See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/221790191

Constraint-induced movement therapy: From history to plasticity

Article in Expert Review of Neurotherapeutics · February 2012

DOI: 10.1586/ern.11.201 · Source: PubMed

CITATIONS READS

23 2,518

3 authors:

Stacy L Fritz Raymond Butts

University of South Carolina American Academy of Manipulative Therapy
68 PUBLICATIONS 5,227 CITATIONS 31 PUBLICATIONS 1,144 CITATIONS

SEE PROFILE SEE PROFILE

Steven L Wolf
Emory University
349 PUBLICATIONS 26,071 CITATIONS

SEE PROFILE

All content following this page was uploaded by Stacy L Fritz on 24 April 2015.

The user has requested enhancement of the downloaded file.

 THEMED ARTICLE y Stroke
For reprint orders, please contact reprints@expert-reviews.com
Stacy L Fritz*1,
Raymond J Butts1 and
Steven L Wolf2,3,4
1
University of South Carolina, Arnold
School of Public Health, Department
of Exercise Science, Physical Therapy
Program, Columbia, SC, USA
2
Emory University, School of Medicine,
Departments of Rehab Medicine,
Medicine, and Cell Biology, Atlanta,
GA, USA
3
Nell Hodgson Woodruff School of
Nursing, Health and Elder Care,
Atlanta, GA, USA
4
Atlanta VA Rehab R&D Center,
Atlanta, GA, USA
*Author for correspondence:
Tel.: +1 803 777 6887
sfritz@mailbox.sc.edu
www.expert-reviews.com
Review
Constraint-induced
movement therapy:
from history to plasticity
Expert Rev. Neurother. 12(2), 191–198 (2012)
Constraint-induced movement therapy (CIMT) is a rehabilitative strategy applied primarily to
the post-stroke population to increase the functional use of the neurologically weaker upper
extremity through massed practice, while restraining the lesser involved upper extremity.
Although recent Cochrane reviews have reported success with CIMT, this therapeutic technique
is difficult to deliver because it requires proper allocation of resources by both clinicians and
patients. Therefore, identifying those individuals who benefit most from the intervention is
essential. Since most studies include heterogeneous populations, the effect of the intervention
for certain subgroups could be masked. Therefore, understanding the possible neuropredictors
of recovery can help target the appropriate populations. This special report briefly presents the
history of CIMT and its underpinnings in the psychology literature; however, the focus is on
brain plasticity with an emphasis on the importance of the type and location of stroke and how
this factor might influence outcomes following CIMT.
Keywords : constraint-induced movement therapy • plasticity • rehabilitation • stroke
Stroke is the leading cause of long-term disability literature. Emphasis is placed on the importance
[1] ; therefore, identifying those individuals who of type and location of the stroke and how this
can recover from directed rehabilitation tech- factor might influence responses to CIMT.
niques is essential. Constraint-induced move- The goal of CIMT is to improve function in
ment therapy (CIMT) is a rehabilitative strategy the more-affected UE [11] . The results of CIMT
used primarily with the post-stroke population. studies have demonstrated significant and last-
This therapy increases the functional use of the ing improvements of UE movement function
neurologically weaker upper extremity (UE) [4,5,12–17] . Collectively, these data have shown
through massed practice while restraining the that CIMT improves function in individuals
lesser involved UE [2] . The signature form of post-stroke with varying levels of impairment.
CIMT includes 10 days of training at 6 h per Patients with less function prior to CIMT tend
day [3,4] . CIMT is reported to significantly to demonstrate less improvements with tradi-
improve functional use of the UE in 20–25% tional CIMT than patients with higher levels
of people with chronic stroke disability [5] . of motor ability [7,18] . CIMT results have been
Limited evidence exists, however, regarding the labeled the most promising evidence that motor
specific characteristics of individuals who can recovery can occur in the post-stroke hand in
best benefit from this intervention [6–10] . Most patients who have some residual, purposeful
of the research has been conducted with hetero- movement [19] . Despite promising evidence for
geneous samples, possibly masking the effect of the efficacy of CIMT, we are just starting to
the intervention for certain subgroups. understand who will benefit from this form of
This review briefly presents the history of therapy. For example, we know that very early
CIMT, including the animal studies upon after a stroke, a high intensity form of CIMT
which its basis was founded and then transi- may be too much [20] , thus a subacute [16] or
tions to suggestions for future CIMT research. chronic [12] application may be more appropriate.
The focus of this review is on brain plasticity, In addition, while active wrist extension is a pre-
but it also addresses the theoretical underpin- dictor of improved motor performance follow-
nings of CIMT as extracted from the psychology ing CIMT [7] , side of stroke, time since stroke
10.1586/ERN.11.201 © 2012 Expert Reviews Ltd ISSN 1473-7175 191
 Review Fritz, Butts & Wolf
(>6 months and beyond) and age of participants are not predictors
of outcomes [6] . However, anatomical predictors of outcomes,
such as size, location or type of stroke, have not been thoroughly
investigated [21] . Selection criteria for participation should be
carefully examined to determine those who best respond to this
intervention and which factors best predict success with CIMT.
Origins of CIMT
The theoretical foundation of CIMT can be traced to the early
1900s with behavioral studies in monkeys rendered hemiplegic
by pyramidal tract lesions [22] . Following observation of these
monkeys moving about freely in their cages, Franz et al. suggested
that motor disabilities were in a large extent the result of disuse.
“The facts which we have already collected indicate that lesions
of the motor cortex or of the upper part of the pyramidal tract in
man do not abolish function, but put the function in abeyance
until such time as the appropriate condition is present for the pro-
duction of movement. We should probably not speak of permanent
paralysis, or residual paralyses, but of uncared-for paralyses. This
we say because many of the conditions which we have met appear
to resemble, if they are not real, phenomena of disuse, rather than
actual inabilities.”
– Franz et al. [23] .
Thereafter, Ogden and Franz [22] provided the initial evidence
for recovery of function through forced use when they immobi-
lized the unimpaired UE of these monkeys and noted use of the
affected UE. They hypothesized that the return of function was
due to behavioral recovery and possible plasticity of the cortex:
“The results are of interest in another direction, in that they
place in the hands of the experimenter the means for the rapid
recovery of motor function so that the ‘vicarious’ functions of other
cerebral parts may be investigated.”
– Ogden and Franz [22] .
After 85 years, the original observations of Ogden and Franz
regarding the possible mechanisms of recovery are still being
echoed in reviews of CIMT [24] . Ogden and Franz’s original work
was followed by studies by Knapp et al. (1963) who observed
that monkeys do not use their UEs in ‘free situations’ follow-
ing unilateral forelimb somatosensory deafferentation [25] . When
the intact UE was restrained, however, the deafferented limb
became the only means by which the monkey could function.
Therefore, when the monkeys were ‘forced’ to use the deaffer-
ented limb, functional return was observed. Taub hypothesized
that the deafferentation led to inactivity and learning on the
part of the animal on how not to use the limb [26] . Functional
return occurred because ‘learned nonuse’ could be overcome with
appropriate behavioral training and subsequent improved limb
use in humans following stroke [27] . Interestingly, when termi-
nal experiments were completed by Pons et al. on some of the
monkeys that had been in Taub’s original experiments, there was
no evidence that overcoming learned nonuse had persisted [28] .
192
Rather, the homuncular representation of the deafferented limb
within the sensory cortex of all monkeys had become invaded by
surrounding facial regions.
A more in-depth explanation of learned nonuse is essential
to better understand the behavioral process and its relationship
to stroke recovery. In the deafferentation model developed by
Taub, the resulting depression of neural activity rendered mon-
keys unable to perform motorically [5] , resulting in less initiation
of movement from the insensate limb and subsequent reluctance
to initiate motion while favoring the intact UE. After a period
of time, however, depression of spinal neuronal shock decreased,
resulting in less edema and greater potential for movement. The
course of events is as follows. The period for suppressed neuronal
activity in monkeys lasted from 2 to 6 months, during which time
they progressively regained the ability to use the affected limb
[18] . Animals first failed in attempts to use the limb immediately
postoperatively, but after continued attempts, they experienced
limited success manifested as ineffective movement, resulting in
decreased use of that extremity. As a result, the monkey learned
to function well in their environment using the remaining three
limbs, and this behavior was positively reinforced. For example,
while using the unaffected arm, the monkey could retrieve food,
groom and be active. Conversely, attempts with the affected UE
resulted in loss of food, possible falls, frustration and general
failure [27,29] . These adverse conditions resulted in suppression of
further attempts, a cycle known as learned nonuse. The monkey
learned there was no benefit to using the affected UE, a behavior
that persisted for several months, even when the limb could poten-
tially become more functional. The movement, therefore, was
available but simply not accessed [27] . Theoretically, the goal of
CIMT is to overcome learned nonuse and to improve functional
use of the affected UE. Restraint of the unaffected arm, follow-
ing the period of diaschisis, necessitates use of the affected arm
to perform activities. This ‘forced shift’ in motivation overcomes
the early learned nonuse.
Translation to human patients after stroke
The early studies involving deafferented monkeys led to a testable
hypothesis in humans with stroke. Following a proof-of-principle
case study [30] , the first formalized study attempting to apply
‘forced use’ in humans to improve UE function following stroke
and brain injury was performed with 25 subjects who were at
least 1-year post-lesion [31] . The subjects chosen had minimal-to-
moderate UE extensor muscle function and wore a sling on the
uninvolved arm that also prevented use of the hand for 2 weeks,
thereby forcing the use of the involved UE. No specific train-
ing was given for the therapy beyond encouragement to use the
affected UE in home-based activities [5] . The results demonstrated
90% improvement of timed scores, suggesting that learned non-
use can be partially reversed via a forced-use paradigm [31] .
The latest systematic review and meta-analysis of 18 CIMT
studies, comprising 755 patients between 1966 and 2010, found
a moderate increase (standardized mean difference = 0.44) in arm
motor function after CIMT, but few of the studies included in this
review demonstrated long-term improvement in patient disability
Expert Rev. Neurother. 12(2), (2012)
 Constraint-induced movement therapy: from history to plasticity
(standardized mean difference = 0.21) [14,32] . The EXCITE trial
demonstrated that some improvements in disability (as measured
by the Stroke Impact Scale) persist for at least 2 years following
10 days of CIMT [10,33] . The EXCITE trial contributed to the
CIMT literature by capturing immediate and long-term change
in a large sample of individuals by using measures of impairment
and disability. The study included 222 individuals and found
statistically significant and clinically relevant changes post-CIMT
compared with the control group and these changes lasted up to
2 years [16,33] .
Wolf cite mean improvements in active wrist and digit exten-
sion to estimate that only 5–30% of patients gain the ability to
‘manipulate and control the environment’ following CIMT [2] ;
however, this distribution is derived from a rather strict opera-
tional definition of improvement and may be an underestimation
of function. In addition, the moderate effects of the Cochrane
review may be a result of the heterogeneity of the sample; in
other words, some individuals may improve a lot, while others
little to none. Therefore, there needs to be better identification of
responders and nonresponders or predictors of success.
Practicality of CIMT methods
Despite aforementioned positive findings of CIMT, a recent
perspective review article by Wolf [2] highlights some possible
shortcomings. CIMT requires proper allocation of time and
personnel, both of which are financially costly. In a time when
reimbursement of physical therapy services is continuously con-
stricting, justifying multiple hours of treatment for CIMT may
be challenging. The practicality of CIMT must also be evaluated
from the patient’s perspective, as 68% of patients appear not to
be interested in participating in the signature form of CIMT
[34] , and only 32% actually comply with the restriction schedule
[35] . Therefore, some options that have been investigated, and
may require further consideration, are to: improve/modify the
methods of CIMT; provide adjunct interventions with CIMT
(e.g., brain stimulation); and better identify those patients who
can be best treated with this intervention.
Various methods of CIMT
As a result of the strict CIMT schedule, some researchers and cli-
nicians have sought alternatives to traditional CIMT. Originally
described by Page and colleagues, modified CIMT (mCIMT)
provides a more practical alternative that demands consecutive
30 min training sessions of therapy, 3 days per week for 10 weeks.
In addition, patients experience shorter constraint times of 5 h
a day during each weekday, as opposed to 90% of waking hours
[36] . Researchers have also attempted many variations of mCIMT
ranging from 30 min to 3 h of treatment a day for 2–10-week
periods with various restraint periods of less than 6 h per day [17] .
The total number of hours activity in mCIMT is often greater
than the total hours in traditional CIMT, but the alternative
version of CIMT may also be less demanding on patients due to
the decreased daily dosage. Conversely, reversal of learned nonuse
may not occur if there is discontinuous restraint of the unaffected
hand. Interestingly, the outcomes of mCIMT are inconsistent.
www.expert-reviews.com
Review
A recent meta-analysis comprising 13 randomized control tri-
als found fairly strong evidence to suggest that participation in
mCIMT results in improved motor ability post-stroke compared
with traditional therapy [17] . Yet, gains in kinematic variables
indicative of the efficiency and smoothness of movement, such a
normalized movement time and normalized total displacement,
were limited and inconsistent [17] . These inconsistencies in kine-
matic findings post-CIMT may be due to variability in dosing and
in the heterogeneity of the inclusion criteria for the studies [37–41] .
Studies comparing long (6 h) versus short (3 h) CIMT
whereby patients were constrained 90% of waking hours for
14 consecutive days have also yielded inconsistent results [42] in
which significant functional improvements of both treatment
types demonstrated effects lasting up to 2 years after treatment
[42] . However, 6 h of supervised CIMT resulted in significantly
greater functional gains than only 3 h of treatment, suggesting
that duration of treatment may be an important consideration
in post-stroke recovery [42] . Yet, a more recent study comparing
6 h of in-clinic, supervised CIMT produced equivalent motor
skill gains compared with 1 h of in-clinic, supervised CIMT fol-
lowed by 5 h of unsupervised practice at home [43] . Neither group
maintained gains 6 months following treatment, but patients
subjectively reported a preference for physical therapist-guided
training, noting greater use and quality of movement of the
affected limb compared with the independent protocol [43] .
Treatment duration must therefore be long enough for patients
to learn and practice new tasks under the supervision of a thera-
pist. Interestingly, a recent retrospective analysis of the EXCITE
trial found that for a 6-h session of CIMT, only about 3.95 h of
the treatment sessions are typically used for task-specific train-
ing [44] . As such, perhaps distributed CIMT provides an appro-
priate solution, as patients receive an equal duration of total
treatment time as traditional CIMT distributed over twice the
number of days. To our knowledge, only one study exists that
has considered distributed CIMT. While participants demon-
strated improvements in both UE movement and function, the
study did not randomize participants, blind graders or include a
control group [45] . Yet to be resolved is determining the relative
contributions of dosing and inherently structured challenges
within the context of task practice. To date, it is still unknown
whether one is more important than the other in producing
meaningful and sustainable improvements in function.
Transition to the role of plasticity
In addition to overcoming learned nonuse, the theoretical
construct of CIMT is based on the plasticity of the cortex
and assumes that plasticity within the nervous system always
remains persistent; thus, functional improvements can occur
at anytime following the insult [5] . In fact, individuals as much
as 18 years post-stroke have demonstrated improvements fol-
lowing CIMT [27] . By engaging the hemiparetic UE in massed
practice of functional tasks, CIMT is believed to cause changes
in the size and excitability of the representation of the paretic
UE within the primary motor cortex, which correspond with
functional improvements [27,46] . Some studies in human and
193
 Review Fritz, Butts & Wolf
nonhuman primates have shown that the neural representation
of hand muscles becomes enlarged when trained on a discrete
motor skill [47–49] or with CIMT [50–53] . However, neuroimag-
ing studies demonstrate a fair amount of variability among use-
dependent, cortical reorganization patterns. While some authors
suggest that differences in plasticity may be due to location of
the lesion, involvement of the corticospinal tract, or changes in
brain architecture, the exact relationship between changes in
brain structure and return of function continues to be a mystery
and warrants further investigation [54] . Furthermore, a better
understanding of the possible neuropredictors of recovery may
help researchers and clinicians target appropriate populations for
CIMT-based interventions.
Intercortical inhibition (ICI) is a well-documented, physiologi-
cal phenomenon that occurs between the two hemispheres of the
brain [55,56] and has the possibility to limit some CIMT outcomes.
Following cortical damage, the ipsilesional hemisphere loses some
of its ability to inhibit the contralesional hemisphere and the con-
tralesional hemisphere tonically inhibits outputs from the dam-
aged hemisphere via transcallosal pathways [55–57] . Persistent ICI
may therefore limit plasticity-dependent functional recovery post-
CIMT. In this regard, bilateral treatment may theoretically be
more advantageous than CIMT to generate an inhibitory signal
from the M1 of the intact and lesioned hemisphere simultane-
ously, resulting in disinhibition of the transcallosal pathway and,
thereby, minimizing ICI. Recent studies suggest that patients with
a severely damaged corticospinal tract may further benefit from
bilateral treatment in order to recruit motor areas from the intact
hemisphere [57,58] . The potential trade off of bilateral treatment,
however, is increased activity of the already overactive hemisphere.
CIMT may help to restore this imbalance by restricting use of
the extremity corresponding with the unaffected hemisphere.
Studies designed to specifically address this question are essential
to understand what form of therapy is best for this subtype of
stroke presentation.
Studies that have investigated active bilateral arm training with
rhythmic auditory cueing post-stroke have demonstrated better
paretic limb function and increased excitation of the ipsilesional
hemisphere compared with patients completing general thera-
peutic excercise [59] . A recent systematic review and meta-ana­lysis
found that bilateral treatment is an effective rehabilitation strategy
in the subacute and chronic stages of stroke recovery (effect size:
0.732; 95% CI: 0.66–0.80) [60] . However, the latest Cochrane
review on this topic notes a lack of well-designed, high-quality
evidence and concludes that bilateral treatment may be no better
(or worse) than usual care or alternative rehabilitation strategies
post-stroke [61] . Moreover, the extent to which bilateral training
fosters greater output from subcortical pathways at the expense
of the residual corticospinal system has yet to be determined but
must be considered in light of the improvements observed in
proximal but not distal joint mobility [62] .
The role of ICI in motor recovery post-stroke is further high-
lighted by brain stimulation studies [63] . Continuous, inhibitory
transcranial magnetic stimulation (TMS) and cathodal trans­
cranial direct cortical stimulation (TDCS) presented over the
194
hand region of the intact motor cortex resulted in increased
excitability of ipsilesional motor areas and improved hand func-
tion post-stroke as compared with placebo stimulation [64,65] .
Another study demonstrated increased voluntary contractions
and purposeful movement of the paretic elbow following 5 days
of low intensity reptitive TMS (rTMS) over the contralesional
M1 combined with motor retraining [66] . Further investigation
is needed to determine the role of ICI in plasticity-dependent,
functional rehabilitation post-stroke. Moreover, a better under-
standing of how ICI may relate to optimal functional training
paradigm selection is required.
The outcome of CIMT interventions post-stroke may therefore
be limited due to persistent ICI, which may inadvertently sup-
press plasticity-dependent recovery. Similarly, an imbalance of
g-aminobutyric acid, which may be due to faulty transporters
within peri-lesional regions, could also limit plastic changes, a
phenomenon known as ‘intracortical inhibition’ [67] . Investigators
have attempted to use rTMS and TDCS within the context of
rehabilitation in order to minimize intracortical inhibition with
varied levels of success. A recent randomized, double-blind, sham-
controlled study found no advantage to using rTMS as an ajunct
to CIMT post-stroke [68] . In contrast, patients with stroke treated
with rTMS-primed physical therapy demonstrated enhanced cor-
tical excitability [69,70] , improved motor skill acquisition [69,70] and
improved function >12 months post-treatment [69] , as compared
with sham stimulation. Following anodal TDCS of the paretic
M1 post-stroke, patients also demonstrated significant improve-
ments on the Jebson–Taylor Hand Function Test compared with
a sham control group [71] .
Investigations aimed at simultaneously minimizing ICI and
intracortical inhibition within the context of motor retraining
strategies, such as CIMT, also require exploration. To our knowl-
edge, only two such studies have examined this possibility. In the
first study, cathodal and anodal TDCS were applied simultane-
ously to the contra and ipsilesional motor cortex, respectively,
during standard physical and occupational therapy [72] . The
combined stimulation group resulted in significantly increased
gains in function compared with the placebo control. In the sec-
ond study, low-intensity, inhibitory TMS applied to the contra­
lesional motor cortex along with high-intensity, excitatory TMS
to the ipsilesional motor cortex resulted in greater pinch force in
the paretic hand than either type of stimulation presented inde-
pendently [56] . More robust, high-quality studies are required to
explore the potential of noninvasive brain stimulation to reduce
ICI and intracortical inhibition in the context of CIMT in order
to achieve more optimal functional outcomes.
Expert commentary
In addition to cortical inhibition, the varied findings of CIMT
studies presently available in the literature are also likely due to
poor research design [32] . In order to better identify those who can
benefit from the intervention, future studies that are appropriately
powered, randomized and inclusive of a matched control group
receiving another (and possibly equally dosed) treatment are essen-
tial. Participant homogeneity is also an important consideration
Expert Rev. Neurother. 12(2), (2012)
 Constraint-induced movement therapy: from history to plasticity Review

that warrants greater attention. Strokes are as unique as the patient
brains in which they reside. As a result, future investigations must
compare patients who are age-matched but also ‘stroke-matched’ in
terms of stroke type as well as lesion location and volume. The best
way to match these patients, however, still needs to be determined.
While one patient may respond well to CIMT, another patient may
benefit from an alternative therapy strategy. As such, heterogeneous
patient populations may lead investigators to conclude erroneously
that there is no difference from the intervention, when subgroups
may have shown success. This type of error can impede progress
toward better rehabilitation strategies.
Although stroke location seems like a logical covariate, this con-
cept remains controversial among investigators. On the one hand,
recent findings suggest that physical and functional improve-
ments in the UE following CIMT are not dependent on regions
of cortical damage [21] . However, the fact that CIMT is a useful
rehabilitation strategy for patients with varied patterns of corti-
cal activation is not in doubt. Whether CIMT results in optimal
plasticity-dependent functional improvement is a different ques-
tion. Studies of patients with a subcortical stroke not involving the
motor cortex or descending motor fibers demonstrate increased
cortical excitability and less blood oxygen level-dependent signal
secondary to decreased intracortical inhibition within the ipsile-
sional motor areas following CIMT, which may be indicative
of enhanced synaptic efficiency [73] . Interestingly, patients with
a cortical stroke and motor cortex and descending motor fiber
involvement have an opposite cortical pattern. The increased
blood oxygen level-dependent response and decreased cortical
excitability may be due to more widespread synaptic requirements
or connectivity secondary to the local damage [73] .
Five-year view
While patterns of cortical recovery are complicated and difficult
to interpret, patients may likely undergo recovery dependent
plasticity in different ways based upon the relative integrity of the
motor cortex and descending corticospinal tract. Believing that
one rehabilitation strategy will fit the needs of all patient types
may be naive. For example, patients with motor cortex lesions
may require more efficient cross-talk between hemispheres,
which might be better facilitated through bilateral training
than with unilateral treatments, such as CIMT. Experiments
designed to disinhibit the contralesional motor areas with low-
intensity TMS and cathodal TDCS may also be less effective for
patients with motor cortex involvement because recovery may
be dependent on communication with the contralateral hemi-
sphere. As such, future investigations of CIMT, with or without
brain stimulation must be, directed toward recruiting a more
neuropathological homogeneous sample to truly evaluate the
effectiveness of the intervention. Therefore, to determine who is
most likely to succeed with this therapy, we further suggest more
stringent classification of patients which should embrace better
criteria for corticospinal tract integrity, inclusive of a measure-
ment of Wallerian degeneration and motor-evoked response via
diffusion tensor imaging and TMS, respectively, as both may
be predictors of patients who will respond favorably to motor
recovery strategies, such as CIMT [74] . Given that plasticity is
possible in the brain regardless of lesion site and all patients have
recuperative potential, optimal motor recovery strategies may
only be realized through use of available technology and better
patient-matched treatments based on cortical recovery patterns.
A strong future direction of this research is to identify the best
responders to CIMT.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with
any organization or entity with a financial interest in or financial conflict
with the subject matter or materials discussed in the manuscript. This
includes employment, consultancies, honoraria, stock ownership or
options, expert testimony, grants or patents received or pending, or
royalties.
No writing assistance was utilized in the production of this
manuscript.

Key issues
• Constraint-induced movement therapy (CIMT) is a rehabilitation strategy that demonstrates that motor recovery is possible following a
stroke.
• Most studies of CIMT have been conducted with heterogeneous populations, possibly masking the effect of the intervention for certain
groups.
• Future studies that are appropriately powered, randomized, have a homogeneous sample, and are inclusive of a matched control group
that receives another (and possibly equally dosed) treatment are essential.
• While recent Cochrane reviews and the EXCITE trial report success with CIMT post-stroke, CIMT is a challenging therapeutic technique
requiring proper allocation of resources by both clinicians and patients.
• While modified CIMT and distributed CIMT have attempted to improve the practicality and feasibility of traditional CIMT, studies that
have looked at these strategies report mixed results, and further investigations are required.
• Understanding the possible neuropredictors of recovery can help researchers and clinicians target the appropriate populations for this
intervention.
• Outcomes of CIMT are believed to be a result of overcoming learned nonuse and plastic changes within the cortex. Bilateral motor
training is an alternative rehabilitation strategy to CIMT that has yielded inconsistent results post-stroke but may be useful in combating
intercortical inhibition and recruiting contralesional motor areas in some patient populations.
• Investigations aimed at simultaneously minimizing intercortical inhibition and intracortical inhibition within the context of motor
retraining strategies such as CIMT are a future direction for this research.

www.expert-reviews.com 195
 Review Fritz, Butts & Wolf
References
Papers of special note have been highlighted as:
• of interest
•• of considerable interest
1 Roger VL, Go AS, Lloyd-Jones DM et al.
Heart disease and stroke statistics – 2011
update: a report from the American Heart
Association. Circulation 123(4), e18–e209
(2011).
2 Wolf SL. Revisiting constraint-induced
movement therapy: are we too smitten with
the mitten? Is all nonuse ‘learned’? and
other quandaries. Phys. Ther. 87(9),
1212–1223 (2007).
3 Page S, Sisto S, Levine P, Johnston M,
Hughes M. Modified constraint induced
therapy: a randomized feasibility and
efficacy study. J. Rehabil. Res. Dev. 38(5),
583–590 (2001).
4 Taub E, Morris DM. Constraint-induced
movement therapy to enhance recovery
after stroke. Curr. Atheroscler. Rep. 3(4),
279–286 (2001).
5 Morris D, Crago J, DeLuca S, Pidikiti R,
Taub E. Constraint-induced (CI)
movement therapy for motor recovery after
stroke. Neurorehabilitation 9, 29–43 (1997).
6 Fritz S, Light K, Clifford S, Patterson T,
Behrman A, Davis S. Descriptive predictors
of outcomes following constraint-induced
movement therapy for individuals with
post-stroke hemiparesis. Phys. Ther. 86(6)
(2006).
• Early investigation into who benefits most
from constraint-induced movement
therapy (CIMT) specifically. It
demonstrated that side of stroke, time
since stroke (>6 months and beyond) and
age of participants are not predictors of
outcomes.
7 Fritz SL, Light K, Patterson T, Behrman A,
Davis S. Active finger extension predicts
outcomes after constraint-induced
movement therapy for individuals with
hemiparesis after stroke. Stroke 36,
1172–1177 (2005).
8 Rijntjes M, Hobbeling V, Hamzei F et al.
Individual factors in constraint-induced
movement therapy after stroke.
Neurorehabil. Neural Repair 19(3),
238–249 (2005).
9 Lin KC, Huang YH, Hsieh YW, Wu CY.
Potential predictors of motor and
functional outcomes after distributed
constraint-induced therapy for patients with
stroke. Neurorehabil. Neural Repair 23(4),
336–342 (2009).
10 Wolf SL, Thompson PA, Winstein CJ et al.
The EXCITE stroke trial: comparing early
196
and delayed constraint-induced movement
therapy. Stroke 41(10), 2309–2315 (2010).
11 Taub E, Uswatt G. Constraint-induced
movement therapy: answers and questions
after two decades of research.
Neurorehabilitation 21(2), 93–95 (2006).
12 Kunkel A, Kopp B, Muller G et al.
Constraint-induced movement therapy for
motor recovery in chronic stroke patients.
Arch. Phys. Med. Rehabil. 80(6), 624–628
(1999).
13 Miltner W, Bauder H, Sommer M,
Dettmers C, Taub E. Effects of constraint-
induced movement therapy on patients
with chronic motor deficits after stroke: a
replication. Stroke 30(3), 586–592 (1999).
14 Corbetta D, Sirtori V, Moja L, Gatti R.
Constraint-induced movement therapy in
stroke patients: systematic review and
meta-analysis. Eur. J. Phys. Rehabil. Med.
46(4), 537–544 (2011).
15 Sirtori V, Corbetta D, Moja L, Gatti R.
Constraint-induced movement therapy for
upper extremities in patients with stroke.
Stroke 41, e57–e58 (2010).
16 Wolf SL, Winstein CJ, Miller JP et al.
Effect of constraint-induced movement
therapy on upper extremity function 3 to 9
months after stroke: the EXCITE
randomized clinical trial. JAMA 296(17),
2095–2104 (2006).
17 Shi YX, Tian JH, Yang KH, Zhao Y.
Modified constraint-induced movement
therapy versus traditional rehabilitation in
patients with upper-extremity dysfunction
after stroke: a systematic review and
meta-analysis. Arch. Phys. Med. Rehabil.
92(6), 972–982 (2011).
Taub E, Crago J, Uswatte G. Constraint-
18
induced movement therapy: a new
approach to treatment in physical
rehabilitation. Rehabil. Psychol. 43(2),
152–170 (1998).
19 Duncan P. Synthesis of intervention trials
to improve motor recovery following
stroke. Top. Stroke Rehabil. 3, 1–20 (1997).
20 Dromerick AW, Lang CE, Birkenmeier RL
et al. Very Early Constraint-Induced
Movement during Stroke Rehabilitation
(VECTORS): a single-center RCT.
Neurology 73(3), 195–201 (2009).
21 Gauthier LV, Taub E, Mark VW, Perkins
C, Uswatte G. Improvement after
constraint-induced movement therapy is
independent of infarct location in chronic
stroke patients. Stroke 40(7), 2468–2472
(2009).
• Demonstrated that while lesion location is
related to motor ability, the degree of
improvement post-CIMT is independent
of lesion location.
22 Ogden R, Franz S. On cerebral motor
control: the recovery from experimentally
produced hemiplegia. Psychobiology 1,
33–47 (1917).
23 Franz SI, Scheetz ME, Wilson AA.
Hemiplegia. J. Am. Med. Assoc. 65(25),
2154 (1915).
• Set the stage for the current intervention
of CIMT and even the idea that ‘other
cerebral parts’ may play a role in recovery
– essentially identifying plasticity as a
mechanism of recovery of function.
24 Wolf SL, Blanton S, Baer H, Breshears J,
Butler AJ. Repetitive task practice: a
critical review of constraint-induced
movement therapy in stroke. Neurologist
8(6), 325–338 (2002).
25 Knapp H, Taub E, Berman A. Movements
in monkeys with deafferented forearms.
Exp. Neurol. 7, 305–315 (1963).
26 Taub E. Movement in nonhuman
primates deprived of somatosensory
feedback. Exerc. Sport. Sci. Rev. 4,
335–374 (1977).
27 Taub E, Uswatte G, Pidikiti R. Constraint-
induced movement therapy: a new family
of techniques with broad application to
physical rehabilitation – a clinical review.
J. Rehabil. Res. Dev. 36(3), 237–251
(1999).
28 Pons TP, Garraghty PE, Ommaya AK,
Kaas JH, Taub E, Mishkin M. Massive
cortical reorganization after sensory
deafferentation in adult macaques. Science
252(5014), 1857–1860 (1991).
29 Russo S. Hemiplegic upper extremity
rehabilitation: a review of the forced-use
paradigm. Neurol. Rep. 19, 17–21 (1995).
30 Ostendorf CG, Wolf SL. Effect of forced
use of the upper extremity of a hemiplegic
patient on changes in function. A
single-case design. Phys. Ther. 61(7),
1022–1028 (1981).
31 Wolf S, Lecraw D, Barton L. Forced use in
hemiplegic upper extremities to reserve the
effect of learned nonuse among chronic
stroke and head-injured patients. Exp.
Neurol. 104, 125–132 (1989).
32 Sirtori V, Corbetta D, Moja L, Gatti R.
Constraint-induced movement therapy for
upper extremities in stroke patients.
Cochrane Database Syst. Rev. (4),
CD004433 (2009).
•• This Cochrane review for CIMT
combined 19 studies with
619 participants to review the efficacy of
Expert Rev. Neurother. 12(2), (2012)
 Constraint-induced movement therapy: from history to plasticity
different forms of CIMT in patients with
hemiparesis.
33 Wolf SL, Winstein CJ, Miller JP et al.
Retention of upper limb function in stroke
survivors who have received constraint-
induced movement therapy: the EXCITE
randomised trial. Lancet Neurol. 7(1),
33–40 (2008).
34 Page SJ, Levine P, Sisto S, Bond Q,
Johnston MV. Stroke patients’ and
therapists’ opinions of constraint-induced
movement therapy. Clin. Rehabil. 16(1),
55–60 (2002).
35 Schaumburg S, Pierce S, Gaffney K,
Gershkoff A. Constraint induced therapy:
moving research into practice. Presented at:
American Congress of Rehabilitation
Medicine Annual Meeting. Orlando, FL,
USA, 11–15 October 1999.
36 Page SJ, Sisto S, Levine P, McGrath RE.
Efficacy of modified constraint-induced
movement therapy in chronic stroke: a
single-blinded randomized controlled trial.
Arch. Phys. Med. Rehabil. 85(1), 14–18
(2004).
37 Wu CY, Chen CL, Tang SF, Lin KC,
Huang YY. Kinematic and clinical analyses
of upper-extremity movements after
constraint-induced movement therapy in
patients with stroke: a randomized
controlled trial. Arch. Phys. Med. Rehabil.
88(8), 964–970 (2007).
38 Caimmi M, Carda S, Giovanzana C et al.
Using kinematic analysis to evaluate
constraint-induced movement therapy in
chronic stroke patients. Neurorehabil.
Neural Repair 22(1), 31–39 (2008).
39 Massie C, Malcolm MP, Greene D, Thaut
M. The effects of constraint-induced
therapy on kinematic outcomes and
compensatory movement patterns: an
exploratory study. Arch. Phys. Med. Rehabil.
90(4), 571–579 (2009).
40 Woodbury ML, Howland DR, McGuirk
TE et al. Effects of trunk restraint
combined with intensive task practice on
poststroke upper extremity reach and
function: a pilot study. Neurorehabil.
Neural Repair 23(1), 78–91 (2009).
41 Nijland R, van Wegen E, Verbunt J, van
Wijk R, van Kordelaar J, Kwakkel G. A
comparison of two validated tests for upper
limb function after stroke: the Wolf Motor
Function Test and the Action Research
Arm Test. J. Rehabil. Med. 42(7), 694–696
(2010).
42 Sterr A, Elbert T, Berthold I, Kolbel S,
Rockstroh B, Taub E. Longer versus shorter
daily constraint-induced movement therapy
of chronic hemiparesis: an exploratory
www.expert-reviews.com
study. Arch. Phys. Med. Rehabil. 83(10),
1374–1377 (2002).
43 Richards L, Gonzalez Rothi LJ, Davis S,
Wu SS, Nadeau SE. Limited dose response
to constraint-induced movement therapy in
patients with chronic stroke. Clin. Rehabil.
20(12), 1066–1074 (2006).
44 Kaplon RT, Prettyman MG, Kushi CL,
Winstein CJ. Six hours in the laboratory: a
quantification of practice time during
constraint-induced therapy (CIT). Clin.
Rehabil. 21(10), 950–958 (2007).
45 Dettmers C, Teske U, Hamzei F, Uswatte
G, Taub E, Weiller C. Distributed form of
constraint-induced movement therapy
improves functional outcome and quality of
life after stroke. Arch. Phys. Med. Rehabil.
86(2), 204–209 (2005).
46 Liepert J, Uhde I, Graf S, Leidner O,
Weiller C. Motor cortex plasticity during
forced-use therapy in stroke patients: a
preliminary study. J. Neurol. 248(4),
315–321 (2001).
47 Friel KM, Heddings AA, Nudo RJ. Effects
of postlesion experience on behavioral
recovery and neurophysiologic
reorganization after cortical injury in
primates. Neurorehabil. Neural Repair
14(3), 187–198 (2000).
48 Friel KM, Nudo RJ. Recovery of motor
function after focal cortical injury in
primates: compensatory movement patterns
used during rehabilitative training.
Somatosens. Mot. Res. 15(3), 173–189
(1998).
49 Nudo RJ, Wise BM, Sifuentes F, Milliken
GW. Neural substrates for the effects of
rehabilitative training on motor recovery
after ischemic infarct. Science 272,
1791–1794 (1996).
50 Liepert J, Bauder H, Miltner WHR, Taub
E, Weiller C. Treatment-induced cortical
reorganization after stroke in humans.
Stroke 31(6), 1210–1216 (2000).
51 Liepert J, Miltner WHR, Bauder H et al.
Motor cortex plasticity during constraint-
induced movement therapy in stroke
patients. Neurosci. Lett. 250(1), 5–8 (1998).
52 Sawaki L, Butler AJ, Leng X et al.
Constraint-induced movement therapy
results in increased motor map area in
subjects 3 to 9 months after stroke.
Neurorehabil. Neural Repair 22(5), 505–513
(2008).
53 Wittenberg GF, Chen R, Ishii K et al.
Constraint-induced therapy in stroke:
magnetic-stimulation motor maps and
cerebral activation. Neurorehabil. Neural
Repair 17(1), 48–57 (2003).
Review
54 Wittenberg GF, Schaechter JD. The neural
basis of constraint-induced movement
therapy. Curr. Opin. Neurol. 22(6),
582–588 (2009).
55 Takeuchi N, Tada T, Toshima M, Chuma
T, Matsuo Y, Ikoma K. Inhibition of the
unaffected motor cortex by 1 Hz repetitive
transcranical magnetic stimulation enhances
motor performance and training effect of
the paretic hand in patients with chronic
stroke. J. Rehabil. Med. 40(4), 298–303
(2008).
56 Takeuchi N, Tada T, Toshima M, Matsuo Y,
Ikoma K. Repetitive transcranial magnetic
stimulation over bilateral hemispheres
enhances motor function and training effect
of paretic hand in patients after stroke.
J. Rehabil. Med. 41(13), 1049–1054 (2009).
57 Stoykov ME, Corcos DM. A review of
bilateral training for upper extremity
hemiparesis. Occup. Ther. Int. 16(3–4),
190–203 (2009).
58 van Delden AL, Peper CL, Harlaar J et al.
Comparing unilateral and bilateral upper
limb training: the ULTRA-stroke program
design. BMC Neurol. 9, 57 (2009).
59 Luft AR, McCombe-Waller S, Whitall J
et al. Repetitive bilateral arm training and
motor cortex activation in chronic stroke: a
randomized controlled trial. JAMA 292(15),
1853–1861 (2004).
60 Stewart KC, Cauraugh JH, Summers JJ.
Bilateral movement training and stroke
rehabilitation: a systematic review and
meta-analysis. J. Neurol. Sci. 244(1–2),
89–95 (2006).
61 Coupar F, Pollock A, van Wijck F, Morris J,
Langhorne P. Simultaneous bilateral
training for improving arm function after
stroke. Cochrane Database Syst. Rev. 4,
CD006432 (2010).
62 Lin KC, Chang YF, Wu CY, Chen YA.
Effects of constraint-induced therapy versus
bilateral arm training on motor
performance, daily functions, and quality of
life in stroke survivors. Neurorehabil. Neural
Repair 23(5), 441–448 (2009).
63 Bolognini N, Pascual-Leone A, Fregni F.
Using non-invasive brain stimulation to
augment motor training-induced plasticity.
J. Neuroeng. Rehabil. 6, 8 (2009).
•• Excellent review on brain stimulation and
how it can augment training-induced
plasticity.
64 Fregni F, Boggio PS, Mansur CG et al.
Transcranial direct current stimulation of
the unaffected hemisphere in stroke
patients. Neuroreport 16(14), 1551–1555
(2005).
197
 Review Fritz, Butts & Wolf
65 Mansur CG, Fregni F, Boggio PS et al. A
sham stimulation-controlled trial of rTMS
of the unaffected hemisphere in stroke
patients. Neurology 64(10), 1802–1804
(2005).
66 Pomeroy VM, Cloud G, Tallis RC,
Donaldson C, Nayak V, Miller S.
Transcranial magnetic stimulation and
muscle contraction to enhance stroke
recovery: a randomized proof-of-principle
and feasibility investigation. Neurorehabil.
Neural Repair 21(6), 509–517 (2007).
67 Staley K. Stroke: recovery inhibitors under
attack. Nature 468(7321), 176–177 (2010).
68 Malcolm MP, Triggs WJ, Light KE et al.
Repetitive transcranial magnetic
stimulation as an adjunct to constraint-
198
View publication stats
induced therapy: an exploratory
randomized controlled trial. Am. J. Phys.
Med. Rehabil. 86(9), 707–715 (2007).
69 Khedr EM, Etraby AE, Hemeda M, Nasef
AM, Razek AA. Long-term effect of
repetitive transcranial magnetic stimulation
on motor function recovery after acute
ischemic stroke. Acta Neurol. Scand. 121(1),
30–37 (2009).
70 Kim YH, You SH, Ko MH et al. Repetitive
transcranial magnetic stimulation-induced
corticomotor excitability and associated
motor skill acquisition in chronic stroke.
Stroke 37(6), 1471–1476 (2006).
71 Hummel F, Cohen LG. Improvement of
motor function with noninvasive cortical
stimulation in a patient with chronic
stroke. Neurorehabil. Neural Repair 19(1),
14–19 (2005).
72 Lindenberg R, Renga V, Zhu LL, Nair D,
Schlaug G. Bihemispheric brain
stimulation facilitates motor recovery in
chronic stroke patients. Neurology 75(24),
2176–2184 (2010).
73 Hamzei F, Liepert J, Dettmers C, Weiller
C, Rijntjes M. Two different reorganization
patterns after rehabilitative therapy: an
exploratory study with fMRI and TMS.
Neuroimage 31(2), 710–720 (2006).
74 DeVetten G, Coutts SB, Hill MD et al.
Acute corticospinal tract Wallerian
degeneration is associated with stroke
outcome. Stroke 41(4), 751–756 (2010).
Expert Rev. Neurother. 12(2), (2012)