Development of a Portable Synergy Resistant EMG-driven FES Device for Intuitive Control of Grasp and Release During Functional Arm Activities Following Stroke
Phase: NA
Conditions: Stroke, Hand Function
Sponsor: Northwestern University

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IRB Protocol STU00072008
Development of a Portable Synergy Resistant EMG-driven FES Device for Intuitive 
Control of Grasp And Release During Functional Arm Activities Following Stroke
Program Director:
Jun Yao, PhD
Northwestern University Feinberg School of Medicine
Department of Physical Therapy and Human Movement Sciences
645 N. Michigan Avenue, Suite 1100
Chicago, IL 60611
Co-Investigators: 
Jane Sullivan, PT, DHS, MS
Julius Dewald, PT, PhD
Northwestern University
Participating Sites: 
Northwestern University Feinberg School of Medicine
Department of Physical Therapy and Human Movement Sciences
645 N. Michigan Avenue, Suite 1100
Chicago, IL 60611
Funding Agency:
National Institutes of Health
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Table of Contents
A.
Importance of the Problem .......................................................................................................3
A.1.
Target population and need ..........................................................................................................3
A.1.1.
Target population.......................................................................................................................................3
A.1.2.
The need.........................................................................................................................................................3
A.2.
Beneficial impact for stroke survivors.......................................................................................4
B.
Design Of Development Activities...........................................................................................5
B.1.
Development Plan.............................................................................................................................5
B.1.1.
Background and Literature Review ...................................................................................................5
B.1.2.
Currently available devices for hand-function rehabilitation following stroke..............6
B.1.3.
Pros and cons for mechanical and NMES devices ........................................................................9
B.1.4.
Gap in the development of the next generation assistive devices ........................................9
C.
Novelty of the proposed ReIn-HAND platform....................................................................9
C.1.
A safe, reliable, intuitive detection of the intention of hand movements during 
functional arm activities ...............................................................................................................................9
C.2.
Portable, subject-dependent configuration, easy-to-setup and low-cost....................10
D.
Specific Objectives .....................................................................................................................10
E.
Selection of Subjects..................................................................................................................11
E.1.
Inclusion and Exclusion criteria................................................................................................11
E.2.
Pre-training Clinical assessments.............................................................................................12
F.
Study Design and Methods......................................................................................................13
F.1.
Lab-based testing............................................................................................................................13
Each PT will be trained for the use of ReIn-Hand by watching a 20-min video, and practice the 
use of ReIn-Hand under the supervision of the research PT, Dr. Carmona, who is experienced in 
using ReIn-Hand device. ...............................................................................................................................13
F.1.1.
A. Pre-training non-EEG Experimental protocols......................................................................13
B. Pre-training EEG Experimental protocols.....................................................................................................13
F.1.2.
The 1st and 2nd lab-based training with ReIn-Hand (2 visits)...............................................14
F.2. Home-based practice ...........................................................................................................................15
F.3. Data collection and procession ........................................................................................................15
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A. Importance of the Problem
A.1.Target population and need 
A.1.1. Target population
The target population of this development is individuals impaired by moderate to severe stroke. 
Stroke, which affects approximately 795,000 people annually, is currently the third ranking cause 
of death and one of the leading causes of disability in adults2.
Since innovative scientific research and improved medical techniques have increased the life 
span of stroke survivors, the incidence and mortality rates of stroke have decreased. However, the 
number of individuals permanently disabled by stroke continues to increase. Sensorimotor deficits 
and restricted mobility are among the more common problems following stroke. Studies of stroke 
survivors six months post-stroke and greater than 65 years of age indicate that 50% experience 
persistent hemiparesis and 26% were dependent in activities of daily living3. The majority of stroke 
survivors report that impaired upper extremity (UE) function, especially the hand, is a major 
problem4.  At 3 months post-stroke only 20% have normal arm function5. The trend toward 
increasing numbers of stroke survivors living with disability suggests that more attention needs to 
be directed towards investigating methods to regain the lost function by reducing the residual 
impairments and secondary complications associated with stroke. 
Years of research results suggest that the intensity and functionality of practice appear to be 
critical elements of successful interventions to improve hand function6-14. Distal arm function 
seems critical to successful integration of the arm into routine daily activities. Individuals with 
moderate to severe arm impairment often lack hand function; and despite proximal arm movement 
they typically do not incorporate the affected arm in function. The evidence for critical 
rehabilitation parameters of intensive task-based functional practice and the reality of that a large 
number of stroke survivors lack sufficient arm movement to engage in this type of practice creates 
a clear gap and unique challenge to rehabilitation professionals. Therefore, hemiparetic stroke 
survivors who have some shoulder and elbow control but lack of basic hand function, i.e., the 
paretic hand cannot even perform the most basic function like grasp and release, are the targets of 
this development proposal (Fugl-Meyer Motor Assessment Scores for UE of 10-40/66). 
A.1.2. The need
The need is to fill the identified gap, and thus creating a chance for our target population 
regaining their UE function. Unfortunately, for the severely affected UE, the evidence for 
conventional therapy on regaining meaningful hand function is poor. Furthermore, due to the 
shortened inpatient rehabilitation stays and reduced funding for outpatient rehabilitation, therapists 
may be forced to focus less on the use of the UE15. All these requirements and realities point out 
that we need an assistive device that allows our target population to Reliably and Intuitively use 
their HAND (ReIn-HAND) during therapy and at home during daily functional arm activities. 
However, currently there is no such an assistive device available, mainly due to the lack of a real 
time platform that can reliably detect a user’s intention (see the review of current assistive devices 
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in section 1.1.2). The development of such a platform combining with a right assistive device 
would regain basic hand function and be highly beneficial to this population.
We have identified four specific requirements (needs) for this real time platform: 1) a non-
invasive interface providing control for the most basic hand function, i.e., grasp and release; 2) an 
intuitive control meaning that the control signal comes from intent of the subject for moving the 
paretic hand; 3) a safe and reliable detection allowing the usage of the paretic hand during 
functional arm activities; and 4) clinical utility including portability, individualized configuration, 
easy setup and low-cost. 
In addition, due to shortened inpatient rehabilitation stays and reduced funding for outpatient 
rehabilitation, therapists have been forced to focus less on the use of the upper extremity15. It is not 
uncommon for stroke survivors to find that once they are ready to work on arm recovery, there is no 
service available or they are no longer eligible16. Barriers like limited resources, transportation, 
assistance, etc. make a compelling argument for a device that is easy-to-use, low-cost, and thus 
employable at home.
Finally, although commonly we believe that recovery plateaus at ~12 months post-stroke, there are 
cases reporting arm/hand function recovery after intensive task-specific intervention in chronic stroke 
survivors17,18. It is therefore proposed that a plateau in motor performance should be re-interpreted as a 
cue to implement new therapy, such as using home-based task-specific device-mediated therapy, rather 
than cease it19. The proposed device will enable us to test whether such a therapy can improve basic 
hand and as a consequence upper extremity function in individuals with moderate to severe stroke. If 
positive, the results can benefit large population of stroke survivors. 
A.2.Beneficial impact for stroke survivors
The majority of stroke survivors report that impaired UE function, especially the hand, is a 
major problem that results in significant functional deficits, often leading to total disuse4. Currently 
there is no effective intervention that can restore basic hand function for individuals with moderate 
to severe stroke. The current proposal seeks to demonstrate that the combination of an intelligent 
detection, the ReIn-HAND platform, and an artificial control device, ‘RECLIAM’ electrical 
stimulator, will allow for possibility of using the paretic hand and arm during activities of daily 
life for this population. Although many different hand-movement aid devices are available on the 
market now, none of them meets all the requirements identified previously (see the next chapter 
for review for the currently available devices). If successful, this proposal will provide a much-
needed scientifically-based rehabilitation platform, accessible for use in the clinic and home, both 
for assistive and therapeutic purposes to regain hand/arm function following stroke. Such a 
platform will have a great impact on current neuro-rehabilitation patient management by providing 
the ability to deliver effective interventions. 
Given that the concepts embedded in the proposed ReIn-HAND real time platform have 
been shown to be effective to increase arm/hand function, the commercial viability of this 
development proposal is substantial. Improvement in functional usage of the impaired upper 
limb in stroke survivors, through the use of an assistive device incorporating ReIn-HAND, 
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may have a direct positive impact on their self-image, life satisfaction, interaction with family 
and environment, and re-integration into society.
B. Design Of Development Activities
B.1.Development Plan
B.1.1.  Background and Literature Review
The loss of basic hand function control following stroke --- physiological reasons, rehabilitation 
and possible solutions 
Hand impairment is one of the leading causes of major, long-term disability following stroke. 
A number of factors contribute to the hand impairment, including abnormalities of muscle tone 
(identified as spastic hypertonia or spasticity), muscle weakness, and disturbances of muscular 
coordination (abnormal muscle and torque synergies). An individual with moderate to severe 
stroke usually experiences difficulty in activating hand muscles, especially wrist/finger 
extensors20-22.  Another commonly observed change in EMG activation following stroke is an 
increased coactivation between antagonist and agonist muscles23-25. Reflex coupling between 
proximal and distal muscles of the upper limb has also been well reported26-29. More prominently, 
studies in both primates30-32 and human subjects22,33 indicate wrist/finger flexors are usually overly 
activated followed stroke, causing hand release to be even more difficult than grasp. 
Although the pathophysiology behind all above features is not fully understood, we believe it 
is primarily due to the loss of corticospinal tract (CST) innervation of relevant motoneurons, and 
an increased reliance on brainstem pathways. Among the different brainstem pathways, the 
reticulospinal tract (RST) is the only tract that has been found to innervate distal muscles. In 
monkeys, RST has been shown to innervate both proximal and distal muscles30-32 particularly 
facilitating shoulder abductors and arm flexors and suppressing extensors ipsilaterally34-37. This 
innervation pattern is equivalent to the aforementioned abnormal flexion synergy, which is 
expressed as obligatory coupling between shoulder abductors and elbow/wrist/finger flexors in the 
paretic upper limb following stroke. Because of this, the reticulospinal tract (RST) is NOT able to 
provide adequate hand control, which makes the CST the main descending pathway that provides 
reliable and adequate hand control. 
Following moderate to severe stroke, the amount of CST innervation is limited. Furthermore, 
the residual CST may not be available for hand-control due to the increased inhibition from the 
non-lesioned hemisphere38-40 and possibly also from the adjacent motor areas41 that control other 
parts of the paretic arm, such as the shoulder and elbow. We believe the intensive functional usage 
is one of the key issues for a joint to win the competition for the residual CST resources. Therefore, 
the loss of the access to remaining CST resources from the hand may be further amplified by 
‘learned non-use,’ a phenomena wherein an individual with stroke virtually learns to function 
without (not use) the paretic limb. Over time, the individual “learns not to use” the paretic hand, 
which may further exacerbate the loss of residual resources, such as the CST, for hand function. 
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Based on our understanding of the underlying neuromechanisms, two possible solutions for 
regaining hand function are: 1), to use a neuroprosthesis if there are not enough CST fibers left to 
provide distal innervation, and 2) to reallocate/re-enable the remaining CST fibers for controlling 
hand function such that the neuroprothesis over time becomes not necessary. With the new imaging 
techniques, like diffusion tensor imaging, we now can quantify the amount of residual CST with 
reasonable accuracy42,43. However, we still do not know what loss of CST will result in a poor 
prognosis for regaining hand control. Therefore, in this proposed development, the goal is to 
optimize the chance of reallocating/re-enabling the remaining CST for the hand control. To make 
this feasible, two conditions are required: 1) the potential for neural plasticity, and 2) the 
implementation of an approach that effectively stimulates the use of residual CST resources.
One of the most exciting findings during the past 20 years is that neural plasticity remains even 
in chronic stroke. This opens the possibility for the reallocation of residual brain resources. The 
remaining question is: what is the right way to trigger the optimal use of remaining neural 
resources? Currently, there is little evidence that any of the exercise interventions that have been 
studied is the best for an individual with stroke8,44-47. Instead, numerous studies have identified the 
intensive practice as the critical element of successful interventions to improve function in the 
hemiparetic UE6-14. Furthermore, the benefits of training in a functional context (task-specific 
training) have been demonstrated as well13,48-55. Most of all above results were obtained in mild 
and moderately impaired stroke individuals, with whom there is assumed to be more preservation 
of the CST. Currently, the recovery of hand function in more severely impaired individuals is poor. 
We believe that this is at least partially because the loss of hand function (despite the preservation 
of some proximal arm movements) makes use of the affected UE non functional, and thus the 
individual learns not to use the arm. On the other hand, new evidence is keeping emerging. These 
results demonstrate that even in severely impaired stroke survivors, recovery of proximal arm 
function can still be obtained if a science-based right intervention is used56,57, and thus suggesting 
preserved neural plasticity of this population. An effective assistive device would allow for further 
investigation of improved use and associated recovery of the paretic arm.
B.1.2. Currently available devices for hand-function rehabilitation following stroke 
We can classify the commercially available devices for enhancing movement of the paretic 
hand into 2 broad categories: mechanical devices and electrical devices. 
Mechanical devices
Mechanical devices range from “not actuated” to “active robotic 
devices”. Typical non-actuated devices included theraband (The Hygienic 
Corporation, 
Akron, 
OH), 
digi-web 
(cando-web™, 
HOSPEQ 
International, Miami, FL), and power web (HandHealth Unlimited). These 
devices all contain some elastic material, which is used to provide external 
resistance during exercise. The goal of use of these non-actuated devices 
is mainly strengthening. In order to utilize these devices, individuals 
require the ability to actively contract muscles against an external load. More recently, the 
Figure 1. Saeboflex
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Saeboflex™ (Saebo, Inc, Charlotte, NC, see figure 1) device and Hand Spring Operated Movement 
Enhancer (the National Rehabilitation Hospital, Washington DC, USA) uses adjustable springs to 
open the hand of more severely impaired individuals with hemiparetic stroke. Although the 
Saeboflex™ has been reported to be useful in enabling subjects to participate in intensive 
functional training 58,59,60, the system is difficult to set up and only overpowers the finger and 
thumb flexion bias to open the hand and requires an active grasp by the subject.  It therefore 
necessitates volitional control of grasp, something many individuals with sever stroke no longer 
have. Given the difficulty to get the paretic hand in, and the lack of required control, the system is 
unlikely to become a prosthetic device that can be used on a daily basis.
The second tier of devices are termed “active robotic devices”61. These devices can impose 
actuated position-controlled movements of the hand, such as passive motion devices (CPM).  CPM 
devices utilize an external motor to passively cycle joints through available range of motion 
(ROM). A review of arm interventions following stroke suggested that CPM combined with 
elevation may have a beneficial effect on hand edema62; however, there is no evidence that this 
intervention conveys a positive effect on regaining active movement since movement is not 
encouraged in this type of a device.
Other active robotic devices61, varying from devices that specifically target forearm and hand 
motion to exoskeletons and gloves for thumb and finger exercise, etc., designed to assist or guide 
patients in one of the pre-set movements while encouraging the user to actively use his/her UE. 
Three recent systematic reviews of robotic therapy in the arm following stroke concluded that there 
are improvements in the proximal arm in both sub acute and chronic stroke63; but no consistent 
influence on function63,64,65. After an extensive review of characteristics of 15 devices ranging 
from non-actuated to robotic, Dovat and colleague concluded that current active mechanical 
devices for hand rehabilitation are often too large to be used at home, have too limited range of 
force or do not offer the possibility for training fingers individually61. 
Electrical Stimulation Devices
Electrical stimulation devices can be subdivided into 4 categories, (1) simple surface electrical 
stimulation, (2) surface electrical stimulation coupled with a wrist hand orthosis, (3) 
electromyographic (EMG) triggered surface electrical stimulation, and (4) invasive electrical 
stimulation. Since our target population desires a non-invasive device, our review only focuses on 
the first 3 categories.
Surface electrical stimulation was first used to enhance arm function in the hand following 
stroke in the early 1960’s66. Numerous studies describe positive effects on decreasing impairment 
and enhancing arm function post stroke8,67-77. The Veterans Administration/Department of 
Defense clinical practice guideline recommends electrical stimulation for patients who have 
impaired “UE muscle contraction, specifically with patients with elbow/wrist motor 
impairment”78. Many of the subjects for whom electrical stimulation has proven beneficial are 
those with mild-moderate motor impairment following stroke. The challenges to widespread use 
of surface stimulation systems include electrode placement, cumbersome equipment, the 
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complexity of achieving consistent distal control, and lack of intuitive control. In addition, many 
systems are not easy for stroke survivors to apply without assistance, limiting use outside of the 
clinic. 
Electrical stimulation has been coupled with a wrist hand orthosis (WFO). The Ness H200 
(Bioness, Inc, Valencia, CA, see figure 2) combines a WFO, 5 surface electrodes that can be 
individually positioned, and an external control system. Studies using either the Ness H200 or an 
earlier version the “Ness Handmaster” report improved grip strength, 
motor scores (Fugl-Meyer Assessment) and better arm function79-83. 
Combined WHO/ES systems are portable and easy for users to manage.  
Difficulties with reliable precision control, and lack of intuitive control 
limit their widespread use. 
Devices have been developed to allow for triggering electrical 
stimulation using the user’s EMG signal (EMG-triggered ES). When 
using these devices, the patient is asked to voluntarily contract the paretic 
muscles. When EMG activity exceeds a preset level, external electrical stimulation of the muscle 
takes place, which increases or triggers muscle contractions. Numerous devices for EMG-triggered 
ES, like Biomove (Israel), Combistim (Galway, Ireland), and etc., are available in the market now. 
The underlying thought behind intention-dependent, EMG triggered functional electrical 
stimulation is a positive influence on neuronal 
plasticity due to proprioceptive and somatosensory 
feedback from the electrically stimulated, active 
muscle contraction. Meta-Analyses of Clinical 
Studies have demonstrated that triggered functional 
electrical stimulation appears to be superior to non-
triggered electrical stimulation on motor control of 
the upper extremities (see figure 3). The total 
number of hours of stimulation and the stimulation 
frequency were not found to be significant. The 
same was true for the various recovery stages after 
the stroke (acute, subacute, chronic). The literature 
supports the use of EMG-triggered ES in the treatment of the hemiplegic wrist and forearm (Level 
1 evidence) 84. Commercially available EMG-triggered ES devices all allow for pre-set movements 
without intuitive control to switch between these movements. Portability, ease of use, lack of 
intuitive control, and cost are also barriers of these type devices to widespread use.
If a simple EMG-triggered electrical stimulation of fixed muscles with pre-programed 
amplitudes can achieve superior recovery than a non-triggered ES, we expect that functional 
practice using the appropriate muscles to implement grasp and release activities during different 
arm activities will be even more successful. The development of the proposed ReIn-HAND real 
time platform will allow us to move one step closer to this idea.
Figure 2. NESS H200
Figure 3. EMG triggered ES is superior in 
motor control recovery than non-triggered 
ES. Meta-analysis involved a total of 588 
acute, subacute and chronic patients 1.
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B.1.3.  Pros and cons for mechanical and NMES devices
Each of the mechanical and electrical devices has pros and cons. A mechanical robotic device 
can provide more complex control to both hand and fingers; however, these usually are big and 
complex. Furthermore, these devices do not have the benefit of adding electrical stimulation, 
which directly activates a person’s own neuromuscular system to generate the assistive force.  
Conversely, ES devices have limited ability in control of fine movements, due to difficulties in 
controlling for contraction speed of individual muscles, or desired kinematic qualities, such as 
speed, trajectory, and motion smoothness85. Furthermore, ES devices can cause muscle fatigue, 
since stimulated contractions are inherently fatiguing due to synchronous muscle firing and 
motoneuron recruitment reversals 86-89, limiting the duration of use. However, many ES are battery 
powered, can be programed, are portable and have been demonstrated to be safe.
B.1.4. Gap in the development of the next generation assistive devices
In summary, current commercially available devices cannot meet the need as identified above. The 
proposed EMG-ES device will fill this significant technical gap. In the long-term, we aim to investigate 
whether individuals with moderate to severe stroke can regain upper extremity function by participating 
intensive task-specific paretic hand practice together with the rest of arm. 
C. Novelty of the proposed ReIn-HAND platform
C.1. A safe, reliable, intuitive detection of the intention of hand movements during functional 
arm activities
The resulted ReIn-HAND platform of this proposal will be novel in its detection algorithms 
that can provide non-invasive, safe, reliable, intuitive and continuous detection of a subject’s 
intention for hand grasp, release and relaxation during different functional arm activities. This will 
be achieved by strictly designed robot-mediated experiments, simulating different environments 
when using the entire UE during various hand activities. These experiments have been designed 
to reflect special characteristics of individuals with stroke, such as muscle weakness, abnormal co-
contraction, and abnormal muscle synergies. Furthermore, we have chosen to only implement the 
detection of grasp, release and relaxation of the paretic hand to optimize the required reliability. 
The developed platform will be implemented using a portable device, the RECLAIM ES designed 
by Simple Systems Inc (Simple Systems Inc, Toronto, Canada). The implemented platform will 
convert a user’s intention to timely assistance of usage of the paretic hand during different 
functional arm activities. 
C.2.Portable, subject-dependent configuration, easy-to-setup and low-cost
The ReIn-HAND platform is envisioned to be portable and customized based on subject 
specific features and desires. The device that incorporates the ReIn-HAND platform will also be 
easy to setup and low cost. Therefore, we propose to test its performance in an ES device (i.e., the 
RECLAIM). Although an ES device can cause muscle fatigue more easily than a mechanical 
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device, it can easily provide assistance to hand movements for at least 15 minutes without fatigue. 
Users can practice in short bouts, multiple times daily.
The device will allow for position-dependent selection of elements from the electrode-array: 
Another challenge for an EMG-driven FES device with surface recording and stimulation electrodes is 
that the relative position of the skin and muscle changes during a functional task. To account for this 
problem, we innovatively propose to add an inertial measurement unit (IMU) to the forearm orthosis to 
detect forearm pro/supination. This information will be used to auto-select elements from the electrode-
array.
The device will translate the use of ReIn-Hand device outside the laboratory/clinic: Home-based 
practice can be beneficial to our targeted population90,91. Due to the large variation in movement ability 
following stroke, the configuration of recording/stimulation electrodes requires it to be subject-specific. 
We therefore propose to perform a 3D scan of the subject’s forearm/hand followed by a 3D-printing of 
a subject-specific orthosis with recording and stimulation electrodes embedded to fit individual user’s 
needs. Together with the ReIn-Hand detecting platform on a smart phone, the proposed device will be 
portable, individualized, easy-to-use, and low-cost, thus having potential for widespread home-based 
practice.
D. Specific Objectives
The realization of this novel EMG-driven FES device that can be used both in the clinic and at home 
will be through the following specific aims:
Objectives 1: Develop a real-time ReIn-Hand opening platform as a portable device for home use
We will design a proof of concept FES device that is portable and user-friendly, incorporates graphical 
user-interfaces, and provides Reliable and Intuitive hand (ReIn-Hand) opening during functional use of 
the shoulder/elbow. The control algorithms of ReIn-Hand have already been developed on a laptop 
system for 4 different functional hand tasks. Preliminary results in 8 participants with moderate to severe 
chronic hand paresis are promising. All subjects learned to use this platform within one 3-hour session, 
which demonstrates the efficacy of our current algorithms and the intuitiveness of our current control. 
After a 7-week laboratory-based intervention using the ReIn-Hand, all subjects demonstrated 
improvements in sensory/motor assessments, and showed changes in related cortical activities and 
integrity of white matter (see preliminary results). These results provide mechanistic evidence of the 
efficacy of the current system, and suggest that it is worthy to improve the ease-of-use utilities of ReIn-
Hand system to make it suitable for a home-based intervention. The necessity of this aim is therefore to 
transfer the current algorithms to a portable device (i.e., smart phone), to enable automatic parameter 
adjustment based on user feedback, and to make this platform sufficiently user-friendly, such that ReIn-
Hand assisted functional intervention can be safely and easily implemented both in the clinic and at 
home. 
Objectives 
2: 
Develop 
a 
subject-specific 
forearm/hand 
orthosis 
with 
embedded 
electromyographic (EMG)-recording and stimulation electrodes
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Besides detecting and controlling hand opening in the context of abnormal synergies, several other 
practical difficulties limit the ease of use of most current EMG-driven FES devices for assisting hand 
opening. This includes the challenge of identifying recording/stimulation sites and a lengthy setup time. 
To resolve this problem, we plan to develop a subject-specific 3D-printed forearm-hand-orthosis (FHO) 
that has EMG recording/ stimulation electrode-array embedded (aim 2A). Furthermore, we will also 
address the changes in the relative positions between the EMG recording/stimulation electrodes and the 
corresponding muscles that occur when moving the forearm between a pronation and a supination 
position. We plan to add an inertial measurement unit (IMU) with a 3D accelerometer and a 3D 
gyroscope with Kalman sensor fusion algorithm to the system. This IMU will detect the amount of 
forearm rotation, which will be used to auto-select the recording/stimulation elements in the electrode-
array (aim 2B). The FHO will allow the device to be user-friendly by providing easy and reproducible 
electrodes placement.
E. Selection of Subjects
We plan to recruit about 100 moderately to severely impaired stroke subjects who have some 
shoulder and elbow control, but lack hand function (UE FMA Scores of 10-40/66, CMcM<=4) to 
participate in the cross-sessional experiments. Individuals with stroke will be selected from the 
Clinical Research Registry (CRR) housed at the ShirleyRyan AbilityLab which contains more 
than 700 members, as well as from stroke survivors residing in the Chicagoland area who wish to 
participate in the study. Recruitment of subjects who are currently enrolled  in the Clinical 
Research Registry will be done via phone call and email. Recruitment of stroke survivors 
residing in the Chicagoland will be done via flyer or on-clinical-site survey for willingness of 
participation. In addition, in order to facilitate recruitment, we will post this study on the The 
New Normal (TNN1) Match matchmaking portal, a National Institutes of Health (NIH) funded 
collaborative project to give communities access to information about healthy research 
opportunities. These stroke subjects will go through 1 or 2 stages (i.e., the 1st stage as remote 
prescreening which is optional and the 2nd one as on-site screening for eligibility test which is 
required) of eligibility tests. Recruitment for stroke participants will be ended when 20 
individuals with moderate to severe impairment post-stroke are enrolled and finished the data 
collection.
Once confirmed their desire and willingness to participante, the potential participant will be 
asked to sign an online e-Consent form, or a hard copy consent form. For individuals who signed 
the e-Consent form and passed the remote pre-screen, a hard copy of consent form will still be 
signed on the first on-campus visit.
We will recruit 10 healthy individuals at least 45 years old. These individuals will participate 
in one session of the EEG experiment, and will provide control data to compare against the  stroke 
individuals who partake in the home-based practice.
1 https://www.nucats.northwestern.edu/news/2020/northwestern-new-normal-launch.html.
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Also, 10 independent physical therapists (PTs) or senior physical therapy students (SPTs), who 
have experience working with stroke subjects and using FES, will be recruited for setting up the ReIn-
Hand device for stroke users, and then teaching stroke users to use the device. Stroke, PT and SPT users 
will provide feedback from clinicians and stroke users’ angles, respectively.
After  the eConsent or Consent form is obtained either online or as a hard copy, a qualified team 
member will call the stroke participant to conduct a phone survey to screen their current medical 
status and history and willingness to participate in the study. If a stroke participant agrees to have 
a remote section using video call, like zoom, FaceTime, WhatsApp etc., a video call will be 
scheduled to assess three short-version clinical assessments (MOCA, FMA and Chedoke).  
These remote sections will allow the team members to pre-screen the eligibility of a stroke 
participant without requiring an in-person visit. These two remote sessions (phone survey and 
video call) may be combined, with a total of about 30 minutes.
E.1.Inclusion and Exclusion criteria
Stroke participants should have sustained a unilateral lesion at least 6 weeks prior to 
participation in this project. The following inclusion criteria will be applied to the participants: 1) 
Paresis confined to one side, with substantial motor impairment of the upper limb; 2) Absence of 
motor impairment in the unimpaired limb; 3) Absence of a brainstem and/or cerebellar lesion; 4) 
Absence of severe concurrent medical problems (e.g. cardiorespiratory impairment, changes in 
management of hypertension); 5) Absence of any acute or chronic painful condition in the upper 
extremities or spine; 6) Absence of cardiac pacemaker; 7) seizure free; 8) no Botox within the last 
6 months; 9) Capacity to provide informed consent; 10）Ability to elevate their limb against 
gravity up to horizontal and to generate some active elbow extension; 11) Ability to achieve 
functional grasp and release with the assistance of an ES device with the help of an experience 
professional physical therapist; and 12) Not in pregnant or planning to become pregnant.  
Overpressure at the end of the range of motion will be used as a medical screening measure to 
verify the absence of inflammatory condition at the shoulder, elbow, wrist, and fingers. The 
shoulder passive range of motion of the affected upper extremity will be measured using a 
goniometer based on adapted methods. Maximum grip and key pinch forces for each participant 
will also be measured using a hand dynamometer and a pinch gauge. The impairment level of the 
upper extremity and the wrist/hand will be evaluated by a research physical therapist using Fugl-
Meyer score. 
While most inclusion criteria will not rule out the potential participation of registry members, 
the greatest impacting criteria are the Fugl-Meyer score and the ability of release with the aid of 
the RECLAIM ES device. We anticipate that a minimum of 50% of registry members will be 
moderately to severely impaired and will be appropriate for participation in this study.
Participating Physical therapists (PTs) should have a valid Illinois PT license and should have 
worked with individuals with stroke.  Senior physical therapy students (SPTs) should be currently 
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enrolled in the third year and have successfully completed  all the course work and clinical 
experiences required for  the first and second year of their program.  Students or employees who 
directly work with the investigators (for example, students who currently work with the 
investigator as part of their coursework or research projects,  employees who are listed as part of 
the research team in this IRB or  are paid by the research grants led by the investigators) will be 
excluded. No penalties will be applied to students or employees who fail to show up for scheduled 
research-related appointments. No  extra credit, besides the participation fee listed in this IRB, will 
be offered. During the recruitment based on an IRB-approved consent form, we will thoroughly  
explain the potential risks and protection that will be used to reduce these risks. Participation in 
the research is entirely voluntary, and after that decision is made,  participants have the right to 
withdraw at any time for any reason.
E.2.Pre-training Clinical assessments
All participants will undergo a series of impairment-level and functional clinical assessments that 
will be performed by a research physical therapist. The Impairment-level assessments will include 
the Upper Extremity Subscale of the Fugl-Meyer Motor Assessment (UE FMA)92, Chedoke-
McMaster Stroke Assessment hand portion (CMcM), the Nottingham Stereognosis Assessment  
(NSA)93,94, the Action Research Arm Test (ARAT)95, Box and Blocks test (BBT)96, the Stroke Impact 
Scale (SIS) 
99-101, Cutaneous Sensory Touch Threshold using Semmes-Weinstein 
Monofilaments (CSTT) 102-103, Montreal Cognitive Assessment (MoCA) 104-105. 
In addition, quantitative measure of hand opening area and closing force (QMHOC) will be 
conducted during the whole course of 12-week home-based practice, using pressure sensors 
(Pressure Profile Systems, Inc., Los Angeles, CA 90045) in conjuction with portable Moire Phase 
Tracking cameras (Metria Innovation, Inc., Wauwatosa, WI) (~1 hour).
 
F. Study Design and Methods
F.1. Lab-based testing
Each PT will be trained for the use of ReIn-Hand by watching a 20-min video, and practice the use 
of ReIn-Hand under the supervision of the research PT, Dr. Carmona, who is experienced in using ReIn-
Hand device.
F.1.1. A. Pre-training non-EEG Experimental protocols
Once confirmed, a stroke participant will be randomly assigned to one of 11 physical therapists 
(10 clinical PTs+1 research PT (i.e., Dr. Carmona)) who will participate this study. The assigned 
PT will determine 1) the electrode positions for recording the muscle activities during performing 
different arm/hand function, and 2) the stimulation electrode positions and stimulation intensities for 
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achieving the best hand opening with the forearm at 0º and 90º positions (~1-1.5 hour). Then, the 
corresponding electrode positions will be marked, and the forearm/hand with these markers will be 
scanned (~0.5-1 hour). This visit is expected to last approximately 3 hours. The scanned results will 
be used to develop a subject-specific forearm-hand orthosis (FHO) that fits to the paretic forearm 
and hand.
B. Pre-training EEG Experimental protocols
Before and after this 12-week home-based practice, these stroke individuals will participate in 
an electroencephalography (EEG) experiment. Additionally, 10 control subjects will be recruited 
to participate in one session of this EEG experiment to provide healthy neuroimaging data for 
comparison. 
At the start of the experiment, we will measure maximum grasping forces (requiring 3 trials 
within a 10% range of each other). During this experiment, we will use the ACT-3D, a robot 
developed by Dewald Rehab Tech, LLC, to simulate the situation of performing different hand 
movements against different loads against gravity. The tested forearm (paretic for stroke, dominant 
for control) will be attached to an orthosis that is linked to the ACT-3D. The subject’s hand will 
be placed around a cylinder on the orthosis with a custom pressure sensor mat (Pressure Profile 
System Inc., CA) to measure grasping forces. A 9x9 mm marker will be placed on the tip of each 
finger, with another on the back of the hand as reference. The position and angle of the fingers/hand 
will be captured by 2 portable Moire Phase Tracking cameras and these markers (180 Hz; Metria 
Innovation Inc. Milwaukee, WI). The subject’s upper limb and forearm lengths will then be 
measured and entered into the computer. A “home” position will then be defined as the position in 
which the arm is placed with 85 shoulder abduction, 40 shoulder flexion, and 90 elbow flexion. 
During the experiment, the subject will be instructed to perform 1 of 2 movements: 1) hand 
opening while resting on a haptic table, or 2) hand opening while lifting against 50% of their 
maximum shoulder abduction (SABD) force. A monitor will continuously display the position 
with a cursor indicating where the subject’s arm is relative to the home position. For each trial, 
subjects will first move to the home position, then relax for 5-7 seconds, and then initiate the 
movement. Subjects will perform 60 trials for each movement, broken up into randomized blocks 
of 20 trials. Subjects will be given 30 seconds of rest between trials, and 10 minute rests between 
blocks to avoid fatigue. Additionally, a 3-minute resting-state block will be recorded in which 
subjects are instructed to fixate on a fixation cross on the screen. The whole experiment will last 
approximately 6 hours.
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Figure 4. EEG Experimental setup showing a subject 
using the ACT3D robot while high-density EEG and 
surface EMG signals will be simultaneously recorded. 
Visual feedback will be displayed on a computer screen.
Throughout the experiment, we will 
measure scalp recordings using a 160-
channel 
EEG 
system 
using 
active 
electrodes (Biosemi, Inc., Active II, 
Amsterdam, The Netherlands). Surface 
EEG electrodes will be mounted on a 
stretchable fabric cap based on the 10/20 
system. The cap will be fitted on the head 
of the subject with the Cz electrode 
aligning with the intersection of the planes 
defined by the nasion, inion, and pre-
auricular points. Eye movement detection 
electrodes will also be placed on the supra- 
and infra-orbital margins for detection of 
vertical eye movement. The skin under 
each electrode site will be prepared by 
clearing away any hair, and conductive gel 
will be injected to achieve electrode impedances lower than 5k throughout the experiment. EEG 
data will be collected at 2048 Hz sampling rate and anti-aliasing filter (100 Hz) will be provided 
before data acquisition. The Biosemi system is equipped with active electrodes that provide a first 
amplification stage, allowing detection of EEG signals with a higher SNR and quicker preparation. 
A Polaris Krios handheld scanner and reflective markers (NDI, Ontario, Canada) will be used to 
record the EEG electrode positions compared to the coordinate system defined by the nasion, inion, 
and pre-auricular notches. EMG will be recorded from the extensor carpi radialis, flexor carpi 
radialis, and deltoid of the arm. The EEG and EMG data will be collected and stored on a computer. 
These sessions will allow us to compare the cortical activity related to these movements pre- 
and post-intervention for the stroke individuals and how these compare to healthy controls to 
investigate any intervention-induced cortical reorganization. 
F.1.2. The 1st and 2nd lab-based training with ReIn-Hand (2 visits)
After the subject-specific FHO is ready, the stroke participant and his/her paired PT will be 
called to participate the 1st and 2nd lab-based training with ReIn-hand device. During these 2 visits, 
the assigned PT (1st test) or the research PT (2nd test) will train the stroke participant to use his/her 
FHO and the ReIn-Hand software on a mobile phone, until the stroke participant demonstrates the 
ability in using the device independently twice in a row. On the 2nd test, the research PT will also re-
test partial of the clinical assessments, however, this time with the assistance of ReIn-Hand device. Each 
of these 2 visits is expected to last about 3 hours. During these 2 visits, we will measure the time 
for a stroke participant to learn the use of ReIn-Hand device. Within 0-3 days after the 1st (for PTs) 
or the 2nd lab-based training (for individuals with stroke), a 5min user survey to report the level of ease-
of-use of the ReIn-Hand device will be conducted.  
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F.2. Home-based practice
After the 3 lab-based visits as listed above, 4 out of 20 stroke participants will further 
participate the home-based practice. They will take the ReIn-Hand device, including his/her FHO, 
the mobile phone with ReIn-Hand software, and the electronic stimulator (300 PV, Empi, 
Minnesota, USA, a FDA approved clinical device) back to home. At home, they will perform 20 trials 
of pre-set tasks, like reaching and grasping, per session (1 hour), 1 session per day, 7 days per week for 
12 weeks. During these 12 weeks. During these 12 weeks, they will visit the lab once per week to make 
necessary device changes, update the partial of the clinical assessments, all without ReIn-hand. These 
clinical tests will also be re-measured at 1 and 3-month after the home-based practice, again without 
ReIn-hand.
Both electrodes and electrical stimulator are commercially available devices (300 PV 
Complete Electrotherapy System, Empi, Inc., St. Paul, MN). Each subject will be assigned task-
specific, functional exercises targeted to their individual abilities, deficits, and personal 
preferences. Stimulation will be provided with the following characteristics:
Amplitude – at motor threshold with the maximum intensity lower than 100 mA
Frequency – 50±20% Hz
Pulse Duration – 300-400 microseconds
Ramp/Fall Times and Duty Cycle – adjusted to the task
F.3. Data collection and procession
Main data collection is listed in table 2.
Day 1
#1, Demographic data, #2, Clinical assessments as listed above, #3, Time for a) determining 
the stimulation /recording electrode positions, b) for scanning, 
Day 2
#1, EEG data, #2, EMG data, #3, finger position during hand-opening and graping force data 
during closing
Day 3 
#1, Time for the stroke subject to a) to attach the FHO, b) use the software, including 
connecting all the cables following the instructions, c) set up the detection rule, and d) clean 
up. #2, The accuracy in detecting grasping and releasing; and #3, EMG data while 
performing task, sampled at 1K Hz.
Day 4
Measures #1-3 on Day 2, #4, ARAT and BBT with the assistance of ReIn-Hand.
Home-
based test
Measures #1-4 on Day 3 and MAL-14, NSA, and hand opening and closing ability weekly 
during the 12-week home-based practice, then again at 1 and 3-month after. To the end of 
the 12-week home-based practice, we will use a GLOC scale (one question survey) to collect 
user overall satisficaory level of the ReIn-Hand supported home practice.
Data analysis for evaluating the engineering aspects is listed on Table 3.
Primary measures
Measured by
Expectation
Time for learn-to-use the 
device
#1 on Day 3 and Day 4
<3 hours in each of the 2 
days, and no difference 
between 2 days1.
Time for setup and cleanup 
#1 a) and d) on Days 3 & 4, and during 
the home-based test
<5 min for each, and 
significantly less than the 
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measure #3 (a) on Day 1
Successful 
rate 
on 
controlling grasping and 
releasing during reaching
#2 on Days 3, 4, and during the home-
based test
a false ‘transfer’ < 10%
Time delay caused by the 
device
We will detect the onset of EMG at the 
extensor measured on days 3 &4, and 
the onset of stimulation artifact. The 
latency 
between 
them 
will 
be 
calculated.
<350 ms
Difference 
in 
Clinical 
assessments 
with 
and 
without ReIn-Hand
Difference between measure #4 on Day 
4 & measure #2 on Day 1
ARAT and BBT with 
ReIn-Hand 
will 
outperform that without 
ReIn-Hand.
Willingness to use ReIn-
Hand at home
#1-3 during the home-based test
Continuous use on daily 
base.
Cortical activity related to 
hand open with and without 
lifting
We will use EEG data to estimate the 
cortical activity related to the 2 motor 
tasks pre- and post-home-practice
Post-intervention cortical 
activity related to these 2 
motor 
tasks 
become 
‘closer to’ that in healthy 
control subjects.
1Ease-of-use feature of the device will be reflected by the <3 hours learning time. We will further 
study effects of 1) PT’s experience with ReIn-Hand, and 2) the number of experimental sessions on the 
time to learn to use the device. For PT’s experience, since Dr. Carmona already has 4-year experience 
in using current ReIn-Hand device in stroke participants, we will compare 1) the learning time on day 
2 of the group 1 (N=10) working with the 10 PTs versus the time of the group 2 (N=10) working with 
Dr. Carmona; and 2) the learning time of group 1 on day 2 with the 10 PTs versus the time of the same 
group on day 3 with Dr. Carmona. A non-significant difference for both comparison will suggest non-
significance for PT’s experience in using the device. For the number of sessions needed to learn to use 
the device, we will compare the learning time of both groups on day 2 versus that on day 3. A non-
significant difference will suggest sufficiency of one session in learning the device.
Evaluation of the usability of the ReIn-Hand: Within 0-3 days after Day 3, the 10 PTs and the 
20 stroke participants will finish a 5min user survey to report the level of ease-of-use of the ReIn-Hand 
device. Items that will be rated (on ordinal scale 0-5, with the easiest use at 5) include: 1) determination 
of the stimulation/recording electrode positions (PT only), 2) setting up the initial detection rule (PT 
only), 3) fine adjustment of the detection rule (both), 4) placement of the FHO (both), 5) using the 
mobile phone software (both), 6) performance of the trained functional task (both). We expect to 
observe users’ grades 4/5, with grades 3/5 will be queried for explanation and compiled for future 
design modifications. 
Transportation: Participants will be given reimbursement for transportation expenses. 
Participants are encouraged to take public transportation, or to drive and park in Northwestern 
Medical School parking lots (located at 321 E. Erie St. or 222 E. Huron St.) where a parking sticker 
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will be provided. If a cab or rideshare car (Uber or Lyft) is needed, it is requested that the 
participant contact lab staff to confirm that the fare can be reimbursed before scheduling pickup. 
Reimbursement and payment will be submitted to the NU accounting department on a weekly 
basis. Alternatively, participants may also be compensated using a pre-stored value card. 
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