Physical Therapy Reviews

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Interventions combined with task-specific training

to improve upper limb motor recovery following
stroke: a systematic review with meta-analyses

Sarah R. Valkenborghs, Robin Callister, Milanka M. Visser, Michael Nilsson &

Paulette van Vliet

To cite this article: Sarah R. Valkenborghs, Robin Callister, Milanka M. Visser, Michael Nilsson
& Paulette van Vliet (2019): Interventions combined with task-specific training to improve upper
limb motor recovery following stroke: a systematic review with meta-analyses, Physical Therapy
Reviews, DOI: 10.1080/10833196.2019.1597439

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PHYSICAL THERAPY REVIEWS
https://doi.org/10.1080/10833196.2019.1597439

Interventions combined with task-specific training to improve upper limb

motor recovery following stroke: a systematic review with meta-analyses
Sarah R. Valkenborghsa,b,c,d , Robin Callistera,c,d , Milanka M. Vissere , Michael Nilssonb,c,e and
Paulette van Vlietb,c
a
Priority Research Centre for Physical Activity and Nutrition, University of Newcastle, Newcastle, NSW, Australia; bPriority Research
Centre for Stroke and Brain Injury, University of Newcastle, Newcastle, NSW, Australia; cCentre for Research Excellence in Stroke
Rehabilitation and Recovery, Hunter Medical Research Institute, Newcastle, NSW, Australia; dSchool of Biomedical Science and
Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; eSchool of Medicine and Public Health,
University of Newcastle, Callaghan, NSW, Australia

ABSTRACT ARTICLE HISTORY

Background: Upper limb (UL) hemiparesis is a common, disabling and persistent problem, Received 17 August 2018
and a major contributor to poor well-being and quality of life in persons after stroke. Revised 15 February 2019
Conventional UL rehabilitation has had limited success. Novel combined interventions are Accepted 17 March 2019
being investigated in an effort to stimulate greater recovery.
KEYWORDS
Objective: To identify and assess the efficacy of interventions combined with task-specific Stroke; rehabilitation; upper
training aimed at UL motor recovery after stroke. limb; task-specific training;
Methods: A systematic search was undertaken in databases including MEDLINE, MEDLINE In- motor function
Process, EMBASE, AMED, CINAHL, OTseeker, and PEDro. Key inclusion criteria were: peer-
reviewed articles published in English, adults after stroke, and an intervention combined
with task-specific training targeted to improve motor function and/or impairment of the UL
following stroke. Findings from included studies were synthesized qualitatively and meta-
analyzed where there was sufficient homogeneity.
Results: From 3494 citations identified, 120 papers (72 randomized controlled trials and 4
pseudo-randomized controlled trials) were included. Adjunctive interventions (21 categories)
identified included electrical stimulation, transcranial magnetic stimulation, robotic devices,
mental practice, action observation, trunk restraint, virtual reality, and resistance training. Of
the interventions meta-analyzed, only peripheral nerve stimulation demonstrated small add-
itional benefits over those of task-specific training alone for UL impairment, as measured by
the Fugl-Meyer scale (MD 2.69, 95% CI 1.12, 4.26). Several individual studies found benefits
for other interventions combined with task-specific training, but further investigations are
needed to provide more comprehensive evidence of their efficacy.
Conclusion: To date, there is little evidence that adding another intervention to TST confers add-
itional benefits and therefore there is no evidence to guide rehabilitation professionals. Further
research is required as heterogeneity of studies limited ability to conduct meta-analyses.

Introduction
Background
Stroke-attributable upper limb (UL) hemiparesis is a
common, disabling and persistent problem. Motor
impairment and limitations in the use of the UL have
been identified as major contributors to poor well-
being and quality of life amongst persons after stroke
[1–3]. UL rehabilitation has been acknowledged as a
‘top ten’ research priority by persons after stroke, as
well as their carers and therapists [4].
Fundamentally, therapy aims to enhance a
patient’s ability to perform particular tasks, and
therefore the reasoning behind one rehabilitation
technique, called task-specific training (TST), is
intuitive i.e. simply practice the task (or part of the
task) itself [5, 6]. TST is an umbrella term used to
describe several approaches including task-orien-
tated training and repetitive task training as well as
any combination of the two. TST is a progressive
training program comprising practice of whole tasks
and, where required, practice of the component
parts that can be systematically reassembled in to
the whole task (chaining), with the aim of improv-
ing ability to carry out activities of daily life (ADLs)
[7, 8]. Biomechanical analysis of the whole task
underpins choice of part-practice to facilitate trans-
fer of learning to the whole task. Motor maps in the
primary motor cortex modify in response to task-
specific training, leading to an increase in the area

CONTACT Sarah R. Valkenborghs sarah.valkenborghs@uon.edu.au ATC301, Priority Research Centre for Physical Activity and Nutrition,
University of Newcastle, Callaghan, NSW 2308, Australia.
Supplemental data for this article can be accessed here.
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 S. R. VALKENBORGHS ET AL.
of motor cortex that controls the muscles used dur-
ing the task [9]. TST is a component of the ‘motor
(re)learning’ or ‘movement science’ rehabilitation
approach [10–12] and is regularly combined with
other interventions [10], such as assistive technolo-
gies [13].
Although there is low-moderate quality evidence
that TST can improve motor function in the hand
(SMD 0.25, 95% CI 0.00–0.51) and arm (SMD 0.25,
95% CI 0.01–0.49), the effect sizes are small and
there does not seem to be a dose-response relation-
ship [7, 14, 15]. Since larger doses of task-specific
training may be of little benefit for humans beyond
the window of spontaneous recovery, this empha-
sizes the need to find another potent stimulus to
further increase neuroplasticity and motor function
after stroke. A range of interventions combined with
TST are being investigated and some have begun to
be recommended by national guidelines [16–18]. To
date, there has been no review to identify all the
combinations trialed or meta-analyses to consolidate
the evidence of their efficacy to improve UL motor
recovery after stroke. Compiling these studies will
determine which novel combinations have been
evaluated, which combinations are beneficial, and
which combinations require further evaluation. This
review will also summarize the details of how these
combinations of treatments are typically applied and
how much time is typically dedicated to their deliv-
ery in reported studies.
Objectives
This review has three objectives. The first is to iden-
tify all interventions combined with TST aimed at
UL recovery after stroke reported in the literature.
Second, the quality of the studies investigating these
combined interventions will be examined. Finally, the
efficacy of the combined interventions will be deter-
mined, including meta-analyses where appropriate.
Methods
Selection criteria
Study characteristics
This review was inclusive with regard to study design,
including randomized controlled trials (RCT), cross-
over trials, non-randomized controlled trials, pre-post
study design, quasi-experiments, and case studies.
Participant characteristics
Study participants were required to be aged 18 years
and older with a clinical diagnosis of stroke and
have a stroke-attributable motor dysfunction in the
UL. Inclusion was regardless of initial UL impair-
ment, co-morbidities, time since onset, lesion site,
tissue plasminogen activator (tPA) drug administra-
tion, cognitive impairment or previous strokes.
Intervention characteristics
Studies must have investigated an adjunctive inter-
vention combined with TST targeted to improve UL
motor function/impairment following stroke. An
intervention was classified as TST if it contained
high repetitions of functional tasks relevant to daily
life that was physically performed, in whole or part,
in real-life with the presence of a real tactile object
that is functionally relevant to the task performed.
Only interventions with the adjunctive component
delivered within the same session (defined as within
30 min of the commencement/completion of TST)
were included.
Outcome measures
To identify all interventions combined with TST
reported in the literature, studies were included
regardless of whether appropriate UL motor func-
tion/impairment outcome measures were reported.
For evaluation of efficacy, measures of UL motor
function or impairment were required to be reported.
Search methods for identification of studies
MEDLINE, MEDLINE In-Process, EMBASE, AMED,
and CINAHL were searched from inception until
April 2017. In addition, the following occupational
therapy and physiotherapy databases OTseeker,
Physiotherapy Evidence database (PEDro), Chartered
Society of Physiotherapy Research Database, and
REHABDATA were searched. A search strategy
(Supplemental Table 1) was developed for MEDLINE
by using a combination of controlled vocabulary
(MeSH) and free text terms, and it was modified to
suit other databases.
Study selection
Two review authors screened the titles of the identi-
fied references to identify obviously irrelevant stud-
ies. The abstracts for the remaining studies were
obtained and, two reviewers independently ranked
these as ‘possibly relevant’ or ’definitely irrelevant’.
If both reviewers identified a trial as ‘definitely
irrelevant’, it was excluded. The full text of trials
categorized as ‘possibly relevant’ were retrieved,
reviewed and classified as ‘include’, ‘exclude’ or
‘unsure’. Trials classified as ‘exclude’ by both
reviewers were excluded. If there was disagreement
between reviewers, consensus was sought through
discussion. A third review author was involved if a
decision could not be reached. Reasons were pro-
vided for excluding any ’possibly relevant’ studies.

Data extraction
Two review authors independently extracted the fol-
lowing study data from the included studies in to
an excel spreadsheet:

Study characteristics: study design, year pub-
lished, inclusion and exclusion criteria, partici-
pant numbers, including gender ratio.

Participant characteristics: age, time since stroke,
side of lesion.

Interventions: brief description of the combined
intervention including type, dose (program
length, session duration, frequency and inten-
sity), and comparison intervention.

Outcomes: measures of motor impairment, func-
tion and kinematic data including within- and
between-group results, where reported.
Study authors were contacted by email to obtain
further information or any missing data
where necessary.
Methodological quality
Two review authors independently assessed the
methodological quality of included RCTs and
pseudo-randomized controlled trials using the
Physiotherapy Evidence Database (PEDro) scale,
which independently assesses studies against 10 cri-
teria and categorizes them by score as follows: excel-
lent (9–10), good (6–8), fair (4–5), and poor (<4).
Any disagreement concerning quality assessment
between the two reviewers was resolved through dis-
cussion, including a third review author if necessary.
Meta-analyses for quantitative evaluation
of efficacy
Meta-analyses were undertaken using RevMan5 to
compare change in measures of UL function and/or
impairment between sufficiently homogenous
randomized controlled trials (RCTs) (i.e. same inter-
vention combined with TST and same outcome
measure). Due to the variability of intervention
components and extrapolation to a relatively gener-
alizable stroke population, a random-effects analysis
model was used. Results were reported as unstan-
dardized mean differences (MDs) and deemed stat-
istically significant at p < 0.05. Confidence intervals
and standard errors were converted to standard
deviations (SDs), where necessary. If a study had
more than one intervention arm that was to be
included in the meta-analysis, the sample size of the
shared control group was divided by the number of
included intervention arms to avoid participants
PHYSICAL THERAPY REVIEWS 3
being counted multiple times, with the means and
SDs left unchanged.
Results
Study selection
A flowchart of the literature search is presented in
Figure 1. In total 3494 records were identified, 839
duplicates were removed, and 2655 titles were
screened of which 2058 were excluded as not rele-
vant; 597 abstracts were screened of which 230 were
identified as definitely irrelevant. In total 367 articles
progressed to full text review of which 247 were
excluded, resulting in 120 full-text papers being
included in the review, comprising 118 outcome
papers reporting data for 4461 participants and two
protocol papers.
Study and participant characteristics
The study and participant characteristics are detailed
in Supplemental Table 2. In summary, there were 72
RCTs, four pseudo-randomized controlled trials,
four non-randomized controlled trials, 19 cohort
studies, 14 case studies, and 15 case series. Mean
(SD) ages ranged from 42.6 (9.0) to 78.8 (8.1) years.
The mean (SD) time since stroke ranged from 0.24
(0.12) to 134.4 (182.7) months. Two studies pro-
vided no details on time since stroke, however, the
inclusion criteria for these studies were <3 months
and 1–5 years since stroke. Eligibility criteria were
commonly 6 months (n ¼ 27) or  12 months
(n ¼ 16) post-stroke, and 10 wrist extension
(n ¼ 16). Persons with severe UL impairment were
included in studies combining electrical stimulation
[19–28], robotics therapy [24, 28], dynamic orthoses
[28], and action observation [29] with TST. Studies
were conducted in the United States (n ¼ 43), Japan
(n ¼ 10), England (n ¼ 9), Canada (n ¼ 8), Italy
(n ¼ 6), Germany (n ¼ 5), Brazil (n ¼ 4), Australia
(n ¼ 4), Hong Kong (n ¼ 4), Netherlands (n ¼ 4),
New Zealand (n ¼ 3), Taiwan (n ¼ 3), Denmark
(n ¼ 3), Republic of Korea (n ¼ 2), India (n ¼ 2),
and Switzerland, Spain, Serbia, Scotland, South
Korea, Poland, Israel, and Egypt (n ¼ 1 each), and
undetermined (n ¼ 1). All studies were published
since 2002. There has been a steadily increasing
body of research into the combination of other
interventions with TST (Figure 2). The earliest non-
invasive brain stimulation studies emerged in 2010
and have since formed a large proportion of the
studies since (22 out of 89 studies) that have com-
bined interventions with TST.
4 S. R. VALKENBORGHS ET AL.
Figure 1. Prisma flow diagram.
Figure 2. No. of publications with interventions combined
with TST per year.
Study quality
PEDro scale score for included RCTs and pseudo-
randomized controlled trials were: good (n ¼ 61),
fair (n ¼ 13), and poor (n ¼ 2) (Supplemental Table
3). Of the 76 rated studies, 72 were determined to
have random allocation, 74 reported point estimates
and variability, 64 showed similarity of motor func-
tion/impairment at baseline between intervention
and control groups, 61 studies were assessor
blinded, and 63 had good retention.
Adjunctive interventions combined with TST
Adjunctive interventions were delivered simultan-
eously with TST in 55% of trials, with 37% being
delivered prior to TST and 8% after TST. Twenty-
one categories of adjunctive interventions were iden-
tified and categorized according to definitions by
Pollock et al. [7] as outlined in Supplemental Section
1. Supplemental Table 4 provides an individual sum-
mary description of the intervention from each study.
Supplemental Table 5 shows the detailed results of
each study.
Theta burst stimulation (TBS)
Five studies combined TBS with TST [30–34]. All
five delivered continuous or intermittent (600

Figure 3. rTMS þ TST vs TST alone (WMFT FAS).
Figure 4. rTMS þ TST vs TST alone (WMFT time).
pulses) TBS at 70% [34] or 90% [30–33] motor
threshold before the participants performed TST.
Where reported, total therapy time ranged from
3.75 h (45 min/day for 5 days over 1 week) [34] to
7.5 h (45 min/day for 10 days over 2 weeks) [30, 31].
Of the five studies of TBS þ TST, three were RCTs
(n ¼ 41) and one was a pseudo-randomized controlled
trial (n ¼ 26) [31–34], but there was insufficient
homogeneity to enable pooling for a meta-analysis.
One study found that ipsilesional TBS þ TST
improved UL motor function significantly more than
sham TBS þ TST but there was no difference in
improvement of UL impairment [31]. Two studies
compared ipsilesional M1 intermittent TBS þ TST,
contralesional M1 continuous TBS þ TST and sham
TBS þ TST [32, 33]. One study found no significant
difference between pre- and post-treatments for any
group [33]. The other study found no significant dif-
ference between pre- and post-treatment for the ipsi-
lesional M1 intermittent TBS þ TST or sham
TBS þ TST groups, and a significant decrement in UL
motor function in response to contralesional M1 con-
tinuous TBS þ TST [32]. The fourth RCT measured
grip strength and reported that the M1 iTBS þ TST
group improved grip strength significantly more than
the parieto-occipital vertex stimulation þ TST
group [34].
Transcranial direct current stimulation (tDCS)
Seven studies combined tDCS with TST [35–40].
Four studies applied stimulation before TST [35, 36,
39, 40], and three during TST [37, 38, 41]. Four stud-
ies applied anodal stimulation to the ipsilesional
motor cortex [35, 36, 38, 39], two applied cathodal
stimulation to the contralateral motor cortex [36, 41],
and two used bi-hemispheric stimulation [37, 40].
Total therapy time ranged from 5 h (30 min/day, 5
days/week for 2 weeks) [36] to 43 h (260 min/day
over 10 sessions) [35]. Of the seven studies that used
PHYSICAL THERAPY REVIEWS 5
tDCS þ TST, five were RCTs (n ¼ 94) [35–39], and
one was a pseudo-randomized controlled trial
(n ¼ 12) [41]. Although four studies used the Fugl-
Meyer scale to measure changes in impairment, it
was not possible to perform a quantitative synthesis
as one study used tDCS þ TST while investigating
whether it should be delivered before or after periph-
eral nerve stimulation [35], and another study did
not report numerical values for the Fugl-Meyer scale
[39]. Data were requested from the authors but no
response was received. In general, there appeared to
be favorable significant differences for tDCS þ TST
for UL motor function as measured by the Action
Research Arm Test (ARAT), Motor Assessment
Scale, and Jebsen–Taylor Test of Hand Function, but
there were inconsistent effects for UL impairment.
Repetitive pulse transcranial magnetic stimula-
tion (rTMS)
Eleven studies combined rTMS with TST [42–52].
All studies applied stimulation before TST. Typical
parameters were 1200–2400 pulses of 1 Hz stimula-
tion at 90–110% of motor threshold. Total therapy
time ranged from 11 h (45 min/day, 5 days/week for
3 weeks) [50] to 55 h (2  150 min/day for 11 days)
[47]. Of these 11 studies, six RCTs (n ¼ 220) investi-
gated the effects on UL function and impairment
[42–44, 50–52]. Results from pooling four RCTs
(n ¼ 110) comparing rTMS þ TST to sham
rTMS þ TST found no significant difference for UL
function as measured by the Wolf Motor Function
Test (WMFT) Functional Ability Scale (FAS) (MD
1.38, 95% CI 0.80, 3.56) (Figure 3). There was also
no significant difference in UL function as measured
by the WMFT time (MD 0.78, 95% CI 1.00, 2.55)
which was reported in 3 RCTs (n ¼ 70) (Figure 4).
In the RCTs unable to be pooled, there were incon-
sistent effects for UL function, impairment, and per-
ceived use (Supplemental Table 5).
6 S. R. VALKENBORGHS ET AL.
Figure 5. PNS þ TST vs TST alone (Fugl-Meyer scale).
Figure 6. MTES þ TST vs TST alone (Fugl-Meyer scale).
Electrical stimulation
In total, 35 studies were included which were div-
ided into the six categories described below.
Peripheral nerve stimulation (PNS). Six studies
combined peripheral nerve stimulation with TST.
Five studies delivered PNS before TST [19, 53–56]
and one study delivered PNS during TST [57].
Stimulation was most commonly delivered to the
median (5 studies), radial (2 studies) or ulnar (2
studies) nerves at a variety of intensities and ampli-
tudes. Total therapy time ranged from 18 h
(120 min/day, 3 days a week for 3 weeks) [56] to
63 h (135 min/day, 7 days a week for 4 weeks) [54].
Of the six studies that combined PNS with TST, five
were RCTs (n ¼ 131) [19, 54–57] that investigated
the effect of PNS þ TST on UL function and impair-
ment, and one was a pseudo-randomized controlled
trial (n ¼ 22) that compared subsensory PNS þ TST
to suprasensory PNS þ TST [53]. Results from pool-
ing three RCTs (n ¼ 90) comparing PNS þ TST to
TST alone found a significant benefit for UL impair-
ment (Fugl-Meyer scale MD 2.69, 95% CI 1.12,
4.26) (Figure 5). In the studies unable to be pooled,
three reported significant differences for UL func-
tion that favored PNS þ TST whereas two studies
reported no significant differences between groups
(Supplemental Table 5).
Motor threshold electrical stimulation (MTES).
Twenty-two studies combined MTES with TST
[20–27, 58–72]. 17 studies delivered stimulation dur-
ing TST, [20–23, 25–27, 58, 59, 61–63, 65–69, 71],
three before TST [24, 60, 64], one after TST [73],
one study both before and during TST [72], and
another both during and after TST [70]. Most
studies applied stimulation to the wrist and finger
extensors, but there was a lot of variability in the
stimulation parameters used. Four studies used the
Bioness H-200 forearm/hand orthosis with stimula-
tion of 11 Hz frequency at 36 Hz bursts, with 1:1
7 seconds on/off [20, 22, 26, 58]. Total therapy time
ranged from 10 h (30 min/day, 5 days/week for 4
weeks) [63] or 10.5 h (30 min/day, 7 days/week for 3
weeks) [67, 68] to 283.5 h (135 min/day, 7 days/week
for 18 weeks) [69] or 300 h (300 min/day, 5 days/
week for 12 weeks) [24]. Of the 22 studies that used
MTES þ TST, 12 RCTs (n ¼ 347) investigated the
effects of MTES þ TST on UL function and impair-
ment. Results from pooling four RCTs (n ¼ 72)
comparing MTES þ TST to TST alone found no sig-
nificant difference for UL impairment (Fugl-Meyer
scale MD 2.74, 95% CI 0.97, 6.45) (Figure 6).
There were greater effects when an additional study
that combined sham stimulation with TST in a con-
trol group was added to the meta-analysis (n ¼ 108),
but the difference was still not significant (MD 2.80,
95% CI 0.03, 5.64) (Figure 7). In the studies
unable to be pooled, there were inconsistent results
for UL function, impairment, spasticity, perceived
use, and kinematics (Supplemental Table 5).
Sensory threshold electrical stimulation (STES).
Four studies combined STES with TST [74–77]. Two
studies delivered stimulation before TST [74, 75] and
two during TST [76, 77]. Electrodes or a glove were
used to deliver 200–250 ls pulses at frequencies vary-
ing from 10 Hz to 90 Hz. Total therapy time ranged
from 25 h (60 min/day, 5 days/week for 5 weeks) [76],
to 80 h (120 min/day, 5 days/week for 8 weeks) [74].
Of the four studies that used STES þ TST, only two
were RCTs (n ¼ 58). One study compared STES þ TST

Figure 7. MTES þ TST vs Sham MTES þ TST or TST alone (Fugl-Meyer scale).
to MTES þ TST and found improvements on WMFT
were significantly greater for MTES þ TST than
STES þ TST, but there were no significant differences
on the Motor Activity Log (MAL) and Fugl-Meyer
scale [65]. The other study compared STES þ TST to
sham stimulation þ TST but found no significant dif-
ferences between groups for improvement in UL func-
tion, impairment or perceived amount of use
(Supplemental Table 5) [77].
Dermatomal electrical stimulation. One pre-post
study delivered dermatomal electrical stimulation
during TST [73]. 250 ls pulses of 100 Hz frequency
stimulation (less than motor threshold) were deliv-
ered to the C8 dermatome. Participants underwent
the intervention for an unspecified session time, once
a week for 3 weeks. Participants showed significant
immediate improvements in three functional tasks
when TST was combined with concurrent dermato-
mal electrical stimulation.
Vagus nerve electrical stimulation. One RCT deliv-
ered this stimulation during TST [78]. The therapist
delivered 15  100 ls 0.8-mA pulses @ 30Hz fre-
quency to left vagus nerve during each movement.
Total therapy time was 36 h (120 min/day, 3 days/
week for 6 weeks). No significant differences
between groups for improvement in UL function
and impairment were found using an intention-to-
treat analyses, but significant differences for impair-
ment were found using a per protocol analysis that
favored the vagus nerve electrical stimulation þ TST
group (Supplemental Table 5).
Cortical electrical stimulation. One RCT delivered
cortical electrical stimulation during TST [79]. An
implantable pulse generator delivered 250 ms, 50 or
100 Hz pulses at 50% of motor threshold to the pri-
mary motor cortex. Total therapy time was 65 h
(150 mins/day, 3–5 days/week for 6 weeks).
The cortical electrical stimulation þ TST group had
significantly greater improvement in terms of UL
impairment as measured by the Fugl-Meyer scale
and UL function as measured by the box and block
test, but not the Arm Motor Ability Test
(Supplemental Table 5).
PHYSICAL THERAPY REVIEWS 7
Segmental muscle vibration (SMV)
One RCT delivered SMV after TST [80]. Low-ampli-
tude (10 lm) vibration (120 Hz frequency) was deliv-
ered to biceps brachii and flexor carpi ulnaris while
participants were supine. Total therapy time was 15 h
(90 min/day, 5 days/week for 2 weeks). Significant
differences were found between groups in improve-
ment in a number of kinematic parameters that
favored SMV þ TST (Supplemental Table 5).
Robotics therapy
Twenty-one studies combined robotics therapy with
TST [24, 28, 81–99]. Seven studies used robotics
therapy before TST, 12 studies during TST, and two
studies after TST. There was much variation in the
robotic devices used: some were EMG/EEG activated
[28, 81, 84, 96], some focused on assisting grasp [83,
84, 97], while others focused on transport of the UL
[24, 81, 86, 87, 91, 93]. Where specified, total ther-
apy time ranged from 1.5 h (1  90 min session) [82]
to 300 h (300 min/day, 5 days/week for 12 weeks)
[24]. Of the 21 studies that combined robotics ther-
apy with TST, 13 RCTs (n ¼ 435) investigated
robotics therapy þ TST on UL function and impair-
ment. Results from pooling 8 RCTs (n ¼ 248)
comparing robotics therapy þ TST to TST alone
found no significant difference for UL impairment
(Fugl-Meyer scale MD 0.48, 95% CI 1.48, 2.43)
(Figure 8). Also, there was no significant difference
in perceived amount (MD 0.02, 95% CI 0.40, 0.43)
(Figure 9) or quality (MD 0.01, 95% CI 0.40, 0.42)
(Figure 10) of UL use as measured by the Motor
Activity Log (MAL) from 3 RCTs (n ¼ 101). In the
studies unable to be pooled, there were inconsistent
results for UL function, impairment, perceived use,
and kinematics (Supplemental Table 5).
Dynamic orthoses
Seven studies combined the use of dynamic orthoses
with TST [60, 97, 100–104]. One study used
dynamic orthoses before TST and six studies during
TST. Four studies used the SaeboFlex orthosis, one
used the SaeboMAS orthosis, and the other two
studies used a similar orthosis that involved both
the proximal and distal UL. Total therapy time
ranged from 17 h (60 min/day for 17 days) [102] to
8 S. R. VALKENBORGHS ET AL.
Figure 8. Robotics þ TST vs TST alone (Fugl-Meyer scale).
Figure 9. Robotics þ TST vs TST alone (MAL AOU).
Figure 10. Robotics þ TST vs TST alone (MAL QOM).
189 h (3  45 min/day, 7 days/week for 12 weeks)
[104]. Of the four studies that combined dynamic
orthoses with TST, three were RCTs (n ¼ 43). One
study compared a wrist-hand orthosis þ TST to a
combination of manual-assisted therapy þ TST and
found no significant between-group differences for
any of the outcome measures [100]. Another study
compared either a pneumatic orthosis þ TST or a
cable orthosis þ TST to TST alone, but found no
significant differences among the three groups [97].
The third study compared dynamic orthoses þ TST
to TST alone and found favorable outcomes for dex-
terity for dynamic orthoses þ TST (Supplemental
Table 5) [103].
Trunk restraint
Five studies used trunk restraint interventions dur-
ing TST [105–109]. All studies used a physical
restraint (e.g. harness, belt, straps) to limit trunk
flexion. Thielman [107] also had an additional
group who were restrained by means of a sensor on
the back of the chair which provided auditory feed-
back in response to reduced trunk pressure. Where
reported, total therapy time ranged from 9 h
(45 min/day, 3 days/week for 4 weeks) [107, 108], to
15 h (60 min/day, 3 days/week for 5 weeks) [105].
All five studies that combined trunk restraint with
TST were RCTs (n ¼ 115). One study compared a
physical stabilizer restraint þ TST to an auditory
sensor feedback þ TST, and found significantly
greater improvement for the auditory sensor group
compared to the stabilizer group [107]. Another
study compared trunk restraint þ TST to resistance
exercise, and found significantly greater improve-
ment in several kinematic measures for the trunk
restraint þ TST [108]. The other three studies com-
pared trunk restraint þ TST to TST alone but were
unable to be combined in a meta-analysis as data
for the Fugl-Meyer scale was either not reported or
not reported in a pool-able form [105, 106, 108].
Data were requested from the authors but no
response was received. Two studies reported signifi-
cantly greater improvement in UL impairment
(Fugl-Meyer scale) and function (Test d’Evaluation
des Membres Sup
erieurs de Personnes Ag
ees
[TEMPA]) for trunk restraint þ TST [105, 109].
The other study reported significantly greater
improvement on kinematic measures of anterior dis-
placement and elbow extension for trunk restraint þ
TST [106].
Virtual reality (VR)
Six studies combined VR with TST [82, 97,
110–113]. Five studies used VR during TST [97,

110–113], and one used VR after TST [114]. Total
therapy time ranged from 10 h (60 min/day, 5 days/
week for 2 weeks) [114] to 45 h (300 min/day for 9
days) [112]. Of the six studies that combined VR
with TST, two were RCTs (n ¼ 39) [97, 114] and
one was a pseudo-randomized controlled trial
(n ¼ 21) [111]. One study compared the effects of
either a pneumatic orthosis þ TST þ VR or a cable
orthosis þ TST þ VR to TST þ VR alone, but no sig-
nificant differences were found between the three
groups [97]. The other two studies compared
VR þ TST to TST alone and had inconsistent results
for improvement of UL impairment (Supplemental
Table 5) [111, 114].
Feedback
Six studies combined feedback with TST, which
were either sub-categories of ‘Feedback on practice’
(4 studies [115–118]) or ‘Prompts to practice’ (2
studies [119, 120]). All feedback on practice was
provided during TST while both prompts to practice
studies provided prompts before TST as well as feed-
back during TST. Prompts were provided by means
of vibrations from a wristwatch. Feedback on prac-
tice was provided by means of movement tracking
sensors with computer screens, internal and external
focus, and cognitive coaching (participants guided
through analytical process to give self-feedback on
movements performed and work out strategies to
improve movement). Total therapy time ranged
from 5 to 7.5 h (20–30 min/day, 5 days/week for 3
weeks) [115] to 42 h (180 min/day, 7 days/week for
2 weeks) [119]. Of the six studies that combined
feedback with TST, three were RCTs (n ¼ 108). One
study compared effects of altering the order of
internal and external focus of attention during TST
and found better effects for feedback inducing an
external focus of attention [116]. The other two
studies compared feedback combined with TST to
TST alone and found inconsistent results
(Supplemental Table 5) [115, 117].
Rhythmic cueing
Two studies combined rhythmic cueing with TST
[121, 122]. Chouhan and Kumar [121] tested two
forms of rhythmic cueing combined with TST
against TST alone: one used visual cueing with dif-
ferent colored boundary markers and objects and
the other used auditory cueing with tasks performed
in pace with a metronome. Hill et al. [122] used an
’interactive metronome’ with a hand sensor to pro-
vide visual and auditory feedback via a computer in
addition to the metronome beat. The total therapy
time was 18 h (120 min/day, 3 days/week for 3
weeks) and 30 h (60 min/day, 3 days/week for 10
weeks), respectively [121, 122]. Both auditory and
PHYSICAL THERAPY REVIEWS 9
visual cueing þ TST resulted in significantly better
improvements than TST alone, but there were no
differences in improvement between the two rhyth-
mic cueing groups (Supplemental Table 5).
Mental practice (MP)
Five studies that combined MP with TST were
included [123–127]. MP guided by an audiotape was
performed after TST in every study. One study had
internal perspective and external perspective groups
[125], and another study had three groups of
increasing duration of MP: 20, 40 or 60 min [124].
The total amount of therapy time varied between
9.6 h (48 min/day, 2 days/week for 6 weeks) to 45 h
(90 min/day, 3 days/week for 10 weeks). Of the five
studies that combined MP with TST, four were
RCTs (n ¼ 91) but were not meta-analyzed due to
heterogeneous outcome measures. Two studies
found that MP þ TST improved motor function and
impairment significantly more than Sham
MP þ TST [126, 127]. One study compared the
effects of internal perspective MP þ TST to external
perspective MP þ TST or TST alone and found no
differences between groups [125]. The other study
compared different durations of MP sessions þ TST
to TST alone and found that MP duration signifi-
cantly predicted improvement on impairment, with
increasing duration related to larger Fugl-Meyer
scale score increases (Supplemental Table 5) [124].
Action observation
Six studies combined action observation with TST, of
which half delivered the action observation before TST
[29, 128, 129] and half delivered it during TST (i.e. par-
ticipant alternated between action observation and task
practice) [130–132]. Action observation occurred via
video in all studies but one [130] where participants
observed performance of tasks by a therapist. The total
amount of time spent doing action observation þ TST
ranged from 6 h (60–90 min/day, 3 days/week for 2
weeks) to 15 h (2  30 min/day, 5 day/week for 3
weeks) although both Franceschini [129] and Sale [29]
adopted a short but frequent 2  15 min/day, 5 day/
week for 4 weeks delivery model.
Of the six studies that combined action observation
with TST, four were RCTs (n ¼ 235). One study com-
pared action observation þ TST þ conventional phys-
ical therapy to conventional physical therapy but
found no significant differences between groups [130].
Two studies compared action observation þ TST to
sham-action observation þ TST, and found significant
differences in improvement for UL function and kine-
matic measures for the experimental group, but no dif-
ferences in improvements between groups for
impairment [129, 131]. The other study compared
action observation þ TST þ standard therapy to sham
10 S. R. VALKENBORGHS ET AL.
action observation þ TST þ standard therapy, and
there were significant differences in improvement
(relative to the maximum recovery potential) for UL
function and impairment that favored the experimen-
tal group (Supplemental Table 5) [29].
Sensory training
Two case series studies combined sensory training
with TST [133, 134]. Sensory training consisted of
sensory discrimination of temperature, weight, tex-
ture, shape, objects, and joint position in the context
of active exploration during TST. The total therapy
time was 40 h (240 min/day, 5 days/week for 2 weeks)
[133] and 55 h (110 min/day for 30 days) [134]. Both
studies had inconsistent results amongst participants.
Aerobic exercise
Two studies delivered aerobic exercise training for
45 min before 45 min of TST [135, 136]. Exercise
was performed on a stationary motor-driven recum-
bent cycle ergometer at 60–80% heart rate reserve
with a voluntary (self-selected) cadence or ‘forced’
(130% self-selected) cadence [136], or 60–69% age-
predicted HRmax at a ‘forced’ cadence [135]. The
total amount of therapy time was 36 h (90 min/day,
3 days/week for 8 weeks) in both studies. Of these
two studies, one was a RCT (n ¼ 17) that compared
either forced exercise þ TST or voluntary exercise þ
TST to TST alone, and found no difference between
the three groups for improvement in UL function,
but a significant difference for improvement in UL
impairment that favored the forced exercise þ TST
group (Supplemental Table 5) [136]. The other
study was a single case study of forced
exercise þ TST and reported improvement in UL
impairment (Fugl-Meyer scale) and function as
measured by the WMFT FAS but not WMFT
Time [135].
Resistance training (RT)
Three RCTs (n ¼ 91) combined RT with TST
[137–139]. Total therapy time varied from 6 h
(30 min/day, 2 days/week, for 6 weeks) to 24 h
(60 min/day, 4 days/week, for 6 weeks). Two studies
used resistance during TST by adding load to objects
(e.g. extra liquid to a jug) [137], or using resistance
bands, weights and varying grip width-span [138].
One study compared RT þ TST to TST alone and
found significant differences in improvement of UL
function and impairment that favored the RT þ TST
group [137]. The other study compared UL RT þ TST
to lower limb RT þ TST and found significant differ-
ences for improvement in UL function based on the
ARAT that favored UL RT þ TST, but no difference
on the 9 Hole Peg Test [138]. The third study [139]
compared RT before TST, including eccentric and
concentric repetitions of various shoulder and elbow
movements at different criterion speeds with an iso-
kinetic dynamometer, to TST alone and found signifi-
cant differences in improvement of UL function that
favored the RT þ TST group, but no differences in
improvement in UL impairment [139].
Discussion
This systematic review identified 118 studies that
had combined another intervention with TST for
UL recovery after stroke. A total of 21 adjunctive
interventions were described, with the most com-
monly combined interventions being robotics and
various forms of electrical stimulation and non-
invasive brain stimulation. Of the 21 interventions
combined with TST, only five were able to be meta-
analyzed, and of these only peripheral nerve stimu-
lation conferred small additional benefits over those
provided by TST alone. A number of other individ-
ual studies found benefits to interventions combined
with TST but further investigations are needed to
provide more comprehensive evidence of their effi-
cacy. This supports a need to continue developing
and researching innovative combinations of inter-
ventions that may prove efficacious in terms of pro-
moting true recovery beyond the window of
spontaneous biological recovery [140].
There was a lot of variability of dose parameters
between studies within and between different cate-
gories of interventions, and it is also noteworthy
that many studies did not have beneficial effects for
TST alone (Supplemental Table 5). Although a
Cochrane review had stated that >20 h of TST was
required to achieve beneficial effects [141], a recent
update has stated that there was no difference
between studies with <20 h and >20 h of TST [15],
and further recent literature has also shown there
is no dose response relationship [14, 142].
Nevertheless, until a minimum dose can be deter-
mined, future studies should provide participants
with a robust dose of the intervention to avoid the
risk of under dosing.
The incremental body of research into the com-
bination of other interventions with TST is an indi-
cation that the field is continuing the search to find
new strategies to improve UL motor recovery after
stroke. The large volume of studies that have com-
bined non-invasive brain stimulation with TST since
2010 suggests greater alignment in the evolution of
assistive technologies with rehabilitation training
that was called for by Timmerman et al.’s systematic
review in 2009 [13]. Other interventions that have
not yet been combined with TST and evaluated for
improving UL motor recovery after stroke in the
research literature include complementary therapy

(e.g. acupuncture, homeopathy), music therapy,
stretching, and surgical interventions [7].
The progressive accumulation of studies combin-
ing different interventions with TST reinforces that
TST is regarded more and more as a core interven-
tion in stroke rehabilitation. Interestingly, guidelines
specify that TST may be used to improve function
in persons with at least some voluntary movement
of the arm and hand [17], but our review identified
the inclusion of persons with more severe impair-
ment in studies combining electrical stimulation
[19–28], robotics therapy [24, 28], dynamic orthoses
[28], and action observation [29] with TST
(Supplemental Table 2). Of these studies, seven were
RCTs of which six found that the combined inter-
vention group improved more than the TST only
group [19–21, 24, 26, 29]. This may indicate that
combining TST with another intervention may
make TST more applicable and accessible to persons
with a more severe disability e.g. use of a robotic
device or motor threshold electrical stimulation to
assist grasp of an object during the repetitive per-
formance of a functional task.
Although many of the interventions combined
with TST yielded no additional improvement, this is
not necessarily a negative finding in all cases.
Several studies that employed robotic devices or
dynamic orthoses during TST were not significantly
different from the groups that performed time-
matched TST alone. If these types of devices are as
effective as therapist-led rehabilitation, they offer a
window of opportunity to reduce costs of staffing as
well as empower patients to practice independently.
Interventions such as virtual reality are also more
engaging for patients and can be employed as means
of increasing the volume of rehabilitation.
A considerable number of new studies have been
published during the time taken to synthesize the
120 papers included in this review, the data from
which may impact upon the findings of this review.
For example, two new adjunctive interventions (1.
mirror therapy and 2. motor
imagery þ EEG þ MTES) have been combined with
task-specific training for the UL after stroke.
Regarding mirror therapy, three studies (one RCT
[143], one crossover RCT [144] and one case series
[145]) have investigated mirror therapy combined
with TST. All three studies found significant, clinic-
ally meaningful within-group improvements in
measures of UL recovery for participants performing
mirror therapy þ TST, which is supported by signifi-
cant between-group differences in the RCT in favor
of mirror therapy þ TST (vs usual care). The sam-
ples of the crossover RCT and RCT were very small
(n ¼ 24 and n ¼ 21, respectively) so further appro-
priately powered trials are required. For motor
PHYSICAL THERAPY REVIEWS 11
imagery, a cohort study innovatively combined
motor imagery, EEG, and MTES (in the form of a
brain-machine interface) with TST and found sig-
nificant improvement in impairment and self-
reported amount of use with medium and large
effect sizes, respectively, suggesting that this too
merits further investigation [146].
The findings of this review were reinforced by
new studies for TST combined with STES [147],
trunk restraint [148], robotic devices [149] and
tDCS [150]. The findings of the review were also
strengthened by new studies on TST combined with
vagus nerve stimulation [151, 152], action observa-
tion [153], feedback to practice [154], and myoelec-
trically triggered MTES [155–157]. Results from two
new RCTs on the effects of MTES þ TST on UL
impairment [158, 159] would have changed the out-
comes of two of the meta-analyses in this review
(Figures 6 and 7) by making the differences between
groups significant in favor of those undergoing
MTES þ TST interventions (previously only trending
towards significant). Therefore it is now plausible
that both PNS þ TST and MTES þ TST may confer
small additional benefits compared to TST alone.
Forest plots for the updated meta-analyses are avail-
able in Supplementary Figures 1 and 2.
Given the extensive existing evidence for some
adjunctive interventions and the further exponential
growth of this literature (as previously illustrated in
Figure 2), we recommend that future reviews of this
literature should focus on a specific category of
adjunctive intervention combined with TST, rather
than combining all of the categories. This would
enhance readability and usability of findings by ena-
bling deeper analysis and interpretation of simi-
lar studies.
Strengths and limitations
The PRISMA statement guided the unbiased con-
ducting of this systematic review with meta-analyses
[160]. All meta-analyses were statistically homoge-
neous, indicating that like studies were being com-
pared, had reasonable participant numbers, and
provided a more robust estimate of likely benefit
than the individual studies alone. Regardless, there
were some unavoidable limitations. Only studies
published in English were included. Another limita-
tion is not using the TIDieR-based data extraction
template for systematic reviews [161]; data extrac-
tion had already commenced when it was published,
and although we considered adopting it, it was
deemed unsuitable for our review given the large
volume of studies that were included. Although 72
RCTS were included in this review, we were limited
in our ability to perform meta-analyses due to
12 S. R. VALKENBORGHS ET AL.
heterogeneity of outcome measures. Even when
some studies had employed the same outcome
measure, they could not be pooled due to the way it
was reported (e.g. omitting standard deviations
(SD), or using the WMFT but only reporting the
score for the functional ability scale or time taken to
complete, but not both).
Suggestions for improving the quality of
conducting and reporting of future studies
It is recommended that investigators of future stud-
ies use the Stroke Recovery and Rehabilitation
Roundtable core outcome measures [162] in order
to increase the homogeneity of measures for future
systematic reviews and meta-analyses. We also sug-
gest that in addition to effect sizes and/or P values,
data should be reported in a form that can be used
in a meta-analysis (either mean changes with SD, or
mean (SD) baseline scores and mean (SD) outcome
scores). Although values such as medians, interquar-
tile ranges, percentage improvement or improve-
ment relative to proportion of possible recovery are
valuable and can enrich a paper, they should be
reported in addition to, but not instead of, means
and standard deviations, so that future systematic
reviews can include them in quantitative syntheses.
To improve the quality and risk of bias of future
studies, designs should include concealed allocation,
blinding of participants and therapists, where pos-
sible, a robust dose of the intervention, and an
intention-to-treat analysis plan.
Conclusion
Many interventions have been combined with TST
with the aim of improving UL motor recovery
after stroke. To date, adding another intervention
to TST has conferred little additional benefits.
Further well-designed and appropriately-reported
studies are required addressing the limitations
identified in this review to determine the efficacy
of combining adjunctive interventions with task-
specific training.
Disclosure statement
No potential conflict of interest was reported by the authors.
Notes on contributors
Sarah Valkenborghs holds a PhD in human physiology.
Her thesis focused on enhancing the efficacy of task-spe-
cific training on upper limb motor recovery after stroke,
with a focus on exercise-induced neuroplasticity.
Professor Robin Callister is an expert in human physi-
ology, with particular expertise in exercise physiology
during recovery from stroke.
Milanka Visser has a background in physiotherapy and is
currently investigating stroke recovery by means of multi-
modal MRI as part of her PhD in Medicine.
Professor Michael Nilsson is a neuroscientist, neurologist
and rehabilitation medicine physician who specialises in
stroke recovery.
Professor Paulette van Vliet is a neuro-rehabilitation
physiotherapist who specialises in upper limb recovery
following stroke.
ORCID
Sarah R. Valkenborghs http://orcid.org/0000-0003-
2259-4682
Robin Callister http://orcid.org/0000-0001-5592-6132
Milanka M. Visser http://orcid.org/0000-0001-
6535-2953
Michael Nilsson http://orcid.org/0000-0002-8826-1621
Paulette van Vliet https://orcid.org/0000-0003-
4122-373X
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