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Acta Neurol Scand 2011: 123: 147159 DOI: 10.1111/j.1600-0404.2010.01417.

x  2010 John Wiley & Sons A S


Review Article
Current trends in stroke rehabilitation.
A review with focus on brain plasticity
Johansson BB. Current trends in stroke rehabilitation. A review with B. B. Johansson
focus on brain plasticity. Department of Clinical Neuroscience, Wallenberg
Acta Neurol Scand: 2011: 123: 147159. Neuroscience Center, Lund University, Lund, Sweden
 2010 John Wiley & Sons A S.

Current understanding of brain plasticity has lead to new approaches

in ischemic stroke rehabilitation. Stroke units that combine good
medical and nursing care with task-oriented intense training in an
environment that provides condence, stimulation and motivation
signicantly improve outcome. Repetitive trans-cranial magnetic
stimulation (rTMS), and trans-cranial direct current stimulation
(tDCS) are applied in rehabilitation of motor function. The long-term
eect, optimal way of stimulation and possibly ecacy in cognitive
rehabilitation need evaluation. Methods based on multisensory
integration of motor, cognitive, and perceptual processes including
action observation, mental training, and virtual reality are being tested.
Dierent approaches of intensive aphasia training are described.
Key words: aphasia; cognition; hemispheric
Recent data on intensive melodic intonation therapy indicate that even sub-specialization; plasticity; multisensory integration;
patients with very severe non-uent aphasia can regain speech through music; stroke units
homotopic white matter tract plasticity. Music therapy is applied in
Barbro B. Johansson, Department of Clinical Neuro-
motor and cognitive rehabilitation. To avoid the confounding eect of science, Wallenberg Neuroscience Center, BMC A13, SE
spontaneous improvement, most trials are preformed 3 months post 221 84 Lund, Sweden
stroke. Randomized controlled trials starting earlier after strokes are Tel.: +46 462 220621
needed. More attention should be given to stroke heterogeneity, Fax: +46 462 220615
cognitive rehabilitation, and social adjustment and to genetic e-mail:
dierences, including the role of BDNF polymorphism in brain
plasticity. Accepted for publication July 14, 2010

have an impact on future design and choice of

rehabilitation methods for individual patients.
Brain plasticity is a broad term for the property of
the human brain to adapt to environmental
The value of stroke units
pressure, experiences, and challenges including
brain damage (15). It occurs at many levels Key principles of stroke rehabilitation include a
from molecules to cortical reorganization. The functional approach targeted at specic activities,
advances in technologies enabling non-invasive frequent and intense practice, and start in the rst
exploration of the human brain have increased days or weeks after stroke (18). These general
our understanding of brain reorganization after principles are applied in stroke units where multi-
ischemic stroke (613). The time after stroke, the disciplinary teams stress the importance of active
lesion location, and the integrity of cortico-spinal participation of the patients in the rehabilitation
tracts and cortical and subcortical connections are process. Stroke unit care is the only treatment that
factors that inuence outcome. Diffusion tensor has so far been shown to have a major impact on
imaging tractography is a recent technique that the outcome after stroke (19). More patients can
enables non-invasive visualization of ber tracts in return home early, and the need for institutional
the human brain in vivo (1417), which is likely to care is reduced. It is highly cost-effective when


compared with general medical ward care (2022). has attained much media interest after a signicant
Also cognitively impaired stroke patients do ben- effect was obtained in a randomized study with a
et from admission to an acute stroke unit (23). 2-week program of CIMT applied to 222 stroke
These data have been supported by a large study patients mostly with mild to moderate impairment
including 105,043 patients with acute stroke 39 months after stroke (33). A follow-up
reported to the Swedish Stroke Register during 24 months after the ischemic event showed a
the years 2001 through 2005 that were followed persistent benet (34). Some limitations with the
until January 2007 (24). Stroke unit care was study include that the controls received usual and
associated with reduced risk for death and institu- customary care that involved less motor training
tional living at 3 months after stroke onset, and than that delivered to the CIMT group. Further-
with better long-term survival in all subgroups more, the separate effects of higher dose of motor
(age, sex, stroke subtypes, and level of conscious- training and immobilization cannot be evaluated.
ness). The benet of stroke units compared to The study included rather few patients with severe
general wards is most likely a combination of impairments, and the participating patients may
optimal medical and nursing care, task oriented, have represented a minority of patients with
and for the individual meaningful training in an chronic stroke (35). A remaining question is
environment that gives them condence, stimula- whether it is superior to other treatment of
tion, and motivation (25). Mere admittance to a comparable intensity.
stroke unit with specially trained staff encouraging There is no evidence that CIMT is of benet in
active participation in the rehabilitation process early stroke rehabilitation. No signicant dier-
and more information to patients and relatives ences were noted in patients randomized within
may increase the motivation and expectation of the 2 weeks after stroke either to 2 weeks of CIMT or
patients. Animal studies have demonstrated that to traditional therapy at an equal frequency of up
environmental enrichment has many functional to 3 h day. The groups were well balanced for
and biological effects and signicantly enhance the frequency, duration, and intensity of the treatment,
effect of other interventions (2, 5, 26, 27). and the results did not show any signicant
dierences between the groups (36). In another
study, patients were randomized within 28 days of
Motor rehabilitation
admission into three groups. Control treatment
Tactile sensibility of the hand is essential for consisted of 1 h of activity of daily living retraining
identifying objects and for motor performance. and 1 h of bilateral training 5 days a week during
When sensory perception is aected in stroke, 2 weeks, The standard CIMT group received 2 h of
rehabilitation of motor skills is more dicult to shaping therapy and wore a mitten 6 h a day; and
achieve (28). Aging is associated with reduced high intensity CIMT underwent 3 h of shaping
tactile discrimination and deterioration of ne therapy and mitten 90% of waking hours. Stan-
manipulative movements and handling of tools. dard CIMT was equally effective but not superior
Sensory stimulation by means of tactile co- to an equal dose of traditional therapy (37), and
activation of ngertips successfully improves tactile the higher intensity CIMT resulted in less improve-
acuity in elderly individuals and, in contrast to ment at 90 days. These two studies on early CIMT
motor training, it does not require active partic- emphasize the need for control groups that match
ipation or attention of the subjects. This lead to therapy intensity and dose in clinical trials.
the suggesting that it might be a useful therapeu- A meta-analysis based on 10 studies of robot-
tic intervention to improve the activity of daily assisted therapy on motor and functional recovery
living in stroke patients with impaired sensory in patients with stroke involving 218 patients
motor abilities (29, 30). A preliminary study on showed a signicant eect on motor recovery of
four individual post-stroke showed that all the upper paretic limb but no signicant eect on
improved in sensory tasks and motor perfor- functional ability. The recommendation was that
mance, effects that remained 4 weeks post treat- future research on the eect should distinguish
ment (31). If those data can be conrmed in between upper and lower robotics arm training and
larger studies, it may have a considerable impact concentrate on kinematic analysis to dierentiate
in stroke rehabilitation. between genuine upper limb motor recovery and
Constraint-induced movement therapy (CIMT) functional recovery owing to compensation strat-
is a method in which a splint is applied to the intact egies by proximal control of the trunk and upper
hand 90% of the day to force the use of the paretic limb (38). Similarly, a Cochrane report based on 11
hand, and combined with shaping by which the trials with 328 participants found no signicant
tasks are made progressively more difcult (32). It improvement in activities of daily although arm

Stroke rehabilitation

motor function and arm motor strength improved However, the anesthetic procedure is not easy,
(39). Rehabilitation program may require different which explains why this intervention has not been
therapy protocols and equipment in acute and much used.
chronic stages of recovery (40, 41). Adding virtual Another approach is based on the concept of
reality to robot-based gate training (42) and arm interhemispheric inhibition. The cortical sensory
(43) training may have benecial effects as will be and motor representation of the hand exerts
discussed later. inhibitory inuences on the homonymous repre-
Bilateral coordination is important in daily life. sentation in the opposite hemisphere (50), an
Bilateral arm training (BAT) may be of value interhemispheric inhibition that is thought to
particular for stroke patients with severe func- contribute to skilled motor performance. Short-
tional decits (44). In a randomized controlled term ischemic nerve block to the hand leads to
trial 667 months after stroke onset, BAT functional reorganization in the de-afferented
improved the spatiotemporal control of the motor cortex, and also to functional changes in
affected arm in both bilateral and unilateral homotopic motor regions in the contra-lateral
tasks and reduced motor impairment (45). Com- cortex (51, 52). Based on the observation of an
paring CIMT, BAT, and a control intervention of abnormally high interhemispheric inhibitory drive
equally intense but less specic therapy for from the motor cortex of the intact hemisphere to
2 hours a day 5 days a week for 3 weeks, both the injured hemisphere during a voluntary move-
CIMT and bilateral arm training resulted in better ment of the paretic hand in patients with sub-
performance than the control intervention. BAT cortical infarcts, it was hypothesized that this
exhibited greater gains in the proximal upper limb abnormality might adversely inuence motor
than the other two groups on motor performance, recovery (53). Different neurophysiologic strate-
and CIMT produced greater functional gains in gies to increase the activity of the injured area
hand functions in patients with mild to moderate have been proposed mainly using transcranial
chronic hemiparesis (46). It has been proposed magnetic stimulation, TMS (54, 55), and trans-
that bilateral training is a necessary adjunct to cranial direct current stimulation, tDCS (56).
unilateral training and that individuals at all level Lower frequencies of repetitive TMS (rTMS = a
of severity can benet from bilateral training train of TMS pulses of the same intensity) in the
although not all approaches are effective at all range 1 Hz range suppress excitability of the
severity levels (47). Specic training approaches motor cortex, while 20 Hz lead to a temporary
need to be matched to the individual case increase in cortical excitability (57). With tDCS, a
characteristics. To achieve bilateral skills impor- weak polarizing electrical current is delivered to
tant in daily life training should not be either the cortex, and the effect depends on the polarity
unilateral or bilateral but both. In a systematic (56). An excitatory effect is obtained with the
review based on 56 studies 19792008, the authors anode placed over the motor cortex, and inhibi-
concluded that the current evaluation scales are tion is induced with the cathode over motor
not optimal for exploring changes in real life of cortex. tDCS is easier to apply and less expensive
the patients and that there is a need for the than TMS, and a feasibility study demonstrated
development of direct measures of arm use in that the participants could not distinguish tDCS
real-life environments (48). from sham stimulation, making it suitable for
larger double-blinded, sham-controlled random-
ized trials (58).
Electrical brain stimulation
Two main approaches to alter the hemispheric
After a cortical lesion, the surrounding intact tissue dominance have been used in clinical studies. 1)
has an inhibitory action on the damaged area, an Reducing the cortical activity on the intact side by
intra-hemispheric inhibition. Most patients with low frequency rTMS (5961) or by reducing the
stroke have better function in the upper arm than somatosensory input to the intact hemisphere (62,
in the hand, and it was postulated that intracortical 63); 2) Enhancing the activity in the damaged
competition from surrounding areas had an inhib- hemisphere by high-frequency rTMS (64), anodal
itory eect on the hand muscles. When the upper tDCS (58, 65), or increasing the sensory input by
part of the brachial plexus was anaesthetized, electrical stimulation of the peripheral nerves in the
intense training of the paretic hand signicantly paretic hand (6668). These manipulations have
enhanced motor function, and the improvement shown 1030% signicant effects in behavioral test
was associated with an increase in TMS-evoked in these pilot studies. Combining peripheral nerve
motor output to the practiced hand muscles. The stimulation with tDCS can facilitate the benecial
eect remained at follow-up 2 weeks later (49). effects motor performance beyond levels reached


with each intervention alone with 41% increase

Hemispheric subspecialization in motor activities
compared to sham (69). The differences were
maintained 6 days after the end of the training Studies on motor lateralization have revealed a
with no further follow-up. consistent dierence in the control strategies of the
Most of the above-mentioned studies have been dominant and non-dominant hand; the perfor-
performed on patients with chronic stroke from mance with the dominant arm hand is most
several months up to 4 years after stroke. How- accurate when reaching from one xed starting
ever, in one study patients were randomized position to multiple targets, whereas performance
57 days after stroke to receive high-frequency with the non-dominant hand is most accurate when
rTMS to enhance neuronal activity on the lesion reaching toward a single target from multiple start
side once a day for 10 days or to a standard locations (77). Studies on patients with stroke have
treatment group (64). Compared to the standard demonstrated deciencies that reect these distinc-
therapy group, the study group had better scores in tions (78), data that may help to explain why
all tests used, and the gains remained at 10 days patients with stroke may have some difculties also
after the end of treatment. The same group has with the hand corresponding to the intact hemi-
reported benecial effects of rTMS on dysphagia in sphere. The subspecialization and function of the
the subacute stage (70). The rst study on long-term ipsilateral hand may be of importance particularly
follow-up of patients treated 515 days after stroke for patients with severe motor dysfunction that
with 5 daily stimulations and followed for 1 year must relay on the ipsilateral intact hand for some
demonstrated a lasting benet (71). Although activities of daily living (79). The side of lesion
stroke leads to changes in the brain tissue that inuences the degree of bilateral activation in
potentially could alter the electrical response prop- chronic post-stroke hemiparesis (80). In healthy
erties, no adverse effects have been reported in the individuals, the interhemispheric inhibition is
studies with rTMS and tDCS after stroke. Thirty- stronger from the dominant to the non-dominant
six authorities in the eld have published a consen- side than in the opposite direction (81). Simulta-
sus statement on safety and ethical considerations neously applying cathodal tDCS over the dominant
together with an application guideline for the use of motor cortex and anodal tDCS over the non-
TMS in clinical practice and research (72). dominant motor cortex produced an additive effect
Epidural cortical stimulation is an invasive that facilitates motor performance in the non-
technique that improves motor rehabilitation in dominant hand (82). Modulation of excitability in
experimental animals. In a preliminary report from the dominant motor cortex signicantly affected
a planned multi-center non-blinded trial, patients performance for the contra-lateral and ipsi-lateral
with stroke were randomized to surgery or to a hands, whereas modulating excitability in the non-
control group at least 4 months after stroke. dominant motor cortex only had a signicant
Subdural electrodes were implanted in the cortex impact for the contra-lateral hand (83). The
of the treatment groups, and both groups under- evidence for a hemispheric asymmetry in the ipsi-
went rehabilitation for 3 weeks after which the lateral effect of modulating excitability in the
electrodes in the treatment group were removed. motor cortex may be important for clinical research
Stimulation plus rehabilitation improved function on motor recovery. The arm use after left or right
in the upper extremity signicantly more then hemiparesis is inuenced by hand preference.
rehabilitation alone, and the eect remained at Although both groups used their ipsi-lesional
12 weeks after the stimulation (73). A multicenter intact arm more than the contra-lesional paretic
feasibility study of safety and efcacy was also arm, the right hemisphere-damaged group used the
promising (74). However, in a phase III study intact arm four times more frequently and the left
based on 146 patients with hemispheric stroke, the hemisphere damaged two times more frequently
outcome of the stimulated group was not better than their paretic arm (84). If this observation was
than in the group that received only rehabilitation related to the frequency of hemi-neglect after right-
(75). hemisphere lesions was not studied. Recent data
Considering many reports on the importance of that successful recovery of motor skills after
cortico-spinal tract integrity for functional recov- hemiparetic stroke involves participation of
ery (7, 8, 10, 17) future studies on motor outcome contra-lesional cortical networks support that we
after stroke should take that into consideration. A need to pay attention to both hemispheres (85).
recent study indicates different effects of rTMS on Whether the hemispheric subspecialization is of the
the ipsi-lesional primary motor cortex in cortical magnitude that it could signicantly inuence the
and subcortical chronic middle cerebral artery rehabilitation strategies in left and right hemi-
stroke (76). spheric stroke remains to be investigated.

Stroke rehabilitation

enhanced the effect of training alone on rehabilita-

Multisensory interaction; Training with a mirror, action
tion of motor decits (96). Brocas area is one of the
observation, motor imagery or mental practice, virtual
cortical areas activated by hand mouth action
observation, and it has been reported that patients
Perception, attention, memory, language and other with frontal aphasia are specically impaired in
cognitive functions consist of distributed inter- their capability to correctly encode observed
active and overlapping networks. The healthy human actions (97).
human brain has a large capacity for automatic Imaging performance of a motor action requires
simultaneous processing and integration of sensory conscious activation of brain regions involved in
information, and multisensory inuences are inte- movement preparation and execution. Mental
gral to primary as well as higher-order cortical training can improve motor function and alter
operations. Multisensory-training protocols can cortical representation areas (4, 91, 98). In a
better approximate natural settings and are more placebo-controlled trial on patients with stroke
eective for learning in healthy individuals (86, 87). with a mean post-stroke time of 3.6 years, mental
Cortical lesions interrupt cortical and cortico- practice induced a signicant effect on motor
subcortical networks, and the capacity for auto- outcome (99). One advantage is that it is not
matic and simultaneous processing of incoming dependent on the ability to execute a movement
stimuli is reduced. Current data indicate that and can thus start early in rehabilitation even in
relearning and compensation for lost functions severely paretic patients with little motor activity
benet from multisensory stimulation. Multisen- and that it can be combined with other treatments.
sory approaches to motor, somatosensory, and However, some patients with left parietal or left
cognitive rehabilitation include action observation, lateral prefrontal lesions may have problem with
mental training, and training in a virtual reality mental imagery (98).
and music-related therapies. Virtual reality (VR) technologies provide multi-
In training with a mirror, the patients aected modal, interactive, and realistic 3-D environments
arm is hidden behind a mirror. While moving the with a high level of control of the parameters and
unaected arm, the patient watches its mirror applications that can be adjusted for each user
image as if it were the aected arm (88). Some pilot (100, 101). VR can enhance velocity and walking
studies have been published, indicting that it might distance in robot-based gate training (42), and VR
be useful in patients with stroke, and two random- games improves attention, speed, precision, and
ized controlled trials have been published with timing in robot-based hand training (43). A virtual
positive results lasting at least 6 months after supermarket provides opportunity for practicing
training (89, 90). The mirror-training patients functional tasks in everyday life (102). Unilateral
regained more distal hand function than control spatial neglect that is present in almost 50% of
patients. Interestingly, across all patients, mirror patients with right-hemisphere stroke has a nega-
training patients improved recovery of surface tive impact on functional recovery (103). VR has
sensibility, and it stimulated recovery from hemi- been successfully used both for assessment and
neglect, suggesting that training with a mirror may treatment of neglect. (104107). A three-dimen-
induce multisensory interactions and be related to sional virtual street crossing program has been
action observation that activates motor and pre- developed for assessment and training extra-per-
motor areas (91). Neurons in the regions that sonal neglect and enable outdoor mobilization
discharge both in association with performance of (108). Computerized VR interfaced with robots,
a motor task and with observation of another movement tracking, and sensing glove systems can
individual performing the same action are named further be coupled to fMRI images providing
mirror neuron and are thought to contribute to modied visual feedback (109). VR spatial brain
imitation and to be important for our understand- processing differs from brain fMRI activation in
ing of other individuals intensions (9294). Four reality. Thus, in evaluation of possible restoration
weeks of action observation signicantly enhanced effects caused by VR training it is important to
motor function with a signicant rise in activity in integrate information about the brain activation
the bilateral ventral premotor cortex, the supple- networks elicited by the training (110). Tele-reha-
mentary motor area, bilateral superior temporal bilitation that allows a therapist to conduct inter-
gyrus, and some other areas in fMRI. The func- active VE treatment sessions with a patient who is
tional improvement remained at 8 weeks after the located at home has shown highly signicant
end of the intervention (95). Combining observa- results in three standard clinical tests after 30 l-h
tion of daily actions concomitant with physical sessions, maintained at 4- month follow-up (111).
training of the same movements signicantly Data from training activities of daily living in a


virtual reality setting are promising. The patients able to sing the text of a song while they are unable to
have to be positive to VR training, continued speak the same text. When allowed to sing and speak
contact with a therapist is essential, and it needs to along with an auditory model, aphasics repeat and
be further evaluated for long-term gains. A low recall more words when singing than when speaking
cost multiple users VR environment system has (131). The intelligibility and naturalness of the
been developed for rehabilitation of patients with speech improved after vocal exercises and singing
stroke (112). training in patients with non-uent aphasia after
stroke or trauma (132).
Intensive melodic intonation therapy for aphasia
Speech and language rehabilitation
is an old method that has been systematically
The brain organization for language involves a applied and evaluated in recent years (133, 134).
combination of cortical structures and white The method includes three important components:
matter tracts, some of which are unilateral and melodic intonation, intense training 1.5 h d 5 days
other bilateral. A dorsal stream, sound to action a week, and simultaneous tapping with the left
(non-uent or Brocas aphasia), is essentially left hand to prime the sensorimotor and premotor
oriented in most persons, and a ventral stream, cortices on the right side for articulation. Melodic
from sound to meaning (semantic aphasia), is to intonation therapy delivered at high intensity to
a considerable extent bilateral (113, 114). The patients with chronic severe Brocas aphasia leads
degree of language lateralization determines sus- to remodeling of the right arcuate fasciculus, a
ceptibility to unilateral brain lesions (115). ber bundle that combines the anterior and pos-
Aphasia or dysphasia can be caused by cortical terior language area in the left hemisphere demon-
lesions and or to damage to white matter tracts strating that plasticity can be induced in the
connecting dierent language areas. Decreased contra-lateral homolog tract (135).
fMRI activation was observed in the remaining Constraint-induced aphasia therapy (CIAT) is a
language area during the rst days after stroke dierent approach. Based on the concept of
(acute phase followed 10 days later by an activa- constraint-induced therapy for motor therapy, it
tion of homolog regions in the right hemisphere. In was hypothesized that gestures and other types of
the chronic phase (about a year later), the activity non-speech communication should be prevented,
had reappeared in the remaining left language and patients forced to use speech while a therapist
areas in patients with good recovery (116). How- is playing language games with two or three
ever, there is a large variability of language aphasic patients. The picture cards and the hands
recovery after rst-ever stroke, and a follow-up are hidden for other players to prevent visual
study 90 days after stroke onset failed to identify input, and all communication, mainly questions
any prognostic factors (117). Several studies indi- and answers, have to be performed by spoken
cate that both hemispheres can be involved in the words and sentences. The game is getting more
recovery process. dicult in small steps and reinforcement is pro-
Language and actions are closely linked in the vided. Extensive training 3 h a day resulted in
brain (118120), and Brocas area, traditionally signicant eect compared to standard training
looked upon an exclusive language area, is now one hour a day during an extended period adding
thought to detect and represent complex hierar- up to the same total amount of training, thus the
chical dependencies regardless of modalities and same training time spread over a longer time (136).
use including gesture, action and music (121124). In a study when all aphasia patients were trained
Listening to speech specically modulates the with CIAT over a 2-week period 19 years after
tongue muscles (125) and language perception stroke, half of the patients received additional
activates the hand motor cortex (126). Integrating training in everyday communication with the
observed facial movements into the speech percep- assistance of family members. Language tests
tion process involves a network of multimodal improved after training in both CIAT groups. No
brain regions associated with speech production alterative treatment group was included. However,
that contribute less to speech perception when only only the patients who were encouraged by their
auditory signals are present (127). Gestures may relatives to be more active verbally during the
facilitate word retrieval in aphasia (128). 2- week training period exhibited more communi-
There is a bihemispheric network for vocal cative activity than before treatment when
production regardless of whether the words re-examined after 6 months (137), demonstrating
phrases are intoned or spoken (129), and words that environmental encouragement is essential
and melody are intertwined in singing (130), which for transforming the effects observed in language
may explain why some patients with aphasia are tests into useful verbal communication. For en

Stroke rehabilitation

extensive review on the theory and practice of composite score based on four subtests of
CIAT, see review by Pulvermuller and Berthier NIHSS was almost as good as the MMSE in
(138). detecting severe cognitive impairment (147).
Using MEG (magneto-encephalography) before, Neglect is an important prognostic factor.
direct after and 3 months after the training, three Among 138 patients with stroke aged 7091 ,
patterns of behavioral and neurophysiologic visual neglect was present in 15% 20 months after
response to constraint-induced language therapy, stroke (141). Cognitive impairment was twice as
not described in detail, were observed (139). common in patients with neglect and three times
Patients with initial response who maintained the as common in those with severe neglect, indicating
gains at 3 months exhibited an increase in left that early rehabilitation of neglect might have
temporal activation (responders, n = 8). Patients important long-term effects.
with initial signicant response to the therapy but In a review based on 78 published quantitative
no eect at 3- month follow-up had greater right- and qualitative studies reporting social conse-
hemisphere activation than other patients at all quences after stroke in patients <65 years of age,
MEG sessions (lost-response, n = 4). Those who the proportions for return to work ranged from
did not improve at any time had increased acti- 0% to 100%. A negative impact on family
vation in left parietal areas (non-responders, relationships ranged from 5% to 79% and for
n = 11). deterioration in leisure activities from 15% to
Decits in auditory single word and sentence 79%. The review highlights the need for robust and
comprehension correlate with the degree of dis- consistent methodologies in future studies on the
ruption of left-right anterior-lateral superior tem- prevalence of social problems and of the eect of
poral cortical connectivity and with local interventions to address them (148).
activation in the superior temporal cortex (118). Attention is closely related to cognition and is
Voxel-based lesion-symptom mapping has con- also important for motor skill training. A signif-
rmed the necessary role for the left anterior icant reduction in the attention decit was
temporal lobe in mapping concepts to words (140). observed at 5 weeks and 6 months in a recent
Also aphasia related to frontal lesions can include randomized controlled trial with an attention-
semantic components. More studies that specify training program starting within 2 weeks after
the location and extension of the lesions and the stroke onset (149). The study included 78 patients
related language problems as to speech uency and with stroke identied via neuropsychological
understanding in daily life situations are needed. assessment as having attention decit. If these
results can be conrmed in further studies, they are
likely to have effects both on motor and cognitive
Rehabilitation of other cognitive deficits
rehabilitation and may improve quality of life after
Post-stroke cognitive impairment interferes with stroke.
recovery and is a major problem for social Whether rTMS and tDCS can inuence cogni-
rehabilitation and post-stroke quality of life at tive decits after stroke has so far been little
all ages (141143). Cognitive activation is clearly explored. In healthy individuals, tDCS may
involved in several examples of multisensory improve language learning (150152) and enhance
interactions already referred to including the planning activity (153). There is some evidence that
effect on neglect in VR training. Although early it may improve naming in aphasia (154, 155),
bedside cognitive assessment is possible in most working memory (156), and attention (157) in
cases (144), specic cognitive rehabilitation is often patients with stroke. These are all small studies
neglected in the early stage after stroke. Two week with no long-term follow-up.
after a rst-ever ischemic infarct, 91.5% of 177
patients (mean age 50  16 years) failed in at least
Music therapy
one cognitive domain, predominantly in working
memory, episodic memory, and executive func- Listening to rhythm activates motor and premotor
tions, compared with education and age-matched cortices (158160). Rhythmic auditory stimulation
control subjects (145). Cognitive dysfunction was and musical motor feedback can improve gait
associated with age, low level of education, NIHSS (161163) and arm training after stroke (164, 165).
score at day 15, and middle cerebral artery Music-supported nger and arm training that
infarcts, suggesting that simple criteria may be a signicantly improved function was accompanied
useful tool for designing clinical trials. (146). In by electrophysiological changes, indicating better
another study on 149 stroke patients 70+ were cortical connectivity and improved activation of
investigated after 18 months suggested that a the motor cortex (166).


Music is a multimodal stimulus with a well- for poor outcome among survivors of aneurismal
established role in cultural and social communica- subarachnoid hemorrhage (177). There are likely
tion and emotional well-being. During the last to be other genetic differences that can inuence
years, a number of studies have demonstrated that outcome.
music listening activates many brain structures
related to sensory processing, attention, and
Concluding remarks
memory and can stimulate complex cognition
and multisensory integration (158, 167). To what Progress of time is an independent covariate that
extent these effects can be transferred to thera- reects spontaneous recovery of functions that
peutic interventions in patients with stroke is occur during the rst months after a stroke. To
currently investigated. Patients with neglect show avoid the confounding eect of time (178), most
enhanced visual awareness associated with studies testing new rehabilitation methods involve
increased fMRI activation of regions related to patients with chronic stroke several months after
emotion and attention while they listen to music stroke onset. Optimal benets for the patients and
they like but not to un-preferred music or silence the society would supposedly be obtained by
(168). Music therapy improves executive function successful interventions in the subacute phase of
and emotional adjustment in traumatic brain stroke as indicated by the benecial effect on
injury rehabilitation (169). It has been reported motor outcome in stroke units. Rehabilitation
to improve attention and verbal memory in program may require different therapy protocols
patients with stroke (170). However, the statistical in acute and chronic stages of recovery, and we
analyses of the data were not adequate, and need to know the optimal time for specic inter-
further studies are needed. Merely listening to ventions. More homogenous groups of patients
music and speech after stroke starting 1 week after need to be studied. Although it has been repeatedly
stroke onset induced long-term plastic changes in shown that the integrity of the corticospinal tracts
early sensory processing that correlated with the is of main importance for a favorable outcome
improvement in verbal memory and focused after stroke (711), the information is lacking in
attention both in music and in speech listening most studies. Cognitive rehabilitation programs
(171). A community-based intervention program starting early after stroke are essential to establish
combining rhythmic music and a specialized reha- whether attention-training, music, and other cog-
bilitation program during 8 weeks resulted in a nitive interventions can lead to better social
wider range of motion and exibility, more adjustment and quality of life post stroke.
positive moods as well as an increased frequency
and quality of interpersonal relationships com-
pared to the control group (172).
1. Seitz RJ, Hung Y, Knorr U, Tellman L, Herzog H, Fre-
und HL. Large-scale plasticity of the human motor cor-
Genetic polymorphism tex. Neuroreport 1995;6:7424.
2. Johansson BB. Brain plasticity and stroke rehabilitation.
Genetic polymorphism is one factor that may The Willis Lecture. Stroke 2000;31:22331.
inuence the response of the brain to injury and 3. Johansson BB. Brain plasticity in health and disease. Keio
disease. Brain-derived growth factor (BDNF) has a J Med 2004;53:2346.
critical role in activity-dependent modulation of 4. Pascual-Leone A, Amedi A, Fregni F, Merabet LB. The
plastic human brain cortex. Annu Rev Neurosci
synaptic plasticity in human motor cortex. A 2005;28:377401.
common single nucleotide polymorphism (BDNF 5. Nithianantharajah J, Hannan AJ. Enriched environments,
val66met), which results in reduced secretion of experience-dependent plasticity and disorders of the ner-
BDNF, reduces the activity-related cortical plas- vous system. Nat Rev Neurosci 2006;7:697709.
ticity in response to motor training in healthy 6. Gerloff C, Bushara K, Sailer A et al. Multimodal
imaging of brain reorganization in motor areas of the
individuals (173) and is associated with greater contralesional hemisphere of well recovered patients after
error and poorer retention in short-term motor capsular stroke. Brain 2006;129:791808.
learning (174). In a cohort of 722 elderly individ- 7. Ward NS, Newton JM, Swayne OB et al. Motor system
uals, the presence of the polymorphism was asso- activation after subcortical stroke depends on corticosp-
ciated with signicantly reduced cognitive inal system integrity. Brain 2006;129:80919.
8. Newton JM, Ward NS, Parker CJM et al. Non-invasive
performance on processing speed, delayed recall, mapping of corticofugal bres from multiple motor areas
and general intelligence (175). It modulates the relevance to stroke recovery. Brain 2006;129:184458.
response to rTMS, which may explain some of the 9. Chouinard PA, Leonard G, Paus T. Change in eective
individual differences in the effect of stimulation connectivity of the primary motor cortex in stroke patients
(176). It has also been proposed to be a predictor after rehabilitative therapy. Exp Neurol 2006;201:37587.

Stroke rehabilitation

10. Stinear CM, Barber A, Smale PR et al. Functional po- 29. Dinse HR, Kleibel N, Kalisch T, Ragert P, Wilimzig C,
tential in chronic stroke patients depends on corticospinal Tegenthoff M. Tactile cooperation resets age-related de-
tract integrity. Brain 2007;130:17080. cline of human tactile discrimination. Ann Neurol
11. Johansen-Berg H. Functional imaging of stroke recovery: 2006;60:8894.
what have we learnt and where do we go from here? Int J 30. Kalisch T, Tegenthoff M, Dinse HR. Improvement of
Stroke 2007;2:716. sensorimotor functions in old age by passive sensory
12. Nair DG, Hutchinson S, Fregni F et al. Imaging corre- stimulation. Clin Intervent Aging 2008;3:67390.
lates of motor recovery from cerebral infarction and their 31. Smith PS, Dinse HR, Kalisch T, Johnson M, Walker-
physiological signicance in well-recovered patients. Batson D. Eects of repetitive electrical stimulation to
Neuroimage 2007;3:25363. treat sensory loss in persons poststroke. Arch Phys Med
13. Richards LG, Stewart KC, Woodbury ML, Senesac C, Rehabil 2009;90:210811.
Cauraugh JH. Movement-dependent stroke recovery: a 32. Taub E, Miller NE, Novack TA et al. Technique to
systematic review and meta-analysis of TMS and fMRI improve chronic motor decit after stroke. Arch Phys
evidence. Neuropsychologia 2008;46:311. Med Rehabil 1993;74:34754.
14. Ciccarelli O, Catani M, Johansen-Berg H, Clark C, 33. Wolf SL, Winstein CJ, Miller JP et al. Eect of con-
Thompson A. Diusion-based tractography in neurologi- straint-induced movement therapy on upper extremity
cal disorders: concepts, applications, and future devel- function 3 to 9 months after stroke. The EXITE
opments. Lancet Neurol 2008;7:71527. randomized clinical trial. JAMA 2006;296:2095104.
15. Gong G, He Y, Concha L et al. Mapping anatomical 34. Wolf SL, Winstein CJ, Miller JP et al. Retention of
connectivity patterns of human cerebral cortex using in upper limb function in stroke survivors who have received
vivo diusion tensor imaging tractography. Cereb Cortex constraint-induced movement therapy in the EXCITE
2009;19:52436. trial. Lancet Neurol 2008;7:3340.
16. Pannek K, Chalk JB, Finnigan S, Rose SE. Dynamic 35. Dobkin BH. Confounders in rehabilitation trials of task-
corticospinal white matter connectivity changes during oriented training lessens from the designs of the EXCITE
stroke recovery: a diusion tensor probabilistic tracto- and SCILT multicenter trials. Neurorehabil Neurol
graphy study. J Magn Reson Imaging 2009;29:52936. Repair 2007;21:313.
17. Lindenberg R, Renga V, Zhu LL, Alsop D, Schlaug G. 36. Boake C, Noser EA, Ro T et al. Constraint-induced
Structural integrity of corticospinal motor bers predicts movement therapy during early stroke rehab. Neurore-
motor impairment in chronic stroke. Neurology habil. Neural Repair 2007;21:1424.
2010;74:2807. 37. Dromerick AW, Lan CE, Birkenmeier RL et al. Very early
18. Dewey HM, Sherry LJ, Collier JM. Stroke rehabilitation constraint-induced movement during stroke rehabilita-
2007: what should it be? Int J Stroke 2007;2:191200. tion (VECTORS): a single center RCT. Neurology
19. Stroke Unit TrialistsCollaboration. Organized inpatients 2009;73:
(stroke unit) care for stroke. Cochrane Database Syst 195201.
Rev, 2007; Art. No.: CD000197. DOI: 10.1002/14651858. 38. Kwakkel G, Kolten BJ, Krebs HI. Eects of robot-as-
20. Indredavik B. Stroke unit care is benecial both for the sisted therapy on upper limb recovery after stroke: a
patient and for the health service and should be widely systematic review. Neurorehabil Neural Repair
implemented. Stroke 2009;40:12. 2008;22:11121.
21. Hsu HF, Newcommon NN, Cooper ME et al. Impact of a 39. Mehrholz J, Plats T, Kugler J, Pohl M. Electromechan-
stroke unit on length of hospital stay and in-hospital case ical and robot-assisted arm training for improving arm
fatality. Stroke 2009;40:1823. function and activities of daily living after stroke. Coch-
22. O mer S, Serra V, Samyshikin Y, McGuire A, Wolfe rane Database Syst Rev 2008;4:CD006876.
CCDA. Cost-eectiveness of stroke unit care followed by 40. Huang VS, Krakauer JW. Robotic neurorehabilitation: a
early supported discharge. Stroke 2009;40:249. computational motor learning perspective. J NeuroEng
23. Rabadi MH, Rabadi FM, Edelstein L et al. Cognitively Rehab 2009;6:5. DOI:10.1186/1743-0003-6-5.
impaired stroke patients do benet from admission to an 41. Krebs HI, Volpe B, Hogan N. A working model of stroke
acute rehabilitation unit. Arch Phys Med Rehabil recovery from rehabilitation robotics practitioners.
2008;89:4418. J NeuroEng Rehab 2009;6:6. DOI:1186 1743-0003-6-6.
24. Terent A, Asplund K, Farahmand B et al. Stroke unit care 42. Mirelman A, Bonato P, Deutsch JE. Eects of training with
revisited who benets the most? A cohort study of a robot-virtual reality system compared with a robot alone
105043 patients in Riks-Stroke, the Swedish Stroke on the gait of individuals after stroke. Stroke 2008;40:
Register. J Neurol Neurosurg Psychiatry 2009;80:8817. 16974.
25. Johansson BB. Environmental inuence on recovery after 43. Takahashi CD, Der-Yeghiaian L, Le V, Motiwala RR,
brain lesions: experimental and clinical data. J Rehab Cramer SC. Robot-based hand motor therapy after
Med 2003;41(Suppl.):116. stroke. Brain 2008;131:42537.
26. Johansson BB. Functional and cellular eects of environ- 44. Stewart KC, Cauraugh JH, Summers JJ. Bilateral move-
mental enrichment after experimental brain infarcts. Re- ment training and stroke rehabilitation. A systematic
stor Neurol Neurosci 2004;22:16374. review and meta-analysis. J Neurol Sci 2006;244:8995.
27. Johansson BB. Environmental eect on functional out- 45. Lin KC, Chen YA, Chen CL, Wu CY, Change YF. The
come after stroke. In: Cramer SC, Nudo RJ, eds. Brain eects of bilateral arm training on motor control and
repair after stroke. Cambridge, UK: Cambridge Univer- functional performance in chronic stroke: a randomized
sity Press, 2010; 4755. controlled study. Neurorehabil Neural Repair 2010;24:
28. Smania N, Montagnana B, Faccioli S. Rehabilitation of 4251.
somatic sensation and related decit of motor control in 46. Lin KC, Chang YF, Wu CYI, Chen YA. Eects of con-
patients with pure sensory stroke. Arch Phys Med straint-induced therapy versus bilateral arm training on
Rehabil 2003;84:1692702. motor performance, daily functions, and quality of life in


stroke survivors. Neurorehabil Neural Repair 66. Sawaki L, Wu CWH, Kaelin-Lang A, Cohen LG. Eect of
2009;23:4418. somatosensory stimulation on use-dependent plasticity in
47. McCombe Waller S, Whittal J. Bilateral arm training: chronic stroke. Stroke 2006;37:2467.
why and who benets? NeuroRehabilitation 2008;23:29 67. Celnik P, Hummel F, Harris-Love M, Wolk R, Cohen LG.
41. Somatosensory stimulation enhances the eects of train-
48. Chen SY, Winstein CJ. A systematic review of voluntary ing functional hand tasks in patients with chronic stroke.
arm recovery in hemiparetic stroke: clincial predictors for Arch Phys Med Rehabil 2007;88:136976.
meaningful outcomes using the international classica- 68. Conforto AB, Cohen LG, dos Santos LR, Scaff M, Marie
tion of functioning, disability, and health. J Neurol Phys SKN. Eects of somatosensory stimulation on motor
Ther 2009;33:213. function in chronic cortico-subcortical stroke. J Neurol
49. Muellbacher W, Richards C, Ziemann U et al. Improving 2007;254:3339.
hand function in chronic stroke. Arch Neurol 2002;59: 69. Celnik P, Paik NJ, Vandermeeren Y, Dimyan M, Cohen
127882. LG. Eects of combined nerve stimulation and brain
50. Di Lazzaro V, Oliviero A, Profice P et al. Direct dem- polarization on performance of a motor sequence task
onstration of interhemispheric inhibition of the human after chronic stroke. Stroke 2009;40:176471.
motor cortex produced by transcranial magnetic stimu- 70. Khedr EM, Abo-Elfetoh N, Rothwell JC. Treatment of
lation. Exp Brain Res 1999;124:5204. post-stroke dysphagia with repetitive transcranial mag-
51. Werhahn KJ, Mortensson J, Von Boven RW, Zeuner KE, netic stimulation. Acta Neurol Scand 2009;119:15561.
Cohen LG. Enhanced tactile spatial acuity and cortical 71. Khedr EM, Etraby AE, Hemeda M, Nasef AM, Razek
processing during acute hand deaerentation. Nat Neu- AAE. Long-term eect of repetitive transcranial magnetic
rosci 2002;5:9368. stimulation on motor function recovery after acute
52. Werhahn K, Mortensson J, Kaelin-Lang A, Boroojerdi B, ischemic stroke. Acta Neurol Scand 2010;121:307.
Cohen LG. Cortical excitability changes induced by de- 72. Rossi S, Hallett M, Rossinin PM, Pascular-Leone A. The
aerentation of the contralateral hemisphere. Brain safety of TMS Consensus Group. Safety, ethical consid-
2002;125:140213. erations, and application guidelines for the use of trans-
53. Murase N, Dunque J, Mazzocchio R, Cohen LG. Inuence cranial magnetic stimulation in clinical practice and
of interhemispheric interactions of motor function in research. Clin Neurophysiol 2009;120:200839.
chronic stroke. Ann Neurol 2004;55:4009. 73. Brown JA, Lutsep HL, Weinand M, Cramer SC. Motor
54. Ward NS, Cohen LG. Mechanisms underlying recovery cortex stimulation for the enhancement of recovery from
of motor function after stroke. Arch Neurol 2004;61: stroke: a prospective, multicenter study. Neurosurgery
18448. 2006;58:46473.
55. Talelli P, Greenwood RJ, Rothwell JC. Arm function 74. Levy R, Ruland S, Weinand M et al. Cortical stimulation
after stroke: neurophysiological correlates and recovery for the rehabilitation of patients with hemispheric stroke:
mechanisms assessed by transcranial magnetic stimula- a multicenter feasibility study of safety and ecacy.
tion. Clin Neurophysiol 2006;117:164159. J Neurosurg 2008;108:70714.
56. Hummel F, Cohen LG. Non-invasive brain stimulation: a 75. Plow EB, Carey JR, Nudo RJ, Pascual-Leone A. Invasive
new strategy to improve neurorehabilitation after stroke? cortical stimulation to promote recovery of function.
Lancet Neurol 2006;5:70812. A critical appraisal. Stroke 2009;40:192631.
57. Hallett M. Transcranial magnetic stimulation: a primer. 76. Ameli M, Grefkes C, Kemper F et al. Dierential eects
Neuron 2007;55:18799. of high-frequency repetitive transcranial magnetic stimu-
58. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC lation over ipsilesional primary motor cortex in cortical
stimulation (tDCS): a tool for double blind sham-con- and subcortical middle cerebral artery stroke. Ann Neu-
trolled clinical studies in brain stimulation. Clin Neuro- rol 2009;66:298309.
physiol 2008;117:84550. 77. Sainburg RL, Schaefer SY. Interlimb dierences in con-
59. Mansur CG, Fregni F, Boggio PS et al. A sham stimu- trol of movement extent. J Neurophysiol 2004;92:1374
lation-controlled trial of rTMS of the unaected hemi- 83.
sphere in stroke patients. Neurology 2005;64:18024. 78. Sainburg RL, Duff SV. Does motor lateralization have
60. Takeuchi N, Chuma T, Matsuo Y, Watanabe I, Ikoma K. implications of stroke rehabilitation? J Rehab Res Rev
Repetitive transcranial magnetic stimulation of contra- 2006;43:31122.
lateral primary motor cortex improves hand function 79. Schaefer SY, Haaland KY, Sainburg RL. Ipsilateral
after stroke. Stroke 2005;36:26816. motor decits following stroke reect hemispheric spe-
61. Fregni F, Boggio PS, Valle AC et al. A sham-controlled cializations for movement control. Brain 2007;130:2146
trial of a 5-day course of repetitive transcranial magnetic 58.
stimulation of the unaected hemisphere in stroke pa- 80. Lewis GN, Perreault EJ. Side of lesion inuences bilateral
tients. Stroke 2006;37:211522. activation in chronic post-stroke hemiparesis. Clin Neu-
62. Floel A, Nagorsen U, Werhahn KJ et al. Inuence of rophysiol 2007;118:205062.
somatosensory input on motor function in patient with 81. Aramaki Y, Honda M, Sadato N. Suppression of the non-
chronic stroke. Ann Neurol 2004;56:20612. dominant motor cortex during bilateral symmetric nger
63. Voller B, Floel A, Werhahn KJ et al. Contralateral hand movement: a functional magnetic resonance imaging
anesthesia transiently improves poststroke sensory de- study. Neuroscience 2007;141:214753.
cits. Ann Neurol 2006;59:3858. 82. Vines BW, Cerruti C, Schlaug G. Dual-hemisphere tDCS
64. Khedr EM, Ahmed MA, Fathy N, Rothwell JC. Thera- facilitates greater improvements for healthy subjectsnon-
peutic trial of repetitive transcranial magnetic stimulation dominant hand compared to uni-hemisphere stimulation.
after acute ischemic stroke. Neurology 2005;65:4668. BMC Neuroscience 2008;9:103. DOI:10.1186/1471-2202-
65. Hummel FC, Celnik P, Giraux P et al. Eects of non- 9-103.
invasive cortical stimulation on skilled motor function in 83. Vines BW, Nair D, Schlaug G. Modulating activity in the
chronic stroke. Brain 2005;128:4909. motor cortex aects performance for the two hands dif-

Stroke rehabilitation

ferently depending upon which hemisphere is stimulated. 106. Broeren J, Samuelsson H, Stibrant-Sunnerhagen K,
Eur J Neurosci 2008;28:166773. Blomstrand C, Rydmark M. Neglect assessment as an
84. Rinehart JK, Singleton RD, Adair JC, Sadek JR, Haaland application of virtual reality. Acta Neurol Scand
KY. Arm use after left or right hemiparesis is inuenced 2007;116:15763.
by hand preference. Stroke 2009;40:54550. 107. Tsirlin I, Dupierrix E, Chokron S, Coquillart S, Ohlmann
85. Schaechter JD, Perdue JD. Enhanced cortical activation T. Uses of virtual reality for diagnosis, Rehabilitation and
in the contralesional hemisphere of chronic stroke pa- study of unilateral spatial neglect: review and analysis.
tients in response to motor skill challenge. Cereb Cortex CyberPsychology & Behavior 2009;12:17581.
2008;18:63847. 108. Kim DY, Ku J, Chang WH et al. Assessment of post-
86. Ghazanfar AA, Schroeder CE. Is neocortex essentially sroke extrapersonal neglect using a three-dimensional
multisensory? Trends Cogn Neurosci 2006;10:27885. immersive virtual street crossing program. Acta Neurol
87. Shams L, Seitz AR. Benets of multisensory learning. Scand 2010;121:17177.
Trends Cogn Sci 2008;12:4117. 109. Adamovich SV, August K, Merians A, Tunik E. A virtual
88. Garry MI, Loftus A, Summers JJ. Mirror, mirror on the reality-based system integrated with fMRI to study neural
wall: viewing a mirror reection of unilateral hand mechanisms of action observation-execution: a proof of
movements facilitates ipsilateral M1 excitability. Exp concept study. Rest Neurol Neurosci 2009;27:20923.
Brain Res 2005;163:11822. 110. Beck L, Wolter M, Mungard NF et al. Evaluation of
89. Yavuzer G, Selles R, Sezer N et al. Mirror therapy im- spatial processing in virtual reality using functional
proves hand function in subacute stroke: a randomized magnetic resonance imaging (fMRI). Cyberspace Behav
controlled trial. Arch Phys Med Rehabil 2009;89:3938. Soc Netw 2010;13:2115.
90. Dohle C, Pullen J, Nakaten A, Kust J, Rietz C, Karbe H. 111. Holden MK, Dyar TA, Dayan-Cimadoro L. Telerehabili-
Mirror therapy promotes recovery from severe hemipa- tation using a virtual environment improves upper
resis: a randomized control trial. Neurorehabil Neural extremity function in patients with stroke. IEEE Trans
Repair 2009;23:20917. Neural Syst Rehabil Eng 2007;15:3642.
91. Mulder Th. Motor imagery and action observation: cog- 112. Sivak M, Mavroidis C, Holden MK. Design of a low cost
nitive tools for rehabilitation. J Neural Transm multiple user virtual environment for rehabilitation
2007;114:126578. (MEVER) of patients with stroke. Stud Health Technol
92. Rizzolatti G, Craighero L. The mirror-neuron system. Inform 2009;142:31924.
Annu Rev Neurosci 2004;27:16992. 113. Hickok G, Poepple D. The cortical organization of speech
93. Buccino G, Solodkin A, Small SL. Functions of the mirror processing. Nat Rev Neurosci 2007;8:393402.
neuron system: implications for neurorehabilitation. 114. Warren JE, Crinion JT, Lambon Ralph L, Wide RJS.
Cogn Behav Neurol 2006;16:5563. Anterior temporal lobe connectivity correlates with
94. Rizzolatti G, Sinigaglia C. The functional role of the functional outcome after aphasic stroke. Brain
parieto-frontal mirror circuit: interpretations and misin- 2009;132:342842.
terpretations. Nat Rev Neurosci 2010;11:26474. 115. Knecht S, Floel A, Drager B et al. Degree of language
95. Ertelt D, Small S, Solodkin A et al. Action observation lateralization determines susceptibility to unilateral brain
has a positive impact on rehabilitation of motor decits lesions. Nat Neurosci 2002;5:6959.
after stroke. NeuroImage 2007;36:T16473. 116. Saur D, Lange R, Baumgaertner A et al. Dynamics of
96. Celnik P, Webster B, Glasser DM, Cohen LG. Eects of language reorganization after stroke. Brain
action observation on physical training after stroke. 2006;129:1137184.
NeuroImage 2007;36:T16473. 117. Lazar RM, Speitzer AE, Festa JR, Krakauer JW, Mar-
97. Facio P, Cantagallo A, Craighero L et al. Encoding of shall RS. Variability in language recovery after rst-ever
human action in Brocas area. Brain 2009;132:19808. stroke. J Neurol Neurosurg Psychiatry 2008;79:5304.
98. Lotze M, Halsband U. Motor imagery. J Physiol Paris 118. Pulvermuller F. Brain mechanisms linking language and
2006;99:38695. action. Nat Rev Neurosci 2005;6:57682.
99. Page SJ, Levine P, Leonard A. Mental practice in chronic 119. Gentilucci M, Corballis MC. From manual gesture to
stroke: result of a randomized, placebo-controlled trial. speech: a gradual transition. Neurosci Biobehav Rev
Stroke 2007;38:12937. 2006;30:94960.
100. Holden MK. Virtual environments for motor rehabilita- 120. Xu J, Gannon PJ, Emmorey K, Smith JF, Braun AR.
tion: review. Cyberpsychol Behav 2005;8:187211. Symbolic gestures and spoken language are processed by
101. Broeren J, Claesson L, Goude D, Rydmark M, Sunnerha- a common neural system. Proc Nat Acad Sci USA
gen KS. Virtual reality in an activity centre for commu- 2009;106:206649.
nity dwelling persons with stroke; the possibilities of 3D 121. Maess BS, Koelch T, Gunder TC, Friederici AD. Musical
computer games. Cerebrovasc Dis 2008;26:28996. syntax is processed in Brocas area: an MEG study. Nat
102. Rand D, Katz N, Weiss PL. Intervention using the VMall Neurosci 2001;4:5405.
for improving motor and functional activity of the upper 122. Patel AD. Language, music, syntax and the brain. Nat
extremity in post stroke participants. Eur J Phys Rehabil Neurosci 2003;6:67481.
Med 2009;45:11321. 123. Koelsch S, Kasper E, Sammler K, Schutze T, Gunder T,
103. Buxbaum LJ, Ferraro MK, Veramonti T et al. Hemispace Friederici AD. Music, Language and meaning: brain
and hemineglect:subtypes, neuroanatomy, and disability. signatures of semantic processing. Nat Neurosci
Neurology 2004;62:74956. 2004;7:3027.
104. Glover S, Castello U. Recovering space in unilateral 124. Fadiga L, Craighero L, DAusilio A. Brocas area in lan-
neglect: a neurological dissociation revealed by virtual guage, action and music. Ann N Y Acad Sci
reality. J Cogn Neurosci 2006;18:83343. 2009;1169:44858.
105. Ansuini C, Pierno AC, Lusher D et al. Virtual reality 125. Fadiga L, Craighero L, Boccino G, Rizzolatti G. Speech
applications for the remapping of space in neglect pa- listening specically modulates the tongue muscles: a
tients. Rest Neurol Neurosci 2006;24:43141. TMS Study. Eur J Neurosci 2002;15:399402.


126. Floel A, Eliger T, Breitenstein C, Knecht S. Language 145. Jaillard A, Naegele B, Trabucco-Miguel S, Lebas JF,
perception activates the hand motor cortex: implications Hommel M. Hidden dysfunction in subacute stroke.
for motor theories or speech perception. Eur J Neurosci Stroke 2009;40:24739.
2003;18:7048. 146. Jaillard A, Grand S, Le Bas JF, Homel M. Predicting
127. Skipper JI, Nusbaum HC, Small SL. Listening to talking cognitive dysfunctioning in nondemented patients early
faces: motor cortical activation during speech perception. after stroke. Cerebrovasc Dis 2010;29:41523.
NeuroImage 2005;25:7689. 147. Cumming TB, Blomstrand C, Bernhardt J, Linden T. The
128. Raymer AM, Singletary F, Rodriguez A, Ciampitti M, NIH stroke scale can establish cognitive function after
Heilam KM, Rothi LJ. Eects of gesture + verbal stroke. Cerebrovasc Dis 2010;30:714.
treatment for noun and verb retrieval in aphasia. J Int 148. Daniel K, Wolfe CDA, Busch MAB, McKevitt C. What
Neuropsychol Soc 2006;12:66782. are the social consequences for stroke for working-aged
129. Ozdemis E, Norton A, Schlaug G. Shared and distinct adults? A systematic review. Stroke 2009;40:43140.
neural correlates of singing and speaking. Neuroimage 149. Barker-Collo SL, Feigin VL, Lawes CMM, Rodgers A.
2006;33:62835. Reducing attention decits after stroke using attention
130. Gordon RL, Schon D, Magne C, Astesano C, Besson M. process training. A randomized controlled trial. Stroke
Words and melody are intertwined in perception of sung 2009;40:32938.
words: EEG and behavioral evidence. PLoS ONE 150. Devlin JT, Watkins KE. Stimulating language: insights
2010;5:e9889. from TMS. Brain 2007;130:61022.
131. Racette A, Bard C, Peretz I. Making non-uent aphasics 151. Floel A, Rosser N, Michka O, Knecht S, Breitenstein C.
speak: sing along! Brain 2006;129:157184. Noninvasive brain stimulation improves language learn-
132. Tamplin J. A pilot study into the eect of vocal exercises ing. J Cogn Neurosci 2008;20:141522.
and singing on dysarthric speech. NeuroRehabilitation 152. Sparing R, Dafotakis M, Meister IG, Thirugnanasamban-
2008;23:20716. dam M, Fink GR. Enhancing language performance with
133. Schlaug G, Marchina S, Norton A. From singing to non-invasive brain stimulation a transcranial direct
speaking: why singing may lead to recovery of expressive current stimulation study in humans. Neuropsychologia
language function in patients with Brocas aphasia. Music 2008;46:2618.
Percept 2008;25:31523. 153. Dockery CA, Hueckel-Weng R, Birbaumer N, Plewnia C.
134. Norton A, Zipse L, Marchina S, Schlaug G. Melodic Enhancement of planning ability by transcranial direct
intonation therapy: shared insights on how it is done and current stimulation. J Neurosci 2009;29:72717.
why it might help. N Y Acad Sci 2009;1169:4316. 154. Monti A, Cogiamania F, Ferrucci R et al. Improved
135. Schlaug G, Marchina S, Norton A. Evidence for plasticity naming after transcranial direct current stimulation in
in white-matter tracts of patients with chronic Brocas aphasia. J Neurol Neurosurg Psychiatry 2008;79:4513.
aphasia undergoing intense intonation-based speech 155. Martin PI, Naeser MA, Ho M et al. Research with
therapy. Ann N Y Acad Sci 2009;1169:38594. transcranial magnetic stimulation in the treatment of
136. Pulvermuller F, Neininger B, Elbert T et al. Constraint- aphasia. Curr Neurol Neurosci Rep 2009;9:4518.
induced therapy for chronic aphasia following stroke. 156. Jo JM, Kim YH, Ko MH, Ohn SH, Lee KH. Enhancing
Stroke 2001;32:16216. the working memory of stroke patients using tDCS. Am J
137. Meinzer M, Djundja D, Barthel G, Elbert T, Rockstroh Med Rehab 2009;88:4049.
B. Long-term stability of improved language functions in 157. Kang EK, Baek MJ, Kim S, Paik NJ. Non-invasive cortical
chronic aphasia after constraint-induced aphasia therapy. stimulation improves post-stroke attention decline. Re-
Stroke 2005;36:14626. stor Neurol Neurosci 2008;27:64650.
138. Pulvermuller F, Berthier ML. Aphasia therapy on a 158. Zatorre RJ, Chen JL, Penhune VB. When the brain plays
neuroscience basis. Aphasiology 2008;22:56399. music: auditory motor interactions in music perception
139. Breier JI, Juranek J, Maher LM, Schmadeke S, Men D, and production. Nat Rev Neurosci 2007;8:54758.
Papanicolaou AC. Behavioral and neurophysiologic 159. Chen JL, Penhune VB, Zatorre RJ. Listening to musical
response to therapy for chronic aphasia. Arch Phys Med rhythms recruits motor regions of the brain. Cereb Cortex
Rehabil 2009;90:202633. 2008;18:284454.
140. Schwartz MF, Kimberg DY, Walker GM et al. Anterior 160. Bengtsson SL, Ullen F, Ehrsson HH et al. Listening to
temporal involvement in semantic word retrieval: voxel- rhythms activates motor and premotor cortices. Cortex
based lesion-symptom mapping evidence from aphasia. 2009;45:6271.
Brain 2009;132:341127. 161. Schauer M, Mauritz KM. Musical motor feedback
141. Linden T, Samuelsson H, Skoog I, Blomstrand C. Visual (MMF) in walking hemiparetic stroke patients: random-
neglect and cognitive impairment in elderly patients ized trails of gait improvement. Clin Rehabil
late after stroke. Acta Neurol Scand 2005;111:163 2003;17:71322.
8. 162. Thaut MH, Leins AK, Rice RR et al. Rhythmic auditory
142. Hofgren C, Bjorkdahl A, Esbjornsson E, Stibrant-Sun- stimulation improves gait more than NDT Bobath
nerhagen K. Recovery after stroke: cognition, ADL training in near-ambulatory patients early poststroke: a
function and return to work. Acta Neurol Scand single-blind, randomized trial. Neurorehabil Neural Re-
2007;115: 7380. pair 2007;21:4559.
143. Hommel M, Trabucco-Miguel S, Joray S, Naegele B, 163. Hayden R, Clair A, Johnson G, Otto D. The eect of
Gonnet N, Jaillard A. Social dysfunctioning after mild to rhythmic auditory stimulation (RAS) on physical therapy
moderate rst-ever stroke at vocational age. J Neurol outcomes for patients in gait training following stroke: a
Neurosurg Psychiatry 2009;80:3715. feasibility study. Int J Neurosci 2009;119:218395.
144. Hoffmann M, Schmitt F, Bromley E. Comprehensive 164. Whithall J, McCombe Waller S, Silver KH, Macko RF.
cognitive neurological assessment in stroke. Acta Neurol Repetitive bilateral arm training with rhythmic auditory
Scand 2009;119:16271.

Stroke rehabilitation

cueing improves motor function in chronic hemiparetic 172. Jeong S, Kim MT. Eects of a theory-driven music and
stroke. Stroke 2000;31:23905. movement program for stroke survivors in a community
165. Malcolm MP, Massie C, Thaut M. Rhythmic auditory- setting. Appl Nurs Res 2007;20:12531.
motor entrainment improves hemiparetic arm kinematics 173. Kleim JA, Chan S, Pringle E et al. BDNF val66met
during reaching movements: a pilot study. TopStroke polymorphism is associated with modied experience-
Rehab 2009;16:6979. dependent plasticity in human motor cortex. Nat Neu-
166. Altenmuller E, Marco-Pallares J, Munte TF, Schneider rosci 2006;7:7357.
S. Neural reorganization underlies improvement in 174. McHughen SA, Rodrigues PF, Kleim JA et al. BDNF
stroke-induced motor dysfunction by music-supported Val66Met polymorphism inuences motor system func-
therapy. Ann N Y Acad Sci 2009;1169:395405. tion in the human brain. Cereb Cortex 2010;20:125462.
167. Koelsch S. A neuroscientic perspective on music ther- 175. Miyajima F, Ollier W, Mayes A et al. Brain-derived
apy. Ann NY Acad Sci 2009;1169:42630. neurotrophic factor polymorphism Val66Met inuences
168. Soto D, Funes MJ, Guzman-Garcia A, Warbrick T, cognitive abilities in the elderly. Genes Brain Behav
Rotshtein T, Humphreys GW. Pleasant music overcomes 2008;7:4117.
the loss of awareness in patients with visual neglect. Proc 176. Cheeran B, Talleli P, Mori F et al. A common poly-
Nat Acad Sci USA 2009;106:60116. morphism in the brain derived neurotrophic factor
169. Thaut MH, Gardiner JC, Holmberg D et al. Neurologic (BDNF) gene modulates human cortical plasticity and
music therapy improves executive function and emotional the response to rTMS. J Physiol 2008;586:571725.
adjustment in traumatic brain injury rehabilitation. Ann 177. Siironen J, Juvela S, Kanarek K, Vilkki J, Hernesniemi J,
N Y Acd Sci 2009;1169:40616. Lappalainen J. The Met allele of the BDNF Val66Met
170. Sarkamo T, Tervaniemi M, Laitinen S et al. Music lis- polymorphism predicts poor outcome among survivors of
tening enhances cognitive recovery and mood after mid- aneurismal subarachnoid hemorrhage. Stroke
dle cerebral artery stroke. Brain 2008;131:86676. 2007;38:285860.
171. Sarkamo T, Pihko E, Laitinen S et al. Music and speech 178. Kwakkel G, Kollen B, Twisk J. Impact of time on
listening enhance the recovery of early sensory processing improvement of outcome after stroke. Stroke
after stroke. J Cogn Neurosci 2009; Nov 19. 2006;37:234853.
PMID:19925203; doi:10.1162/jocn.2009,21376