervention (i.e., at baseline and post intervention), we 
will assess functional outcomes through standardized clinical tests of walking speed and 
endurance, as well as changes in muscle activity, kinematics and spinal excitability. We 
will also examine the participant’s spasticity and pain using standardized assessments. 
Each assessment session will last about 3 hours and no longer than 6 hours.  
 
 
 
Overall, the testing and intervention procedures of this study will be as follows (see Fig. 
1 for details): 

1. Aim 1’s first visit will consist of clinical testing and collection of basic demographic 
information (see Information Sources and Identifier attachments for demographics 
form) to characterize the participant. Neuromechanical assessments of walking 
and reflex testing prior to and after 30 minutes of tsDCS at one of the two dosages 
delivered while walking on a treadmill will be conducted. 
2. Aim 1’s second visit will involve identical procedures for stimulation and 
neuromechanical assessments as compared to visit 1 except for crossover of the 
tsDCS dosage. It will also include any clinical testing not completed on day 1. 
3. Aim 2’s pre-test will consist of neuromechanical assessments of walking and reflex 
testing as well as clinical assessments of pain, spasticity, and physical function. 
4. 16 sessions of locomotor training will be conducted over 4 weeks with one of the 
two dosages of tsDCS applied during the training. 
5. Aim 2’s post-test will repeat the measures completed at pre-test. 
 
A physical therapist will oversee study procedures. Vital signs, such as blood pressure, 
heart rate and blood oxygen saturation, will be monitored for safety.  Rest breaks will be 
provided at regular intervals and at any time the participant requests. Participants will be 
informed that they may choose not to perform any aspect of the study. We will adjust the 
assessment protocol, outlined below, as needed in response to our participants, such as 
reducing the assessments due to fatigue or individual tolerance. 
 
Neuromechanical assessments of walking 
Neuromechanical assessments, such as the analysis of muscle activation and movement 
during walking, will be conducted during testing for both Aim 1 and 2. During Aim 1, the 
assessments will occur before and after the completion of up to 30 minutes of treadmill 
walking. As most participants will not tolerate 30 minutes of uninterrupted walking, the 
session will be divided with rest breaks as needed to deliver a total of ~30 minutes of 
walking. tsDCS at one of the two dosages will be applied for up to 30 minutes. The goal 
of the protocol is to complete 30 minutes of walking with stimulation. However, we 
recognize that this protocol may need to be adjusted slightly for some individuals based 
on aspects such as comfort or fatigue. During Aim 2, neuromechanical assessments of 
walking will be conducted before and after the 16 sessions of locomotor training. To 
perform these neuromechanical assessments, participants may be asked to perform 
activities such as treadmill walking or overground walking at self-selected or fastest-
comfortable walking speeds, walking backward, and stepping over an obstacle. 
Participants may use any typically used orthotics (i.e. AFOs) or gait assistive devices 
required by the participant.  
 
All testing procedures will be closely monitored by a physical therapist who will monitor 
the participant’s vital signs for safety and provide rest breaks as needed or requested. A 
safety harness attached to an overhead support system may be used when performing 
walking overground. Testing will also occur while walking on a treadmill using a harness 
to secure the participant to an overhead support system to provide partial body weight 
support if needed. Participants may opt not to perform any walking task, and all tasks will 
be adjusted for each participant’s functional level. Study procedures will be explained 
ahead of time and participants will be asked to wear appropriate clothing for participation. 
Participants will be able to sit comfortably during the set-up procedures. During the set-

up, small reflective markers and EMG sensors will be affixed to the skin and will be 
removed at the conclusion of the assessment (details below). 
 
The following procedures will be completed during the neuromechanical assessments: 
 Measurement of joint motions during standing and walking- To quantify trunk 
and lower extremity joint motions, a 12-camera three-dimensional motion 
analysis system will be used to collect marker data and measure joint 
kinematics during walking tasks.62 Small, lightweight reflective markers will be 
placed on the upper and lower extremities and the trunk using an established 
marker set. To reduce artifact and improve accuracy of motion analysis data, 
reflective markers will be placed directly on the skin when possible using 
hypoallergenic double-sided tape. Individuals will be asked to wear tight, 
minimal clothing, such as tank tops and athletic shorts, to provide access to 
bony, anatomical landmarks as able.  
 Recording 
of 
muscle 
activation- 
A 
wireless, 
16-channel 
surface 
electromyography (EMG) system will be used to record muscle activation 
during the standing and walking activities. In the small area over the muscle 
where the sensors will be placed, the skin will be shaved and cleaned with 
alcohol prior to attaching the sensors with hypoallergenic double-sided tape. 
These procedures optimize EMG signals by reducing noise and impedance. 
EMG signals will be recorded using the motion capture software to synchronize 
collection of the EMGs and motion data (kinematics).   
 Assessment of kinetics and spatio-temporal movement characteristics- 
Ground reaction forces (kinetics) will be recorded during the walking activities. 
The participants will be asked to walk over the standard built-in force plates, 
which are flush with the floor and are not an obstacle or tripping hazard. This 
will be done while they also are wearing the EMGs and reflective markers so 
that all data are captured simultaneously. During the session, the participant 
may be asked to stand or walk over a 12’ instrumented walkway (i.e. GaitRite). 
The walkway appears like a flat, carpeted surface and has embedded sensors 
to record foot falls and foot placement. The edges of the walkway will be taped 
down to be nearly flush with the floor and to minimize the possibility of tripping. 
Participants will be guarded at all times and/or an overhead harness may be 
used. The instrumented walkway will provide 
quantitative data regarding the spatial and 
temporal characteristics of standing and walking.  
 Recording of cortical activity- Functional near 
infrared spectroscopy (fNIRS) will be used to 
assess brain/neural activity required for the 
individual to perform the standing and walking 
tasks assessed during the motion capture 
biomechanical testing. fNIRS uses non-invasive 
sensors that are light-emitting diodes to illuminate 
oxygenated hemoglobin 
in 
superficial brain 
tissue.63 This approach is used to indirectly 
quantify neural activity. The sensors are attached 

to a lightweight strap which will be placed around the participant’s forehead to 
monitor neural activity in the pre-frontal cortex. No skin preparation is required. 
The data are transmitted wirelessly to a computer to record the data and for 
future analysis. This information can be used to better understand the cognitive 
and attentional efforts used while performing the walking tasks, which may 
relate to safety and fall risk.  
 
Reflex testing 
To quantify stimulation induced effects on spinal activation, H-reflex assessment of the 
soleus muscle will be conducted according to accepted and widely used methodology.64,65 
First, the H-reflex will 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. Stimulation will be delivered via a cathode placed in the popliteal fossa 
and an anode placed above the patella. EMGs will be recorded from the soleus with 
bipolar surface electrodes placed 3 cm apart. M-waves and H-waves will be recorded 
over a range of intensities to acquire a full recruitment curve, starting at subthreshold 
intensities and increasing until the reflex amplitude reaches a plateau. The range of 
intensities is necessary so that a response equivalent to 50% of Hmax can be elicited for 
use in analyses comparing between individuals.36 Second, modulation of the H-reflex may 
be examined during walking. The cathode and anode will be secured with adhesive tape 
or a self-adhering wrap (e.g., Coband) with care being taken to avoid restricting 
movement of the knee. Mmax will be re-established in the standing position for analysis 
of walking H-waves. During walking, stimulation intensity will be adjusted every 
stimulation to maintain a consistent M-wave amplitude relative to the maximum M-wave 
(M-max). We will visually determine events of the gait cycle to manually trigger every two 
to five seconds and collect H-waves during both mid-stance and mid-swing. 
 
The electrical stimulation for H-reflex testing may be uncomfortable at times, but it is not 
dangerous. The discomfort is temporary and lasts only a few seconds. Evidence of 
stimulation induced effects on spinal excitability will provide insight into the potential 
underlying mechanisms mediating changes in muscle activation and limb control during 
tsDCS and walking. 
 
Clinical assessments 
Clinical assessments will be used to characterize the participants during Aim 1 and to 
examine changes following the regimen of locomotor training in Aim 2. These 
assessments will include: 
 Spinal Cord Assessment Tool for Spastic Reflexes (SCATS)- The SCATS is a 
reliable and valid tool for assessing spasm activity of flexor and extensor 
muscle groups as well as spastic hypertonia in patients with spinal cord 
injury.56  
 10-Meter Walk Test (10MWT)- This validated measures assesses forward 
walking speed.59,60 
 6-Minute Walk Test (6MWT)- The 6MWT is a reliable and valid tool for 
assessing walking endurance.59,60 

 International Standards for the Neurologic Classification of Spinal Cord Injury 
(ISNCSCI)- Clinical tests of sensory and motor function to classify level and 
severity of spinal cord injury (ASIA impairment scale)55 
 30-second Chair Stand Test (30-s CST)- Performance assessment to measure 
functional lower limb muscle strength used to move from sitting to/from 
standing66 
 Activities Specific Balance Confidence (ABC) Scale- Questionnaire to assess 
self-reported balance confidence in varied functional situations such as 
walking in a parking lot or in the home67 
 Neuromuscular Recovery Scale (NMRS)- Performance assessment of 
functional motor recovery such as sitting and standing function68 
 3-meter Backward Walk Test- An assessment of backward walking speed77 
 Postural muscle strength assessment – Seated clinical test of postural muscle 
strength using hand-held force dynamometry78 
 
Delivery of tsDCS 
tsDCS will be delivered to the low back, over the lumbar region of the spinal cord, 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 electrodes will be placed on the participant using a previously established 
configuration to target the lumbosacral cord with two electrodes on the abdomen placed 
to the left and right of the umbilicus and 
one over the lumbar spinal cord at the 
level of the 11th and 12th thoracic 
vertebrae. A large elastic bandage with 
Velcro closure will be wrapped around 
the abdomen to hold the electrodes 
firmly in place. Participants will be 
closely monitored for any adverse 
responses such as skin irritation and 
pain. This electrode configuration has 
been shown to appropriately target the 
lumbosacral spinal cord, as validated 
by modeling of electrical current flow69 and by gains in lower extremity motor 
performance.70 A low dosage of ≤ 2.5 mA stimulus will be used for the “higher” dosage. 
This dosage (or very 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.18,20,21,36,47,70,71 An identical montage and stimulation 
arrangement will be used for the “lower” dosage, except the stimulation will be delivered 
in a brief ramp-like manner for 30 seconds at the beginning and end of the stimulation 
period. The “lower” dosage condition is effectively a “sham” procedure. This approach is 
widely used in the field of direct current stimulation, and has been reported to be 
indistinguishable from the “higher” dosage protocol.20,72 This is because participants 
quickly habituate to the sensation of active stimulation. To assess the effectiveness of our 
low dose/sham stimulation, participants will be asked during Aim 2 post-testing which 

dosage they believe they received and how certain they are of their opinion. They will 
then be informed which dosage they received. 
 
Locomotor training 
Participants will be randomized to either the combined intervention of higher dosage 
tsDCS with locomotor training or lower dosage tsDCS with locomotor training. Each 
participant will receive up to 16 sessions of training with each session including up to 40 
minutes of walking. The goal is to have participants attend 4 sessions per week for 4 
weeks, but the individual schedules might vary. All sessions will be led by a licensed 
physical therapist with experience in walking rehabilitation after ISCI. There will be two 
components to the locomotor training session: 1) body-weight supported treadmill 
locomotor training with tsDCS (LT-TM) and 2) overground walking without tsDCS (OG).   
 
1) LT-TM (30 min):  This portion of the intervention will consist of 30 minutes of  
locomotor training on a treadmill and will follow standard procedures for body-
weight supported treadmill locomotor training that have been published by our 
group and others.3,4,25,73 tsDCS, as described above, will be applied during 
body-weight supported treadmill locomotor training. Briefly, participants will 
walk on a treadmill with verbal feedback and manual assistance provided by 
training staff. This assistance is provided as needed to help move the leg 
during stepping and/or to maintain stability and balance. Avoidance of falls is 
assured while walking on the treadmill by an overhead body weight support 
safety attached to a trunk/pelvis harness. Body weight support will be set low 
as possible in order to allow balance responses and to afford support only as 
needed. Performance without compensation strategies (hip hiking, leaning to 
one side) will be emphasized. Rest breaks will be provided as needed. 
 
The physical therapist leading the training will monitor for both safety and 
intensity of training. Self-reported level of exertion, based on the Borg scale, 
will be recorded. A chest-worn heart rate monitor will be used to ensure 
sufficient training intensities by encouraging participants to maintain a training 
heart rate between 70-80% of their predicted maximal heart rate. Based on this, 
the target training heart rate will be calculated as (220 – age) * 70. Furthermore, 
the duration of stepping will be tracked and step counts will be measured using 
an ankle-worn accelerometer.25,74-76 This heart rate range is based on recent 
evidence indicating that this intensity is safe and tolerated, and is an important 
factor associated with gains in locomotor function.74 Locomotor training 
parameters, such as walking speed, level of assistance, treadmill incline, body 
weight support and frequency of rest breaks will be adjusted as needed to 
respond to the participant’s exercise tolerance and to advance the training as 
appropriate. A record of both training parameters and participant response will 
be kept in the Daily Training Log (see Information Sources and Identifier 
attachments). All training parameters will be adjusted for participant’s 
tolerance, comfort and safety.  
 
2) OG (10 min):  After completing the training portion described above, the tsDCS 
will be removed and the participant will then practice walking overground for 

approximately 10 minutes.  Assistance of trainers will be provided as needed 
and the participant may use assistive device or orthotics.  Rest breaks may be 
taken at any time. 
 
The intervention sessions will aim to include a total of 40 minutes of stepping time, which 
may take up to 2 hours to complete due to set up time and rest breaks.  
 
Statistical Plan 
A descriptive analysis of demographic data and injury characteristics will be conducted 
using a frequency distribution for categorical data and means for continuous variables. 
These data will be used to characterize general information about the study population. 
Sample size and data distribution will guide statistical analysis. If data assumptions are 
achieved, for Aim 1, we will determine the effects of tsDCS during walking using two-way 
repeated measures ANOVAs. The within factors will be time (before or at the end of 
walking bout) and stimulation (higher or lower dosage tsDCS). We will then examine the 
interaction effect to determine differences in the changes during walking with the two 
dosages of tsDCS. For Aim 2, mixed method ANOVAs will be used to determine the 
effects of tsDCS dosage during locomotor training. The within factor will be time (pre- or 
post-test) and between factor will be group (higher or lower dosage tsDCS). We will then 
examine the interaction effect to determine differences in the improvement during 
locomotor training with the two dosages of tsDCS. Differences will be considered 
significant at p<.05. Data will be analyzed using professional statistical software.  
 
Safety monitoring 
Although numerous studies indicate tsDCS is easily tolerated and no adverse responses 
have been reported,15,51 we will closely monitor participant responses. At each session 
the participant and physical therapist will complete a questionnaire to document any side 
effects such as stimulation site discomfort or skin irritation. While we do not expect any 
issues, we will monitor the skin closely. If any changes are observed beyond mild redness 
or if persistent discomfort is reported, stimulation intensity will be reduced (or 
discontinued, if necessary) during that training session and increased to 2.5mA in 
subsequent sessions if tolerated. Irritation could also occur if the harness is not fitted or 
positioned correctly, so this will be closely monitored and adjustments will be made as 
needed. In accordance with University of Florida IRB policy, adverse events that are both 
unexpected and serious will be reported within 5 working days. 
 
The testing and intervention procedures could be tiring for some individuals.  All 
participants will be given rest breaks and informed that they may rest or terminate their 
participation at any time. Blood pressure (BP) and heart rate (HR) will be monitored during 
each testing and intervention session. BP and HR must be within a medically-acceptable 
range for the participant to participate in a testing or training session. Resting diastolic BP 
must be less than 100mmHg to begin the session. The criteria for termination include 
complaints or symptoms of confusion, dyspnea, onset of angina, excessive blood 
pressure changes (systolic BP greater than 200mmHg or diastolic BP greater than 
110mmHg). In addition, should the participant’s HR exceed 85% of the predicted 
maximum HR or the participant reports a Borg rating of perceived exertion (RPE) rate of 
greater than 17/20, then the session will be slowed and/or halted. If the session is halted, 

the participant will be asked to rest while BP and HR are monitored and will resume only 
when BP and HR return to acceptable values and the participant reports no other 
symptoms. If any of these conditions persist after rest, the participant’s primary physician 
and/or the study physician may be contacted and the participant may be referred for 
evaluation. If the participant complains of angina at rest, loss of consciousness occurs, or 
cardiac arrest, emergency medical services through 911 will be called immediately. 
 
7. 
Possible Discomforts and Risks: 
During the testing procedures, participants may become fatigued. Participants will be 
allowed to rest at any time. To prevent falls, a harness attached to an overhead support 
system may be used during overground testing procedures with any individual that 
requires assistance or who is unsteady. A harness with overhead support will be used for 
any testing that occurs on the treadmill. Despite these safety measures, as with any 
walking activity, there is a risk that participants may lose their balance, stumble or fall and 
experience an injury. While the harness will prevent falling to the ground, it is still possible 
for participants to experience an injury due to the harness catching their body weight 
during the potential fall. 
 
The proposed assessments are routine and pose minimal risk to study participants. These 
techniques have been used extensively for many years in those with functional 
impairments without significant occurrence of adverse events. Fatigue may occur due to 
physical exertion associated with testing, and could result in muscle soreness, but this is 
a normal and temporary response to unaccustomed activity. Sufficient rest will be 
provided to minimize discomfort for participants. Also, heart rate and blood pressure will 
be monitored during testing, as well as signs of autonomic dysreflexia. As noted in the 
“safety monitoring” section above, there is a slight risk of stimulation site discomfort or 
skin irritation from the tsDCS, which will be monitored and adjustments to stimulation 
intensity will be made if necessary. Furthermore, transient discomfort may be caused 
during H reflex testing. There is a slight risk of skin irritation with the use of surface EMG 
electrodes, markers and tape. To avoid skin irritation, hypoallergenic tape will be used 
and the participants’ skin will be inspected periodically during testing procedures.  
 
Some participants may not feel comfortable responding to the questionnaires or telling 
research personnel that they are uncomfortable or fearful of performing a certain activity. 
All questionnaires will be administered in-private with only the research personnel and 
the participant. Participants will be instructed that they do not need to complete the 
questionnaires if they prefer not to. The participant will be informed that they may opt not 
to participate in any of the study procedures. 
 
During the intervention sessions, the participants may also experience fatigue while 
performing locomotor training. While similar to walking, this training occurs at a higher 
intensity to promote neuromuscular changes. The participants will be allowed to rest at 
any time and rest breaks will be incorporated at regular intervals. The risks in undergoing 
locomotor training are minimal and include a loss of balance while walking, a risk of injury 
from falls while walking, experience of an elevated heart rate with exercise, temporary 
muscle fatigue, nervousness when attempting to walk while on the treadmill or off the 
treadmill, muscle strains or sprains, skin irritation from wearing a harness, and skin 

irritation from contact with the trainer’s hands assisting leg movement. Heart rate and 
blood pressure will be checked regularly throughout each session. Participants will be 
monitored for signs and symptoms of autonomic dysreflexia such as high blood pressure, 
flushing and profuse sweating above the level of injury with piloerection and paleness 
below the level of injury, and/or intense headache. Study activities will be carried out with 
the close supervision of a physical therapist and a harness with overhead support will be 
used at all times. As noted above, there could be discomfort or injury associated with the 
harness catching their body weight if a stumble or loss of balance occurs while walking in 
the harness. Parameters of the locomotor training sessions will be adjusted to ensure 
comfort and safety. 
 
Confidentiality and protecting subject privacy 
The risks related to collecting and sharing protected health information and study-related 
data will be addressed in several ways.  First, upon enrollment in the study, a study ID 
will be assigned to the participant so that all study-related information pertaining to the 
subject uses the study ID. The document that links study-IDs to participant information 
will be stored in a separate location, not with the study-related data. The study procedures 
will be conducted in private locations at Brooks Rehabilitation, so that participant privacy 
may be maintained when conducting procedures such as clinical testing, administering 
questionnaires, or answering individual questions.  All study procedures will be conducted 
in limited access areas with minimal traffic and personnel.   
 
Protected health information collected as part of this study will be limited to the minimal 
necessary information to carry out procedures in this approved protocol. All hard-copy 
study related documents will be stored in locked file cabinets in locked offices.   All 
electronic study related information and data will be stored on password protected 
computers and on password-protected institutional servers or encrypted electronic 
storage devices. Only approved study personnel will have access to research records.   
 
For participants who provided consent for photography and/or video, recordings or 
photographs may be obtained during their session.  Recordings or photographs will only 
occur based on the consent provided by each participant. The participant will be informed 
that they may refuse the use of photography or video recordings at any time during the 
procedures. All photographs and videos will be acquired digitally, and stored on computer 
servers with secure passwords, or encrypted electronic storage devices. Photographs 
and/or videos will only be used in the manner that the subject consents to, as indicated 
on the Informed Consent Form (i.e., photos/videos must be destroyed once the study is 
closed; photos/videos may be used as described in the Informed Consent Form, and for 
the purposes of education at UF; or, as described in the ICF, for the purposes of education 
at UF, and for presentations at scientific meetings outside of UF). Photos/videos will be 
used by the study team to review and share study procedures, methods, and 
dissemination of study findings. Videos may also be used to ensure consistency of study 
procedures. 
 
8.        Possible Benefits: 
Health: 

Each participant may or may not benefit from this study. The possible benefits are that 
the participant may experience improvements in walking function. These improvements 
may include increased walking speed, endurance, or increased movement coordination. 
The participant’s balance may improve and they may become more confident in their 
balance and walking ability. Overall ability to perform daily functional activities may or 
may not improve. Such improvements may result from increased standing and walking 
function and/or increased cardiovascular function secondary to daily exercise (i.e. 30 min 
of locomotor training). 
 
Financial: 
Participants will be compensated $20 for each Aim 1 session, $20 each for the Aim 2 pre-
test and post-test and $10 for each Aim 2 intervention session. Payment will be issued 
using a gift card to participants. Thus, upon full completion of all visits, subjects will have 
been provided with $240.00 for their participation in the study. This compensation is for 
the participant’s time and travel to complete the study. Compensation will be pro-rated 
and the participant will be paid on a weekly basis. Participants will not need to complete 
the study to receive payment. 
 
9. 
Conflict of Interest: 
There are no conflicts of interests relating to any of the investigators and this protocol 
beyond the professional benefit from academic publication or presentation of the results. 
 
 

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