523679

research-article2014
NNRXXX10.1177/1545968314523679Neurorehabilitation and Neural RepairShiner et al

Clinical Research Article

Neurorehabilitation and

Bilateral Priming Before Wii-based

Neural Repair
2014, Vol. 28(9) 828­–838
© The Author(s) 2014
Movement Therapy Enhances Upper Limb Reprints and permissions:
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Rehabilitation and Its Retention After DOI: 10.1177/1545968314523679

nnr.sagepub.com

Stroke: A Case-Controlled Study

Christine T. Shiner1, Winston D. Byblow, PhD2, and Penelope A. McNulty, PhD1

Abstract
Background. Motor deficits after a stroke are thought to be compounded by the development of asymmetric interhemispheric
inhibition. Bilateral priming was developed to rebalance this asymmetry and thus improve therapy efficacy. Objective. This
study investigated the effect of bilateral priming before Wii-based Movement Therapy to improve rehabilitation after
stroke. Methods. Ten patients who had suffered a stroke (age, 23-77 years; 3-123 months after stroke) underwent a 14-day
program of Wii-based Movement Therapy for upper limb rehabilitation. Formal Wii-based Movement Therapy sessions
were immediately preceded by 15 minutes of bilateral priming, whereby active flexion-extension of the less affected wrist
drove mirror-symmetric passive movements of the more affected wrist through a custom device. Functional movement
was assessed at weeks 0 (before therapy), 3 (after therapy), and 28 (follow-up) using the Wolf Motor Function Test
(WMFT), upper limb Fugl-Meyer Assessment (FMA), upper limb range of motion, and Motor Activity Log (MAL). Case-
matched controls were patients who had suffered a stroke who received Wii-based Movement Therapy but not bilateral
priming. Results. Upper limb functional ability improved for both groups on all measures tested. Posttherapy improvement
on the FMA for primed patients was twice that of the unprimed patients (37.3% vs 14.6%, respectively) and was significantly
better maintained at 28 weeks (P = .02). Improvements on the WMFT and MAL were similar for both groups, but the
pattern of change in range of motion was strikingly different. Conclusions. Bilateral priming before Wii-based Movement
Therapy led to a greater magnitude and retention of improvement compared to control, especially measured with the
FMA. These data suggest that bilateral priming can enhance the efficacy of Wii-based Movement Therapy, particularly for
patients with low motor function after a stroke.

Keywords
rehabilitation, cortical excitability, interhemispheric inhibition, upper limb, brain priming

Brain priming has emerged as a strategy to improve the effi-
cacy and retention of rehabilitation after stroke and help
reduce the global disease burden of stroke. The aim of prim-
ing is to enhance the brain’s responsiveness to motor rehabili-
tation by modulating cortical excitability to create a more
neuroplastic environment prior to therapy.1-5 Priming may be
used to rebalance the asymmetry in inhibition known to
develop between the hemispheres after stroke.1-3 This inhibi-
tory imbalance reduces the excitability of the lesioned motor
cortex,1 further reducing motor output and limiting functional
movement and the potential for motor recovery.3,6,7 Therefore,
rebalancing interhemispheric excitability to prime the brain
after a stroke and improve rehabilitation outcomes is a devel-
oping clinical construct. 4,5,7-11
Bilateral priming with repetitive, mirror-symmetric
active-passive movements (active-passive bilateral priming
[APBP]) is a novel priming approach in which a peripheral
movement paradigm circumvents many of the limitations of
more conventional priming strategies.4,5,12-14 A custom device
facilitates rhythmic, bimanual flexion-extension movements
of the wrists in which mechanical coupling enables active
flexion and extension of the less affected wrist to drive the
passive, more affected wrist. Active-passive movements have
been shown to modulate corticomotor excitability when per-
formed specifically in a mirror-symmetric manner.12,14,15 Brief
bilateral priming sessions can (1) increase excitability in the
resting, ipsilesional hemisphere; (2) increase transcallosal
1
Neuroscience Research Australia and the University of New South
Wales, Sydney, Australia
2
Centre for Brain Research, The University of Auckland, Auckland, New
Zealand
Corresponding Author:
Penelope A. McNulty, PhD, Neuroscience Research Australia, Barker
Street, Randwick, NSW 2031, Australia.
Email: p.mcnulty@neura.edu.au
Shiner et al 829

Table 1.  Patient Demographics.

Time after Pretherapy Pretherapy

Patient Age, y Sex stroke, mo Stroke type More affected side Dominant side WMFT time,a s FMA scoreb
1 75 M 10 Hemorrhagic L R 3.2 59
2 23 F 13 Hemorrhagic R R 74.4 42
3 62 M 123 Ischemic R R 8.1 54
4 60 F 24 Hemorrhagic L L 105.2 18
5 77 F 34 Ischemic L R 120.0 5
6 74 M 7 Hemorrhagic R R 12.1 48
7 64 M 24 Ischemic R R 97.3 20
8 68 M 19 Hemorrhagic L L 67.5 46
9 71 F 108 Hemorrhagic R R 4.1 61
10 72 M 4 Ischemic R R 82.8 19

F, female; L, left; M, male; R, right.

a. Wolf Motor Function Test (WMFT) mean time for 15 timed tasks (maximum possible time of 120 seconds per task).
b. Fugl-Meyer Assessment (FMA) upper limb motor subscale (maximum score of 66).

inhibition from the ipsilesional (passive) to the contrale-
sional (active) hemisphere; and (3) increase intracortical
inhibition in the contralesional hemisphere.4,12 These
changes outlasted the priming session, were shown to accel-
erate motor learning in a healthy cohort,14 and contributed to
rebalancing interhemispheric excitability after stroke that
was associated with improved performance in subsequent
motor therapy and increased retention of therapy benefits.4
Few studies have trialed APBP in a population after
stroke. Since the feasibility of this technique was first estab-
lished after stroke in 2004,12 only three studies have inves-
tigated the use of this active-passive movement paradigm as
a brain-priming strategy before stroke therapy: one with
self-directed therapy;4 and a pilot study,13 and a randomized
control trial5 in conjunction with standard in-patient physi-
cal and occupational therapy. The present study extends this
work into a chronic patient cohort undertaking a highly
structured rehabilitation program without the confounding
of concurrent rehabilitation strategies. Here, we assessed
the efficacy of APBP as an adjuvant priming modality to
Wii-based Movement Therapy16 after stroke. We hypothe-
sized that the combined therapy protocol would be well tol-
erated by patients after a stroke and that those who
underwent bilateral priming before Wii-based Movement
Therapy would have greater functional improvement imme-
diately after therapy and better retention at 6 months than a
case-matched cohort of patients who had suffered a stroke
who received Wii-based Movement Therapy alone.
Methods
Participants
Ten community-dwelling patients who had suffered a stroke
were consecutively recruited (Table 1), with a mean ± stan-
dard deviation age of 64.6 ± 15.7 years and 36.6 ± 42.8
months after a stroke. Patients were recruited from Prince
of Wales and St Vincent’s Hospitals, Sydney, and all were
hemiparetic with an upper limb deficit following a unilat-
eral stroke. Inclusion criteria included ≥3 months after a
stroke, stable blood pressure, able to communicate in
English, and cognitive competency assessed as a Mini-
Mental State Examination score ≥24. Exclusion criteria
included receptive aphasia, comorbidities affecting upper
limb sensorimotor function, and participation in other for-
mal rehabilitation programs. All patients gave informed,
written consent, and the study was approved by the Human
Research Ethics Committee, St Vincent’s Hospital, and
conducted in accordance with the Declaration of Helsinki.
Each patient was case matched to an unprimed control
patient from an historic cohort who received the same stan-
dardized protocol of Wii-based Movement Therapy but with-
out bilateral priming. A weighted, hierarchical algorithm was
developed to identify the most appropriate case match for
each patient based on assessments of pretherapy functional
ability and demographic information (Table 2). Each item in
the algorithm was scored for the match between the primed
patient and the candidate case match. The weighting assigned
to each parameter reflected its perceived importance to case
matching. To verify the accuracy of this algorithm, each
primed patient was scored against 4 potential unprimed case
matches by 8 blinded assessors. The case match with the
highest overall score was identified as the most appropriate
unprimed control. Case-matching results are summarized in
Table 3. There were no significant differences between
primed and unprimed groups for any parameter at baseline.
Motor functional assessments were performed at week 0
(immediately before therapy), week 3 (immediately after
the 14-day protocol), and week 28 (6-month follow-up).
Patients’ upper limb functional ability was assessed using
the upper limb motor Fugl-Meyer Assessment17 (FMA) and
the Wolf Motor Function Test18 (WMFT). The Motor
830 Neurorehabilitation and Neural Repair 28(9)

Table 2.  Criteria and Scoring System Used for Case Matching. Active and passive ranges of motion at the shoulder,
elbow, wrist, and digits I and II were assessed using a hand-
Case-matching criteria Score
held goniometer.20 Spasticity of the shoulder, elbow, and
Functional status   wrist was assessed using the Tardieu Scale.21 Lower limb
  WMFT timed tasks, mean time 0-3 function was assessed using the Berg Balance Scale22 and
  Upper limb FMA score 0-3 6-minute walk test.23,24 Patient satisfaction and self-per-
  MAL-QOM score 0-3 ceived functional improvement were rated on a 10-point
Demographics   visual analog scale during posttherapy assessments.
  Months after stroke 0-3 The Box and Block Test25 (BBT) of gross manual dex-
  Dominant vs nondominant hemiparesis 0-3 terity was used before therapy to stratify patients accord-
  Stroke type (ischemic vs hemorrhagic) 0-2 ing to upper limb motor function. Patients capable of
 Age 0-2
picking up and moving >1 block before therapy were clas-
 Sex 0-1
sifed as having high motor function, and those unable to
Maximum possible score 21
pick up or move blocks were classified as having low
Each primed patient was compared to 4 potential control patients motor function.26
(from a total pool of 28) using the functional and demographic criteria
outlined. A score was assigned to each parameter, indicating how closely
the primed patient matched a given control, with weighting assigned Therapy Protocol
so that the maximum possible score for each component reflected
its perceived importance to case matching. For each potential match, Patients completed an intensive 14-day combined protocol
component scores were added to give a total case-matching score out of bilateral priming prior to the standardized Wii-based
of 21. The control patient with the highest total score was selected as
Movement Therapy program, which specifically targeted
the most appropriate case match. FMA, Fugl-Meyer Assessment; MAL-
QOM, Motor Activity Log Quality of Movement subscale; WMFT, Wolf the more affected upper limb (Figure 1). Formal sessions
Motor Function Test. were guided by a therapist, while home practice was self-
directed and when necessary supervised by a carer.
Table 3.  Comparison of Mean Demographics of Primed and
Case-Matched Control Cohorts. Bilateral priming. Each formal therapy session began
with 15 minutes of bilateral priming using a customized
Case-matched table-mounted device. Patients were seated with elbows
Primed patients controls
flexed, forearms semipronated, and both hands secured to
Age, y 64.6 (23-77) 60.5 (22-74) the adjustable hand pieces (Figure 1). They were instructed
Sex, n   to perform rhythmic, voluntary flexion and extension of
 Male 6 6 the less affected wrist and allow the more affected wrist to
 Female 4 4
be passively driven through mirror-symmetric movements
  Time after stroke, mo 36.6 (4-123) 20.3 (5-46)
Etiology, n  
via a mechanical linkage that confers an inertial advan-
 Ischemic 4 5 tage.4 Patients were instructed to focus on the active, less
 Hemorrhagic 6 5 affected wrist, keeping the more affected side relaxed. The
Hand dominance, n   number of wrist flexion-extension cycles in each session
  Dominant more affected 8 5 was recorded, and patients were encouraged to increase the
  Nondominant more affected 2 5 number of movements per session.
Pretherapy WMFT time,a s 57.6 (3.2-120) 56.1 (3.2-120)
Pretherapy FMA scoreb 37.2 (5-61) 36.8 (4-61)
Wii-based Movement Therapy.  The intensive 14-day pro-
Pretherapy MAL-QOM scorec 49.5 (0-133) 51.2 (0-134)
tocol was that developed by Mouawad and colleagues.16
Data are presented as mean (range) unless otherwise specified. APBP, active- Patients completed 60 minutes of formal, supervised ther-
passive bilateral priming.
a. Wolf Motor Function Test (WMFT) mean time for 15 timed tasks (maximum
apy on 10 consecutive weekdays, immediately after bilat-
possible time of 120 seconds per task). eral priming. Home training commenced on day 2 of the
b. Fugl-Meyer Assessment (FMA) upper limb motor subscale (maximum score of program and progressively increased from 15 to 180 min-
66).
c. Total score for 30 items of the Motor Activity Log Quality of Movement utes per day depending on progress and motor ability. Nin-
subscale (MAL-QOM) (maximum score of 150). There were no significant tendo Wii and Wii Sports (Nintendo, Kyoto, Japan) were
differences between groups for any parameter.
used as an upper limb rehabilitation tool. Depending on
individual deficits and functional progress, different games
Activity Log Quality of Movement subscale19 (MAL- were introduced and varied to tailor rehabilitation to each
QOM) was used as an index of the transfer of therapy- patient’s needs. Progress was monitored daily via a motor
induced improvements to the performance of unrelated activity diary, completion of the MAL-QOM, and patient-
activities of daily living. centered problem solving and goal setting.
Shiner et al 831
Data Analysis
Data that were normally distributed were analyzed using
repeated-measures 2-way analyses of variance (ANOVAs)
with factors of group (primed, unprimed) and time (week 0,
3, 28) and post hoc Holm-Sidak analyses for multiple pair-
wise comparisons. Data that were not normally distributed
were analyzed using a 1-way ANOVA on ranks with a post
hoc Tukey test for multiple pairwise comparisons. Normally
distributed data are presented as mean ± standard error of
the mean, and data that were not normally distributed are
presented as median and interquartile range (IQR).
Differences were considered significant when P < .05.
Results
The primed Wii-based Movement Therapy protocol was
well tolerated and successfully completed by all 10 patients.
The 6 patients who could not move any BBT blocks with
their more affected hand before therapy were classified as
having low motor function. The remaining 4 patients with
high motor function moved a mean of 41 blocks (range,
29-51) with the more affected hand. Due to an unrelated
medical condition, 1 patient from the primed group was
unable to complete week-28 follow-up assessments. For
this reason, follow-up data are reported for the 9 remaining
primed patients and 9 unprimed case matches.
FMA
There was a main effect of time on FMA upper limb motor
scores for all patients. The FMA scores improved from
37.2 ± 6.3 to 43.7 ± 5.6 for the primed cohort (F2,17 = 16.8,
P = .002) and from 36.8 ± 7.4 to 40.0 ± 7.3 (F2,17 = 5.238,
P = .008) for the unprimed cohort at week 3 (Figure 2D).
When normalized to pretherapy values, the increased FMA
scores for the primed cohort of 37.3% ± 12.8% were more
than twice those of the unprimed group of 14.6% ± 7.0%.
Despite this, post hoc analyses revealed no difference
between the primed and unprimed groups immediately
after therapy (P = .08). At week 28, there was an interac-
tion between group and time for the FMA, with primed
patients making greater improvements than unprimed
patients (F2,32 = 4.3, P = .02). Primed patients demonstrated
additional improvement at week 28 with a mean score of
48.9 ± 4.7 (F2,17 = 16.8, P = .02), whereas unprimed patients
scored 42.2 ± 8.1, maintaining but not extending the imme-
diate posttherapy gains.
The FMA data from each upper extremity subsection (A:
shoulder, elbow, forearm; B: wrist; C: hand; D: coordina-
tion, speed) were examined independently. There was a
group by time interaction for the coordination and speed sec-
tion (F2,34 = 3.5, P = .04), with primed patients improving
from 2.1 ± 0.5 to 3.1 ± 0.6 at week 3 and unprimed patients
remaining unchanged (2.3 ± 0.7 at week 0 and 2.4 ± 0.7 at
week 3). There were no other subsection interactions
between group and time.
WMFT
The 2 WMFT strength-based assessments showed no sig-
nificant differences with time or group, and therefore, the
WMFT data hereafter refer only to the 15 timed tasks. The
mean WMFT time for the primed patients revealed a non-
significant trend toward improvement at week 3, decreasing
from 57.6 ± 14.6 seconds to 53.1 ± 14.7 seconds (P = .059)
(Figure 2F). At week 28, there was additional improvement
for the primed patients, with the WMFT mean time further
reduced to 40.8 ± 13.5 seconds (F2,17 = 5.5, P = .015). The
WMFT mean time also improved for the unprimed patients
at week 3, decreasing from 56.1 ± 15.1 seconds to 53.0 ±
14.3 seconds, but not significantly. At week 28, the mean
time taken by unprimed patients to complete the WMFT
timed tasks was further reduced to 48.7 ± 15.1 seconds
(F2,17 = 8.2, P = .003). There was no interaction between
group and time for the WMFT (P > .1).
Use of the Hand in Everyday Activities
There was a main effect of time on the MAL-QOM (P <
.001), indicating that both groups made significant improve-
ments in the use of the more affected upper limb in activi-
ties of daily living. Median MAL-QOM scores at week 3
increased from 44 (IQR, 8.8-68.5) to 69 (IQR, 27.3-109) for
the primed cohort (H(2) = 13.6, P < .001) and from 41
(IQR, 4.5-79.3) to 66 (IQR, 27.5-114.25) for the unprimed
group (H(2) = 11.6, P = .001). These improvements were
sustained without differences by both primed and unprimed
groups at week 28, scoring 69 (IQR, 26-131) and 61 (IQR,
50-117), respectively. There was no effect of group on
MAL-QOM scores.
Range of Motion
Passive and active ranges of motion increased at all joints
for primed patients (Figure 3). Improvements were seen at
week 3 for passive measures at digit I of 6.25° ± 2.5° (F2,36
= 6.4, P = .04) and active measures at digit I of 12.1° ± 4.3°
(F2,36 = 6.4, P = .004) and digit II of 13.0° ± 4.9° (F2,36 = 4.3,
P = .02), but not at the shoulder and elbow. The pattern of
improvements in the unprimed group was different. Passive
range of motion increased by 9.2° ± 4.8° at digit II (F2,34 =
3.8, P = .03), with no changes in active range of motion,
although there was a nonsignificant trend for increased
shoulder movement of 4.5° ± 2.4° (P = .07). At week 28,
primed patients maintained their gains in distal active range
832 Neurorehabilitation and Neural Repair 28(9)

pre pre-therapy assessments (week-0)

APBP + formal WMT
WMT home training
Wii Fitness

Guest C
Wii Fitness Age: 60
20
30
Balance
40

post post-therapy assessments (week-3)

50
60
70
80
APR MAY
Speed Stamina

Done

SO N Y

Wii

hours
1
2

pre post
1 2 3 4 5 6 7 8 9 10 11 12 13 14
days

Figure 1.  Combined active-passive bilateral priming (APBP) and Wii-based Movement Therapy (WMT) protocol. During the 14-day
protocol, patients participated in 10 formal therapy sessions (filled symbols). These commenced with 15 minutes of bilateral priming,
which was delivered via a custom table-mounted device (left) in which patients performed rhythmic flexion-extension movements of
their less affected wrist to drive their passive, more affected wrist through mirror-symmetric movements. Priming was immediately
followed by 1 hour of formal Wii-based Movement Therapy. Home practice consisting of Wii-based Movement Therapy activities
began on day 2 of the program (open symbols) and progressively increased in duration. Functional assessments were conducted
before (week 0), immediately after (week 3), and 6 months after (week 28) the intervention period. Patient progress was monitored
daily throughout the 14-day protocol.

of motion in addition to making improvements at the shoul- Priming Repetitions

der of 11.6° ± 3.5° (F2,55 = 9.0, P < .001) and at the elbow of
19.5° ± 7.3° (F2,17 = 5.3, P = .017). There were no changes
in range of motion for the unprimed patients at week 28.
Spasticity
There were no between-group differences for pretherapy
Tardieu Scale scores of shoulder, elbow, and wrist spasticity
or between joints (mean, 1.8 ± 0.3 primed patients and 2.2
± 0.3 unprimed patients). Neither the primed nor unprimed
group had any change in upper limb spasticity at week 3 or
week 28.
The number of wrist flexion-extension cycles completed in
the first priming session varied between patients from 113
to 962. Regardless of the initial count, all patients increased
by a mean of 101.0% ± 20.3%. In session 1, the mean was
626.5 ± 96.47 repetitions, which increased to 1156.4 ±
175.96 by session 10 (P < .001). There was no correlation
between the number of priming repetitions and patient
improvement on the FMA, the most sensitive measure of
functional ability. Similarly, patient improvements on the
FMA, WMFT, and MAL did not correlate with (1) age, (2)
time after stroke, or (3) lesion location for either the primed
or unprimed group.

Lower Limb Measures

For both balance and walking, there was a main effect of
time but not of group. Berg Balance Scale scores at week 3
were increased from 42.2 ± 4.3 to 45.1 ± 3.3 for primed
patients (F2,17 = 3.5, P = .02) and from 44.9 ± 4.3 to 47.8 ±
3.5 for unprimed patients (F2,17 = 6.3, P = .02). Improvements
were maintained at week 28, with primed and unprimed
patients scoring 48.5 ± 2.3 and 47.7 ± 3.8, respectively. The
mean distance of the 6-minute walk test increased for the
primed patients from 340.2 ± 56.2 m to 375.4 ± 63.2 m at
week 3 and increased further to 401 ± 60.1 m at week 28
(F2,17 = 3.7, P = .045). Similarly, the unprimed patients’
mean distance increased from 305.3 ± 59.2 m to 338.3 ±
63.5 m at week 3 and further improved to 346.0 ± 61.8 m at
week 28 (F2,17 = 4.7, P = .027). There were no between-
group differences on measures of lower limb performance.
Satisfaction and Improvement
Regardless of age and level of impairment, all patients
reported high satisfaction with the combined therapy proto-
col. The mean satisfaction score for the primed patients was
9.0 ± 0.4, and their self-perceived improvement was rated
6.9 ± 0.6. The scores for the unprimed group were 8.7 ± 0.4
and 6.8 ± 0.5, respectively.
Discussion
This is the first study to combine bilateral priming with a
comprehensive structured therapy protocol in the chronic
phase after a stroke. The dual therapy of bilateral priming
and Wii-based Movement Therapy was well tolerated and
improved functional movement ability for all patients. This
Shiner et al 833

A stratification - primed B stratification - unprimed primed low

primed high
60

BBT blocks moved

unprimed low
unprimed high
40

20

0
0 20 40 60 80 100 120 0 20 40 60 80 100 120
WMFT mean time (s) WMFT mean time (s)

C baseline (week-0) D change

70 20

60
16
50
pre FMA score

12
40

Δ FMA
30 8
20
4
10

0 0

E F
120 10

0
pre WMFT mean time (s)

96
Δ WMFT (s)

72 -10

48 -20

24 -30

0 -40
primed unprimed week-3 week-28 week-3 week-28

primed unprimed

Figure 2.  Improvements in functional movement ability. All panels contain individual patient data, with mean (solid line) and standard
errors (dashed line). Primed (filled) and unprimed (open) patients with low upper limb motor function are denoted by circles,
and those with high motor function are denoted by diamonds. (A, B) Pretherapy Box and Block Test (BBT) scores plotted against
pretherapy Wolf Motor Function Test (WMFT) mean time for primed (A) and unprimed (B) groups. There was a bimodal distribution
of functional ability in both groups used to stratify patients with high or low motor function. (C) Total upper limb Fugl-Meyer
Assessment (FMA) scores at week 0 for primed and unprimed patients. Maximum possible score of 66 indicated by dashed line. (D)
Change in FMA scores at week 3 and week 28. Primed patients had significantly greater changes than unprimed patients at week 28
(P = .02). (E) Mean time per task at week 0 for 15 timed tasks of the WMFT for primed and unprimed patients. Maximum time
allowed per task (120 seconds) indicated by dashed line. A lower time indicates better function, F. Change in mean time per WMFT
task at week 3 and week 28. Pretherapy completion time indicated by dashed line. A reduction in time represents an improvement.

was despite the heterogeneity of the cohort, ranging from completion of in- and out-patient therapy. While the sample
very low to high motor function before therapy; the extent size of this study is small, its demographic and functional
of chronicity after stroke (up to 123 months); and the prior diversity (Table 1) reflect the broad spectrum of
834 Neurorehabilitation and Neural Repair 28(9)

A 25 primed B 25 unprimed week-3

week-28

20 20

15 15

Δ degrees
Δ degrees

10 10

5 5

0 0

-5 -5
shoulder elbow wrist dig I dig II shoulder elbow wrist dig I dig II

Figure 3.  Changes in range of motion. Pooled patient data, with mean changes in active range of motion at each site tested and
standard errors. (A) Change in active range of motion for primed patients (filled symbols). The solid line indicates change at week 3,
and the dashed line indicates change at week 28. Primed patients had significant gains at digit I (P = .004) and digit II (P = .02) at both
time points, in addition to improvements at the shoulder (P < .001) and elbow (P = .017) at week 28. (B) Change in active range of
motion for unprimed patients (open symbols). Again, the solid line indicates change at week 3, and the dashed line indicates change at
week 28.

impairments after stroke. In this study, patients who
received bilateral priming before Wii-based Movement
Therapy had a significantly greater functional improvement
on the FMA than unprimed patients from an historic cohort
who received Wii-based Movement Therapy alone. This
extends previous findings4 and suggests that bilateral prim-
ing can increase the efficacy of Wii-based Movement
Therapy, particularly for patients with low motor function
after a stroke.
APBP modulates inhibitory pathways both within and
between hemispheres in healthy patients and after
stroke.4,5,12,14 There is growing evidence to suggest that
these inhibitory changes occur via GABAergic pathways in
the cortex,14,15 and it is hypothesized that priming promotes
plasticity in the lesioned hemisphere via down-regulation of
GABAergic inhibition.4,5,14,15 In the present study, bilateral
priming may have enhanced the efficacy of Wii-based
Movement Therapy by creating a cortical environment
more conducive to therapy-induced plasticity.
Functional Status and Its Impact on
Rehabilitation
The exclusion criteria for this study were deliberately mini-
mal to capture patients who may otherwise not receive
upper limb rehabilitation due to their functional impair-
ment. Wii-based Movement Therapy provides a unique
opportunity for patients with low motor function to receive
rehabilitation.27 While the efficacy of more conventional
strategies such as constraint-induced movement therapy is
well documented,28-30 safety concerns31,32 and stringent
selection crtieria29 may render them less suitable for patients
with low motor function. The present results demonstrate
that with appropriate rehabilitation, even patients with
extremely low motor function are capable of substantial
improvement and should be targeted for rehabilitation..
This study was the first to investigate the effect of bilat-
eral priming in patients with low and very low motor func-
tion after stroke. The 6 patients with low motor function in
the present study were unable to move any BBT blocks
before therapy and could not have performed the block
manipulation tasks previously used for bilaterally primed
self-directed therapy.4 When stratified according to motor
function, the FMA and WMFT results of the present study
suggest that these patients may benefit the most from APBP
and Wii-based Movement Therapy (Figure 2). Given the
challenge of identifying suitable and effective rehabilitation
strategies for patients with low motor function after
stroke,33,34 these results suggest that further investigation of
adjunctive bilateral priming is warranted.
The quantitative assessment of motor ability and its
improvement in patients with low motor function is chal-
lenging. The FMA was the most sensitive measure in this
study comprised of patients with predominantly low motor
function. This replicates previous findings, which suggest
that the FMA may be a more salient assessment for patients
after stroke with low motor function than the WMFT.27,35,36
Despite a comprehensive suite of functional assessments
including the FMA, it was evident that no single test ade-
quately captured the diversity of improvements made by
Shiner et al 835
patients with extremely low motor function. The 6 patients
with low motor function in the current study perceived their
improvement as equivalent to that of the pooled unprimed
group (6.2 ± 0.8 vs 6.8 ± 0.5, respectively). This suggests
that the improvements of those with low motor function
were functionally relevant, even when such changes may
not have reached statistical significance or the minimal
clinically important difference.
Differences Between Primed and Control Groups
When FMA data for each upper extremity subsection were
examined independently, a significant effect of priming was
observed for the coordination and speed subsection only. It
is possible that the rhythmic, bilateral nature of priming
movements contributed to greater improvements in coordi-
nation for the primed group. However, this effect has not
been seen previously4,5,13 and requires further investigation.
The patterns of improved active range of motion for
primed and unprimed patients at week 3 were strikingly dif-
ferent (Figure 3). The most prominent improvements for
primed patients occurred distally at the digits, while
unprimed patients showed greater changes in the more prox-
imal elbow and shoulder joints. Bilateral priming may focus
therapy-induced improvement to distal muscles by preferen-
tially modulating inhibition in cortical areas that supply the
muscles directly engaged in the priming movements of wrist
flexion-extension. Passive stretching of the muscles cross-
ing the wrist during priming may also have contributed to
these differences by altering muscle tone. The different
proximal-to-distal patterns of improvement for the primed
and unprimed groups were less divergent at week 28. Primed
patients retained the distal gains in addition to substantial
improvements at the elbow and shoulder, resembling those
of the unprimed group immediately after Wii-based
Movement Therapy. It is possible that priming masked or
delayed posttherapy improvements in proximal range of
motion for the primed group. However, it is uncertain
whether between-group differences in active range of motion
are a direct consequence of priming or reflect the natural
variability of the population with stroke and the inherent
challenge of accurate joint goniometry after stroke.37
Assessments from week 28 indicate that bilateral prim-
ing may influence the retention of therapeutic effects as
well as their magnitude. Monitoring during therapy and
detailed histories at week 28 suggest that between-group
differences at week 3 and week 28 were not due to dispari-
ties in patient compliance and real-world activity levels.
The groups were well balanced for both adherence during
therapy and for later continuation of self-directed therapy
and/or return to real-world activities. The lack of any sys-
tematic differences between groups suggests that compli-
ance, daily activity levels, and/or continuation of therapy
activities were not confounding factors.
Methodological Considerations
There is growing evidence to support the efficacy of both
APBP and Wii-based Movement Therapy, although optimal
therapy implementation is yet to be fully characterized for
either. We saw no evidence of a correlation between the
effect of priming and (1) patient age, (2) lesion location, or
(3) time after stroke, suggesting that these parameters may
have a limited influence on individual responsiveness to
priming. In contrast, stratified FMA data suggest that base-
line functional ability may influence priming efficacy,
whereby patients with low motor function made the greatest
gains (Figure 2). Significant spasticity at the wrists or digits
was previously an exclusion criterion for APBP4,5 but not in
the present study (n = 4). Bilateral priming was well toler-
ated by those with distal spasticity, although preliminary
heat and passive stretching were applied before positioning
in the priming device. Movement speed during priming was
limited by spasticity, paresis, and bradykinesia in the pres-
ent study, and this introduced considerable variability in the
number of priming repetitions per session. It is not clear
whether either movement speed or the number of repeti-
tions is a critical factor for the efficacy of APBP. We saw no
correlation between the number of priming repetitions and
FMA improvements, suggesting that simply increasing the
number of repetitions may not increase the net effect of
priming. However, patients with the most priming repeti-
tions had high motor function, and thus, their improvements
may have been underestimated when using the FMA.36
Similarly, such patients may have less asymmetric inhibi-
tion to rebalance and hence less scope for priming-induced
improvement.
An unexpectedly high incidence of contraindications to
transcranial magnetic stimulation (TMS) in our primed
cohort (9/10) prevented neurophysiological investigations
of priming-induced changes in cortical excitability and is a
limitation of the present study. We can only hypothesize
that similar cortical inhibitory changes to those previously
reported4,5 were induced by bilateral priming in the present
study, but how these interacted with underlying cortical
changes induced by Wii-based Movement Therapy remains
uncertain. We acknowledge that adopting a case-controlled
design for the present study also has limitations. However,
taking into account the sample size and inherent variability
in the population with chronic stroke, this design circum-
vents the potential for significant differences between ran-
domized patient groups at baseline, which may confound
later comparisons.
Advantages of Bilateral Priming and Wii-Based
Movement Therapy
Both Wii-based Movement Therapy and APBP are inexpen-
sive, portable, and suitable for home implementation,
836 Neurorehabilitation and Neural Repair 28(9)
overcoming the rehabilitation limitations of geography,38
resources, and service availability.39,40 Growing evidence
supports the benefits and suitability of Wii-based Movement
Therapy for a diverse patient population, including those
with little residual function after stroke who rarely receive
conventional upper limb rehabilitation.27 The present study
provides the first evidence that bilateral priming is also effi-
cacious for patients with low or very low motor function
after stroke. The active-passive design and inbuilt inertial
advantage of APBP minimize fatigue to accommodate all
patients after a stroke, including those with little or no vol-
untary movement of the more affected upper limb.4 Also,
APBP is suitable for patients with contraindications to more
conventional brain-priming strategies including those that
use cortical stimulation.8,41-43 The high incidence of TMS
contraindications encountered in the present study high-
lights the need for safe and effective priming alternatives.
Rehabilitation strategies have diversified recently to
include nontraditional methods of upper limb rehabilitation,
such as bimanual upper limb training.44,45 While some stud-
ies suggest that bimanual therapies promote superior motor
outcomes to unimanual interventions,46,47 the evidence is
inconclusive,48 and the translation of bimanual therapy
gains to everyday tasks is less successful than more conven-
tional approaches.46,47 In the present study, we used Wii-
based Movement Therapy as a unimanual therapeutic
approach to reflect our primary focus on translating therapy
gains to improved functional ability and quality of life.
Bilateral priming was used as a rehabilitation adjuvant
rather than a therapeutic intervention and as such is distinct
from other bilateral or bimanual arm therapies. However,
by combining a bilateral priming paradigm with a unilateral
therapy, this protocol may confer some advantages of both
bilateral and unilateral approaches to rehabilitation.45,49
Ancillary Benefits of Therapy
Wii-based Movement Therapy benefits a broad spectrum of
impairments after stroke, despite being specifically designed
to target upper limb function.16,27,50 Balance and walking
distance improved for both primed and unprimed patients
after Wii-based Movement Therapy. The absence of a dif-
ference between groups for lower limb measures suggests
that bilateral priming does not confer additional benefits for
uninvolved limbs, nor does it impede generalized improve-
ments promoted by subsequent therapy. Although the main
objective of APBP is to facilitate use-dependent plasticity
by rebalancing cortical inhibition, secondary therapeutic
benefits for range of motion and muscle spasticity become
evident. Patients with wrist spasticity (n = 4) liked the pas-
sive stretching received during priming movements.
Although there were no significant changes in posttherapy
spasticity assessed using the Tardieu Scale, it is possible
that this assessment tool lacked the sensitivity to detect the
improvements in spasticity after APBP reported by patients.
By encouraging an awareness of upper limb movement and
coordinated controlled actions, bilateral priming also
appeared to promote more purposeful and efficient move-
ments bilaterally.
In conclusion, this study provides preliminary evidence
that a novel movement-based method of brain priming can
enhance the efficacy of a novel upper limb rehabilitation
protocol after stroke. Patients who received bilateral prim-
ing prior to Wii-based Movement Therapy had functional
improvements assessed using the FMA that were approxi-
mately twice those of unprimed patients who received Wii-
based Movement Therapy alone. This improvement was
significantly better maintained at week 28, suggesting that
APBP can enhance both the magnitude and retention of
therapy-induced improvements after stroke.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest
with respect to the research, authorship, and/or publication of this
article: Professor Byblow is a named inventor on a patent for a
training device assigned to Uniservices Ltd. Ms Shiner and Dr
McNulty declare no conflicts of interest.
Funding
The author(s) received the following financial support for the
research, authorship, and/or publication of this article: The authors
gratefully acknowledge funding from the National Health and
Medical Research Council of Australia and the New South Wales
Office for Scientific and Medical Research of Australia.
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