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Concomitant sensory stimulation during therapy to enhance hand functional recovery post stroke


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Background Post-stroke hand impairment is prevalent and persistent even after a full course of rehabilitation. Hand diminishes stroke survivors’ abilities for activities of daily living and independence. One way to improve treatment efficacy is to augment therapy with peripheral sensory stimulation. Recently, a novel sensory stimulation, TheraBracelet, has been developed in which imperceptible vibration is applied during task practice through a wrist-worn device. The objective of this trial is to determine if combining TheraBracelet with hand task practice is superior to hand task practice alone. Methods A double-blind randomized controlled trial will be used. Chronic stroke survivors will undergo a standardized hand task practice therapy program (3 days/week for 6 weeks) while wearing a device on the paretic wrist. The device will deliver TheraBracelet vibration for the treatment group and no vibration for the control group. The primary outcome is hand function measured by the Wolf Motor Function Test. Other outcomes include the Box and Block Test, Action Research Arm Test, upper extremity use in daily living, biomechanical measure of the sensorimotor grip control, and EEG-based neural communication. Discussion This research will determine clinical utility of TheraBracelet to guide future translation. The TheraBracelet stimulation is delivered via a wrist-worn device, does not interfere with hand motion, and can be easily integrated into clinical practice. Enhancing hand function should substantially increase stroke survivors' independence and quality of life and reduce caregiver burden. Trial registration NCT04569123 . Registered on September 29, 2020
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S T U D Y P R O T O C O L Open Access
Concomitant sensory stimulation during
therapy to enhance hand functional
recovery post stroke
Na Jin Seo
, Viswanathan Ramakrishnan
, Michelle L. Woodbury
, Leonardo Bonilha
, Christian Finetto
Christian Schranz
, Gabrielle Scronce
, Kristen Coupland
, Jenna Blaschke
, Adam Baker
, Keith Howard
Caitlyn Meinzer
, Craig A. Velozo
and Robert J. Adams
Background: Post-stroke hand impairment is prevalent and persistent even after a full course of rehabilitation.
Hand diminishes stroke survivorsabilities for activities of daily living and independence. One way to improve
treatment efficacy is to augment therapy with peripheral sensory stimulation. Recently, a novel sensory stimulation,
TheraBracelet, has been developed in which imperceptible vibration is applied during task practice through a wrist-
worn device. The objective of this trial is to determine if combining TheraBracelet with hand task practice is
superior to hand task practice alone.
Methods: A double-blind randomized controlled trial will be used. Chronic stroke survivors will undergo a
standardized hand task practice therapy program (3 days/week for 6 weeks) while wearing a device on the paretic
wrist. The device will deliver TheraBracelet vibration for the treatment group and no vibration for the control group.
The primary outcome is hand function measured by the Wolf Motor Function Test. Other outcomes include the
Box and Block Test, Action Research Arm Test, upper extremity use in daily living, biomechanical measure of the
sensorimotor grip control, and EEG-based neural communication.
Discussion: This research will determine clinical utility of TheraBracelet to guide future translation. The
TheraBracelet stimulation is delivered via a wrist-worn device, does not interfere with hand motion, and can be
easily integrated into clinical practice. Enhancing hand function should substantially increase stroke survivors'
independence and quality of life and reduce caregiver burden.
Trial registration: NCT04569123. Registered on September 29, 2020
Keywords: Stroke, Upper extremity, Physical rehabilitation, Hand function, Subliminal stimulation, Physical
stimulation, Stroke rehabilitation, Neurologic rehabilitation, Occupational therapy, Upper limb paresis, Hand, EEG,
Paralysis, Randomized controlled trial
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* Correspondence:
Ralph H. Johnson VA Medical Center, Charleston, SC, USA
Full list of author information is available at the end of the article
Seo et al. Trials (2022) 23:262
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Administrative information
Note: the numbers in curly brackets in this protocol
refer to SPIRIT checklist item numbers. The order of
the items has been modified to group similar items (see
Title {1} Concomitant sensory stimulation
during therapy to enhance hand
functional recovery post stroke
Trial registration {2a and 2b}. NCT04569123.
Protocol version {3} #6. 7/28/2021
Funding {4} NIH/NICHD 1R01HD094731-01A1
Author details {5a} Na Jin Seo, PhD, Department of
Rehabilitation Sciences, Department of
Health Science and Research, Medical
University of South Carolina, Charleston,
SC, USA. Ralph H. Johnson VA Medical
Center, Charleston, SC, USA. ORCID
151B Rutledge Ave, MSC 962, Charles-
ton, SC 29425. 843-792-0084.
Viswanathan Ramakrishnan, PhD,
Department of Public Health Sciences,
Medical University of South Carolina,
Charleston, SC, USA. ORCID 0000-0002-
4098-0539. 135
Cannon St, Charleston, SC 29425. 843-
Michelle L. Woodbury, PhD, OTR/L,
Department of Health Science and
Research, Medical University of South
Carolina, Charleston, SC, USA. 0000-
77 President St, MSC 700, Charleston,
SC 29425. 843-792-1671.
Leonardo Bonilha, MD, PhD,
Department of Neurology, Medical
University of South Carolina, Charleston,
Jonathan Lucas St, MSC 606, Charleston,
SC 29425. 843-876-8311.
Christian Finetto, PhD, Department of
Health Sciences and Research, Medical
University of South Carolina, Charleston,
SC, USA. ORCID 0000-0003-0520-2034. 77 President St, MSC
700, Charleston, SC 29425. 843-792-
Christian Schranz, PhD, Department of
Health Sciences and Research, Medical
University of South Carolina, Charleston,
SC, USA. ORCID: 0000-0003-1102-7180. 77 President St,
MSC 700, Charleston, SC 29425.
Gabrielle Scronce, PT, DPT, PhD,
Department of Health Sciences and
Research, Medical University of South
Carolina, Charleston, SC, USA. ORCID
0000-0002-3861-1371. scronce@musc.
edu. 77 President St, MSC 700, Charles-
ton, SC 29425.
Kristen Coupland, MS, OTR/L, CSRS,
CDRS, Department of Health Sciences
and Research, Medical University of
Administrative information (Continued)
South Carolina, Charleston, SC, USA. 77 President St,
MSC 700, Charleston, SC 29425.
Jenna Blaschke, BA, Division of
Occupational Therapy, Department of
Rehabilitation Sciences, Medical
University of South Carolina, Charleston,
SC, USA. 151B
Rutledge Ave, MSC 962, Charleston, SC
29425. 803-459-6403.
Adam Baker, BS, Department of Health
Sciences and Research, Medical
University of South Carolina, Charleston,
President St., MSC 700, Charleston, SC
Keith Howard, BS, Department of
Health Sciences and Research, Medical
University of South Carolina, Charleston,
President St, MSC 700, Charleston, SC
29425. 843-792-2917.
Caitlyn Meinzer, PhD, Department of
Public Health Sciences, Medical
University of South Carolina, Charleston,
SC, USA. 135
Cannon St, Charleston, SC 29425. 843-
Craig A. Velozo, PhD, Division of
Occupational Therapy, Department of
Rehabilitation Sciences, Medical
University of South Carolina, Charleston,
SC, USA. 151B
Rutledge Ave, MSC 962, Charleston, SC
29425. 803-459-6403.
Robert J. Adams, MD, Department of
Neurology, Medical University of South
Carolina, Charleston, SC, USA. 96 Jonathan Lucas
St, MSC 606, Charleston, SC 29425. 843-
Name and contact
information for the trial
sponsor {5b}
Medical University of South Carolina,
College of Health Professions 843-792-
3328, 151B Rutledge Ave, Charleston,
SC, 29425
NIH/NICHD, 1-800-370-2943
Fax: 1-866-760-5947
Mail: P.O. Box 3006, Rockville, MD,
Role of sponsor {5c} Oversight for regulatory requirements.
Background and rationale {6a}
Stroke is a leading cause of long-term disability in the
USA [1]. More than two thirds of nearly 7 million stroke
survivors in the USA [1] have persistent hand impair-
ment even after a full course of rehabilitation [2]. Hand
impairment diminishes stroke survivorsabilities for ac-
tivities of daily living including self-care, hygiene, leisure,
and employment, which lowers their independence and
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increases caregiver burdens [3,4]. Due to increasing lim-
itations on access to therapy, improving the efficacy of
rehabilitation treatment to improve hand function is of
significant importance.
Recent meta-analysis shows that upper extremity
motor function improves more when therapy is aug-
mented by peripheral sensory stimulation, compared
with therapy alone [5]. The scientific rationale is that af-
ferent input is a powerful driver of change in the motor
cortex [6,7]. Specifically, direct projections from the
cortical hand sensory areas to motor areas are evidenced
in intracortical microstimulation studies in animals [8
11] and in the long-latency cutaneomuscular reflex in
humans [12,13]. These direct projections from the sen-
sory to motor cortex enables afferent sensory stimula-
tion to directly affect motor output [1416]. For
example, corticomotoneuronal excitability as measured
using transcranial magnetic stimulation (TMS) has been
shown to increase during muscle vibration, compared to
no vibration [17,18]. After 30 min of electrical stimula-
tion of the whole hand via a mesh glove, functional mag-
netic resonance imaging blood-oxygen-level-dependent
signals during finger movement in the primary motor
and somatosensory area increased, compared to that be-
fore the stimulation [19]. After 2 h of transcutaneous
electrical nerve stimulation (TENS), corticomotoneuro-
nal excitability increases via GABAergic mechanism
[20]. Daily 1-h TENS over 3 weeks led to increased cor-
tical motor map area and volume of involved muscles
(assessed using TMS) [21].
Based on this framework, peripheral sensory
stimulation has been used in conjunction with therapy
to increase neuroplasticity and motor recovery more
than therapy alone in patients with neurologic motor
impairment [2234]. Specifically, 30-min vibration to
the upper limb muscles followed by 1-h physiotherapy,
repeated for 3 consecutive days, resulted in greater im-
provement in the Wolf Motor Function Test (WMFT)
than dose-matched physiotherapy alone, which sustained
2 weeks after the intervention (n= 30 chronic stroke
survivors, randomized to n= 15/group) [24]. This
greater functional improvement was associated with
greater corticomotor excitability and motor map areas
(assessed using TMS) for the stimulation + therapy
group compared with the therapy only group [24]. In an-
other study, 2-h TENS followed by 4-h task practice
therapy, repeated for 10 days, resulted in greater im-
provements in the Fugl-Meyer Upper Extremity Assess-
ment and Action Research Arm Test (ARAT) than dose-
matched therapy alone, which sustained at 1-month
follow-up (n= 36 chronic stroke survivors randomized
to n= 18/group) [29]. Meta-analysis supports this prem-
ise of using sensory stimulation to augment motor re-
covery [5].
Unfortunately, most modalities of peripheral sensory
stimulation interfere with natural hand tasks.
Specifically, suprathreshold stimulation causes sensation
irrelevant to tasks at hand, including TENS-induced tin-
gling sensation [19,21]. Wearing of a glove or a finger
cap hampers dexterous finger movement and causes a
sense of discomfort [35,36]. Thus, most modalities of
sensory stimulation are administered prior to each ther-
apy session while a person is in a sedentary posture, re-
quiring additional time commitment ranging from 30
min to 2 h a day [2230]. These constraints make it dif-
ficult for implementation and patient adherence to a
stimulation regimen [37]. Furthermore, the effect dimin-
ishes 2030 min after the stimulation [20,38], weaken-
ing its effect during therapy. Studies that used sensory
stimulation during therapy had no control group (with
no stimulation) [31,32] or did not test stroke survivors
[33,34] and used suprathreshold stimulation causing
sensation irrelevant to tasks.
To address this practical limitation of the current
sensory stimulation method and fully leverage the
therapeutic benefits of sensory stimulation, we have
developed an innovative sensory stimulation:
TheraBraceletis imperceptible random-frequency vi-
bration applied to wrist skin via a wrist-worn device.
TheraBracelet does not interfere with natural hand tasks
since the stimulation is imperceptible and delivered via a
device worn on the wrist [3941]. The theoretical frame-
work is that imperceptible random-frequency vibration
stimulates mechanoreceptors in wrist skin and afferents
[42], adds small random currents to neurons in the sen-
sorimotor cortex, triggering coherent [43] firing [4446]
at the peak of inputs related to hand tasks, and conse-
quently enhances neural communication [47,48] for
hand tasks [4952] and functional recovery. Pilot studies
showed preliminary efficacy [53,54].
A randomized controlled trial to determine clinical
utility of TheraBracelet is described herein. This
research is expected to result in an efficacious
therapeutic adjunct to enhance upper extremity
rehabilitation outcomes for people with stroke.
Enhancing hand motor function and therapy outcome
with TheraBracelet is expected to contribute to
improving stroke survivorsabilities to perform activities
of daily living, increasing functional independence, and
reducing caregiver burden, thereby leading to increased
quality of life for both stroke survivors and caregivers.
Objectives {7}
The objective of this study is to determine if
combining TheraBracelet with hand task practice is
superior to hand task practice alone in an adequately
powered study.
Seo et al. Trials (2022) 23:262 Page 3 of 15
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Trial design {8}
The trial design is a double-blind randomized controlled
trial involving two parallel groups. Participants will be
randomly assigned to either the experimental or control
group. Half will be in the experimental group and the
other half will be in the control group. Both groups will
undergo standardized hand task practice therapy while
wearing a device on the paretic wrist. The device will de-
liver TheraBracelet vibration for the treatment group
and no vibration for the control group during therapy.
The superiority of the experimental condition over the
control condition will be examined.
Methods: participants, interventions, and
Study setting {9}
The study setting is the research laboratory of the
Medical University of South Carolina, Charleston, SC,
Eligibility criteria {10}
Inclusion criteria:
Adult (> = 18 years old)
Survived a stroke at least 6 months ago
WMFT [55] total average time > 10 s
WMFT hand task average time < 120 s
Exclusion criteria:
Concurrent upper limb therapy
Change in spasticity medication or botulinum toxin
injection in the upper limb within 3 months prior to
or during enrollment
Severe spasticity (Modified Ashworth Scale [56]=
45 out of 5) that prohibits engagement in task
Comorbidity such as complete upper extremity
deafferentation, orthopedic conditions limiting
motion [57], premorbid neurologic conditions, or
compromised skin integrity of the wrist due to burn
or long-term use of blood thinners
Language barrier or cognitive impairment that
precludes following instructions and/or providing
Who will take informed consent? {26a}
Research staff approved by the Institutional Review
Board (IRB) will take informed consent. The consent
process will take place in a private room when the
potential participant comes to the laboratory on a
scheduled time agreed upon between the study
personnel and the participant. The content of the
consent will be verbally explained to the participant and
the participant will be asked to raise any questions and
Additional consent provisions for collection and use of
participant data and biological specimens {26b}
The consent includes sharing of de-identified data with
the public and other investigators in publications and In addition, authorization for use and
release of individually identifiable health information
collected for research with the Medical University of
South Carolina IRB and the funding agency will be ob-
tained in writing. This trial does not involve collecting
biological specimens for storage.
Explanation for the choice of comparators {6b}
The control group will receive standardized task practice
therapy while receiving no vibration from the device on
the paretic wrist. The control condition represents the
standard task practice therapy [58] without the
TheraBracelet stimulation. For both groups, the device is
worn during therapy only (not outside therapy).
Intervention description {11a}
Intervention schedule: All participants will undergo 6
weeks of standardized task practice therapy. The therapy
schedule will be 3 sessions/week for 6 weeks, with each
session lasting 12 h to complete 300 movement
repetitions. This therapy schedule is chosen to simulate
the outpatient rehabilitation model [59] and facilitate
potential translation of the protocol for implementation
in rehabilitation practice. This therapy schedule is also
similar with other stroke upper limb rehabilitation
programs with distributed practice schedules, enabling
comparisons [6064].
Task practice therapy: Therapists will be trained to
administer the task practice therapy according to
standardized procedures. The treatment manual,
containing a menu of task practice activities, was
developed by two experienced occupational therapists,
based on the EXCITE trial [65] manual and Dr. Langs
Task Specific Practice text [58]. The main principles of
the therapy program are detailed below.
(1) Specificity: All therapy tasks address hand/finger
motions, because TheraBracelet has been shown to
impact hand/finger control in our preliminary
studies [51,53]. Selected tasks naturally require
several repetitions of the specified motion.
(2) Structure: For organizational purposes, the tasks are
categorized into self-care, household care, leisure,
and vocation. Each category contains two types of
tasks: tasks requiring (i) primarily in-hand manipu-
lation and (ii) reaching. The in-hand manipulation
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tasks will be performed within the subjects reach-
able workspace (e.g., in front of the torso) to exclu-
sively focus on hand dexterity which is the
intervention target using TheraBracelet. The reach-
ing tasks will be performed by reaching to grasp/
place objects throughout the reachable workspace
to integrate hand dexterity skills with the proximal
upper limb motion to maximize the functional rele-
vance of the treatment. A total of 4 tasks (2 in-hand
and 2 reaching, from each of 2 categories of choice)
will be practiced in each session. Repetitions for in-
hand vs. reaching will be balanced.
(3) Saliency: To assure the task practice is meaningful,
thus motivating for the subject, the therapist and
subject will work together to select the tasks from
the task menu. This maximizes the potential for the
subject to apply skills learned in clinic to their real
world tasks and goals [58].
(4) Repetitions: To standardize therapy dosage, we will
aim for each participant to achieve 300 movement
repetitions per session. This dosage is feasible in a
12 h timeframe [61,66] with no excessive pain or
fatigue [60], results in functional improvements
[61], and corresponds to the lower end of the
repetitions in animal and motor learning studies
that have been shown to promote neural plasticity
and behavioral changes [67,68]. One repetition will
be defined for each activity in the task manual to
ensure consistency in counting repetitions. For in-
hand tasks, one repetition will be defined as one
hand manipulation (e.g., place three coins in the
paretic palm, and transfer to fingertips and insert
into a slot with one coin at a time for 3 repetitions).
For reaching tasks, one repetition will be reach-
grasp-manipulate-release [61] (e.g., reach for/grasp
a toothbrush, apply toothpaste, simulate brushing
motions four times, and replace the toothbrush on
the table, Fig. 1).
(5) Difficulty: Brain reorganization occurs through
motor learning that requires problem solving, not
simple repetition of mastered skills, as shown in
human [69,70] and animal studies [67,71,72].
Thus, tasks will be at a just-rightdifficulty level
that does not overwhelm or underwhelm
participants. Specifically, we will implement tasks
such that the participant practices movements that
s/he can partially perform, as opposed to easily
perform or cannot perform. We will increase or
decrease difficulty based on the participants success
rate of the task (90% or 50%), task pace, and
patient input [58] following the Challenge Point
Framework [73]. Grading of tasks will be
accomplished by changing the object weight, size
[7476], shape [77,78], slipperiness [7984],
compliance, stability [85], and location, use of
adaptive materials (e.g., nonslip mat to prevent
items from moving), task complexity, and speed and
accuracy of movement.
TheraBracelet stimulation: TheraBracelet is
imperceptible random-frequency vibration applied to
wrist skin via a wrist-worn device. TheraBracelet stimu-
lation parameters were determined based on literature
and our previous data as detailed below.
(1) Frequency: The vibrator will be driven by random-
frequency signal low-pass filtered at 500 Hz for the
following reasons. Literature in stochastic resonance
collectively demonstrates that broadband random-
frequency (white noise) stimulation enhances neural
communication and signal detection (see reviews
[43,44,86] and applications [47,49,8792]). The
benefit of the random-frequency stimulation com-
pared to constant frequency stimulation is that it is
less subject to desensitization (or sensory habitu-
ation). Literature comparing the two types of stimu-
lation shows that temporally non-uniform
stimulation improves tactile sensation and modu-
lates the central nervous system excitability, while
such effects could not be obtained with constant
frequency stimulation [93,94]. By preventing
desensitization, TheraBracelet is expected to pro-
vide a benefit that persists throughout therapy ses-
sions. As for the bandwidth, existing evidence
shows that ones ability to detect 25 Hz signal was
enhanced when accompanied by random-frequency
vibration bandwidth filtered at 0.12550 Hz, and
similarly, ability to detect 250 and 400 Hz signal
was enhanced with random-frequency vibration of
Fig. 1 An example therapy session with the wrist-worn device that
can deliver TheraBracelet stimulation
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50500 Hz [87]. For various sensorimotor tasks in-
cluding hand grip, touch detection, and texture dis-
crimination, random-frequency vibration low-pass
filtered at 300 Hz (i.e., 0300 Hz) was used to suc-
cessfully enhance sensorimotor performance [89].
Since human mechanoreceptors can detect vibra-
tion from 0.4 to 500 Hz [95], we decided to use
random-frequency vibration low-pass filtered at
500 Hz to span the entire frequency spectrum for
human mechanoreceptors.
(2) Location: The vibration will be applied to the dorsal
wrist, because the same beneficial effects on
improved detection of fingertip touch during
vibration vs. no vibration were obtained for all
vibration locations we testedvolar wrist, dorsal
wrist, dorsum of the hand near the first and the
second knuckle, thenar area, and hypothenar area,
in chronic stroke survivors [50] as well as healthy
adults [52]. The wrist is optimal for a wearable
device, as the device can be worn on the wrist
similar to wearing a wristwatch.
(3) Intensity: Vibration intensity 60% of the sensory
threshold (imperceptible) will be used, because that
intensity enhanced finger touch detection the most
(as assessed by the monofilament test [96]), while
40% and 80% of the sensory threshold had lesser
effects [50,97]. Further, vibration 120% of the
sensory threshold (perceptible) degraded finger
sensation [52]. This intensity-effect relationship is
consistent with the bell-shaped curve (i.e., inverted
U-shape function) reported in stochastic resonance
literature in which vibration intensities at 3367%
of the sensory threshold improved sensory percep-
tion to a greater extent than did intensities of 0%,
83%, and 100% of the sensory threshold [87], and
suprathreshold vibration degraded sensation [88].
These results suggest that vibration intensity should
be high enough to facilitate signal transmission but
not too high to mask other signals [87].
For both groups, the participants sensory threshold
will be determined at the beginning of each therapy
session using a custom-developed software program that
utilizes the staircase method [98]. Specifically, the vibra-
tion amplitude will be increased or decreased until the
participant verbally indicates that s/he could or could
not perceive the wrist vibration, respectively. The thresh-
old will be determined as the average of 6 amplitudes
that the participant could barely feel.
For the treatment group, TheraBracelet stimulation
will be turned on when movement is detected at or
higher than the acceleration magnitude that corresponds
to movement of one finger only. Upon movement
detection, TheraBracelet stimulation will be turned on
for 1 s, after which the stimulation will continue if
movement is detected again, or stop if no movement
is detected, such that stimulation will be on during
all movements but not for more than 1 s after the
movement ends to minimize potential habituation to
the stimulation. The consistency in the frequency
characteristics from the device will be verified weekly
using a laser vibrometer (OMS Corp, Laguna Hills,
Transfer package: To achieve greater independence at
home using the participants improved motor capacities
from therapy, we will implement a transfer package [99].
Transfer package is adopted from the behavioral
intervention field specifically for physical
neurorehabilitation, based on the principles of self-
monitoring [100,101], contracting/negotiating for spe-
cific behaviors [102], phone contacts to increase compli-
ance [103105], and problem-solving to overcome
barriers [106110]. Components of the transfer package
are detailed below.
(1) Behavioral contracts: The researcher will negotiate
a contract with the participant and separately with
the caregiver, if any, in which they agree to comply
with the intervention including completion of all
assignments and using the paretic hand on specific
activities of daily living as much as possible outside
the lab. The negotiated document will be signed by
the participant, caregiver, and researcher to
emphasize the character of the document as a
(2) Activity tracking: The Motor Activity Log (MAL)
[111] will be administered at baseline and reviewed
weekly (in person during 6-week intervention and
in weekly phone contacts following intervention) to
track amount and quality of paretic hand use in
daily living and to keep participantsattention on
use of the paretic hand at home.
(3) Problem solving: The therapist will help
participants think through barriers to using the
paretic hand at home and ways to overcome them
(e.g., use modified tools, ensure safe environment)
at each visit during the 6-week intervention and in
weekly phone contacts following intervention.
(4) Daily home diary: Specific activities that the
participant can try using the paretic hand at home
will be determined and written down. The
participant will record how many times s/he has
used the paretic hand for the specified activity.
(5) Home skill assignment: Participants will be assigned
to perform 4 specific tasks with the paretic hand
daily with specified repetitions and record on a
written check-off sheet during 6-week intervention.
The tasks will be chosen to improve the
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participants most significant movement deficits.
Following intervention, participants will be pre-
scribed a written individualized home skill practice
program entailing specific tasks to practice with
specified repetitions for each day of the week for 4
weeks. When noncompliance is indicated for the
daily home diary and home skill assignment, the
therapist will inquire into the reasons and problem-
solve with the participant/caregiver on how to re-
verse the trend.
Criteria for discontinuing or modifying allocated
interventions {11b}
Participants with repeated no shows will be withdrawn.
Strategies to improve adherence to interventions {11c}
The intervention requires in-person visit to the labora-
tory. Support for parking and transportation assistance
will be provided as necessary. The visit schedule will be
printed and handed out to each participant. Reminder
phone calls will be made. A waiting room will be pro-
vided within the building for caregivers. Remuneration
for participation will be provided. All COVID-19 precau-
tions will be taken to ensure health and safety of partici-
pants and study personnel.
Relevant concomitant care permitted or prohibited during
the trial {11d}
Concurrent upper limb rehabilitation is prohibited
during participation in the study. Change in spasticity
medication or botulinum toxin injection in the upper
limb is prohibited during the study. Concomitant care
for other issues is permitted.
Provisions for post-trial care {30}
Participants will be followed up until 1 month post
intervention for adverse events. Necessary medical
treatment will be participantsresponsibilities.
Outcomes {12}
The primary outcome measure is hand function
measured by the WMFT time [55]. The primary time
point is from the baseline to 1-month follow-up. Hand
function will also be assessed using the Box and Block
Test (BBT) [112] and ARAT [113]. Paretic upper limb
use in daily living will be measured using accelerometers
[114] and MAL [111]. The patient-centered outcome
measures of the Stroke Impact Scale, perceived mean-
ingfulness of the intervention [115], and usability feed-
back on TheraBracelet will also be obtained. Other
outcome measures will include sensorimotor grip con-
trol and neural communication for hand grip, quantified
as the digit force directional control [116,117] and EEG
connectivity in the cortical sensorimotor network [118].
Participant timeline {13}
The participant timeline is shown in Fig. 2. A baseline
assessment will take place prior to the intervention. The
intervention will entail a total of 18 task practice
sessions with or without TheraBracelet stimulation over
6 weeks. Hand function assessments will be performed
weekly during the 6-week intervention to examine the
pattern of progress. The post assessment will take place
within a week from the last intervention session. The 1-
month follow-up is to assess retention.
Sample size {14}
The primary objective is to determine clinical potential
of TheraBracelet as measured by WMFT time. Insight
on its minimal clinically important difference (MCID) is
available in literature. Since the minimum detectable
change ranges from 1.0 to 3.4 s [119], it could be
interpreted that greater than 3.4 s change represents true
clinical change. Anchor-based and distribution-based
minimum detectable change and MCID range from 1.5
to 4.36 s [120]. Lang et al. (2008) report change of 19 ±
16 s was perceived as meaningful by acute stroke survi-
vors, while 4 ± 7 s was not perceived as meaningful for
the dominant hand [115]. Variability was high in that
study, where patientsperception of meaningfulness
ranged between 3 and 11 s. In a recent ICARE trial [62],
improvement in WMFT time of 8 ± 3 s after inpatient
rehabilitation for acute stroke survivors (1.5 month post
stroke) was associated with improvement in Stroke Im-
pact Scale hand portion of 37 ± 5 (in percent points)
which substantially exceeded MCID of 25 points (repre-
senting easement for tasks by a full category, e.g., from
very difficultto somewhat difficult)[121]. Based on
these, 4 to 7 s between-group difference in improvement
Fig. 2 Participation timeline. All participants will have a baseline assessment, 6 weeks of task practice therapy with weekly hand function
assessments, post assessment, and 1-month follow-up assessment
Seo et al. Trials (2022) 23:262 Page 7 of 15
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
in WMFT time will be considered minimally clinically
This study will be powered to detect sustained
difference at follow-up of at least 4 s in WMFT between
the treatment and control groups. For the repeated mea-
sures design with a significance level of 0.017 (adjusted
for simultaneously comparing 3 outcomes), at least 80%
power, and 4 time points, for a standard deviation (SD)
of 5.1 s and compound symmetry correlation of 0.92
(both based on our pilot study [53]), sample size of 32
per group will be adequate. We believe this is a very
conservative estimate since we used data from a 2-week
pilot intervention [53] to compute power, and this 6-
week intervention is expected to yield greater effects
[54]. Adjusting for 15% attrition, 38 per group is planned
(total n= 76).
This sample size is sufficient for other outcome
measures at follow-up by allowing detection of the mini-
mum between-group difference in (i) BBT of 5.3 (with
SD = 4.9 from our pilot study [53]) which is approxi-
mately the minimum detectable change of 5.5 [122], (ii)
digit force directional control of 4.9° (SD = 4.54) which
is approximately the group difference at follow-up ob-
served in our pilot study and distinguishes grip control
impairment levels [116], and (iii) EEG connectivity of
0.017 (SD = 0.016) which associates with psychophysical
behavior change [123].
Recruitment {15}
Participants will be recruited from the MUSC Registry
for Stroke Recovery (RESTORE). Currently, the
RESTORE has information of more than a thousand
stroke survivors who have agreed to be contacted for
research (approved MUSC IRB PRO# 37803). The
registry is growing every day, as approximately 500 new
stroke cases are treated at the MUSC Stroke Center
every year. All eligible stroke patients in the inpatient
stroke units as well as the outpatient clinic are contacted
by a dedicated recruiter supported by the NIH-funded
Center of Biomedical Excellence for Stroke Recovery at
MUSC to be enrolled in the registry. In addition to
recruiting stroke survivors from the hospital, we recruit
stroke survivors from the community by having a dedi-
cated outreach therapist from the center visit local
stroke support group meetings and develop relationships
with stroke survivors, caregivers, and clinicians, and also
by organizing community outreach events such as stroke
caregiver summits and stroke recovery community en-
gagement, to establish grassroots connections with
stroke survivors and caregivers in the community. The
center also sends newsletters to survivors, caregivers,
local clinics, and local clinicians to inform them of news,
new events, and new projects. With this effort, the regis-
try has been growing with > 10 new enrollees per month.
In addition, trial information is available via internet
(e.g.,, South Carolina Research Studies
Assignment of interventions: allocation
Sequence generation {16a}
A computer-generated random allocation sequence will
be used. Block randomization will be used to ensure bal-
ance (half in the experimental, half in the control). Block
sizes will be randomly chosen between 8 and 38.
Concealment mechanism {16b}
At the beginning of each intervention session, the
custom-developed software program is used to deter-
mine the sensory threshold. The program requires a par-
ticipant number. Upon completion of the sensory
threshold determination, the program will access the
computer-generated random allocation sequence, find
the assignment information for the participant number,
and apply that group assignment information to the de-
vices vibration output. Therefore, the research
personnel will not be involved in assigning groups and
thus be blinded to the group assignment. Participants
will be blinded, because TheraBracelet stimulation is
subthreshold and both groups will not feel any vibration.
Implementation {16c}
The allocation sequence will be generated by the
computer. The approved study staff will enroll
participants. The custom-developed program will assign
participants to the group according to the computer-
generated allocation sequence.
Assignment of interventions: blinding
Who will be blinded {17a}
Participants, care providers, intervention providers,
outcome assessors, and data analysts except for the
primary biostatistician will be blinded to the group
Procedure for unblinding if needed {17b}
A permission for unblinding will be deliberated and
reviewed by the Data and Safety Monitoring Board
(DSMB) if unanticipated intervention-related serious ad-
verse events warrant investigation using the group as-
signment information.
Data collection and management
Plans for assessment and collection of outcomes {18a}
The outcome assessment timeline is provided in Fig. 2.
All clinical hand function tests (WMFT, BBT, and
ARAT) will be administered by a blinded research
therapist, videotaped, coded in names, and scored by
raters who are blinded to the group assignment as well
Seo et al. Trials (2022) 23:262 Page 8 of 15
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
as timing of the videos (i.e., before or how many weeks
after the intervention). Raters will be trained until
excellent intra/interrater reliability is met with
correlation greater than 0.9.
WMFT time has been validated for test-retest and
interrater reliability in chronic stroke survivors [124,
125], and its minimal detectable change has been estab-
lished [119]. WMFT time showed responsiveness to
TheraBracelet treatment in our pilot study [54]. BBT
and ARAT have also been validated for test-retest and
interrater reliability [122,126128] and shown to be re-
sponsive to changes [112,129] in stroke survivors. Min-
imal detectable change for BBT [122] and minimal
clinically important difference for ARAT have been re-
ported [115].
To gauge what participants perceive they can do
functionally that they could not do before, we will obtain
the Stroke Impact Scale hand and activities of daily
living subscales [121,130]. MAL [111] is used to assess
the perceived quantity and quality of the paretic hand
use in activities of daily living as part of the transfer
package. The perceived meaningfulness of the
intervention will be obtained on a 7-point Likert scale
[115] (1 = much better, 2 = a little better, meaningful, 3
= a little better, not meaningful, 4 = about the same, 5 =
a little worse, not meaningful, 6 = a little worse, mean-
ingful, 7 = much worse) after completion of the inter-
vention. Usability feedback [131] will also be obtained
for TheraBracelet.
Accelerometers have been used to objectively capture
changes in stroke survivorsupper limb usage in daily
living before and after therapy [132]. Although
accelerometer data can be influenced by the whole body
motion (e.g., walking) or non-purposeful upper limb
movement, accelerometer data have been shown to sig-
nificantly correlate with the number of observed pur-
poseful repetitions [133135] and adequately represent
changes in the amount of functional upper limb use
[114]. Tri-axial accelerometers (GT9X Link, ActiGraph,
Pensacola, FL, USA) will be worn on each wrist for 3
days to capture upper limb activity of an average day
[114]. Accelerometers will not interfere with TheraBra-
celet, as accelerometers are worn outside the laboratory
and TheraBracelet is worn in the laboratory during ther-
apy only. From 3-dimensional limb acceleration data re-
corded in 1 s bins over days [132], we will compute the
duration and intensity of the paretic upper limb move-
ment relative to the nonparetic limb (use ratioand
magnitude ratio,respectively) [132,135] as objective
outcome measures.
Sensorimotor grip control will be quantified using the
well-established biomechanical sensorimotor integration
measures of digit force directional control [116,117,
136138] and efficient scaling of grip force [139144].
Neural communication for hand grip will be quanti-
fied as EEG connectivity [118,145] in the cortical
sensorimotor network during the paretic hand grip.
Accelerometer and sensorimotor grip control will be
analyzed using a custom-scripted code in MATLAB
(The MathWorks, Natick, MA, USA), and neural
communication will be analyzed using Brainstorm
[146] to obtain the final metrics by the blinded re-
searcher post data collection.
Plans to promote participant retention and complete
follow-up {18b}
To promote participant retention and complete follow-
up, effective communication will be maintained between
study staff and participants. Schedules, changes to
schedules, and expectation for each visit will be clearly
Data management {19}
All electronic data will be stored in a password-
protected secure research server. Visit records in paper
will be scanned and stored in the password-protected se-
cure research server. Data will be entered into a
computer-based database. Quarterly data quality assess-
ments will be performed by examining the outcomes da-
tabases for missing data, unexpected distributions or
responses, irregularities, and outliers. Accuracy and
completeness of the data collected will also be ensured.
Confidentiality {27}
The consent and HIPAA forms where personally
identifiable information is recorded will be stored in a
locked cabinet in a locked office. Only study personnel
will have access to this personally identifiable
information. For the video recording of the upper limb
function tests, we will set the camera angle such that the
video recording does not capture the participants face,
while capturing the hand and arm movements and the
interaction between the hand and objects in hand
manipulation. All data will be coded with a participant
code, and no personally identifiable information will be
used to label the data. This means individual results
would not be able to be linked to the participant by
others who review the results of this research. De-
identified paper data including testing sheets document-
ing testing sequences and notes will be stored in a cabi-
net in a key-locked room that is accessible to study
personnel only. The linkage between the participant
identities and participant codes will be stored in a locked
cabinet in a locked room and will be accessible to study
personnel only.
Seo et al. Trials (2022) 23:262 Page 9 of 15
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Plans for collection, laboratory evaluation, and storage of
biological specimens for genetic or molecular analysis in
this trial/future use {33}
This trial does not involve collecting biological
specimens for storage.
Statistical methods
Statistical methods for primary and secondary outcomes
The primary analysis will be a repeated measures
general linear model with compound symmetry
covariance structure (although other structures will be
compared) for each outcome. The dependent variables
will be the change from baseline at the evaluation times.
The primary independent variables are group (treatment
vs. control), evaluation time, and their interaction. We
will also include sex as a biological independent variable
along with its interactions to study sex difference. If the
group×time interaction is significant, the main
hypothesis that there is a group difference at follow-up
will be tested using post hoc tests. Diagnostics will be
performed on the residuals and appropriate actions will
be taken if assumptions are not met. Summary statistics
and graphs with a scatter plot matrix of the outcomes
across time will be reviewed. Analyses will be performed
using SAS© v.9.4. Greater increase in hand function for
the treatment than control (with a significant group×-
time interaction) will support the hypothesis.
In secondary analysis, we will examine the time course
of effects by analyzing the group differences in outcomes
longitudinally (baseline at week 0, intervention week 1
6, post, and follow-up at 10 weeks) and finding the best
fit regression model. This analysis will also inform the
minimum duration to observe a significant effect. We
will also test if the treatment group perceives the inter-
vention more meaningful than the control group. An or-
dinal logistic regression assuming proportional odds will
be considered.
Interim analyses {21b}
No interim analysis is planned. The DSMB may
recommend stopping the study if the study has
unanticipated safety concerns that warrant stopping.
Methods for additional analyses (e.g., subgroup analyses)
There will be no other additional analysis other than the
analyses mentioned above.
Methods in analysis to handle protocol non-adherence and
any statistical methods to handle missing data {20c}
We will use intent-to-treat analysis. If missing data arise,
multiple imputation methods will be applied under the
assumption of missing at random.
Plans to give access to the full protocol, participant level-
data and statistical code {31c}
The protocol will be shared in De-
identified participant-level dataset and/or statistical code
will be shared upon reasonable request in writing.
Oversight and monitoring
Composition of the coordinating center and trial steering
committee {5d}
Study oversight will be provided by the DSMB. The
DSMB will be composed of a board-certified stroke
neurologist, a registered and licensed occupational ther-
apist, and a biostatistician with expertise in design and
analysis of clinical trials. The DSMB members will be
experienced in care of stroke survivors and/or stroke re-
covery research. The DSMB will convene semiannually
to review enrollment and study progression.
The trial management will be performed by the
principal investigator, co-investigators, and the IRB-
approved study personnel. The trial team will meet
weekly or as necessary to discuss the trial setup, oper-
ation, progression, data analysis, interpretation, and dis-
semination. The principal investigator and study
personnel are responsible for day-to-day operation and
organization of the trial including identifying potential
recruits and taking consent.
Composition of the data monitoring committee, its role and
reporting structure {21a}
The DSMB will also ensure the safety of participants
and the validity and integrity of data collected during
the study. The DSMB will review adverse event data and
provide a report to the IRB. The DSMB will be
independent from the sponsor and competing interests.
Adverse event reporting and harms {22}
Adverse events will be solicited at each visit, recorded,
and coded in terms of frequency, severity, relatedness to
the intervention, and unanticipated nature using
established guidelines [147149]. All serious adverse
events will be investigated by an independent medical
monitor to determine relatedness to the intervention.
The report by the independent medical monitor will be
reviewed by the DSMB. All related serious adverse
events will be reported to the IRB as they occur. All
adverse event data will be tabulated and reported to the
DSMB and
Frequency and plans for auditing trial conduct {23}
The sponsor will audit the study at random. The
sponsor will review the study progression, regulatory
compliance, and training compliance of all study
Seo et al. Trials (2022) 23:262 Page 10 of 15
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Plans for communicating important protocol amendments
to relevant parties (e.g., trial participants, ethical
committees) {25}
Any changes will be approved by the IRB prior to being
in effect. Changes will be updated in
Dissemination plans {31a}
Trial results will be disseminated in,in
publications, and in conferences, and in-service/commu-
nity presentations.
In case the sensory threshold changes over time, we will
determine the participants sensory threshold at each
intervention session for both groups. Participants might
request wearing the device more than during therapy
(e.g., at home) but will not be allowed based on the
study need to control wear time. This research will
determine clinical utility of TheraBracelet. If
TheraBracelet is found efficacious, it is expected that
TheraBracelet can be easily integrated in clinical
practice. Enhancing hand function should increase
stroke survivorsindependence and quality of life.
Trial status
Protocol #6. July 28, 2021. Recruitment began
November 2, 2020, and is expected to conclude in
November 2025.
ARAT: Action Research Arm Test; AR(1): Autoregressive; BBT: Box and Block
Test; DSMB: Data and Safety Monitoring Board; EEG: Electroencephalogram;
GABA: Gamma aminobytyric acid; IRB: Institutional Review Board; MAL: Motor
Activity Log; MCID: Minimal clinically important difference; MUSC: Medical
University of South Carolina; NIH: National Institutes of Health;
RESTORE: MUSC Registry for Stroke Recovery; SC: South Carolina;
SD: Standard deviation; TENS: Transcutaneous electrical nerve stimulation;
TMS: Transcranial magnetic stimulation; USA: United States of America;
WMFT: Wolf Motor Function Test
We are grateful for the contribution from Dr. Ashley Wabnitz as an
independent medical monitor. We are grateful for the contribution from
the Zucker Institute of Applied Neurosciences for the device
development. We are grateful for the intellectual input and infrastructure
provided by the NIH/NIGMS P20GM109040 Center of Biomedical
Research Excellence in Stroke Recovery at the Medical University of
South Carolina directed by Dr. Steven Kautz.
Authorscontributions {31b}
NS is the principal investigator and conceived the study. NS, VR, MW, and LB
contributed to study design and development of the proposal. VR is a trial
biostatistician and designed the sample size and statistical analysis plan. GS
and JB administer the intervention. KC administers clinical assessments. CF
developed and KH administers motion capture assessments. CS and AB
administer EEG assessment. CM, CV, and RA serve in the Data and Safety
Monitoring Board. All authors reviewed and approved the final manuscript.
Funding {4}
This work was supported by NIH/NICHD 1R01HD094731-01A1. The study
funder is not involved nor has responsibility in the collection, analysis, and
interpretation of data and writing a manuscript.
Availability of data and materials {29}
Reasonable requests for access to the final trial dataset should be submitted
to the principal investigator.
Ethics approval and consent to participate {24}
The protocol has been approved by the Medical University of South Carolina
IRB Pro00090790. Written informed consent to participate will be obtained
from all participants.
Consent for publication {32}
Not applicable.
Competing interests {28}
NJS is an inventor of the TheraBracelet stimulation. All other authors declare
that they have no competing interests.
Author details
Department of Rehabilitation Sciences, Department of Health Science and
Research, Medical University of South Carolina, 151B Rutledge Ave, MSC 962,
Charleston, SC 29425, USA.
Ralph H. Johnson VA Medical Center, Charleston,
Department of Health Science and Research, Medical University of
South Carolina, 77 President St, MSC 700, Charleston, SC 29425, USA.
Department of Public Health Sciences, Medical University of South Carolina,
135 Cannon St, Charleston, SC 29425, USA.
Department of Neurology,
Medical University of South Carolina, 96 Jonathan Lucas St, MSC 606,
Charleston, SC 29425, USA.
Received: 14 February 2022 Accepted: 28 March 2022
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... Although we were able to show the differences in corticortical connectivity and ERSP between the two groups in this pilot study, a future study may employ a larger study sample and a longer treatment duration as well as a longer follow-up duration. 85 The future larger study may also investigate the influence of other factors on recovery and neural plasticity including sex as a biological variable and lesion size. In addition, this study did not capture EEG channel positions for individual participants. ...
This study investigated the effect of using subthreshold vibration as a peripheral sensory stimulation during therapy on cortical activity. Secondary analysis of a pilot triple-blinded randomized controlled trial. Twelve chronic stroke survivors underwent 2-week upper extremity task-practice therapy. Half received subthreshold vibratory stimulation on their paretic wrist (treatment group) and the other half did not (control). EEG connectivity and event-related de-/re-synchronization for the sensorimotor network during hand grip were examined at pre-intervention, post-intervention, and follow-up. Statistically significant group by time interactions were observed for both connectivity and event related spectral perturbation. For the treatment group, connectivity increased at post-intervention and decreased at follow-up. Event related desynchronization decreased and event related resynchronization increased at post-intervention, which was maintained at follow-up. The control group had the opposite trend for connectivity and no change in event related spectral perturbation. The stimulation altered cortical sensorimotor activity. The findings complement the clinical results of the trial in which the treatment group significantly improved gross manual dexterity while the control group did not. Increased connectivity in the treatment group may indicate neuroplasticity for motor learning, while reduced event related desynchronization and increased event related resynchronization may indicate lessened effort for grip and improved inhibitory control. EEG may improve understanding of neural processes underlying motor recovery.
Full-text available
Rehabilitation device efficacy alone does not lead to clinical practice adoption. Previous literature identifies drivers for device adoption by therapists but does not identify the best settings to introduce devices, the roles of different stakeholders including rehabilitation directors, or specific criteria to be met during device development. The objective of this work was to provide insights into these areas to increase clinical adoption of post-stroke restorative rehabilitation devices. We interviewed 107 persons including physical/occupational therapists, rehabilitation directors, and stroke survivors and performed content analysis. Unique to this work, care settings in which therapy goals are best aligned for restorative devices were found to be outpatient rehabilitation, followed by inpatient rehabilitation. Therapists are the major influencers for adoption because they typically introduce new rehabilitation devices to patients for both clinic and home use. We also learned therapists’ utilization rate of a rehabilitation device influences a rehabilitation director’s decision to acquire the device for facility use. Main drivers for each stakeholder are identified, along with specific criteria to add details to findings from previous literature. In addition, drivers for home adoption of rehabilitation devices by patients are identified. Rehabilitation device development should consider the best settings to first introduce the device, roles of each stakeholder, and drivers that influence each stakeholder, to accelerate successful adoption of the developed device.
Full-text available
Peripheral sensory stimulation augments post-stroke upper extremity rehabilitation outcomes. Most sensory stimulations interfere with natural hand tasks and the stimulation duration is limited. We developed TheraBracelet, low-level random-frequency vibration applied via a wristwatch, to enable stimulation during hand tasks and potentially extend stimulation durations. To determine safety of prolonged exposure to TheraBracelet. Single-site double-blind crossover randomized controlled trial. Chronic stroke survivors were instructed to wear a device on the affected wrist for > 8 h/day everyday for 2 months while coming to the laboratory weekly for evaluations, with a 2-week break between each month. The device applied vibration at 60% and 1% of the sensory threshold for the real and sham month, respectively. The order of the real and sham months was randomized/balanced. Adverse events (AEs) were assessed weekly, including worsening of hand sensation, dexterity, grip strength, pain, or spasticity and occurrence of skin irritation or swelling. Device-related AE rates were compared between the real and sham month. Twenty-five participants completed the study. Six participants (24%) experienced mild AEs involving worsened sensory scores that may be related to the intervention with reasonable possibility. Two experienced them in the real stimulation month only, 3 in the sham month only, and 1 in both months. Therefore, less participants experienced device-related AEs in the real than sham month. Daily stimulation using the device for a month is safe for chronic stroke survivors. Future studies examining the efficacy of pairing TheraBracelet with therapy for increasing neurorehabilitation outcomes are a logical next step. Trial registration: NCT03318341
Full-text available
Peripheral sensory stimulation has been used as a method to stimulate the sensorimotor cortex, with applications in neurorehabilitation. To improve delivery modality and usability, a new stimulation method has been developed in which imperceptible random-frequency vibration is applied to the wrist concurrently during hand activity. The objective of this study was to investigate effects of this new sensory stimulation on the sensorimotor cortex. Healthy adults were studied. In a transcranial magnetic stimulation (TMS) study, resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation for the abductor pollicis brevis muscle were compared between vibration on vs. off, while subjects were at rest. In an electroencephalogram (EEG) study, alpha and beta power during rest and event-related desynchronization (ERD) for hand grip were compared between vibration on vs. off. Results showed that vibration decreased EEG power and decreased TMS short-interval intracortical inhibition (i.e., disinhibition) compared with no vibration at rest. Grip-related ERD was also greater during vibration, compared to no vibration. In conclusion, subthreshold random-frequency wrist vibration affected the release of intracortical inhibition and both resting and grip-related sensorimotor cortical activity. Such effects may have implications in rehabilitation.
Full-text available
Background: Enhancement of sensory input in the form of repetitive peripheral sensory stimulation (RPSS) can enhance excitability of the motor cortex and upper limb performance. Objective: To perform a systematic review and meta-analysis of effects of RPSS compared with control stimulation on improvement of motor outcomes in the upper limb of subjects with stroke. Methods: We searched studies published between 1948 and December 2017 and selected 5 studies that provided individual data and applied a specific paradigm of stimulation (trains of 1-ms pulses at 10 Hz, delivered at 1 Hz). Continuous data were analyzed with means and standard deviations of differences in performance before and after active or control interventions. Adverse events were also assessed. Results: There was a statistically significant beneficial effect of RPSS on motor performance (standard mean difference between active and control RPSS, 0.67; 95% CI, 0.09-1.24; I2 = 65%). Only 1 study included subjects in the subacute phase after stroke. Subgroup analysis of studies that only included subjects in the chronic phase showed a significant effect (1.04; 95% CI, 0.66-1.42) with no heterogeneity. Significant results were obtained for outcomes of body structure and function as well as for outcomes of activity limitation according to the International Classification of Function, Disability and Health, when only studies that included subjects in the chronic phase were analyzed. No serious adverse events were reported. Conclusions: RPSS is a safe intervention with potential to become an adjuvant tool for upper extremity paresis rehabilitation in subjects with stroke in the chronic phase.
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Background. The Motor Activity Log (MAL) and Lower-Functioning MAL (LF-MAL) are used to assess the amount of use of the more impaired arm and the quality of movement during activities in real-life situations for patients with stroke. Objective. This study used Rasch analysis to examine the psychometric properties of the MAL and LF-MAL in patients with stroke. Design. This is a methodological study. Methods. The MAL and LF-MAL include 2 scales: the amount of use (AOU) and the quality of movement (QOM). Rasch analysis was used to examine the unidimensionality, item difficulty hierarchy, targeting, reliability, and differential item functioning (DIF) of the MAL and LF-MAL. Results. A total of 403 patients with mild or moderate stroke completed the MAL, and 134 patients with moderate/severe stroke finished the LF-MAL. Evidence of disordered thresholds and poor model fit were found both in the MAL and LF-MAL. After the rating categories were collapsed and misfit items were deleted, all items of the revised MAL and LF-MAL exhibited ordering and constituted unidimensional constructs. The person-item map showed that these assessments were difficult for our participants. The person reliability coefficients of these assessments ranged from .79 to .87. No items in the revised MAL and LF-MAL exhibited bias related to patients’ characteristics. Limitations. One limitation is the recruited patients, who have relatively high-functioning ability in the LF-MAL. Conclusions. The revised MAL and LF-MAL are unidimensional scales and have good reliability. The categories function well, and responses to all items in these assessments are not biased by patients’ characteristics. However, the revised MAL and LF-MAL both showed floor effect. Further study might add easy items for assessing the performance of activity in real-life situations for patients with stroke.
Background: Uncertain prognosis presents a challenge for therapists in determining the most efficient course of rehabilitation treatment for individual patients. Cortical Sensorimotor network connectivity may have prognostic utility for upper extremity motor improvement because the integrity of the communication within the sensorimotor network forms the basis for neuroplasticity and recovery. Objective: To investigate if pre-intervention sensorimotor connectivity predicts post-stroke upper extremity motor improvement following therapy. Methods: Secondary analysis of a pilot triple-blind randomized controlled trial. Twelve chronic stroke survivors underwent 2-week task-practice therapy, while receiving vibratory stimulation for the treatment group and no stimulation for the control group. EEG connectivity was obtained pre-intervention. Motor improvement was quantified as change in the Box and Block Test from pre to post-therapy. The association between ipsilesional sensorimotor connectivity and motor improvement was examined using regression, controlling for group. For negative control, contralesional/interhemispheric connectivity and conventional predictors (initial clinical motor score, age, time post-stroke, lesion volume) were examined. Results: Greater ipsilesional sensorimotor alpha connectivity was associated with greater upper extremity motor improvement following therapy for both groups (p < 0.05). Other factors were not significant. Conclusion: EEG connectivity may have a prognostic utility for individual patients' upper extremity motor improvement following therapy in chronic stroke.
Subthreshold vibratory stimulation to the paretic wrist has been shown to prime the sensorimotor cortex and improve 2-week upper extremity (UE) therapy outcomes. The objective of this work was to determine feasibility, safety, and preliminary efficacy of the stimulation over a typical 6-week therapy duration. Four chronic stroke survivors received stimulation during 6-week therapy. Feasibility/safety/efficacy were assessed at baseline, posttherapy, and 1-month follow-up. For feasibility, all participants wore the device throughout therapy and perceived the stimulation comfortable/safe. Regarding safety, no serious/moderate intervention-related adverse events occurred. For efficacy, all participants improved in Wolf Motor Function Test and UE use in daily living based on accelerometry and stroke impact scale. Mean improvements at posttherapy/follow-up were greater than the minimal detectable change/clinically important difference and other trials with similar therapy without stimulation. In conclusion, the stimulation was feasible/safe for 6-week use. Preliminary efficacy encourages a larger trial to further evaluate the stimulation as a therapy adjunct.
Background: Peripheral sensory stimulation has been used in conjunction with upper extremity movement therapy to increase therapy-induced motor gains in patients with stroke. The limitation is that existing sensory stimulation methods typically interfere with natural hand tasks and thus are administered prior to therapy, requiring patients' time commitment. To address this limitation, we developed TheraBracelet. This novel stimulation method provides subthreshold (ie, imperceptible) vibratory stimulation to the wrist and can be used during hand tasks/therapy without interfering with natural hand tasks. Objective: The objective was to determine the feasibility of using TheraBracelet during therapy to augment motor recovery after stroke. Design: The design was a triple-blinded pilot randomized controlled trial. Methods: Twelve chronic stroke survivors were assigned to the treatment or control group. All participants completed 2-hour task practice therapy sessions thrice weekly for 2 weeks. Both groups wore a small vibrator on the paretic wrist, which was turned on to provide TheraBracelet stimulation for the treatment group and turned off for the control group to provide sham stimulation. Outcome measures (Box and Block Test [BBT] and Wolf Motor Function Test [WMFT]) were obtained at baseline, 6 days after therapy, and at follow-up 19 days after therapy. Results: The intervention was feasible with no adverse events. The treatment group significantly improved their BBT scores after therapy and at follow-up compared with baseline, whereas the control group did not. For WMFT, the group × time interaction was short of achieving significance. Large effect sizes were obtained (BBT d = 1.43, WMFT d = 0.87). No indication of desensitization to TheraBracelet stimulation was observed. Limitations: The limitation was a small sample size. Conclusions: TheraBracelet could be a promising therapy adjuvant for upper extremity recovery after stroke.
Active and sports fashion in the high-end market focuses on fit, superior comfort and functional performance for various end-uses. However, the engineering design of sports gloves in relation to hand anthropometry measurements remains unclear. In this study, two types of ready-to-wear sport gloves, namely, war-gaming glove and hiking glove were purchased from the market. The glove dimensions, fabrication properties and the effect of glove fit on hand and finger dexterity were investigated. Thirty female individuals (20–29 years old) participated a series of hand performance tests and subjective perception rating assessments towards the gloves. Results indicated that the active range of motion of fingers, finger tactile sensitivity, gripping strength and ability to handle pegs and marbles decreased with the use of gloves compared with bare hands. The perceptions of comfort and ease of hand motions decreased with the increased of wear time. The glove fit in terms of finger length dimensions was significantly correlated with hand grip force. The glove fit in hand, wrist and finger circumference dimensions had significant impact on the ability to handle small objects. It is suggested that hand length, hand circumference, finger circumference and the ratio of finger length to palm length should be considered in the design and development of gloves to improve hand performance and comfort.
This historical review describes in the first section endeavors to develop a method to record the normal traffic of impulses in human nerves, designated microneurography. The method was developed in the Department of Clinical Neurophysiology of the Academic Hospital in Uppsala, Sweden, starting in 1965. Microneurography involves the impalement of a peripheral nerve with a tungsten needle electrode. Electrode position is adjusted by hand until activity of interest is discriminated. A similar technique had not previously been tried in animal preparations; hence the large number of successful studies based on recording afferent activity in other mammals did not offer pertinent methodological guidance. For two years, the two scientists involved impaled their own nerves for testing various kinds of needle electrodes and exploring neural systems, while carefully watching for signs of nerve damage. Temporary paresthesiae were common, whereas enduring sequelae never followed. Single unit impulse trains may be discriminated, even those originating from unmyelinated fibers. An explanation for the discrimination of unitary impulses with the coarse electrode employed is inferred on the basis of electrical circumstance of the electrode in the flesh and impulse shapes, as discussed in the second section. Microneurography, and the microstimulation of identified single afferents, combined with psychophysical methods and behavioral tests have generated new knowledge particularly regarding four neural systems, namely the proprioceptive system, the cutaneous mechanoreceptive system, the cutaneous nociceptive system, and the sympathetic efferent system to skin structures and muscular blood vessels. Examples of achievements based on microneurography are presented in the last section.