Volume 87, Issue 3, Pages 351-357 (March 2006)

10 of 34

ABSTRACT

FULL TEXT

FULL-TEXT PDF (367 KB)

Influence of Electric Somatosensory Stimulation on Paretic-Hand Function in Chronic Stroke

Abstract

Wu CW, Seo H-J, Cohen LG. Influence of electric somatosensory stimulation on paretic-hand function in chronic stroke.

Objective

To test the influence of electric somatosensory stimulation on performance of the Jebsen-Taylor Hand Function Test (JTHFT), a widely used assessment of functional hand motor skills, by the paretic arm in patients with chronic stroke.

Design

Initially, patients trained for several sessions until reaching plateau performance on the JTHFT. Subsequently, they entered a crossover randomized study, designed to evaluate the influence of somatosensory stimulation on JTHFT performance.

Setting

A research laboratory.

Participants

Nine patients with chronic stroke (≥1.5y) who acutely had marked weakness (paralysis of the upper extremity is evaluated as equal or below Medical Research Council [MRC] grade 2) followed by improvement to an MRC grade of 4.24±0.43 (range, 3.5–4.9) and Fugl-Meyer Assessment (FMA) score of 86.43%±2.02% at the time of testing.

Interventions

Two hours of electric somatosensory stimulation was applied to the (1) paretic hand, (2) paretic leg, or (3) no stimulation in different sessions, in a randomized order.

Main Outcome Measure

The time required to complete the JTHFT was analyzed by using repeated-measures analysis of variance (ANOVA) with factors time (pre-, postintervention) and intervention (paretic hand, paretic leg, no stimulation) followed by post hoc testing.

Results

Significant effects of intervention and intervention by time interaction (P<.01) on JTHFT time was revealed by repeated-measures ANOVA. Post hoc testing documented improvements in JTHFT time with paretic hand stimulation alone (P<.005), an effect that appeared more prominent in subjects with lower FMA scores.

Conclusions

Somatosensory stimulation applied to a paretic limb can benefit performance of a functional test in patients with chronic stroke. This result supports the proposal that electric sensory stimulation in combination with training protocols may enhance the benefit of customary neurorehabilitative treatments and possibly motor learning.

Key Words: Electric stimulation , Neuronal plasticity , Rehabilitation

Article Outline

• Abstract

• Methods

• Participants

• Experimental Design

• Behavioral testing

• Interventions

• Somatosensory stimulation of the paretic hand

• Somatosensory stimulation of the paretic leg

• No stimulation

• Data Analysis

• Results

• Discussion

• Conclusions

• References

• Copyright

SOMATOSENSORY INPUT IS required for accurate motor control1 and for the acquisition of motor skills.2 In patients with stroke, somatosensory deficits are usually associated with slower recovery of motor function.3 Previous studies have tried to elucidate the mechanisms underlying this influence. In healthy subjects, peripheral nerve stimulation, which activates group Ia large muscle afferents, group Ib afferents from Golgi organs, group II afferents from slow and rapidly adapting skin afferents and cutaneous afferent fibers,4, 5 elicits an increase in motor cortical excitability of body part representations that control the stimulated body part6, 7, 8, 9, 10 and results in reorganization of the motor and somatosensory cortices.11, 12 Peripheral nerve stimulation, as used in these studies, led to specific task-related increases in functional magnetic resonance imaging activity that outlast the stimulation period in various cortical areas including primary motor (M1) and somatosensory (S1) cortices.11, 12 Direct connections between S1 and M1 could provide the anatomic substrate for the influence of electric somatosensory stimulation on motor cortical organization.13

These findings raised the hypothesis that electric somatosensory stimulation, by eliciting motor cortical reorganization, could influence motor behavior and possibly functional recovery in patients with brain lesions. In tune with this proposal, previous investigations showed that similar interventions applying electric stimulation to nerve trunks or muscles could elicit improvements in motor function in patients with chronic stroke.14, 15, 16, 17, 18, 19, 20, 21, 22 It would now be important to determine if it could also influence performance of activities of daily living (ADLs). To address this issue, we studied the effects of electric somatosensory stimulation on performance of the Jebsen-Taylor Functional Hand Test (JTFHT), a validated tool commonly used in neurorehabilitation,23, 24, 25, 26 in a group of patients with chronic stroke who experienced moderate motor recovery. We hypothesized that electric somatosensory stimulation applied to the paretic limb would result in improvements in JTHFT performance compared with stimulation of a different body part (leg) and to no stimulation.

Methods

Participants

Nine patients, an average of 64.5±4.4 years old (4 women; all right-hand dominant), with history of a single ischemic cerebral infarct (6 subcortical, 1 cortico-subcortical, 2 cortical) (table 1, fig 1) equal to or more than 1.5 years (6.5±1y; range, 1.5–13.3y) before testing participated in the study. All had initially severe motor paresis (below Medical Research Council [MRC] scale grade 2) as described in the patients’ chart and subsequently recovered to MRC grade 3.5 to 4.9 and Fugl-Meyer Assessment (FMA) score 87.6%±2.2% at the time of testing. Visual and somatosensory functions were within normative limits, and the Mini-Mental State Examination scores ranged from 26 to 30. All patients participated in 3 different experimental sessions studying the effect of 3 interventions on performance of the JTHFT in a randomized crossover design in which the investigator testing JTHFT was blind to intervention type.

Table 1.

Summary of Patients’ Characteristics


Patient	Age (y)	Sex	Years After Stroke	Lesion Site	Motor Function
Patient	Age (y)	Sex	Years After Stroke	Lesion Site	MRC	FMA (%)
1	79	M	5.0	Right centrum semiovale	4.4	94
2	60	F	3.0	Left frontoparietal cortex, corona radiata	3.8	82
3	66	M	8.6	Left internal capsule, centrum semiovale	4.3	87
4	75	F	2.7	Right lacunar infarct, putamen, corona radiata	4.7	89
5	60	M	3.3	Left basal ganglia	4.5	79
6	71	M	1.5	Left occipital lobe andencephalomalacia, posterior and middle artery ischemia	4.7	91
7	58	M	6.0	Right middle cerebral artery, basal ganglia	3.5	84
8	36	F	2.0	Subcortical white matter lesion in both sides	4.9	100
9	76	F	13.3	Left internal capsule to centrum semiovale	4.0	83
Mean ± SEM	64.5±4.4		6.5±1.0		4.3±0.2	87.6±2.2

Abbreviations: F, female; FMA, Fugl-Meyer Assessment; M, male; MRC, Medical Research Council Scale; SEM, standard error of the mean.

View Large Image
Download to PowerPoint

Fig 1. Magnetic resonance imaging lesion locations. Numbers refer to patients in table 1.

Experimental Design

Initially, patients familiarized with the task in order to reach stable performance (up to 3–4 training sessions consisting of 10 repetitions of the JTHFT each day; entire familiarization process ranged from 3–7d; fig 2). Subsequently, they moved to the crossover portion of the study, which consisted of 3 consecutive counterbalanced sessions testing the effects of 2-hour periods of electric somatosensory stimulation applied to the paretic hand, paretic leg, and no stimulation on JTHFT function. Intersession interval was 24 hours.

View Large Image
Download to PowerPoint

Fig 2. (A) Motor performances. Subtests of the JTHFT: picking up small objects and placing them in a can, pick up beans with a teaspoon placing them in a can (mimicking a feeding function), stacking checkers, turning over cards, and moving large light cans (89g [3.2oz]), and heavy cans (592g [1lb]). The subtest order is based on the patients’ report of task difficulty (most difficult: picking up small objects, easiest: moving cans). The JTHFT preceding and during familiarization (1–4) and in baseline determinations in the 3 testing sessions (5–7) expressed as (B) total time and (C) normalized to the initial performance level preceding familiarization. Note the progressive improvement in JTHFT time during familiarization providing a stable baseline performance that was comparable in the 3 subsequent testing sessions (5–7). Abbreviation: NS, not significant.

Behavioral testing

The JTHFT is used for assessment of functional hand motor skills,24 has good validity and reliability, and normative data are available for different ages and sexes.24, 27 Six of the 7 JTHFT subtests were included in this study: turning over cards, picking up small objects and placing them in a can, picking up small objects with a teaspoon and placing them in a can (mimicking a feeding function), stacking checkers, moving large light cans, and moving heavy cans. Patients were instructed to perform the tasks as fast and accurately as possible according to the written standardized instructions in the testing set.23, 24 Patients were allowed frequent breaks to avoid fatigue during familiarization and testing. Because some patients were unable to perform writing tasks (the seventh JTHFT subtest) due to dominant hemisphere strokes, we excluded this particular subtest from the study (see fig 2A). Total JTHFT time and partial subtest JTHFT times were recorded for analysis. Feedback on task performance was not provided. JTHFT measurements before (pre) and after (post) each intervention were calculated as the average of 3 determinations. On completion of the experiment, patients rated their perception of the difficulty in performing each subtest by using visual analog scales ranging from 0 to 10.

Interventions

In each session, patients sat reading a book or magazine and were allowed to adjust their arm/hand position to be more comfortable. Baseline JTHFT performance was tested 3 times preceding each intervention. Subsequently, patients underwent a 2-hour period of peripheral nerve stimulation of the paretic hand, paretic leg, and no stimulation.

Somatosensory stimulation of the paretic hand

In this peripheral nerve stimulation protocol, adapted from previous studies in our laboratory,11 3 pairs of Ag-AgCl electrodes (diameter, 10mm) were placed at the wrist overlying the median, ulnar, and radial nerves (cathode proximal). Trains of electric stimulation were delivered at 1Hz by using an isolation unit connected to a square pulse stimulator.a Each train consisted of 5 (pulse width, 1ms) single pulses at 10Hz over 500ms, with 50% duty cycle. Stimulus intensity was adjusted to stay barely below motor threshold. Stimulation usually evoked a tickling sensation and mild paresthesias. Neither pain nor discomfort was reported throughout the experiment.

Somatosensory stimulation of the paretic leg

Three pairs of Ag-AgCl electrodes (diameter, 10mm) were placed at the ankle overlying the peroneal, sural, and tibial nerves (cathode proximal). Parameters of stimulation were identical to those used for stimulation of the paretic hand, except for stimulus intensities, which were adapted to the stimulated peripheral nerves.

No stimulation

During this period, subjects remained sitting and reading in the absence of stimulation. At the end of each intervention, JTHFT was tested 3 times.

Data Analysis

Familiarization effects were evaluated by using 1-way repeated-measures analysis of variance (ANOVA), with time as the repeated measure. Because JTHFT time was not normally distributed (Kolmogorov-Smirnov test) and given interindividual differences in baseline JTHFT time, intervention effects were additionally expressed relative to baseline performance in each session and patient. Intervention effects were studied by a blind investigator by using repeated-measures ANOVA with factors time (pre-, postintervention) as the repeated measure and intervention (paretic hand, paretic leg, no stimulation) as the within-subject factor. Post hoc testing was conducted by using a Scheffé test. Linear correlation was used to evaluate the relation between performance improvements after somatosensory stimulation and motor impairment (FMA score28). All data are expressed as mean ± standard error of the mean.

Results

The familiarization period resulted in progressive performance improvements in the paretic hand expressed as reductions in JTHFT time (for raw and normalized data, P<.05; see figs 2B, 2C). JTHFT time at the end of the familiarization period was comparable to baseline JTHFT determinations (taken from the average of 3 repetitions before each intervention) in the 3 testing sessions.

Repeated-measures ANOVA showed significant effects of intervention and intervention by time interaction on JTHFT time (expressed relative to baseline performance in each session; F2,100=5.115, P<.01; F2,100=5.565, P<.005, respectively; Fig 3, Fig 4A). Post hoc testing revealed a significant reduction in JTHFT time after electric somatosensory stimulation of the paretic hand, in the absence of changes with stimulation of the paretic leg and no stimulation (P<.05; see fig 4A). JTHFT time after paretic hand stimulation was shorter than after paretic leg stimulation and after no stimulation (P<.05, P<.01, respectively; see fig 4A). Patients who experienced more prominent shortening in JTHFT time were those with lower scores in the FMA scale and consequently with more impairment (F1,8=44.23, R2=.863, P<.005; see fig 4B). The most prominent performance improvements in partial JTHFT subtest time after stimulation of the paretic hand were documented with small object picking, stacking checkers, and moving cans. Two patients reported transient improvement in hand motility after hand stimulation, 1 improved gait after leg stimulation, and 1 both.

View Large Image
Download to PowerPoint

Fig 3. Effects of electric somatosensory stimulation on motor performance (individual subjects). JTHFT total time is shown in individual patients at baseline (Pre) and after (Post) stimulation of the paretic hand, the paretic leg, and no stimulation. Initials identify patients described in table 1. Patients 1, 4, and 7 had hand stimulation first; patients 6, 8, and 9 had leg stimulation first; and patients 2, 3, and 5 had no stimulation first. Paretic hand stimulation resulted in shortening of JTHFT times in 6 of the 9 patients tested.

View Large Image
Download to PowerPoint

Fig 4. (A) Effects of electric somatosensory stimulation on motor performance (group data). JTHFT performance expressed as a post-/preratio in the 3 sessions (no stimulation, stimulation of the paretic hand, stimulation of the paretic leg). Note the shortening in JTHFT times with hand stimulation in the absence of changes with stimulation of the paretic leg or no stimulation. (B) Performance improvements in JTHFT with stimulation of the paretic hand as a function of motor impairment (FMA hand component score). The abscissa shows the FMA score at entrance into the study (lower scores reflect more impairment). The ordinate displays changes in JTHFT time measured as a post-/preratio with stimulation of the paretic hand (lower scores reflect improvements). Note that patients with more impairment experienced more prominent improvement.

Discussion

The main result of this study was that a single 2-hour application of electric somatosensory stimulation of the paretic hand in patients with chronic stroke led to improvement in performance of a functional hand motor test relative to stimulation of the paretic leg and to no stimulation.

Hand motor deficits play an important role in stroke disability.29 Previous reports showed that application of electric somatosensory stimulation in patients with chronic stroke over weeks to months led to improvements in hand functional tests.15, 17, 22, 30, 31, 32. Here, we intended to characterize functional changes elicited by a short, single, 2-hour session of electric somatosensory stimulation on performance of complex and highly coordinated motor tasks involved in ADLs. The JTHFT evaluates functional hand motor skills,24 has good validity and reliability,24, 27 and has been studied in rehabilitative settings.26, 33, 34, 35 Neural pathways controlling performance of these tasks include fast corticospinal projections36, 37 that originate in the primary motor cortex.38, 39 Improvement in JTHFT correlates with functional gains during rehabilitative training.34, 35

We studied a group of patients with chronic stroke, substantial weakness immediately after the event, and moderate recovery over the following years (from MRC score <2 to a mean of 4.3 at the time of testing). Initially, patients became familiar with the JTHFT, which they performed repeatedly for several days, until their performance stabilized. Baseline JTHFT obtained in the 3 testing sessions (stimulation of paretic hand, stimulation of paretic leg, no stimulation) showed levels comparable to those at the end of the familiarization sessions (see figs 2B, 2C). The main finding of the study was that a single 2-hour period of stimulation of the paretic hand, in the absence of physical training, elicited improvements in JTHFT that lasted for less than 24 hours in the absence of changes with stimulation of the paretic leg and no stimulation. The magnitude of this improvement was more prominent in patients with more impairment (see fig 4B), raising the hypothesis that this interventional strategy may be useful in people with poorer remaining functions, when hand weakness makes motor training more difficult or impossible.14 The 3 interventions did not elicit side effects, the order was counterbalanced across subjects, and investigators testing JTHFT were blind to the intervention applied. Patients did not express expectations of improvement with any of the 3 interventions. On questioning at the end of the study, 2 patients felt transient improvement in hand motility with hand stimulation, 1 felt transient locomotor improvement with leg stimulation, and 1 patient felt both. The other 5 patients did not report any difference.

These results are in tune with previous findings showing that short periods of electric somatosensory stimulation influence muscle strength, swallowing, and reaching in patients with chronic stroke.9, 14, 15, 16, 18, 19 Our results now expand these findings, showing that even a short session of 2 hours of electric somatosensory stimulation can transiently facilitate motor functions involved in ADLs in patients with chronic stroke, supporting the proposal of an adjuvant role to customary neurorehabilitative treatments.14, 16, 20, 21, 22, 35, 40, 41 It is of note that peripheral nerve stimulation under our experimental design allowed simultaneous activation of nerve fibers transmitting input originating in peripheral receptors critical for performance of the JTHFT.

Performance of the JTHFT engages a distributed network of interconnected cortical regions including frontal and parietal cortices.37, 39, 42 The somatosensory cortex, which received direct input from the stimulated hand, has direct anatomic projections to motor, premotor, and parietal cortices.43, 44, 45, 46 These projections modulate neuronal activity in primary motor cortex and association frontal and parietal areas,47, 48 providing a likely anatomic substrate for the effects described in this study. Possibly mediated through these pathways, electric somatosensory stimulation elicits cortical reorganization not only in the somatosensory but also in the primary motor cortex of healthy volunteers11, 12 and patients with chronic stroke.17 The net functional result of electric somatosensory stimulation on the primary motor cortex is increased excitability of the motor cortical representations that control the stimulated body part,9, 49, 50 possibly through modulation of GABAergic neurotransmission8, 10 and long-term potentiation-like processes.51, 52, 53

Conclusions

Somatosensory stimulation applied to a paretic limb can benefit performance of a functional test in patients with chronic stroke, supporting the proposal that in combination with training protocols electric somatosensory stimulation may enhance the benefit of customary neurorehabilitative interventions and possibly motor learning.

Supplier

References

1. 1 Pearson KG . Plasticity of neuronal networks in the spinal cord (modifications in response to altered sensory input) . Prog Brain Res . 2000;128:61–70 . MEDLINE | CrossRef

2. 2 Pavlides C , Miyashita E , Asanuma H . Projection from the sensory to the motor cortex is important in learning motor skills in the monkey . J Neurophysiol . 1993;70:733–741 . MEDLINE

3. 3 Reding M , Potes E . Rehabilitation outcome following initial unilateral hemispheric stroke (Life table analysis approach) . Stroke . 1988;19:1354–1358 . MEDLINE

4. 4 Campbell W . Electrodiagnostic medicine . Baltimore: Williams & Wilkins; 1999; .

5. 5 Kimura J . Electrodiagnosis in diseases of nerve and muscle (principles and practice) . New York: Oxford Univ Pr; 2001; .

6. 6 Ridding MC , Brouwer B , Miles TS , Pitcher JB , Thompson PD . Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects . Exp Brain Res . 2000;131:135–143 . MEDLINE | CrossRef

7. 7 Luft AR , Kaelin-Lang A , Hauser TK , et al. Modulation of rodent cortical motor excitability by somatosensory input . Exp Brain Res . 2002;142:562–569 . MEDLINE | CrossRef

8. 8 Kobayashi M , Ng J , Theoret H , Pascual-Leone A . Modulation of intracortical neuronal circuits in human hand motor area by digit stimulation . Exp Brain Res . 2003;149:1–8 . MEDLINE

9. 9 Hamdy S , Rothwell JC , Aziz Q , Singh KD , Thompson DG . Long-term reorganization of human motor cortex driven by short-term sensory stimulation . Nat Neurosci . 1998;1:64–68 . MEDLINE | CrossRef

10. 10 Kaelin-Lang A , Luft AR , Sawaki L , Burstein AH , Sohn YH , Cohen LG . Modulation of human corticomotor excitability by somatosensory input . J Physiol . 2002;540:623–633 . MEDLINE | CrossRef

11. 11 Wu CW , van Gelderen P , Hanakawa T , Yaseen Z , Cohen LG . Enduring representational plasticity after somatosensory stimulation . Neuroimage . 2005;27:872–884 . MEDLINE | CrossRef

12. 12 Golaszewski SM , Siedentopf CM , Koppelstaetter F , et al. Modulatory effects on human sensorimotor cortex by whole-hand afferent electrical stimulation . Neurology . 2004;62:2262–2269 .

13. 13 Wu CW , Kaas JH . The effects of long-standing limb loss on anatomical reorganization of the somatosensory afferents in the brainstem and spinal cord . Somatosens Mot Res . 2002;19:153–163 . MEDLINE | CrossRef

14. 14 Conforto AB , Kaelin-Lang A , Cohen LG . Increase in hand muscle strength of stroke patients after somatosensory stimulation . Ann Neurol . 2002;51:122–125 . MEDLINE | CrossRef

15. 15 Powell J , Pandyan AD , Granat M , Cameron M , Stott DJ . Electrical stimulation of wrist extensors in poststroke hemiplegia . Stroke . 1999;30:1384–1389 . MEDLINE

16. 16 Sullivan JE , Hedman LD . A home program of sensory and neuromuscular electrical stimulation with upper-limb task practice in a patient 5 years after a stroke . Phys Ther . 2004;84:1045–1054 . MEDLINE

17. 17 Kimberley TJ , Lewis SM , Auerbach EJ , Dorsey LL , Lojovich JM , Carey JR . Electrical stimulation driving functional improvements and cortical changes in subjects with stroke . Exp Brain Res . 2004;154:450–460 . MEDLINE | CrossRef

18. 18 Struppler A , Angerer B , Havel P . Modulation of sensorimotor performances and cognition abilities induced by RPMS (clinical and experimental investigations) . Suppl Clin Neurophysiol . 2003;56:358–367 . CrossRef

19. 19 Fraser C , Power M , Hamdy S , et al. Driving plasticity in human adult motor cortex is associated with improved motor function after brain injury . Neuron . 2002;34:831–840 . MEDLINE | CrossRef

20. 20 Wong AM , Su TY , Tang FT , Cheng PT , Liaw MY . Clinical trial of electrical acupuncture on hemiplegic stroke patients . Am J Phys Med Rehabil . 1999;78:117–122 . MEDLINE | CrossRef

21. 21 Perennou DA , Leblond C , Amblard B , Micallef JP , Herisson C , Pelissier JY . Transcutaneous electric nerve stimulation reduces neglect-related postural instability after stroke . Arch Phys Med Rehabil . 2001;82:440–448 . Abstract | Full Text | Full-Text PDF (93 KB) | CrossRef

22. 22 Peurala SH , Pitkanen K , Sivenius J , Tarkka IM . Cutaneous electrical stimulation may enhance sensorimotor recovery in chronic stroke . Clin Rehabil . 2002;16:709–716 . MEDLINE | CrossRef

23. 23 Stern EB . Stability of the Jebsen-Taylor Hand Function Test across three test sessions . Am J Occup Ther . 1992;46:647–649 . MEDLINE

24. 24 Jebsen RH , Taylor N , Trieschmann RB , Trotter MJ , Howard LA . An objective and standardized test of hand function . Arch Phys Med Rehabil . 1969;50:311–319 . MEDLINE

25. 25 Hummel F , Celnik P , Giraux P , et al. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke . Brain . 2005;128:490–499 . CrossRef

26. 26 Spaulding SJ , McPherson JJ , Strachota E , Kuphal M , Ramponi M . Jebsen Hand Function Test (performance of the uninvolved hand in hemiplegia and of right-handed, right and left hemiplegic persons) . Arch Phys Med Rehabil . 1988;69:419–422 . MEDLINE

27. 27 Hackel ME , Wolfe GA , Bang SM , Canfield JS . Changes in hand function in the aging adult as determined by the Jebsen Test of Hand Function . Phys Ther . 1992;72:373–377 . MEDLINE

28. 28 Fugl-Meyer AR , Jaasko L , Leyman I , Olsson S , Steglind S . The post-stroke hemiplegic patient. 1 (A method for evaluation of physical performance) . Scand J Rehabil Med . 1975;7:13–31 . MEDLINE

29. 29 Whitall J , McCombe Waller S , Silver KH , Macko RF . Repetitive bilateral arm training with rhythmic auditory cueing improves motor function in chronic hemiparetic stroke . Stroke . 2000;31:2390–2395 .

30. 30 Johansson K , Lindgren I , Widner H , Wiklund I , Johansson BB . Can sensory stimulation improve the functional outcome in stroke patients? . Neurology . 1993;43:2189–2192 . MEDLINE

31. 31 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

32. 32 Gritsenko V , Prochazka A . A functional electric stimulation-assisted exercise therapy system for hemiplegic hand function . Arch Phys Med Rehabil . 2004;85:881–885 . Abstract | Full Text | Full-Text PDF (250 KB) | CrossRef

33. 33 Neistadt ME . The effects of different treatment activities on functional fine motor coordination in adults with brain injury . Am J Occup Ther . 1994;48:877–882 . MEDLINE

34. 34 Kraft GH , Fitts SS , Hammond MC . Techniques to improve function of the arm and hand in chronic hemiplegia . Arch Phys Med Rehabil . 1992;73:220–227 . MEDLINE

35. 35 Alon G , Sunnerhagen KS , Geurts AC , Ohry A . A home-based, self-administered stimulation program to improve selected hand functions of chronic stroke . NeuroRehabilitation . 2003;18:215–225 . MEDLINE

36. 36 Muller K , Homberg V . Development of speed of repetitive movements in children is determined by structural changes in corticospinal efferents . Neurosci Lett . 1992;144:57–60 . MEDLINE | CrossRef

37. 37 Porter R , Lemon RN . Corticospinal function and voluntary movement . Oxford: Oxford Univ Pr; 1993; .

38. 38 Jancke L , Steinmetz H , Benilow S , Ziemann U . Slowing fastest finger movements of the dominant hand with low-frequency rTMS of the hand area of the primary motor cortex . Exp Brain Res . 2004;155:196–203 . MEDLINE | CrossRef

39. 39 Passingham R . The frontal lobes and voluntary action . Oxford: Oxford Univ Pr; 1993; .

40. 40 van Dijk KR , Scherder EJ , Scheltens P , Sergeant JA . Effects of transcutaneous electrical nerve stimulation (TENS) on non-pain related cognitive and behavioural functioning . Rev Neurosci . 2002;13:257–270 . MEDLINE

41. 41 Tyson S . Use of transcutaneous nerve stimulation to treat sensory loss after stroke . Physiother Res Int . 2003;8:53–57 . MEDLINE | CrossRef

42. 42 Ehrsson HH , Fagergren E , Forssberg H . Differential fronto-parietal activation depending on force used in a precision grip task (an fMRI study) . J Neurophysiol . 2001;85:2613–2623 . MEDLINE

43. 43 Wu CW , Kaas JH . Somatosensory cortex of prosimian Galagos (physiological recording, cytoarchitecture, and corticocortical connections of anterior parietal cortex and cortex of the lateral sulcus) . J Comp Neurol . 2003;457:263–292 . MEDLINE | CrossRef

44. 44 Stepniewska I , Preuss TM , Kaas JH . Architectonics, somatotopic organization, and ipsilateral cortical connections of the primary motor area (M1) of owl monkeys . J Comp Neurol . 1993;330:238–271 . MEDLINE | CrossRef

45. 45 Strick PL , Preston JB . Two representations of the hand in area 4 of a primate. II (Somatosensory input organization) . J Neurophysiol . 1982;48:150–159 . MEDLINE

46. 46 Jones EG , Coulter JD , Hendry SH . Intracortical connectivity of architectonic fields in the somatic sensory, motor and parietal cortex of monkeys . J Comp Neurol . 1978;181:291–347 . MEDLINE | CrossRef

47. 47 Asanuma H , Kosar E , Tsukahara N , Robinson H . Modification of the projection from the sensory cortex to the motor cortex following the elimination of thalamic projections to the motor cortex in cats . Brain Res . 1985;345:79–86 . MEDLINE | CrossRef

48. 48 Farkas T , Kis Z , Toldi J , Wolff JR . Activation of the primary motor cortex by somatosensory stimulation in adult rats is mediated mainly by associational connections from the somatosensory cortex . Neuroscience . 1999;90:353–361 . MEDLINE | CrossRef

49. 49 Ridding MC , McKay DR , Thompson PD , Miles TS . Changes in corticomotor representations induced by prolonged peripheral nerve stimulation in humans . Clin Neurophysiol . 2001;112:1461–1469 . Abstract | Full Text | Full-Text PDF (412 KB) | CrossRef

50. 50 Chen R , Corwell B , Hallett M . Modulation of motor cortex excitability by median nerve and digit stimulation . Exp Brain Res . 1999;129:77–86 . MEDLINE | CrossRef

51. 51 Godde B , Spengler F , Dinse HR . Associative pairing of tactile stimulation induces somatosensory cortical reorganization in rats and humans . Neuroreport . 1996;8:281–285 . MEDLINE

52. 52 Stefan K , Kunesch E , Cohen LG , Benecke R , Classen J . Induction of plasticity in the human motor cortex by paired associative stimulation . Brain . 2000;123(Pt 3):572–584 . CrossRef

53. 53 Stefan K , Kunesch E , Benecke R , Cohen LG , Classen J . Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation . J Physiol . 2002;543:699–708 . MEDLINE | CrossRef

Human Cortical Physiology Section and Stroke Neurorehabilitation Clinic, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD

Reprint requests to Leonardo G. Cohen, MD, Human Cortical Physiology Section, NINDS, NIH, Bethesda, MD 20817

Published as an abstract of the Fifth World Stroke Congress, June 2004, Vancouver, BC, Canada.

No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated.

a Grass stimulator S8800 with SIU5 stimulus isolation unit; Grass Instrument Div, Astro-Med Inc, 600 E Greenwich Ave, West Warwick, RI 02893.

PII: S0003-9993(05)01430-9

doi:10.1016/j.apmr.2005.11.019

10 of 34