Neuroscience & Medicine, 2013, 4, 253-262
Published Online December 2013 (http://www.scirp.org/journal/nm)
http://dx.doi.org/10.4236/nm.2013.44036
Open Access NM
253
Neurorestorative Effects of Constraint-Induced Movement
Therapy after Stroke: An Integrative Review
Marina Lucas1, Pedro Ribeiro1,2,3, Mauricio Cagy4, Silmar Teixeira1,5,6, Fernanda Chaves1,
Diana Carvalho1, Caroline Peressutti1,3, Sérgio Machado7,8, Juliana Bittencourt1, Bruna Velasques1,3,
Roberto Piedade1
1Brain Mapping and Sensory Motor Integration, Institute of Psychiatry of Federal University of Rio de Janeiro (IPUB/UFRJ), Rio de
Janeiro, Brazil; 2School of Physical Education, Bioscience Department, Federal University of Rio de Janeiro (EEFD/UFRJ), Rio de
Janeiro, Brazil; 3Institute of Applied Neuroscience (INA), Rio de Janeiro, Brazil; 4Division of Epidemiology and Biostatistic, Insti-
tute of Health Community, Federal Fluminense University (UFF), Rio de Janeiro, Brazil; 5Physiotherapy Laboratory, Veiga de
Almeida University (UVA), Rio de Janeiro, Brazil; 6Physiotherapy Department, Piquet Carneiro Policlinic, State University of Rio
de Janeiro (UERJ), Rio de Janeiro, Brazil; 7Laboratory of Panic and Respiration, Federal University of Rio de Janeiro (UFRJ), Rio de
Janeiro, Brazil; 8Physical Activity Neuroscience Laboratory, Salgado de Oliveira University, Rio de Janeiro, Brazil.
Email: silmar_teixeira@yahoo.com.br
Received July 15th, 2013; revised August 15th, 2013; accepted September 10th, 2013
Copyright © 2013 Marina Lucas et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Stroke has been considered as one of the main causes of death and of motor and cognitive sequels. Especially, many
patients with upper limb hemiparesis improved their motor action and showed meaningful cortical changes after treat-
ment with constraint-induced movement therapy. Therefore, this review aims to verify the literature about neuroimag-
ing and behavioral evidences in the cortical reorganization through the use of the constraint-induced movement therapy.
So, we conducted the literature research in indexed journals from many databases like Pubmed, Medline, Cochrane Da-
tabase, Lilacs and Scielo. We concluded that the behavioral and neuroimaging studies using traditional and modified
constraint-induced movement therapy promote cortical reorganization.
Keywords: Stroke; Constraint-Induced-Movement-Therapy; Neuroplasticity; Cerebral Reorganization
1. Introduction
The cerebral vascular accident (CVA) is a frequent injury
caused by the interruption of blood supply to the brain,
resulting in oxygen deprivation. The CVA is one of the
main causes of motor and cognitive impairments and
death [1]. Particularly, upper limb hemiparesis, in many
cases, has been the first complication of the vascular ac-
cident [2]. Experiments using cortical stimulation and
functional image in animals and humans indicated that
certain rehabilitation techniques tend to promote brain
reorganization and improve upper limbs’ activity [3]. Spe-
cifically, Constraint-Induced Movement Therapy (CIMT)
[4,5] has shown positive results in th e treatment of upper
limb motor s equels [5].
In the beginning, this treatment model was developed
from observations in primates, which had their upper
limbs deprived of motor action; later, this model was ap-
plied by Eduard Taub in hemiparesis patients during
motor function recovery. This treatment was initially
explored in order to observe changes in compromised
adjacent cortical regions [6]. Since then, many studies
have been conducted with the objective of improving the
technical knowledge about the benefits of CIMT. It is
known that this technique provides positive results re-
garding the imp rovement of the affected upper limbs, re-
sulting in increased quality of life for the patient [5]. Re-
searchers relate these behavioral gains with enlargement
of the cortical excitability area [7,8], and neurophysi-
ologic principles and neuroimaging tools promote an
understanding of how this reorganization of the central
nervous system influences the recovery process of the
individu al [9].
The present literature review focuses on comparing
new models of CIMT with the traditional view, in order
to observe how much this new approach may benefit pa-
tients, and supposedly, the cortical changes were involv-
ed. Additionally, we present the foundations of brain re-
search, and evidence linking cortical reorganization with
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review
254
CIMT. For this reason, we searched for English-written
articles indexed in Pubmed, Medline, Cochrane, Lilacs
and SciELO databases, using the key words “stroke”,
“stroke rehabilitation”, “constraint-induced movement
therapy”, “cortical reorganization” and “neuroplasticity”.
1.1. Methodology
We conducted a PubMed academic paper search focus-
ing on articles written in English from 1985 to the pre-
sent day (i.e., twenty eight years); only researches con-
ducted with people and case-reports or original articles
were included. Thus, for this integrative review, we em-
ployed the following search terms: constraint-induced
movement therapy, modified constraint induced therapy,
stroke, stroke rehabilitation, cortical reorganization, hu-
man brain, neurophysiology, neuroplasticity, hemiparesis
and upper extremity. In our research, we combined the
term “CIMT” with the afore-mentioned terms and we
only selected the articles that reported the parietal areas
as search term. Search results were then manually re-
viewed and the articles were considered for analysis;
their relevance was determined by our consensus and by
overall manuscript quality.
1.2. Results
We selected 23 articles with the combination of the
terms “CIMT” and “CIMT modified” 14 articles with
“stroke” and “stroke rehabilitation”; 13 articles with
“cortical reorganization” and “human brain”; 13 articles
with “neurophysiolo gy” and “neuro p lasticity”, 12 articles
with “hemiparesis”, and “upper extremity”. After this
selection, we used 75 articles which fulfilled the objec-
tive of the study.
2. Types of Constraint-Induced Movement
Therapy
Experiments using behavioral assessments, cortical stimu-
lation and neuroimaging tools showed us that these reha-
bilitation techniques generate positive results in the re-
covery of Stroke patients. [10,11]. A recent form of re-
habilitation for th ese patien ts is con straint-indu ced move-
ment therapy [4,5]. Specifically, the treatment developed
by Edward Taub in the late 1970s and early 1980s con-
sists in restricting the movement of the unaffected upper
limb during 90% of the patient’s awake time for a period
of 14 consecutive days, and it involves specific training
for about 6 hours a day for 10 consecutive days [12,13].
During the intervention, the patient wears a glove on the
free hand that can be removed to perform activities such
as washing hands and using the restroom [14]. Specific
training, known as “shaping”, is a conditioning method
in which the difficulty of the motor tasks increases pro-
gressively [15].
However, for many post-stroke patients, the traditional
protocol can be hardly accessible, due to the intense
workout routines, the program d uration [16] and the cost
of treatment in a specialized clinic. Thus, with the obj ec-
tive of facilitating the application of the technique, Page
et al. [16] created a new protocol in which they de-
creased the intensive training session of the affected up-
per limb and the retention time of the unaffected upper
limb. The training began to be conducted three days a
week and at the same time they restricted the unaffected
limb for 5 hours per day, 5 days a week for a period of 10
weeks, and they found positive resu lts.
Therefore, a more accessible modified version of the
CIMT protocol (mCIMT) has been proposed by some
researchers [16,17]. The mCIMT also aims to the immo-
bilization of the unaffected limb, conditioning the af-
fected one; however, the periods of immobilization and
attendance at the clinic are shorter [18]. The convenience
of this procedure provided greater clinical implementa-
tion of the technique in a larger number of patients [16].
Furthermore, the effectiveness of the techniqu e originally
developed by Eduard Taub was not compromised after
its modification. This has been observed in several stud-
ies showing that mCIMT can improve the ability of the
paretic upper extremity [1,3] (Table 1).
2.1. Neuroimaging and Electrophysiology
Foundations
More non-invasive neuroimaging techniques have been
of crescent interest to examine the behavioral changes
and neural mechanisms, thus resulting in the develop-
ment of new approaches to improve motor rehabilitation
[19]. The neuroimaging techniques have been considered
as promising to assess cortical connectivity. Because of
their importance, many studies have utilized these tools
to improve knowledge about CIMT, understand the neu-
rophysiological variab les related to the application of the
technique and ultimately provide a better understanding
as to its benefits. Non-invasive brain research tools such
as functional magnetic resonance imaging (fMRI), posi-
tron emission tomography (PET), electroencephalogra-
phy (EEG) and transcranial magnetic stimulation (TMS)
have been used to examine changes in the neural mecha-
nisms during treatments with CIMT [19]. Therefore, the
following paragraphs will provide a brief review of elec-
tro-physiological fundaments and their importance, in
order to answer questions about the cortical changes
caused by CIMT.
2.1.1. Electroencephalography
The electroencephalogram (EEG) records electrical cur-
rents from the variations of neuron’s action potentials in
the cerebral cortex. For this purpose, electrodes are placed
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review 255
Table 1. Studies developed using EEG, TMS, PET, fMRI tools and MAL, WMFT and FM scales.
Study N Tool CIMT protocolResults
Milter et al., [6] 15 MAL and WMFT 90%REST-
07hrsT.14D Significant increase of upper limb functionality and a f fe ct e d hemisphere.
Lipert et al., [7] 13 TMS 90%REST
06hrsT.12D Significant increase of hand functionality and affect ed hemisphere.
Sterr et al., [4] 15 MAL and WMFT 90%REST-
06hrsT. 14D. Significant improvements in motor function and increased use o f the
affected hand.
Schaechter et al., [61] 4 MAL, FM and
fMRI 90%REST-
4hrsT.14D Significant increase in cortical activation in affected hemisphere.
Wittenberg et al., [59] 16 MAL, WMFT,
PET and TMS 90%REST-
06hrsT. 10D. Cerebral activation during a motor task decreased significantly, and motor
map size increased in the affected hemisphere motor cortex.
Könönen et al., [72] 12 PET 90%REST-
06hrsT. 14D. Significant increase of blood perfusion in pre-motor affected hemisphere;
cingulate unaffected hemisphere and in two cerebellum hemispheres.
Szaflarski et al., [17] 7 MAL, FMA and
fMRI 5hrs REST-
30minT. 10D Significant increase in cort ical activation in affected and
unaffected hemisphere.
Taub et al., [50] 21 MAL, WMFT 90%REST-
03hrsT. 14D. Significant increase of a ff ec ted upper limb functionality.
Junger et al., [71].
10 fMRI 90%REST-
06hrsT.12 D. Significant increase of affected hand functionality and more activation in
primary sensorimotor cortex in affected hemisphere.
Page et al., [53] 4 MAL and FM 5hrs REST-
12-hrT. 10D. Significantly increased use of the affected arm a nd
increased ability to perform valued activities
Boake et al., [75] 23 MAL, TMS and
FM 90%REST-
03hrsT. 14D.
Improvement in affected hand motor function on the FM assoc i a t e d wi t h a
greater number of sites on the affec ted cerebral he misphere where responses
of the affected hand were evoked by TMS
Wu et al., [56] 6 MAL and fMRI 2hrs/dia REST.
2hrsT. 3 week Significant improvement in motor function of affected upper limb and
affected hemisphere with increase of the cortical activation.
Tarkka et al. [25] 13 EEG 90%REST-
06hrsT. 14D
Significant increase of affected hand functionality a n d more activation in
motor cortex, pre-motor cortex an d the primary motor area in
both hemispheres.
on the scalp [20] at specific positions where changes of
neural patterns are identified [21]. The neurons generate
small electrical currents around cell membranes, specifi-
cally along the dendrites, and they receive input signals
from other neurons [22]. These electrical activities result
from the electrochemical communication among neurons
and correspond to th e information flow occurring in sev-
eral cortical regions [21].
The EEG allows monitoring, identifying and classify-
ing electrophysiological bioelectrical signals in frequency
ranges, bands of activity, or brain rhythms, relating them
to waking and non-waking states [23]. The power spec-
trum of clinical interest is generally considered starting
from about 1 - 20 Hz. This frequency range has been tra-
ditionally divided into frequency bands typically defined
as delta (1.5 to 3.5 Hz), theta (3.5 to 7.5), alpha (7.5 to
12.5 Hz) and beta (12.5 to 20 Hz). The recorded activity
at each electrode can be represented as the absolute
power in each band, relative power (percentage of total
energy in each band), coherence (a measure of synchro-
nization between the activity in two channels), or asym-
metry (the power ratio in each band between a pair of
symmetric electrodes) [24].
Due to the efficiency of this tool, many studies have
been performed with the objective of investigating the
cortical changes resulting from CIMT [25]. The answers
to these questions are crucial to understand the mecha-
nisms of the brain plasticity that may ultimately result in
behavioral gains for the individual affected by stroke
[15].
2.1.2. Transcranial Magnetic Stimulation
In 1985, Barker and colleagues [26] showed that it was
possible to stimulate brain regions with little or no pain
using transcranial magnetic stimulation (TMS). TMS is a
non-invasive technique originally introduced to investi-
gate neural propagation [27]. It is a procedure in which a
magnetic field stimulates electrical activity in the brain
[28]. It induces electrical currents in cortical neurons by
placing a small coil on the scalp. Constant changing of
these currents inside the coil results in the formation of a
magnetic field, which is able to overcome different lev els
of various structures such as skin, muscle and bone [29].
The maximum force field generated by the stimulator
is able to activate cortical neurons at a depth of 1.5 to 2
cm under the scalp [30]. It is assumed that magnetic
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review
256
stimulation (100 ms duration) excites a neural population,
inducing rapid changes in the rate of neural networks for
only a few milliseconds [31]. The magnitude of the in-
duced current is dependent on both the magnitude and
variation rate discharged through the coil; this current
then produces a brief, but powerful electric field through
the brain tissue, depolarizing neurons [30]. TMS has dif-
ferent intensities, frequencies and locations, so the
stimulus probably occurs in different groups of neurons
[32].
As a research tool, TMS has been applied in several
studies [33,34]. For instance, Pallanti and Bernardi [35]
reported that the use of TMS in the dorsolateral prefron-
tal cortex region reduces the symptoms of anxiety and
panic disorder. Thus, it is necessary to clearly determine
the role of TMS for rehabilitation and several studies
have applied it to inv estigate cortical changes in subjects
undergoing CIMT after stroke [36].
2.1.3. Functio n al Ma gnetic Resonance Imagi n g
(fMRI)
Magnetic resonance imaging (MRI) is a technique that
allows the visualization of three-dimensional high reso-
lution tomographic images without ionizing radiation.
This technology has also allowed the evaluation of pa-
thological features in a non-invasive way [37]. Further-
more, MRI is widely used to study the functional or-
ganization (fMRI) of the human brain, in which neu-
ronal signals recordings are presented in response to
magnetic stimuli [38]. The fMRI is not geared specifi-
cally to investigate clinical aspects. It is also used to
study healthy individuals and their brain functional
changes [39].
The fMRI analysis is based on a techno logy that uses a
strong magnetic field and radio waves to capture the
hemodynamic and metabolic changes induced by neural
activity, i.e. by local increases in the blood volume, flow
and oxygenation [40]. This increase activates an intense
magnetic field resulting from the alignment of its nu clear
spins (orientation of subatomic particles when immersed
in a magnetic field). So, when the radiofrequency pulse is
launched on the representation of blood, the spins move
from their original orientation to an excited energy state.
During this process, the nuclear spins tend to return to
their initial condition, i.e. the state of lowest energy;
however, when this occurs, the excess energy is emitted
in the form of electromagnetic radiation. This energy is
detected by the fMRI device and allows the formation of
anatomical images [39].
fMRI has been a widely used tool in brain mapping
research. It allows the studying of neural networks dy-
namically by tracking specific responses in several spa-
tial scales; however, fMRI can measure only hemody-
namic changes such as variations in blood volume, or
intravascular magnetic susceptibility [41]. Moreover,
regardless of whether it is an incipient technique, fMRI
has been applied to a variety of functional studies, rang-
ing from simple to complex experiments such as neuro-
psychological investigations [39]. Thus, it stands out by
allowing the exploration of various brain functions, due
to its high ability to differentiate tissues. In particular,
some researchers have used fMRI to observe cortical
changes in subjects undergoing CIMT. Therefore, Kim et
al. [42] observed changes in the neural plasticity of the
premotor cortex and supplementary motor area. These
studies are very important to understand the efficiency of
the technique and its effects in post-stroke patients. This
way, we can offer to patients a therapy to improve their
functional limitations.
2.1.4. Positron Emission Tomography (PET)
Brain mapping techniques are vital for understanding
molecular, cellular and functional mechanisms [43].
Among them, PET is an extremely effective tool for
mapping functional organization in the human brain,
contributing not only to rehabilitation, but also to re-
search [44]. This technique produces a three dimensional
image of functional processes in the organism [45]. In
order to perform a scan, a short radioactive tracer isotope
is injected in the subject (usually in the bloodstream).
The tracer is chemically incorporated to a biologically
active molecule, typically a substance such as glucose,
which can be metabolized by the body cells. [46]. PET
produces mainly functional and physiological informa-
tion; anatomical structures are, in turn, difficult to iden-
tify. Therefore, PET usually has to be combined with
anatomical methods such as computed tomography or
magnetic resonance imaging [47].
2.1.5. Advantages and Disadvant ages
There are several additional methods that can be used to
study the contribution of specific cortical networks for
cognitive and motor functions. For example, PET and
fMRI are able to reveal brain networks involved in spe-
cific functions; however, these techniques have poor
temporal resolution and cannot demonstrate per se
whether a particular cortical area is essential for a spe-
cific function [47]. TMS, on the other hand, can inhibit,
activate, and temporarily disrupt brain activity, allowing
the function evaluation on a scale of milliseconds [30,
36,48]. Yet, EEG studies typically suffer from poor spa-
tial resolution with a relatively imprecise location of
electromagnetic patterns associated with the neural cur-
rent flow [38]. Notwithstanding, the low cost of the ex-
amination and its great ability to measure spontaneous
brain activity seem to attract p rofession als to use th is tool
[21]. The high density of the EEG, combined with TMS,
provides a direct and non-invasive measure of cortical
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review 257
excitability and connectivity in humans. These tech-
niques may be used to track changes over time, such as
pathological, plastic and therapy-induced modifications
in cortical circuits [49].
2.2. Effects of Constraint-Induced Movement
Therapy on Post-Stroke Patients:
Behavioral Results
Several investigations have been conducted in order to
analyze whether CIMT is effective in individuals with a
hemiparetic upper limb after stroke [50]. Milter et al. [6]
restricted the movement of the unaffected upper extreme-
ity of 15 hemiplegics for 90% of the time when they
were awake. Patients underwent the CIMT for 14 con-
secutive days with a daily 7 hour intervention. In this
study they used Motor Activity Log (MAL) and Wolf
Motors Functional Test (WMFT) scales to verify the
functional condition of individuals. They executed the
evaluations with this scale on five occasions: 1) 15 days
before treatment, 2) one day before and 3) one day after
treatment, 4) four weeks and 5) six months after treat-
ment. In this experiment they concluded that the CIMT
shows positive results in the hemiparetic upper limb re-
habilitation in Stroke patients.
Kuntel et al. [51] conducted a study with five chronic
and moderate motor deficit Stroke patients. They re-
stricted the unaffected upper end of the limb with a sling
for 14 days. The patients used the sling 6 hours per day
and executed the task with the affected extremity. The
researchers observed changes in the affected upper limb
through the Motor Activity Log (MAL), Wolf Motor
Function Test (WMFT) and Arm Motor Ability Test
(AMAT) before and after treatment. They found large
improvement in the amplitude of the movements, with
significant changes in the scale results used to monitor
the groups studied.
Edward Taub, one of the creators of CIMT, said that
techniques that induce the patient to use the affected limb
should be considered efficient because they stimulate
cortical reorganization and increase the use of such limb
[52]. Based on this information, several au thors modified
the applicability of the technique in order to facilitate its
use for both the therapist and the patient [10,13,18,53,
54].
Thus, the mCIMT has various protocols; one of the
most used is for 30 minutes a day, 3 days a week for 10
consecutive weeks with specific training for daily living
activities. At home, the patient uses the immobilizer on
the affected limb 5 hours a day, 5 days a week for 10
weeks [17,18,54]. In another protocol the patient trains 5
hours per day (2 morning hours and 3 afternoon hours)
for two consecutive weeks. During these 5 hours, the
patient performs physiotherapy tasks for 2 hours, and
during the other 3 hours, he/she is instructed to perform a
self-training at home [55]. Furthermore, the mCIMT has
been used for 2 hours per day, five days per week for 3
weeks [56]. The mCIMT protocols described here have
reported a significant improvement in the affected upper
limb motor function [1,8,56]. Another experiment util-
ized the mCIMT for two weeks in 15 patients who were
divided into two training groups. In such groups, the in-
dividuals remained with their limb restricted for 90% of
the time during which they were awake. However, the
first group trained 6 hours per day, while the second
group trained three hours per day. They used two scales
before and after intervention, the MAL and WMFT.
Their results showed that in all scales mCIMT is an ef-
fective treatment in hemiparetic individuals; however,
the benefits were greater in the group th at trained 6 hours
a day [4].
In the past, the effects of CIMT were studied in sub-
jects who had been injured for more than one year,
though the present studies suggest that also subacute pa-
tients who have suffered a stroke can benefit from the
therapy [6]. Wo lf et al. [57] after comparing the efficacy
of treatment among subacute (3 to 9 months) and chronic
(over 12 months) patients via behavioral scales such as
Wolf Motor Function Test, Motor Activity Log and SIS,
concluded that functionality improved in both groups;
however, the group in which the technique is applied
earlier shows significantly greater changes compared
with the group in which the technique is applied later.
This finding agrees with the study by Biernaskie et al.
[58] which demonstrates that early rehabilitation pro-
vides functional recovery and greater plasticity compared
with late rehabilitation.
Furthermore, several studies show that the affected
limb remains in good conditions even after a long time
[59,60,61]. Blanton and Wolf [62] studied the efficacy of
CIMT after 3 months of therapy application and ob-
served a continuous improvement in the patient. This
result provides evidence that the increased functionality
does not only occur immediately after treatment but it
also appears to last for a long time. This study supports
Milter et al. [6] who concluded through a behavioral
analysis performed in three steps (immediately after the
therapy application, 4 weeks and 6 months after treat-
ment) that, even after some time, functionality does not
decrease, and this also supports the hypothesis that CIMT
produces a permanent improvement of motor functions.
In addition, Winstein et al. [60] evaluated the immedi-
ate and long-term effects using two rehabilitation ap-
proaches: strength and endurance training with the af-
fected limb and a training of functional daily life active-
ties, but without hand immobilization. The study con-
cluded that the immediate benefit of a functional ap-
proach was similar to the applicatio n of force and endur-
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review
258
ance, however, the former was more beneficial in the
long term. This result underscores the importance of in-
serting the application of daily activities in CIMT, be-
cause this reduces the dependence of individuals [63].
2.3. Effects of Constraint-Induced Movement
Therapy on Post-Stroke Patients: Evidence
through Cerebral Reorganization
Several studies with CIMT and mCIMT have used elec-
trophysiological analysis tools to observe the cortical
changes which occur when this technique is employed
[64]. In particular, most studies about Stroke using fMRI
associated the gains in motor functions of the affected
hand after CIMT with cortical activation increase in the
ipsilateral hemisphere related to the hemiparesis [56,61].
The PET and fMRI have been useful tools in analyzing
changes in post-Stroke patients who were treated with
CIMT and mCIMT. Thus, many studies observed that
this restriction treatment therapy produces cortical reor-
ganization [65]. This showed a broad neural network
involved in the occurrence of motor skills recovery in
stroke patients; among these networks, we find the ipsi-
lateral sensorimotor cortex, premotor area, supplemen-
tary motor area and parietal cortex [5,65]. Especially
when CIMT was associated with TMS, we observed a
significant increase in cortical reorganization through
fMRI [52], and a significant increase in limb motor func-
tion recovery through MAL scale [66,67]. The cortical
reorganization of the cerebral functions indicates poten-
tial changes that include mechanisms like those involved
in the self-repair phenomenon [68,69].
Liepert et al. [7] u sed TMS to study six p atients b efore
and after 14 days of CIMT, and observed neural recovery
in the motor areas adjacent to the damaged neural region.
In another study, Wittenberg et al. [59] restrained the
unaffected upper limb of 17 post-stroke patients for 10
days and carried out the TMS three days prior to CIMT
and 3 days after its completion. They noted that there
were limitations in the use of TMS to measure physio-
logical changes resulting from therapy, due to its inabil-
ity to evoke responses in some patients with severe hemi-
paresis. These patients could recover motion through the
action of some neurons in the corticospinal tract, but the
TMS could not activate these neurons sufficiently.
Liepert et al. [70] restricted the unaffected upper limb
movement in 13 hemiparetics post-Stroke patients. In
this study they used th e TMS and behavioral assessments
one day before, one day, four days and six months after
CIMT application. The researchers concluded that, one
day after treatment, the injured hemisphere was 40%
inactive while compared with the uninjured hemisphere.
However, the injured hemisphere, after the first day of
treatment, showed 37.5% more neural activation than the
uninjured hemisphere. This fact demonstrates that corti-
cal activation in the injured hemisphere almost doubled
between pre-CIMT and post-CIMT.
Before treatment, the excitability of the cortical area
related to the muscles of the affected hand decreased.
They suggested that this was probably due to the reduc-
tion in the use of this hand and to the presence of the
lesion itself. After therapy, a nearly complete reversal of
this abnormality was found; because of this, the re-
searchers suggested that the most likely mechanism to
justify this reversal is due to: reduced activity of local
inhibitory interneurons, increased excitability in affected
neurons and an extension of the neuronal tissue excitabil-
ity in the affected hemisphere. However, regardless of
the mechanisms, rehabilitation seems to lead to the
growth of a large number of neurons in the affected pre-
motor cortex.
When they analyzed the hemispheres 4 weeks after
CIMT therapy, they observed that cortical activation in
the affected hemisphere was greater than before CIMT
therapy, and in the uninjured hemisphere a discrete in-
crease occurred. Finally, when the researchers observed
the patients six months after CIMT therapy, they found
more cortical normalization in the affected hemisphere.
In another experiment, researchers observed 10 hemi-
parectic patients (i.e., 5 women and 5 men) with unilat-
eral cortical and sub-cortical ischemic lesion. This treat-
ment (i.e., CIMT) was used during 12 days and fMRI
was used 48 hours before and 48 hours after treatment.
The non-paretic upper limb was immobilized 10 hours
per day with 30 minutes interval for lunch, dinner and
personal hygiene. The study results demonstrated that,
after CIMT, consistent activations in the primary sen-
sorimotor cortex of the affected hemisphere occurred.
Moreover, even extensive lesions appear not to inhibit
the formation of neural circuits adjacent to the affected
brain area. In spite of observing neural modulation ef-
fects predominantly in the affected hemisphere, one pa-
tient showed this modulation in the right and left hemi-
spheres [71].
This result contradicts the study by Szaflarski et al.
[17] in which they analyzed the cortical and behavioral
changes in 4 patients (3 with right hemisphere damage
and only 1 with left hemisphere damage) using func-
tional magnetic resonance imaging (fMRI) and rating
scales such as Action Research Arm Test (ARAT), up-
per-extremity portion of the Fugl-Meyer Assessment
(FMA) and Motor Activity Log (MAL). The researchers
said that in patients with unilateral brain lesions, the
hemisphere opposite to the lesion is known to play an
important role during the reorganization of manual func-
tions.
Könönen et al. [72] analyzed 12 post-Stroke patients
who were enrolled in a rehabilitation program during 2
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review 259
weeks. The patients remained with the upper limb im-
mobilized for 10 hours a day. Moreover, the patients
executed adapted exercise for 6 hours a day; the exer cise
gradually became more and more difficult throughout the
two weeks. Researchers observed, through PET before
and after CIMT therapy, that blood perfusion increased
in the unaffected primary motor cortex and cingulated
regions. Thus, in the affected hemisphere, the blood per-
fusions increased in the pre-motor area. In the pre-central
gyrus, the lateral pre-motor area and medial supplemen-
tary motor area, they found an increase in perfusion not
only in the affected hemisphere but also in the contralat-
eral one. The researchers suggested that the increased
electrical and metabolic activities found in both hemi-
spheres occur before the execution of voluntary move-
ments, especially of the more complex movements. Ac-
cording to them, the two hemispheres are activated, as
they are intimately connected through the corpus callo-
sum. However, a fact that deserved attention was that
blood perfusion increased in two cerebellar hemispheres.
The authors believe that, as the cerebellum plays a criti-
cal role in the coordination of voluntary movement and
control of muscle tone and posture, perfusion increased
so that these functions could be performed properly.
In addition to this, Tarkka et al. [25] agree with this
information, as they also found plastic changes resulting
from CIMT in four hemiparetic subjects using EEG as a
method of evaluation. After treatment, EEG signals
showed a large activation in the motor cortex, pre-motor
cortex and the primary motor area in both hemispheres.
The researchers suggest that changes in these locations
may reflect an expansion or displacement of cortical re-
gions, providing a recovery of the affected limb move-
ment.
In addition to this, the neural functional state network
is dependent on balance between inhibition and excita-
tion received by the cortical areas [73]. Furthermore, the
new functional architecture in the cortical reorganization
is different among individuals with Stroke. This depends
on lesion anatomy, biological age and chronicity [74].
Therefore, the mCIMT and CIMT have been effective
therapies in upper limb movement rehabilitation and
neural changes in post-Stroke patients [9].
3. Conclusion
We conclude that the behavioral and neuroimaging stud-
ies using mCIMT and CIMT promote cortical reorgani-
zation. Studies observed that many cortical areas like
primary motor cortex, dorsal pre-motor cortex and sup-
plementary motor area are activated by mCIMT and
CIMT. However, there is no consensus about why some
patients show a greater activation in the affected hemi-
sphere, and why other patients experience a greater acti-
vation in the unaffected hemisphere. Consequently, the
motor behavior in post-stroke patients is benefited from
using mCIMT or CIMT; therefore, this therapy should be
taken more into consideration by the professionals, due
to its benefit. Finally, the world researchers still n eed un-
countable studies to understand the gaps of cortical reor-
ganization, and that restriction period and treatment are
more effective with CIMT.
REFERENCES
[1] Y. Shi, H. J. Tian, K. H. Yang and Y. Zhao, “Modified
Constraint-Induced Movement Therapy versus Tradition-
al Rehabilitation in Patients with Upper-Extremity Dys-
function after Stroke: A Systematic Review and Meta-
Analysis,” Archives of Physical Medicine and Rehabilita-
tion, Vol. 92, No. 6, 2011, pp. 972-982.
http://dx.doi.org/10.1016/j.apmr.2010.12.036
[2] P. M. Rossini and G. D. Forno, “Neuronal Post-Stroke
Plasticity in the Adult,” Restorative Neurology and Neu-
roscience, Vol. 22, No. 3-5, 2004, pp. 193-206.
[3] S. J. Page and P. Levine, “Modified Constraint-Induced
Therapy in Patients with Chronic Stroke Exhibiting Mini-
mal Movement Ability in the Affected Arm,” Physical
Therapy, Vol. 87, No. 7, 2007, pp. 872-878.
http://dx.doi.org/10.2522/ptj.20060202
[4] A. Sterr, T. Elbert, I. Berthold, S. Kolbel, B. Rockstroh
and E. Taub, “Longer versus Shorter Daily Constraint-In-
duced Movement Therapy of Chronic Hemiparesis: An
Exploratory Study,” Archives of Physical Medicine and
Rehabilitation, Vol. 83, No. 10, 2002, pp. 1374-1377.
http://dx.doi.org/10.1053/apmr.2002.35108
[5] E. Taub and G. Uswatte, “Contraint-Induced Movement
Therapy: Bridging from the Primate Laboratory to the
Stroke Rehabilitation Laboratory,” Journal of Rehabilita-
tion Medicine, Vol. 41, 2003, pp. 34-40.
http://dx.doi.org/10.1080/16501960310010124
[6] W. H. R. Miltner H. Bauder, H. Sommer, M. Dettmers
and E. Taub, “Effects of Constraint-Induced Movement
Therapy on Patients with Chronic Motor Deficits after
Stroke: A Replication,” Stroke, Vol. 30, No. 3, 1999, pp.
586-592. http://dx.doi.org/10.1161/01.STR.30.3.586
[7] J. Liepert, H. Bauder, H. R. Wolfgang, W. H. Miltner, E.
Taub and C. Weiller, “Treatment-Induced Cortical Reor-
ganization after Stroke in Humans,” Stroke, Vol. 31, No.
6, 2000, pp. 1210-1216.
http://dx.doi.org/10.1161/01.STR.31.6.1210
[8] C. Y. Wu, L. L. Chuang, K. C. Lin, H. C. Chen and P. K.
Tsay, “Randomized Trial of Distributed Constraint-Induc-
ed Therapy versus Bilateral Arm Training for the Reha-
bilitation of Upper-Limb Motor Control and Function af-
ter Stroke,” Neurorehabilitation and Neural Repair, Vol.
25, No. 2, 2011, pp. 130-139.
http://dx.doi.org/10.1177/1545968310380686
[9] S. W. Ward, “Plasticity and the Functional Reorganiza-
tion of the Human Brain,” International Journal of Psy-
chophysiology, Vol. 58, No. 2-3, 2005, pp. 158-161.
http://dx.doi.org/10.1016/j.ijpsycho.2005.02.009
[10] C. E. Naylor and E. Bower, “Modified Constraint Induc-
ed Movement Therapy for Young Children with Hemiple-
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review
260
gic Cerebral Palsy: A Pilot Study,” Developmental Medi-
cine & Child Neurology, Vol. 47, No. 6, 2005, pp. 365-
369. http://dx.doi.org/10.1017/S0012162205000721
[11] F. Pulvermüller, B. Neininger, T. Elbert, B. Mohr, B.
Rockstroh, P. Koebbel and E. Taub, “Constraint-Induced
Therapy of Chronic Aphasia after Stroke,” Stroke, Vol.
32, No. 7, 2001, pp. 1621-1626.
http://dx.doi.org/10.1161/01.STR.32.7.1621
[12] E. Taub, N. E. Miller, T. A. Novack, E. W. Cook, W. C.
Fleming, C. S. Nepomuceno, J. S. Connell and J. E.
Crago, “Technique to Improve Chronic Motor Deficit af-
ter Stroke,” Archives of Physical Medicine and Rehabili-
tation, Vol. 74, No. 4, 1993, pp. 347-354.
[13] A. M. Gordon, J. S. Charles and S. L. Wolf, “Methods of
Constraint-Induced Movement Therapy for Children with
Hemiplegic Cerebral Palsy: Development of a Child-
Friendly Intervention for Improving Upper-Extremity
Function,” Archives of Physical Medicine and Rehabilita-
tion, Vol. 74, No. 4, 2005, pp. 837-844.
http://dx.doi.org/10.1016/j.apmr.2004.10.008
[14] D. M. Morris, E. Taub and V. W. Mark, “Contraint-In-
duced Movement Therapy. Characterizing the Interven-
tion Protocol,” Europa Medicophysica, Vol. 42, No. 3,
2006, pp. 257-268.
[15] E. Taub, S. L. Ramey, S. DeLuca and K. Echols, “Effi-
cacy of Constraint-Induced Movement Therapy for Chil-
dren with Cerebral Palsy with Asymmetric Motor Impair-
ment,” Pediatrics, Vol. 113, No. 2, 2004, pp. 305-312.
http://dx.doi.org/10.1542/peds.113.2.305
[16] S. J. Page, S. Sisto, P. Levine, M. V. Johnston and M.
Hughes, “Modified Contraint Induced Therapy: A Rando-
mized Feasibility and Efficacy Study,” Journal of Reha-
bilitation Research & Development, Vol. 38, No. 5, 2001,
pp. 583-590.
[17] J. P. Szaflarski, S. J. Page, B. M. Kissela, J. H. Lee, P.
Levine and S. M. Strakowski, “Cortical Reorganization
Following Modified Constraint-Induced Movement Ther-
apy: A Study of 4 Patients with Chronic Stroke,” Ar-
chives of Physical Medicine and Rehabilitation, Vol. 87,
No. 8, 2006, pp. 1052-1058.
http://dx.doi.org/10.1016/j.apmr.2006.04.018
[18] S. J. Page, S. Sisto, P. Levine and R. E. McGrath, “Effi-
cacy of Modified Constraint-Induced Movement Therapy
in Chronic Stroke: A Single-Blinded Randomized Con-
trolled Trial,” Archives of Physical Medicine and Reha-
bilitation, Vol. 85, No. 1, 2004, pp. 14-18.
[19] M. S. George, Z. Nahas, S. H. Lisanby, T. Schlaepfer, F.
A. Kozel and B. D. Greenberg, “Transcranial Magnetic
Stimulation,” Neurosurgery Clinics of North America,
Vol. 14, No. 2, 2003, pp. 283-301.
http://dx.doi.org/10.1016/S1042-3680(02)00120-1
[20] K. Wendel, O. Väisänen, J. Malmivuo, N. G. Gencer, B.
Vanrumste, P. Durka, R. Magjarevic, S. Supek, L. M.
Pascu, H. Fontenelle and R. G. P. Menendez, “EEG/MEG
Source Imaging: Methods, Challenges, and Open Issues,”
Computational Intelligence and Neuroscience, Vol. 2009,
No. 12, 2009, pp. 1-12.
http://dx.doi.org/10.1155/2009/656092
[21] V. R. Badrakalimuthu, R. Swamiraju and H. Waal, “EEG
in Psychiatric Practice: To Do or Not To Do?” Advances
in Psychiatric Treatment, Vol. 17, No. 2, 2011, pp. 114-
121. http://dx.doi.org/10.1192/apt.bp.109.006916
[22] B. Draganski, C. Gases, V. Busch, G. Schuierer, U. Bog-
dahn and A. May, “Neuroplasticity: Changes in Grey
Matter Induced by Training,” Nature, Vol. 427, 2004, pp.
311-312. http://dx.doi.org/10.1038/427311a
[23] T. M. Lau, J. T. Gwin, K. G. McDowell and D. P. Ferris,
“Weighted Phase Lag Index Stability as an Artifact Re-
sistant Measure to Detect Cognitive EEG Activity during
Locomotion,” Journal of NeuroEngineering and Rehabi-
litation, Vol. 9, No. 42, 2012, p. 47.
[24] J. R. Hughes and E. R. John, “Conventional and Quanti-
tative Electroencephalography and Psichiatry,” The Jour-
nal of Neuropsychiatry and Clinical Neurosciences, Vol.
11, No. 2, 1999, pp. 190-208.
[25] I. M. Tarkka, M. Kononen, K. Pitka, J. Sivenius and E.
Mervaala, “Alterations in Cortical Excitability in Chronic
Stroke afte r Constraint-Induced Movement Thera py,” Neu-
rological Research, Vol. 30, No. 5, 2008, pp. 504-510.
http://dx.doi.org/10.1179/016164107X252519
[26] A. T. Barker, R. Jalinous and I. L. Freeston, “Noinvasive
Magnetic Stimulation of Human Motor Cortex,” Lancet,
Vol. 1, No. 8437, 1985, pp. 1106-1107.
http://dx.doi.org/10.1016/S0140-6736(85)92413-4
[27] M. Hallett. “Transcranial Magnetic Stimulation and the
Human Brain,” Nature, Vol. 406, No. 6792, 2000, pp.
147-150.
[28] S. Machado, B. Velasques, M. Cunha, L. Basile, H.
Budde, M. Cagy, R. Piedade and P. Ribeiro. “Aplicações
Terapêuticas da Estimulação Cerebral por Corrente Con-
tínua na Neuroreabilitação Clínica,” Revista Neurociên-
cias, Vol. 17, No. 3, 2009, pp. 298-300.
[29] F. Fregni, S. C. Schachter and A. Pacual-Leone, “Tran-
scranial Magnetic Stimulation Treatment for Epipepsy:
Can It Also Improve Depression and Vice Versa?” Epi-
lepsy & Behavior, Vol. 7, No. 2, 2005, pp. 182-189.
http://dx.doi.org/10.1016/j.yebeh.2005.06.004
[30] S. Machado, F. Paes, B. Velasques, S. Teixeira, R. Pie-
dade, P. Ribeiro, A. E. Nardi and O. Arias-Carrión, “Is
rTMS an Effective Therapeutic Strategy That Can Be
Used to Treat Anxiety Disorders?” Neuropharmacology,
Vol. 62, No. 1, 2011, pp. 125-134.
http://dx.doi.org/10.1016/j.neuropharm.2011.07.024
[31] A. Pascual-Leone, V. Walsh and J. Rothwell, “Transcra-
nial Magnetic Stimulation in Cognitive Neuroscience-
Virtual Lesion, Chronometry, and Functional Connec-
tivity,” Current Opinion in Neurobiology, Vol. 10, No. 2,
2000, pp. 232-237.
http://dx.doi.org/10.1016/S0959-4388(00)00081-7
[32] Z. Nahas, X. Li, J. H. Chae, N. C. Oliver, B. Anderson, B.
Kapp and M. S. George, “What Does ECS Stand for?
Repetitive Transcranial Magnetic Stimulation in Depres-
sion,” Epilepsy & Behavior, Vol. 2, No. 3, 2001, 2001, p.
375.
[33] A. Valentin, R. Arunachalam, A. Mesquita-Rodrigues, J.
J. Garcia, M. P. Richardson, K. R. Mills and G. Alarcon,
“Late EEG Responses Triggered by Transcranial Mag-
netic Stimulation (TMS) in the Evaluation of Focal Epi-
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review 261
lepsy,” Epilepsia, Vol. 49, No. 3, 2007, pp. 470-480.
http://dx.doi.org/10.1111/j.1528-1167.2007.01418.x
[34] N. Osaka, Y. Otsuka, N. Hirose, T. Ikeda, T. Mima, H.
Fukuyama and M. Osaka, “Transcranial Magnetic Stimu-
lation (TMS) Applied to Left Dorsolateral Prefrontal Cor-
tex Disrupts Verbal Working Memory Performance in
Humans,” Neuroscience Letters, Vol. 418, No. 3, 2007,
pp. 232-235.
http://dx.doi.org/10.1016/j.neulet.2007.01.087
[35] S. Pallanti and S. Bernardi. “Neurobiology of Repeated
Transcranial Magnetic Stimulation in the Treatment of
Anxiety: A Critical Review,” International Clinical Psy-
chopharmacology, Vol. 24, No. 4, 2009, pp. 163-173.
http://dx.doi.org/10.1097/YIC.0b013e32832c2639
[36] F. Paes, S. Machado, O. Arias-Carrión, B. Velasques, S.
Teixeira, H. Budde, M. Cagy, R. Piedade, P. Ribeiro, J. P.
Huston, A. T. Sack and A. E. Nardi, “The Value of Re-
petitive Transcranial Magnetic Stimulation (rTMS) for
the Treatment of Anxiety Disorders: An Integrative Re-
view,” CNS & Neurological Disorders-Drug Targets, Vol.
10, No. 5, 2011, pp. 610-620.
http://dx.doi.org/10.2174/187152711796234943
[37] G.M. Pohost and A.V. Ratner, “Nuclear Magnetic Reso-
nance. Potential Applications in Clinical Cardiology,”
JAMA, Vol. 251, No. 10, 1984, pp. 1304-1309.
http://dx.doi.org/10.1001/jama.1984.03340340044026
[38] N. R. Logothetis, J. Pauls, M. Augath, T. Trinath and A.
Oeltermann, “Neurophysiological Investigation of the
Basis of the fMRI Signal,” Nature, Vol. 412, No. 6843,
2011, pp. 150-157. http://dx.doi.org/10.1038/35084005
[39] M. S. Sercheli, E. Bilevicius, A. Alessio, H. Ozelo, F. R.
Pereira, J. M. Rondina, F. R. Cendes and J. Covolan,
“EEG Spike Source Localization before and after Surgery
for Temporal Lobe Epilepsy: A BOLD EEG-fMRI and
Independent Component Analysis Study,” Brazilian Jour-
nal of Medical and Biological Research, Vol. 42. No. 6,
2009, pp. 582-587.
http://dx.doi.org/10.1590/S0100-879X2009000600017
[40] M. S. Meneses, J. C. M. Pedroso, R. F. Fuzza and J. B.
Milano, “Comparative Analysis of Human Brains Slices
with Three Different Staining Techniques,” Arquivos de
Neuro-Psiquiatria, Vol. 62. No. 2, 2004, pp. 276-281.
http://dx.doi.org/10.1590/S0004-282X2004000200016
[41] S. P. Ku, A. S. Tolias, N. K. Logothetis and J. Goense,
“fMRI of the Face-Processing Network in the Ventral
Temporal Lobe of Awake and Anesthetized Macaques,”
Neuron, Vol. 70. No. 2, 2011, pp. 352-362.
http://dx.doi.org/10.1016/j.neuron.2011.02.048
[42] Y. H. Kim, J. W. Park, M. H. Ko and P. K. Lee, “Plastic
Changes of Motor Network after Constraint-Induced
Movement Therapy,” Yonsei Medical Journal, Vol. 45.
No. 2, 2004, pp. 241-246.
[43] J. C. Eliassen, E. L. Boespflug, M. Lamy, J. Allendorfer,
W. J. Chu and J. P. Szaflarski, “Brain-Mapping Tech-
niques for Evaluating Poststroke Recovery and Rehabili-
tation: A Review,” Topics in Stroke Rehabilitation, Vol.
15. No. 5, 2008, pp. 427-450.
http://dx.doi.org/10.1310/tsr1505-427
[44] M. A. Macleod, G. H. Adkisson, M. J. Fox and R. P.
Pearson, “99Tcm-HMPAO Single Photon Emission To-
mography in the Diagnosis of Cerebral Barotraumas,”
British Journal of Radiology, Vol. 61. No. 732, 1988, pp.
1106-1109.
http://dx.doi.org/10.1259/0007-1285-61-732-1106
[45] G. Muehllehner and J. S. Karp, “Positron Emission To-
mography,” Physics in Medicine and Biology, Vol. 51,
No. 13, 2006, pp. 117-137.
http://dx.doi.org/10.1088/0031-9155/51/13/R08
[46] F. Lomeña and M. Soler, “Clinical Application of Pet,”
Brazilian Archives of Biology and Technology, Vol. 48,
No. 2, 2005, pp. 179-183.
http://dx.doi.org/10.1590/S1516-89132005000700027
[47] H. Lundqvist, M. Lubberink and V. Tolmachev, “Positron
Emission Tomography,” European Journal of Physics,
Vol. 19, No. 6, 1998, pp. 537-552.
http://dx.doi.org/10.1088/0143-0807/19/6/007
[48] O. Arias-Carrion, S. Machado, F. Paes, B. Velasques, S.
Teixeira, L. Cardenas-Morales, R. Piedade, R. Ribeiro
and A. E. Nardi, “Is rTMS an effective Therapeutic Strat-
egy That Can Be Used to Treat Parkinson’s Disease?”
CNS & Neurological Disorders-Drug Targets, Vol. 10.
No. 6, 2011, pp. 693-702.
[49] S. Casarotto, L. J. R. Lauro, V. Bellina, A. G. Casali, M.
Rosanova, A. Pigorini, S. Defendi, M. Mariotti and M.
Massimini, “EEG Responses to TMS Are Sensitive to
Changes in the Perturbation Parameters and Repeatable
over Time,” PLoS ONE, Vol. 5. No. 4, 2010, Article ID:
10281. http://dx.doi.org/10.1371/journal.pone.0010281
[50] E. Taub, G. Uswatte, D. K. King, D. Morris, J. E. Crago
and A. Chatterjee, “A Placebo-Controlled Trial of Con-
straint-Induced Movement Therapy for Upper Extremity
After Stroke,” Stroke, Vol. 37, 2006, pp. 1045-1049.
http://dx.doi.org/10.1161/01.STR.0000206463.66461.97
[51] A. Kunkel, B. Kopp, G.K. Miiller, A. Villringer, E. Taub
and H. Flor, “Constraint-Induced Movement Therapy for
Motor Recovery in Chronic Stroke Patients,” Archives of
Physical Medicine and Rehabilitation, Vol. 80, No. 6,
1999, pp. 624-626.
http://dx.doi.org/10.1016/S0003-9993(99)90163-6
[52] E. Taub, G. Uswatt and R. Pidikiti, “Constraint-Inducel
Movement Therapy: A New Family of Techniques with
Broad Application to Physical Rehabilitation—A Clinical
Review,” Journal of Rehabilitation Research & Devel-
opment, Vol. 36. No. 3, 1999, pp. 237-251.
[53] S. J. Page and P. L. Levine. “Modified Constraint In-
duced Therapy Extension: Using Remote Technologies to
Improve Function,” Archives of Physical Medicine and
Rehabilitation, Vol. 36, No. 3, 2007, pp. 922-927.
http://dx.doi.org/10.1016/j.apmr.2007.03.038
[54] S. J. Page, S. Sisto, M. V. Johnston and P. Levine, “Mo-
dified Constraint-Induced Therapy after Subacute Stroke:
A Preliminary Study,” Neurorehabilitation and Neural
Repair, Vol. 16, No. 3, 2002, pp. 290-295.
[55] M. Hosomi, T. Koy ama, T. Ta kebay ashi, S. Teray ama , N.
Kodama, K. Matsumoto and K. Domen, “A Modified
Method for Constraint-Induced Movement Therapy: A
Supervised Self-Training Protocol,” Journal of Stroke
and Cerebrovascular Diseases, Vol. 21. No. 8, 2011, pp.
Open Access NM
Neurorestorative Effects of Constraint-Induced Movement Therapy after Stroke: An Integrative Review
Open Access NM
262
767-75.
[56] C. Y. Wu, Y. W. Hsieh, K. C. Lin, L. L. Chuang, Y. F.
Chang, H. L. Liu, C. Chen, K. H. Lin and Y. Y. Wai,
“Brain Reorganization after Bilateral Arm Training and
Distributed Constraint-Induced Therapy in Stroke Pa-
tients: A Preliminary Functional Magnetic Resonance
Imaging Study,” Chang Gung Medical Journal, Vol. 33,
No. 6, 2010, pp. 628-638.
[57] S. L. Wolf, P. A, Thompson, C. Winstein, J. P. Miller, S.
R. Blanton, D. S. N. Larsen, D. M. Morris, G. Usmatte. E.
Taub, K. E. Light and L. Sawaki, “The EXCITE Stroke
Trial Comparing Early and Delayed Constraint-Induced
Movement Therapy,” Stroke, Vol. 41, No. 10, 2010, pp.
2309-2315.
http://dx.doi.org/10.1161/STROKEAHA.110.588723
[58] J. Biernaskie, G. Chernenko and D. Corbett, “Efficacy of
Rehabilitati ve Experience Declines with Time after Foca l
Ischemic Brain Injury,” The Journal of Neuroscience, Vol.
24, No. 5, 2004, pp. 1245-1254.
http://dx.doi.org/10.1523/JNEUROSCI.3834-03.2004
[59] G. F. Wittenberg, R. Chen, K. Ishii, K. O. Bushara, E.
Taub, L. H. Gerber, M. Hallett and L. G. Cohen, “Con-
straint-Induced Therapy in Stroke: Magnetic-Stimulation
Motor Maps and Cerebral Activation,” Neurorehabilita-
tion and Neural Repair, Vol. 17, No. 1, 2003, pp. 48-57.
http://dx.doi.org/10.1177/0888439002250456
[60] C. J. Winstein, C. J. Miller, J. P. Blanton, E. Taub, G.
Uswatte, D. Morris, D. Nichols and S. Wolf, “Methods
for a Multisite Randomized Trial to Investigate the Effect
of Constraint-Induced Movement Therapy in Improving
Upper Extremity Function among Adults Recovering
from a Cerebrovascular Stroke,” Neurorehabilitation and
Neural Repair, Vol. 17, No. 3, 2003, pp. 137-152.
http://dx.doi.org/10.1177/0888439003255511
[61] J. D. Schaechter, E. Kraft, T. S. Hilliard, R. M.
Dijkhuizen, T. Benner, S. P. Finklestein, B. R, Rosen and
S. C. Cramer, “Motor Recovery and Cortical Reorganiza-
tion after Constraint-Induced Mo vement Therapy in Stroke
Patients: A Preliminary Study,” Neurorehabilitation and
Neural Repair, Vol. 16, No. 4, 2002, pp. 326-328.
http://dx.doi.org/10.1177/154596830201600403
[62] S. Blanton, S. L. Wolf. “An Application of Upper-Extre-
mity Constraint-Induced Movement Therapy in a Patient
with Subacute Stroke,” Physical Therapy, Vol. 79, No. 9,
1999, pp. 847-853.
[63] S. Hakkennes and J. L. Keating, “Constraint-Induced
Movement Therapy Following Stroke: A Systematic Re-
view of Randomised Controlled Trials,” Australian Jour-
nal of Physiotherapy, Vol. 51, No. 4, 2005, pp. 221-231.
http://dx.doi.org/10.1016/S0004-9514(05)70003-9
[64] W. C. Huang, Y. J. Chen, C. L. Chien, H. Kashima and K.
C. Lin, “Constraint-Induced Movement Therapy as a
Paradigm of Translational Research in Neurorehabilita-
tion: Reviews and Prospects,” American Journal of Tran-
slational Research, Vol. 3. No. 1, 2011, pp. 48-60.
[65] A. Feydy, R. Carlier, A. Roby-Brami, B. Bussel, F, Ca-
zalis, L. Pierot, Y. Burnod and M. A. Maier, “Longitudi-
nal Study of Motor Recovery after Stroke: Recruitment
and Focusing of Brain Activation,” Stroke, Vol. 33 No. 6,
2002, pp. 1610-1617.
http://dx.doi.org/10.1161/01.STR.0000017100.68294.52
[66] B. Sheng and M. Lin, “A Longitudinal Study of Func-
tional Magnetic Resonance Imaging in Upper-Limb
Hemiplegia after Stroke Treated with Constraint-Induced
Movement Therapy,” Brain Injury, Vol. 23. No. 1, 2009,
pp. 65-70. http://dx.doi.org/10.1080/02699050802635299
[67] C. E. Levy, D. S. Nichols, P. M. Schmalbrock, P. Keller
and D. W. Chakeres, “Functional MRI Evidence of Cor-
tical Reorganization in Upper-Limb Stroke Hemiplegia
Treated with Constraint-Induced Movement Therapy,”
American Journal of Physical Medicine & Rehabilitation,
Vol. 80, No. 1, 2001, pp. 4-12.
http://dx.doi.org/10.1097/00002060-200101000-00003
[68] P. Rossini, P. Mand and S. Rossi. “Transcranial Magnetic
Stimulation: Diagnostic, Therapeutic, and Research Po-
tential,” Neurology, Vol. 68. No. 7, 2007, pp. 484-488.
http://dx.doi.org/10.1212/01.wnl.0000250268.13789.b2
[69] Z. R. Hunter, “Plasticity of the Adult Human Brain and
Motor Recovery after Stroke,” Institute of Cognitive Sci-
ence, Vol. 36, No. 213, 2005, p. 5:1.
[70] J. Liepert, W. H. R. Miltner, H. Bauder, M. Sommer, C.
Dettmers, E. Taub and C. Weiller, “Motor Cortex Plastic-
ity during Constraint-Induced Movement Therapy in Stroke
Patients,” Neuroscience Letters, Vol. 250, No . 1 , 1998, pp.
5-8. http://dx.doi.org/10.1016/S0304-3940(98)00386-3
[71] H. Juenger, M. Linder-Lucht, M. Walther, S. Berweck, V.
M. Mall and S. Taudt, “Cortical Neuromodulation by
Constraint-Induced Movement Therapy in Congenital
Hemiparesis: An fMRI Study,” Neuropediatrics, Vol. 38,
No. 3, 2007, pp. 130-136.
http://dx.doi.org/10.1055/s-2007-985904
[72] M. Könönen, J. T. Kuikka, M. Husso-Saastamoinen, E.
Vanninen, R. Vanninen, S. Soimakallio, E. Mervaala, J.
Sivenius, K. Pitkänen and I. M. Tarkka, “Increased Perfu-
sion in Motor Areas after Constraint-Induced Movement
Therapy in Chronic Stroke: A Single-Photon Emission
Computerized Tomography Study,” Journal of Cerebral
Blood Flow & Metabolism, Vol. 25, No. 12, 2005, pp.
1668-1674. http://dx.doi.org/10.1038/sj.jcbfm.9600158
[73] M. N. Economo and J. A. White, “Membrane Properties
and the Balance between Excitation and Inhibition Con-
trol Gamma-Frequency Oscillations Arising from Feed-
back Inhibition,” PLOS Computational Biology, Vol. 8,
No. 1, 2012, Article ID: 1002354.
http://dx.doi.org/10.1371/journal.pcbi.1002354
[74] A. Kleim and T. A. Jones, “Principles of Experience-De-
pendent Neural Plasticity: Implications for Rehabilitation
after Brain Damage,” Journal of Speech, Language, and
Hearing Research, Vol. 51, No. 1, 2008, pp. 225-239.
http://dx.doi.org/10.1044/1092-4388(2008/018)
[75] C. Boake, E.A. Noser, T. Ro, S. Baraniuk, M. Gaber, R.
Johnson, E. T. Salmeron, T. M. Tran, J. M. Lai, E. Taub,
L. A. Moye, J. C. Grotta and H. S. Levin, “Constraint-
Induced Movement Therapy during Early Stroke Reha-
bilitation,” Neurorehabilitation and Neural Repair, Vol.
21, No. 1, 2007, pp. 14-24.
http://dx.doi.org/10.1177/1545968306291858