ORIGINAL ARTICLE

Effects of Integrated Volitional Control Electrical Stimulation(IVES) on Upper Extremity Function in Chronic Stroke

Tomofumi Yamaguchi,1 Shigeo Tanabe, 2 Yoshihiro Muraoka, 3 Syuji Imai, 2 Yoshihisa Masakado, 2 Kimitaka Hase,1Akio Kimura2 and Meigen Liu1
1 Department of Rehabilitation Medicine, School of Medicine, Keio University, Tokyo, Japan
2 Keio University Tsukigase Rehabilitation Center, Shizuoka, Japan

3 National Hospital Organization, Murayama Medical Center, Tokyo, Japan(Received for publication on January 6, 2011)(Revised for publication on March 10, 2011)(Accepted for publication on April 21, 2011)

We evaluated the efficacy of a novel electromyogram (EMG)-controlled electrical stimulation system,
called the integrated volitional control electrical stimulator (IVES), on the recovery of upper extremity
motor functions in patients with chronic hemiparetic stroke. Ten participants in the chronic stage (morethan 12 months post-stroke with partial paralysis of their wrist and fingers) received treatment with
IVES to the extensor carpi radialis and extensor digitorum communis 6 h/day for 5 days. Before andafter the intervention, participants were assessed using upper-extremity Fugl-Meyer motor assessment(FMA), the active range of motion (A-ROM), the nine-hole peg test (NHPT), and surface EMG recordings. The upper extremity FMA showed a statistically significant increase from 50.8 ± 5.8 to 56.8 ± 6.2
after the intervention (P < 0.01). The A-ROM of wrist extension was also significantly improved from
36.0° ± 15.4° to 45.0° ± 15.5° (P < 0.01). The NHPT significantly decreased from 85.3 ± 52.0 to 63.3 ± 29.7
(P = 0.04). EMG measurements demonstrated statistically significant improvements in the coactivation
ratios for the wrist flexor and extensor muscles after the intervention. This study suggested that 5 daysof IVES treatment yields a noticeable improvement in upper extremity motor functions in patients withchronic hemiparetic stroke. (Keio J Med 60 (3) : 90–95, September 2011)

Keywords: electric stimulation therapy, motor paralysis, neural plasticity, functional recovery,
rehabilitation

Introduction

mented by electrical stimulation that assists the muscles
to execute a full range of motion.
However, there is a problem associated with this technique. Conventional systems cannot control the intensityof electrical stimulation to make it proportional to voluntary EMG signals because the EMG activities are notmonitored once the preprogrammed electrical stimulation is delivered. Therefore, it is difficult to use the system in daily life outside of therapy sessions because theelectrical stimulation disturbs voluntary movements.
Recently, our group has developed a novel EMG-controlled electrical stimulator called an integrated volitional
control electrical stimulator (IVES).6 With this type ofMany patients with stroke suffer from impairments of
the upper extremity motor functions, including limited
functional use of the affected arm and limitation in theiractivities of daily living (ADL).1
One of the rehabilitation techniques employed to facilitate motor restoration in chronic stroke survivors is electromyogram (EMG)-triggered electrical stimulation.2–5
This technique requires patients to voluntarily initiate
arm/hand muscle activities above a target threshold before the onset of electrical stimulation. If the EMG activity reaches the threshold, the muscle activities are aug-

Reprint requests to: Meigen Liu, MD, PhD, Department of Rehabilitation Medicine, School of Medicine, Keio University, 35 Shinanomachi,
Shinjuku-ku, Tokyo 160-8582, Japan, E-mail: meigenliukeio@me.com
Copyright © 2011 by The Keio Journal of Medicine

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Keio J Med 2011; 60 (3): 90–95

91

Table 1 Characteristics of the participants before IVES treatment
Number of patients
Gender (male / female)
Mean age (years) *Side affected by stroke (right / left)
Time since stroke (years) **Mechanism of stroke (ischemia / hemorrhage)
Finger function of the stroke impairment assessment set (score 3 / score 4)
Functional independence measure *** Mean (range).
** Median (range).

10
8/2
74.6 (67–86)
6/4
4.1 (1.0–19.6)
6/4
6/4
112 (91–121)

Table 2 The stroke impairment assessment set (SIAS)
Finger function test0:
No voluntary movement
1:
1a, Minimal voluntary movement; 1b, mass extension; 1c, minimal individual movement
2:
Minimal individual movement of each finger is possible, but flexion and extension are not complete
3:
Minimal individual movement of each finger is possible, with adequate flexion and extension of digits.
However, the patient carries out tasks with severe or moderate clumsiness4:
The patient carries out tasks with mild clumsiness5:
The patient carries out tasks as smoothly as on the unaffected side

EMG-controlled stimulator, it is possible to use the system for many hours during daily activities, and so prolonged intensive therapy sessions can be avoided. If nomuscle contraction is detected, the IVES stimulates thetarget muscles at the submotor-threshold level. However,
if muscle contraction is detected, IVES stimulates themuscles at an intensity level proportional to the detected
volitional EMG signals. With regard to IVES treatment
for patients with chronic stroke, Hara et al.7 indicated thatdaily IVES therapy at home resulted in enhanced motor
recovery in patients with partial hand or shoulder motion.
In addition, they reported the efficacy of combined IVES
and motor point block for antagonist muscles in patientswith chronic stroke.8 Fujiwara et al.9 showed that the facilitated use of the paretic upper extremity in daily living
by combining IVES with a wrist-hand splint could improve both the paretic upper extremity and corticospinal
modulation in chronic stroke. However, the efficacy of
IVES treatment alone has never been tested in patientswith hemiparetic stroke. The purpose of this study was toevaluate the efficacy of IVES treatment applied for 6 h/
day for 5 days, including during daily activities, on upper
extremity functions in patients with chronic hemiparetic
stroke.
Methods
Participants
Ten patients in the chronic phase of stroke (more than
12 months post onset) who were admitted to our rehabilitation center for physical reconditioning participatedin the experiments (Table 1). All patients had functional

impairment of their upper extremities after stroke, withpartial paralysis of the wrist and fingers and difficultyin voluntarily initiating and controlling extension movements of the fingers.
The following inclusion criteria were used for patient
selection: (1) first stroke episode, (2) stroke impairment
assessment set (SIAS)10 scores ranging from 2 to 4 forfinger paresis (Table 2), and (3) capable of voluntarily
extending the wrist to 20° against gravity from a flexed
position11 as measured by goniometry. The exclusion
criteria were: (1) unstable medical disorders, implanted
electronic pacing or defibrillation devices, unstable vital
signs, or potentially fatal cardiac arrhythmias (because
the safety of electrical stimulation under these conditions
is unknown); (2) active reflex sympathetic dystrophy or
existing residual weakness due to lower motor neuron lesions of either upper extremity; (3) a mini mental status
examination test12 score of 21 or lower; (4) severe spatial
neglect or aphasia; and (5) marked sensory deficit in theaffected upper extremity. The study was approved by theinstitutional ethics committee, and all the patients gave
their informed consent to participate in the study prior
to the start of the experiments, in conformity with the
Declaration of Helsinki.
IVES instrumentation
The IVES system (OG GIKEN, Okayama, Japan) is aportable electrical stimulator that is used to elicit wrist
and finger extension during voluntary movements (Fig.
1). The IVES system continually changes its stimulation
intensity in direct proportion to the amplitude of volitional EMG signals and applies an electrical stimulation

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Yamaguchi T, et al: Integrated Volitional Electrical Stimulation; IVES

device that indicates the surface EMG. The light indicator for hand opening is programmed to turn on and off
in proportion to the detected voluntary EMG amplitudeof the target muscle. The specifications of the equipment
and the details of the system and the results of performance tests are presented elsewhere.6
Intervention

Fig. 1 The integrated volitional control electrical stimulation(IVES) system.
The IVES system is composed of three conductive gel surface
electrodes: two recording electrodes (R1 and R2) and one groundelectrode (G). The recording electrode is separated into two parts
so that it can work as a pair of EMG detecting electrodes. The
ground electrode (G) works as a ground in EMG detection. During the short interval between EMG detections, electric stimulation is delivered between the electrodes R and G.

of submotor-threshold intensity (i.e., no visible muscle
contraction, but a tingling feeling) when there is no voluntary contraction. The novelty of the IVES system isthat the three surface electrodes (R1, R2, and G in Fig. 1)
together work in a time-sharing manner as an EMG detector and also as a stimulator. R1 and R2 are 5 mm apartand are packed into a single soft carbon sheet. When in
EMG mode, R1 and R2 work as a pair of electrodes (both
30 mm × 12 mm) for recording an EMG, while G works asa ground electrode (30 mm × 30 mm). When stimulating
the target muscles, R1 and R2 serve as a single electrode,R, and electric current pulses are delivered between R
and G. In other words, the same surface electrodes detect
the EMG signals at the target muscles and stimulate themat a stimulus intensity proportional to the integrated EMG
signals (with the exception of an initial approximately 25ms interval after the delivery of each stimulation pulse,when stimulation artifacts and M waves are observed).
The device delivers three trains of biphasic square-wave
pulses with a duration of 0.3ms (300-μs positive pulse,
0.3ms off, 300-μs negative pulse, and 0.3ms off, repeatedthree times) are applied at 20 Hz. The stimulus intensity
is continuously changed in proportion to the detectedvoluntary EMG amplitude of the target muscle. Control
buttons can be used to select detection sensitivities between 1,000 and 100,000 times and to adjust the electricalstimulation pulse width for the device. The muscle activities are monitored by means of a red light indicator on the

IVES therapy sessions were undertaken for 6 h/day for
5 days, including during therapy sessions and daily activities. The target muscles were the extensor carpi radialis (ECR) and extensor digitorum communis (EDC)on the hemiparetic side. Electrodes R were placed on theposterior region of the forearm (on the ECR) 2 cm above
the elbow crease, while electrode G was placed on theposterior area of the forearm (on the EDC) approximately
3–4 cm proximal to the ulnar styloid, just radial to theulnar shaft. The minimum and maximum stimulus intensities were determined for each patient individually. The
minimum intensity (submotor-threshold intensity) was
defined as the minimally applied stimulation level thatwas perceivable but with no visible muscle contraction
when there was no voluntary contraction. The maximum
intensity was defined as the maximal stimulation levelthat generated wrist and finger extension without any discomfort. Individual settings were stored in the stimulator
device for portable use.
IVES treatment was applied regularly during the scheduled physical therapy and occupational therapy sessions;
all other routine interdisciplinary stroke rehabilitation activities proceeded as usual. In addition, the patients wereasked to voluntarily extend their wrist and fingers outside
the therapy sessions, and they were encouraged to use theaffected arm during daily activities.
Electrodes and lead wires were positioned under theclothes and the portable stimulator was carried in asmall waist bag. As the IVES is portable and lightweight(300 g), patients could perform activities of daily living(ADL) using the hemiparetic hand and arm. All patients
underwent a standard rehabilitation program consistingof 1 h each of daily physical and occupational therapy at
our rehabilitation center.
Outcome measures
The upper extremity motor functions were assessed before and after the therapy sessions. The assessment was
conducted using upper extremity Fugl-Meyer motor assessment (FMA), the active range of motion (A-ROM)
test, the nine-hole peg test (NHPT), and EMG measurement. However, due to the diverse physical conditions of
the patients, the NHPT could be carried out by only 8of the 10 patients, and the EMG measurement could be
performed in only 8 of the 10 patients. The FMA upper
extremity section consists of four subsections: shoulder-Keio J Med 2011; 60 (3): 90–95

93Fig. 2 Changes in the EMG activities of the ECR and FCR and the wrist joint angle in a typical patient.
Each EMG change was determined by taking the average of 10 EMG measurements recorded during dorsal flexion and palmar flexion.
In the pre- and post-treatment recordings, a decrease of the EMG activities of the antagonist muscles during dorsal and palmar flexion
was observed.

arm, wrist, hand, and coordination. Each subsection assesses voluntary movement, reflex activity, grasp, and coordination. Performance was measured for 33 tasks witha 3-point ordinal scale (0 to 2), with a maximum score of
66.13 A-ROM was assessed by asking the patients to extend their wrists maximally while they were seated with
their forearm restrained in a neutral position to reduce
the effect of gravity. EMG was measured based on the
EMG activities during wrist movement (palmar flexion
or dorsal flexion). Patients were instructed to attempt palmar flexion or dorsal flexion of the wrist as quickly as
possible and to the maximum range possible. After theskin was abraded with abrasive cream and cleaned withalcohol, the source impedance at the junction of the skinand the detection surface was checked on a computer. Patients were asked to relax their muscles before starting
the evaluation. After every task, we observed the baseline
EMG output level (in microvolts) displayed on the monitor screen. EMG activities were recorded with two pairsof recording electrodes (F32mm, Blue Sensor P-00-S,
Medico Test, Denmark) placed over the muscle belliesof the flexor carpi radialis (FCR) and ECR muscles. A
ground electrode was placed on the elbow. The placement of recording electrodes was marked and checked for
EMG measurements to assure consistency in their placement before and after the evaluation. The EMG and thegoniometer signals were stored in a computer after being
processed by an amplifier with a 10-Hz to1-kHz filter andan A/D converter (sampling frequency: 10 kHz). The root
mean square (RMS) of the EMG signal was calculated
over the entire duration of the signal (duration of contraction and voltage time wave of the EMG signal) from theonset to the termination. As a measure of hypertonicity,
the coactivation ratio, defined as the ratio of the RMSof the antagonist muscles to that of the antagonist plus
agonist muscles,14 was calculated by measuring the RMS
from 10 EMG recordings during active palmar or dorsal
flexion movements.
Statistical analyses
Wilcoxon signed rank tests were used to compare
the pre-/post-intervention results of the FMA, A-ROM,
NHPT, and the EMG measurement. A P value of 0.05
was chosen as the level of significance. We analyzed thedata using SPSS 15.0 for Windows.
Results
The upper extremity score of the FMA showed a statistically significant increase from 50.8 ± 5.8 before theintervention to 56.8 ± 6.2 after the intervention (P < 0.01).
The wrist part of the upper extremity subsection scoresshowed a statistically significant improvement from 6.5± 1.6 to 8.6 ± 1.9 (P < 0.01). The A-ROM of wrist extension was also significantly improved from 36.0° ± 15.4°

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Yamaguchi T, et al: Integrated Volitional Electrical Stimulation; IVES

to 45.0° ± 15.5° (P = 0.01), and the NHPT significantly
decreased from 85.3 ± 52.0 to 63.3 ± 29.7 (P = 0.01). The
EMG measurements demonstrated statistically significant improvements in the coactivation ratios for the wrist
flexor and extensor muscles after the intervention (from0.506 ± 0.238 to 0.295 ± 0.117 for wrist flexors, P < 0.01
and from 0.999 ± 0.544 to 0.590 ± 0.183 for wrist extensors, P < 0.01). A typical example of the changes in the
ECR and FCR signals during palmar and dorsal flexion
movements are shown in Figure 2.

arm was stimulated electrically to promote not only voluntary movements but also movements related with ADL.
Therefore, prolonged use of the IVES system offered an
opportunity of increased use of the affected arm. These
effects of IVES treatment might include the ameliorationof deconditioning.
Other studies24–26 have reported that prolonged andintensive use of the affected arm is highly important toenhance the recovery of upper extremity functions after
stroke. Moreover, Charlton et al.27 demonstrated that peripheral afferent stimulation with or without simultaneous brain stimulation can induce plastic changes in theorganization of the motor cortex that persist for at least 2
h after the cessation of the stimulus. These observations
support our contention that the prolonged and intensive
use of IVES for 6 h/day on the affected arm has potential
to lead to therapeutic reorganization of the damaged cortex. The present study showed positive effects of IVES
on the FMA, A-ROM, and NHPT. These results indicatethat the unique characteristics of IVES contribute to therecovery of upper-limb motor functions.
The IVES system can be employed with minimal supervision to provide a high-intensity therapy, i.e., 6 h/
day or more, without necessitating one-to-one attention
by therapists. In fact, once the clinician has set up the
portable stimulator device, the patient can exercise on
their own with the IVES system, and the individual settings need to be reset only with respect to the recovery ofvoluntary movements. These aspects, together with theproven therapeutic efficacy of IVES on the paretic upper
limb,7–9 suggest that the device can be effectively used instroke rehabilitation programs.
However, our study has the limitation of using surface
EMG to compare values over the long interval of 5 days.
RMS values depend on the state of the electrode (site andelectrode distance), cross-talk, and impedance. Although
we applied several measures to secure reliable data, thereliability of surface EMG is limited. Furthermore, thepresent study was not a controlled trial and the numberof participants was small. In the future, we propose to
conduct a larger-scale study with masked assessors andan appropriate control group for further assessment of
the efficacy of the IVES system. In conclusion, our study
indicates that IVES provides substantial improvement in
the upper extremity motor functions and performance inpatients with chronic hemiparetic stroke.

Discussion
The present study provides preliminary evidence suggesting that IVES alone serves as an effective means ofimproving upper limb motor function in chronic stroke
survivors with hemiparesis. The improvement observedwith IVES could be attributed to the following two factors.
First, the IVES system per se could have beneficial effects on the recovery of upper extremity functions. Oneof the effects is the recruitment of alternative motor pathways that assist impaired efferent pathways.15 Anothereffect is a more ideal learning process provided by accurate feedback.16,17 Because EMG is recorded steadily
from the stimulating electrodes, sensory input from the
movement of an affected limb directly influences subsequent motor output, and this proprioceptive sensory feedback may have an important role in the recovery of upper extremity functions. Furthermore, the improvementof abnormal coactivation of the wrist muscles suggeststhat the continuous sensory input by IVES may have an
important effect on the improvement of voluntary movements, facilitation of reciprocal inhibition18 and recurrent
inhibition,19 and intensive sensory fiber activation.20 Fujiwara et al.9 reported that treatment with IVES combinedwith a wrist-hand splint induced restoration of presynaptic and long loop inhibitory connections as well as disynaptic reciprocal inhibition. Previous studies3,5,7,8 havedemonstrated that electrical stimulation combined withvolitional efforts or additional therapy is more effective
than electrical stimulation alone in the recovery process.
Bhatt et al.21 showed that combined intervention may
have a more beneficial influence on brain reorganization than either treatment alone. Increased motor corticalexcitability facilitates greater voluntary activation of its
neuronal networks,22 which could lead to improved functions.23 These studies support our contention that IVES
treatment is associated with improvements in upper extremity motor functions.
Second, there exists a possibility of increased use of
the affected arm facilitated by the IVES system. In thepresent study, while the patients were executing repetitions of voluntary movements, electrical stimulation wasapplied to the wrist and finger extensors of the affected
arm, and sensory feedback was provided. The affected

Acknowledgment
This research was partly supported by Strategic Research Program for Brain Sciences (SRPBS) of the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Keio J Med 2011; 60 (3): 90–95

References
1. Nichols-Larsen DS, Clark PC, Zeringue A, Greenspan A, Blanton
S: Factors influencing stroke survivors’ quality of life during subacute recovery. Stroke 2005; 36: 1480–1484. [Medline] [CrossRef]
2. Cauraugh J, Light K, Kim S, Thigpen M, Behrman A: Chronic
motor dysfunction after stroke: recovering wrist and finger extension by electromyography-triggered neuromuscular stimulation.
Stroke 2000; 31: 1360–1364. [Medline] [CrossRef]
3. Woldag H, Hummelsheim H: Evidence-based physiotherapeutic
concepts for improving arm and hand function in stroke patients:
a review. J Neurol 2002; 249: 518–528. [Medline] [CrossRef]
4. Bolton DA, Cauraugh JH, Hausenblas HA: Electromyogramtriggered neuromuscular stimulation and stroke motor recovery
of arm/hand functions: a meta-analysis. J Neurol Sci 2004; 223:
121–127. [Medline] [CrossRef]
5. de Kroon JR, Ijzerman MJ, Chae J, Lankhorst GJ, Zilvold G: Relation between stimulation characteristics and clinical outcome
in studies using electrical stimulation to improve motor controlof the upper extremity in stroke. J Rehabil Med 2005; 37: 65–74.
[Medline] [CrossRef]
6. Muraoka Y: Development of an EMG recording device from stimulation electrodes for functional electrical stimulation. Front Med
Biol Eng 2001; 11: 323–333. [Medline] [CrossRef]
7. Hara Y, Ogawa S, Tsujiuchi K, Muraoka Y: A home-based rehabilitation program for the hemiplegic upper extremity by powerassisted functional electrical stimulation. Disabil Rehabil 2008;
30: 296–304. [Medline]
8. Hara Y, Ogawa S, Muraoka Y: Hybrid power-assisted functional
electrical stimulation to improve hemiparetic upper-extremity
function. Am J Phys Med Rehabil 2006; 85: 977–985. [Medline][CrossRef]
9. Fujiwara T, Kasashima Y, Honaga K, Muraoka Y, Tsuji T, Osu
R, Hase K, Masakado Y, Liu M: Motor improvement and corticospinal modulation induced by hybrid assistive neuromuscular
dynamic stimulation (HANDS) therapy in patients with chronic
stroke. Neurorehabil Neural Repair 2009; 23: 125–132. [Medline]
10. Chino N, Sonoda S, Domen K, Saitoh E, Kimura A: Stroke Impairment Assessment Set (SIAS). In: Chino, N., Melvin, J.L.,(Ed.), Functional evaluation of stroke patients. Springer-Verlag,
Tokyo, 1996; 19–31.
11. Fugl-Meyer AR: Post-stroke hemiplegia assessment of physicalproperties. Scand J Rehabil Med Suppl 1980; 7: 85–93. [Medline]
12. Folstein MF, Folstein S, Mchugh P: “Mini-mental state:” a practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 1975; 12: 189–198. [Medline] [CrossRef]
13. Duncan PW, Propst M, Nelson SG: Reliability of the Fugl-Meyer
Assessment of sensorimotor recovery following cerebrovascular
accident. Phys Ther 1983; 63: 1606–1610. [Medline]

95
14. Musampa NK, Mathieu PA, Levin MF: Relationship between
stretch reflex thresholds and voluntary arm muscle activation inpatients with spasticity. Exp Brain Res 2007; 181: 579–593. [Medline] [CrossRef]
15. Cauraugh JH, Kim S: Stroke motor recovery: active neuromuscular stimulation and repetitive practice schedules. J Neurol Neurosurg Psychiatry 2003; 74: 1562–1566. [Medline] [CrossRef]
16. Flanagan EM: Methods for facilitation and inhibition of motor
activity. Am. J Phys Med 1967; 46: 1006–1011. [Medline]
17. Nudo RJ: Recovery after damage to motor cortical areas. Curr
Opin Neurobiol 1999; 9: 740–747. [Medline] [CrossRef]
18. Cavallari P, Fournier E, Katz R, Pierrot-Deseilligny E, Shindo M:
Changes in reciprocal Ia inhibition from wrist extensors to wrist
flexors during voluntary movement in man. Exp Brain Res 1984;
56: 574–576. [Medline] [CrossRef]
19. Nielsen J, Pierrot-Deseilligny E: Pattern of cutaneous inhibitionof the propriospinal-like excitation to human upper limb motoneurones. J Physiol 1991; 434: 169–182. [Medline]
20. Alfieri V: Electrical treatment of spasticity. Reflex tonic activity
in hemiplegic patients and selected specific electrostimulation.
Scand J Rehabil Med 1982; 14: 177–182. [Medline]
21. Bhatt E, Nagpal A, Greer KH, Grunewald TK, Steele JL, Wiemiller JW, Lewis SM, Carey JR: Effect of finger tracking combinedwith electrical stimulation on brain reorganization and hand function in subjects with stroke. Exp Brain Res 2007; 182: 435–447.
[Medline] [CrossRef]
22. Wu CW, Van Gelderen P, Hanakawa T, Yaseen Z, Cohen LG:
Enduring representational plasticity after somatosensory stimulation. Neuroimage 2005; 27: 872–884. [Medline] [CrossRef]
23. Wu CW, Seo HJ, Cohen LG: Influence of electric somatosensory
stimulation on paretic-hand function in chronic stroke. Arch Phys
Med Rehabil 2006; 87: 351–357. [Medline] [CrossRef]
24. Bütefisch C, Hummelsheim H, Denzler P, Mauritz KH: Repetitive
training of isolated movements improves the outcome of motor rehabilitation of the centrally paretic hand. J Neurol Sci 1995; 130:
59–68. [Medline] [CrossRef]
25. Ploughman M, Corbett D: Can forced-use therapy be clinicallyapplied after stroke? An exploratory randomized controlled trial.
Arch Phys Med Rehabil 2004; 85: 1417–1423. [Medline] [CrossRef]
26. Wolf SL, Winstein CJ, Miller JP, Taub E, Uswatte G, Morris D,
Giuliani C, Light KE, Nichols-Larsen D: Effect of constraintinduced movement therapy on upper extremity function 3 to
9 months after stroke: the EXCITE randomized clinical trial.
JAMA 2006; 296: 2095–2104. [Medline] [CrossRef]
27. Charlton CS, Ridding MC, Thompson PD, Miles TS: Prolonged
peripheral nerve stimulation induces persistent changes in excitability of human motor cortex. J Neurol Sci 2003; 208: 79–85.
[Medline] [CrossRef]