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Medicine » Diagnostics » "Novel Frontiers of Advanced Neuroimaging", book edited by Kostas N. Fountas, ISBN 978-953-51-0923-5, Published: January 9, 2013 under CC BY 3.0 license. © The Author(s).

Chapter 4

Activation of Brain Sensorimotor Network by Somatosensory Input in Patients with Hemiparetic Stroke: A Functional MRI Study

By Hiroyuki Kato and Masahiro Izumiyama
DOI: 10.5772/51693

Article top

Overview

fMRI of a 68-year old man (patient 1) who had a cerebral infarct in the right corona radiata (arrow in a, diffusion-weighted MRI). After 28 days of stroke onset, palm brushing of the right (unaffected) hand (b-d) induced activation in the left primary sensorimotor cortex (1), the supplementary motor area (2), and right cerebellum (3). During palm brushing of the left (paretic) hand (e-g), activation in contralateral primary sensorimotor cortex (1) was seen, although less extensive, and no activation was seen in the supplementary motor areas and the cerebellum.
Figure 1. fMRI of a 68-year old man (patient 1) who had a cerebral infarct in the right corona radiata (arrow in a, diffusion-weighted MRI). After 28 days of stroke onset, palm brushing of the right (unaffected) hand (b-d) induced activation in the left primary sensorimotor cortex (1), the supplementary motor area (2), and right cerebellum (3). During palm brushing of the left (paretic) hand (e-g), activation in contralateral primary sensorimotor cortex (1) was seen, although less extensive, and no activation was seen in the supplementary motor areas and the cerebellum.
fMRI of a 79-year old man (patient 5) who had a cerebral infarct in part of the right middle cerebral artery territory (arrow in a, diffusion-weighted MRI). After 13 days of stroke onset, passive movement of the left (unaffected) hand (e-g) induced activation in the right primary sensorimotor cortex (1) and left cerebellum (3). During passive movement of the right (paretic) hand (b-d), activation in contralateral primary sensorimotor cortex (1) was observed.
Figure 2. fMRI of a 79-year old man (patient 5) who had a cerebral infarct in part of the right middle cerebral artery territory (arrow in a, diffusion-weighted MRI). After 13 days of stroke onset, passive movement of the left (unaffected) hand (e-g) induced activation in the right primary sensorimotor cortex (1) and left cerebellum (3). During passive movement of the right (paretic) hand (b-d), activation in contralateral primary sensorimotor cortex (1) was observed.
fMRI of a 61-year old man (control). Active right hand movement (a-c) induced a normal activation pattern in the left primary sensorimotor cortex (1), supplementary motor areas (2) and right cerebellum (3).
Figure 3. fMRI of a 61-year old man (control). Active right hand movement (a-c) induced a normal activation pattern in the left primary sensorimotor cortex (1), supplementary motor areas (2) and right cerebellum (3).

Activation of Brain Sensorimotor Network by Somatosensory Input in Patients with Hemiparetic Stroke: A Functional MRI Study

Hiroyuki Kato1 and Masahiro Izumiyama2

1. Introduction

Stroke is one of the leading causes of disability in the elderly in many countries. Residual motor impairment, especially hemiparesis, is one of the most common sequelae after stroke. Motor recovery after stroke exhibits a wide range of difference among patients, and is dependent on the location and amount of brain damage, degree of impairment, and nature of deficit (Duncan et al., 1992). Full recovery of motor function is often observed when initial impairment is mild, but recovery is limited when there were severe deficits at stroke onset. The motor recovery after stroke may be caused by the effects of medical therapy against acute stroke, producing a resolution of brain edema and an increase in cerebral blood flow in the penumbra and remote areas displaying diaschisis. However, functional improvements may be seen past the period of acute tissue response and its resolution. The role of rehabilitation in facilitating motor recovery is considered to be produced by promoting brain plasticity.

Non-invasive neuroimaging techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), enable us to measure task-related brain activity with excellent spatial resolution (Herholz & Heiss, 2000; Calautti & Baron, 2003; Rossini et al., 2003). The functional neuroimaging studies usually employ active motor tasks, such as hand grip and finger tapping, and require that the patients are able to move their hand. Neuroimaging studies in stroke patients have reported considerable amounts of data that suggest the mechanisms of motor functional recovery after stroke. Initial cross-sectional studies at chronic stages of stroke have demonstrated that the pattern of brain activation is different between paretic and normal hand movements, and suggested that long-term recovery is facilitated by compensation, recruitment and reorganization of cortical motor function in both damaged and non-damaged hemispheres (Chollet et al., 1991; Weiller et al., 1992; Cramer et al., 1997; Cao et al., 1998; Ward et al., 2003a). Subsequent longitudinal studies from subacute to chronic stages (before and after rehabilitation) have revealed a dynamic, bihemispheric reorganization of motor network, and emphasized the necessity of successive studies (Marshall et al., 2000; Calautti et al., 2001; Feydy et al., 2002; Ward et al, 2003b).

When the stroke patients are unable to move their hand, alternative paradigms are necessary to study their brain function. Passive, instead of active, hand movement has been employed for this purpose, and increases in brain activities are found not only in sensory but also motor cortices (Nelles et al., 1999; Loubinoux et al., 2003; Tombari et al., 2004). Functional neuroimaging studies suggest that a change in processing of somatosensory information in the sensorimotor cortex may play an important role in motor recovery after stroke (Schaechter et al., 2006).

Most significant recovery of motor function takes place within the first weeks after stroke and an early introduction of rehabilitation is crucial for a good outcome. Rehabilitation at the early stages of stroke uses physiotherapy, such as massage and passive movement of the paretic hand, as an initial step of rehabilitation, especially in patients with severe motor impairment. However, it is difficult to assess the effects of physiotherapy in patients with severe impairment early after stroke. In this fMRI study, we investigated the effects of somatosensory input on the activity of brain sensorimotor network in stroke patients. Since somatosensory feedback is essential for the exact execution of hand movement, the result can provide a scientific basis for the establishment of rehabilitation strategies.

2. Materials and methods

2.1. Subjects

We selected 6 stroke patients with pure motor hemiparesis (4 men and 2 women, 63-85 years old). Three of them received fMRI during a task of unilateral palm brushing (stimulation of tactile sensation using a plastic hairbrush at approximately 1 Hz), and three other patients received fMRI during a task of unilateral passive hand movement (stimulation of proprioceptive sensation by passive flexion-extension of fingers at approximately 1 Hz). The fMRI studies were performed 5 days to 2 months after stroke onset.

The patients presented with neurological deficits including moderate to severe hemiparesis, and were admitted to our hospital. They received standard medical therapy for stroke and rehabilitation. All of them were right-handed. All the cerebral infarcts were evidenced by MRI, and were located in various regions of the cerebrum. They could hardly move their hands when the fMRI was performed. Clinical data are summarized in Table 1. Three right-handed, normal subjects (59-68 years of age; 2 men and 1 woman) served as controls for a comparison to show normal brain activation during a unilateral hand grip task. This study was approved by the ethics committee of our hospital and informed consent was obtained from all subjects in accordance with the Declaration of Helsinki.

Age
Sex
H
Stroke
location
PMH
day
fMRI activation
Palm brushing
168MLR corona
radiata
HT
DM
28
N: L S1M1, L SMA, R Cbll
P: R S1M1, R SMA
275MLR internal
capsule
DM
39
N: L S1M1, L SMA
P: R S1M1, R SMA, Blt IPC
363FRL corona
radiata
HT
DM
HL
5

N: R S1M1
P: L S1M1, Blt SPC, R IPC
Passive movement
485FLR internal
capsule
HT
HL
72
N: L S1M1
P: R S1M1
579MRL MCA
cortex
HT
HL
af
13

N: L S1M1, R Cbll
P: R S1M1
676MLR ponsDM
HT
21
N: L S1M1, L SMA, R Cbll
P: R S1M1

Table 1.

Patient characteristics

2.2. Functional MRI

The fMRI studies were performed using a 1.5 T Siemens Magnetom Symphony MRI scanner as described previously (Kato et al., 2002). Briefly, blood oxygenation level-dependent (BOLD) images were obtained continuously in a transverse orientation using a gradient-echo, single shot echo planar imaging pulse sequence. The acquisition parameters were as follows: repetition time 3 s, time of echo 50 ms, flip angle 90°, 3-mm slice thickness, 30 slices through the entire brain, field of view 192 x 192 mm, and 128 x 128 matrix. During the fMRI scan, the patients and normal controls received or performed a task as mentioned above. This task performance occurred in periods of 30 s, interspaced with 30 s rest periods. The cycle of rest and task was repeated 5 times during each hand study. Therefore, the fMRI scan of each hand study took 5 min to complete, producing 3,000 images. A staff member monitored the patient directly throughout the study, and gave the sensory stimulations or the start and stop signals of hand grip by tapping gently on the knee.

Data analysis was performed using Statistical Parametric Mapping (SPM) 2 (Wellcome Department of Cognitive Neurology, London, UK, http://www.fil.ion.ucl.ac.uk/spm/) implemented in MATLAB (The MathWorks Inc., Natick, MA, USA). After realignment and smoothing, the general linear model was employed for the detection of activated voxels. The voxels were considered as significantly activated if p<0.05 using the FWE analysis. All the measurements were performed with this same statistical threshold. The activation images were overlaid on corresponding T1-weighted anatomic images.

3. Results

Both tactile and proprioceptive inputs via the unaffected hand activated contralateral primary sensorimotor cortex (S1M1) in all the patients, and the supplementary motor areas (SMA) and the ipsilateral cerebellum in part of the patients (Table, Figs. 1 & 2). This activation pattern is similar to that activated during active hand movement (Fig. 3), although the activation was less extensive. Both tactile and proprioceptive inputs via the paretic hand also activated the contralateral S1M1 in all the patients, and in SMA and superior and inferior parietal cortices in part of the patients (Table, Figs. 1 & 2), although to a lesser extent as compared with unaffected hand. No cerebellar activation was observed when paretic hand was stimulated.

media/image2_w.jpg

Figure 1.

fMRI of a 68-year old man (patient 1) who had a cerebral infarct in the right corona radiata (arrow in a, diffusion-weighted MRI). After 28 days of stroke onset, palm brushing of the right (unaffected) hand (b-d) induced activation in the left primary sensorimotor cortex (1), the supplementary motor area (2), and right cerebellum (3). During palm brushing of the left (paretic) hand (e-g), activation in contralateral primary sensorimotor cortex (1) was seen, although less extensive, and no activation was seen in the supplementary motor areas and the cerebellum.

media/image3_w.jpg

Figure 2.

fMRI of a 79-year old man (patient 5) who had a cerebral infarct in part of the right middle cerebral artery territory (arrow in a, diffusion-weighted MRI). After 13 days of stroke onset, passive movement of the left (unaffected) hand (e-g) induced activation in the right primary sensorimotor cortex (1) and left cerebellum (3). During passive movement of the right (paretic) hand (b-d), activation in contralateral primary sensorimotor cortex (1) was observed.

media/image4_w.jpg

Figure 3.

fMRI of a 61-year old man (control). Active right hand movement (a-c) induced a normal activation pattern in the left primary sensorimotor cortex (1), supplementary motor areas (2) and right cerebellum (3).

4. Discussion

4.1. Activation of sensorimotor network by somatosensory input

The results demonstrated that somatosensory stimulation of the unaffected hand, both tactile and proprioceptive input, activated sensorimotor network in the brain, and that the activation pattern was similar to that induced by active hand movement. Somatosensory input to the paretic hand also activated the sensorimotor network in the brain, although to a lesser degree. Of importance was that the activation involved not only postcentral S1 but also precentral M1, as observed in previous reports employing somatosensory stimulation as a task.

Passive movement studies have shown that brain activation during passive movement is seen in regions such as the contralateral sensorimotor cortex, the bilateral premotor cortex, supplementary motor areas, and inferior parietal cortex (Nelles et al., 1999; Loubinoux et al., 2003; Tombari et al., 2004). The similarity of activation patterns between passive and active hand movements highlights the contribution of afferent synaptic activity for central motor control, and suggests that the sensory systems play an important role in central motor control. Additional explanation may be that the repetitive sensory input induces motor imagery in the patients. Imagery of movement activates largely the same brain areas that are activated when movements are actually executed (Decety, 1996; Grezes & Decety 2001).

The brain activation during paretic hand sensory stimulation in this study was reduced as compared to that during unaffected hand sensory stimulation. This reduction may reflect the sensorimotor network damage caused by stroke, although the fMRI BOLD response could be reduced in the cerebral hemisphere of the lesion side (Murata et al., 2006; Mazzetto-Betti et al., 2010). Nevertheless, the result confirms the possibility of inducing sensorimotor transformations even in severely impaired stroke patients.

The observation of S1 and M1 activation during sensory input as well as active movement suggests that the sensorimotor network is functionally connected with each other. Actually, human motor and sensory hand cortices overlap, and are not divided in a simple manner by the central sulcus (McGlone et al., 2002; Morre et al.; 2000; Nii et al., 1996). Furthermore, S1 and M1 are heavily interconnected (Jones et al., 1978) and both are the sites of origin of pyramidal tract neurons in the monkey (Fromm & Evarts, 1982). Proprioceptive afferents from the muscle spindles (fibers IA, II), along with the projections from other articular and cutaneous receptors (fibers I to IV), gain access not only to S1 but also to M1 in the monkey (Lemon, 1999; Lemon & Porter, 1976).

Previous studies have also demonstrated the activation of secondary sensorimotor areas induced by passive hand movements, as seen in our study. SMA has rich anatomical connections with many areas in the central nervous system, such as thalamus, dorsal premotor cortex (PMd), spinal cord, and contralateral hemisphere (Juergens, 1984; Rouiller et al.,1994; Dum & Strick, 1996; Dum & Strick, 2005), and may be an important source of descending commands for the generation and control of distal movements in the monkey(He et al., 1995). SMA is also involved in motor learning in man (Halsband & Lange, 2006). Therefore, SMA has been suggested to play a crucial role in the early processes of recovery after lesions of primary motor pathways (Loubinoux et al., 2003).

Ventral premotor cortex (PMv) receives strong projections from S1 (Stepniewska et al., 2006), and PMv neurons project onto cervical and thoracic motoneurons in the monkey (He et al., 1993; Rouiller et al., 1994). The PMv corticospinal neurons supply part of the hand function after M1 lesion in the monkey (Liu & Rouiller, 1999). Nudo and colleagues demonstrated rewiring from M1 to PMv after ischemic brain injury, with substantial enlargements of the hand representation in the remote PMv that are proportional to the amount of hand representation destroyed in M1(Frost et al., 2003; Dancause et al., 2005). Nelles et al. (2001) pointed out the crucial role of a network including the lower part of BA40 and PMv, bilaterally, in task-oriented passive training aimed at improving motor recovery in severely impaired stroke patients. These areas could also be crucial for promoting reorganization in the rest of the brain.

4.2. Activation of sensorimotor network by active motor task

Previous functional neuroimaging studies on poststroke cerebral reorganization from acute to chronic stages revealed several activation patterns during active paretic hand movement (Ward & Cohen, 2004; Jang, 2007; Kato & Izumiyama, 2010). These include (1) a posterior shift of contralateral S1M1 activation (Pineiro et al., 2001; Calautti et al., 2003), (2) peri-infarct reorganization after infarction involving M1 (Cramer et al., 1997; Jang et al., 2005a), (3) a shift of M1 activation to the ipsilateral (contralesional) cortex (Chollet et al., 1991; Marshall et al., 2000; Feydy et al., 2002), (4) contribution of the secondary motor areas (Cramer et al., 1997; Carey et al., 2002; Ward et al., 2006), and (5) higher contralateral activity in the cerebellar hemisphere (Small et al., 2002).

These studies have also shown that the expanded activations may later decrease with functional improvements, indicating that best recovery is obtained when there is restitution of activation toward the physiological network over time. The contralesional shift of activation may return to ipsilesional S1M1 activation with functional gains (Feydy et al., 2002; Takeda et al., 2007), but worse outcome may correlate with a shift in the balance of activation toward the contralesional S1M1 (Calautti et al., 2001; Feydy et al., 2002; Zemke et al., 2003). Thus, the patterns of cerebral activation evoked by active hand movement show impaired organization and reorganization of brain sensorimotor network, and best recovery may depend on how much original motor system is reusable. The patterns of activation may also be dependent on the patient’s ability to recruit residual portions of the bilateral motor network (Silvestrini et al., 1998).

Early involvement of secondary sensorimotor areas after M1 lesion may temporarily substitute for the original sensorimotor network involving M1. This step may be a prerequisite to M1 functional reconnection through indirect pathways and to its efficacy in processing motor signals. The previous data suggest that different motor areas operate in parallel rather than in a hierarchical manner, and they are able to substitute for each other (Traversa et al., 1997; Loubinoux et al., 2003). Thus, remodeling of activation within a pre-existing network may be an important process for recovery.

4.3. Implication of somatosensory input as a rehabilitation strategy

There is consensus on the efficacy of physiotherapy. Active training is more efficient than passive training, but active training cannot be applied to very impaired patients. We need to consider other approaches for patients who cannot move the paretic limbs at the early phase of recovery. Physiotherapists apply sensory stimulation and passive movement daily to acute stroke patients and only these approaches are possible when the patients have complete paralysis. A few studies have validated the efficacy of sensory or proprioceptive stimulation on motor recovery.

Carel et al. (2000) have shown that proprioceptive training induces a reorganization of sensorimotor representation in healthy subjects, and that the anatomical substrates are SMA and S1M1 contralateral to the stimulation. Subsequently, Dechaumont-Palacin et al. (2008) showed that paretic wrist proprioceptive training produced change in SMA, premotor cortex, and a contralesional network including inferior parietal cortex (lower part of BA 40), secondary sensory cortex, and PMv. Thus, increased contralateral activity in secondary sensorimotor areas may facilitate control of recovered motor function by simple proprioceptive integration in severely impaired patients. Brain activation during passive movement increase with time after stroke(Nelles et al., 1999; Loubinoux et al., 2003; Tombari et al., 2004). Nelles et al. (2001) tested a mixed, task-oriented rehabilitative program that is at first passive, then active as recovery permits, and observed hyperactivation of the bilateral low parietal cortex and premotor cortex and a smaller hyperactivation of the ipsilateral M1.Thus, the changes might represent increased processing of sensory information relevant to motor output.

Somatosensory input to the motor cortex, via corticocortical connections with the somatosensory cortex, is important for learning new motor skills (Sakamoto et al., 1989; Pavlides et al., 1993; Vidoni et al., 2010). Somatosensory input may also play a critical role in motor relearning after hemiparetic stroke (Dechaumont-Palacin et al., 2008; Conforto at al. 2007; Vidoni et al., 2009). Schaechter et al. (2012) showed that increased responsiveness of the ipsilesional S1M1 to tactile stimulation over the subacute posrstroke period correlated with concurrent motor recovery and predicted motor recovery experienced over the year. This finding suggests that a strong link between change in processing of somatosensory information in the S1M1 during the early poststroke period and motor recovery in hemiparetic patients.

Muscular and peripheral nerve electrical stimulation increases motor output after stroke (Conforto et al., 2002; Kimberley et al., 2004; Wu et al., 2006; Conforto et al., 2010). Peripheral nerve stimulation increases corticomotoneuronal excitability (Kaelin-Lang et al., 2002; Ridding et al., 2000), and activation of S1M1 and PMd in healthy subjects (Wu et al., 2005). If applied to paretic hand of stroke patients paired with motor training, electrical nerve stimulation may enhance training effects on corticomotoneuronal plasticity in stroke patients (Sawaki et al, 2006; Yozbatiran et al., 2006; Celnik et al., 2007).

Thus, increased activity in brain sensorimotor network by somatosensory input may facilitate control of recovered motor function by operating not only at a high-order processing level but also at a low level of simple sensory integration. Therefore, early post-stroke fMRI studies using sensory stimulation as a task may be of great clinically importance and somatosensory stimulation over the poststroke recovery period may form a basis for improving motor recovery in stroke patients.

Another merit of massage or touch therapy may be the psychological effects produced by tactile stimulation, such as relaxation, alleviation of anxiety and depression. These effects may be evoked by stimulation of dopamine and serotonin secretion since increased levels of dopamine and serotonin have been shown in the urine following tactile skin stimulation (Field et al., 2005). Tactile stimulation in the rat evokes an increased dopamine release in the nucleus accumbens of the brain, which is thought to play a key role in motivational and reward processes (Maruyaka et al.; 2012). Relieving anxiety and depression seems important in the early steps of rehabilitation for patients with acute stroke.

5. Conclusion

The findings of this study demonstrate that the somatosensory inputs via the normal hand can activate brain sensorimotor network to a comparable extent with the areas that are activated during active hand movement, and that the somatosensory inputs via the paretic hand at the early stages of stroke before clinical motor recovery can also induce activities to some of the brain sensorimotor network. The result suggests that physiotherapy that employs somatosensory input via the paretic hand may be used as a first step to activate rehabilitation-dependent changes in the motor network in the brain toward restoration of motor function.The result may provide new insight into the establishment of rehabilitation strategiesafter stroke.

Acknowledgement

We thank the staff members of the MRI section of Sendai Nakae Hospital, Ms. Fumi Kozuka, Ms. Satsuki Ohi, Mr. Takeru Ohmukai, Ms. Yoko Sato, Ms. Aya Kanai, and Mr. Katsuhiro Aki, for their help to perform fMRI studies. We also thank Dr. Naohiro Saito, Department of Physiology, Tohoku University School of Medicine, Sendai, Japan, for his expert assistance on the fMRI-spm analysis. This study was supported by Grant-in-Aid for Scientific Research (22500473), Japan Society for the Promotion of Science.

References

1 - Y. Cao, L. D’Olhaberriague, E. M. Vikingstad, S. R. Levine, K. M. A. Welch, 1998Pilot study of functional MRI to assess cerebral activation of motor function after poststroke hemiparesis. Stroke, 29112122
2 - C. Calautti, J. Baron, C. , 2003Functional neuroimaging studies of motor recovery after stroke in adults. A review. Stroke,3415531566
3 - C. Calautti, F. Leroy, J. Y. Guincestre, J. Baron, C. , 2001Dynamics of motor network overactivation after striatocapsular stroke: a longitudinal PET study using a fixed-performance paradigm. Stroke, 3225342542
4 - C. Carel, I. Loubinoux, K. Boulanouar, C. Manelfe, O. Rascol, P. Celsis, F. Chollet, 2000Neural substrate for the effects of passive training on sensorimotor cortical representation: a study with functional magnetic resonance imaging in healthy subjects. J. Cereb. Blood Flow Metab., 20478484
5 - J. R. Carey, T. J. Kimberley, S. M. Lewis, E. J. Auerbach, L. Dorsey, P. Rundquist, K. Ugurbil, 2002Analysis of fMRI and finger tracking training in subjects with chronic stroke. Brain,125773788
6 - P. Celnik, F. Hummel, M. Harris-Love, R. Wolk, L. G. Cohen, 2007Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke. Arch. Phys. Med. Rehabil., 8813691376
7 - F. Chollet, V. Di Piero, R. J. S. Wise, D. J. Brooks, R. J. Dolan, R. S. J. Fracowiak, 1991The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Ann. Neurol.,296371
8 - A. B. Conforto, L. G. Cohen, Santos. R. L. dos, M. Scaff, S. K. Marie, 2007Effects of somatosensory stimulation on motor function in chronic cortico-subcortical strokes. J. Neurol., 254333339
9 - A. B. Conforto, K. N. Ferreiro, C. Tomasi, Santos. R. L. dos, V. L. Moreira, S. K. Marie, S. C. Baltieri, M. Scaff, L. G. Cohen, 2010Effects of somatosensory stimulation on motor function after subacute stroke. Neurorehabil. Neural Repair, 24263272
10 - A. B. Conforto, A. Kaelin-Lang, L. G. Cohen, 2002Increase in hand muscle strength of stroke patients after somatosensory stimulation. Ann. Neurol., 51122125
11 - S. C. Cramer, G. Nelles, R. R. Benson, J. D. Kaplan, R. A. Parker, K. K. Kwong, D. N. Kennedy, S. P. Finklestein, B. R. Rosen, 1997A functional MRI study of subjects recovered from hemiparetic stroke. Stroke,2825182527
12 - N. Dancause, S. Barbay, S. B. Frost, E. J. Plautz, D. Chen, E. V. Zoubina, A. M. Stowe, R. J. Nudo, 2005Extensive cortical rewiring after brain injury.J. Neurosci., 251016710179
13 - J. Decety, 1996The neurophysiological basis of motor imagery. Behav. Brain Res., 774552
14 - S. Dechaumont-Palacin, P. Marque, X. De Boissezon, E. Castel-Lacanal, C. Carel, I. Berry, J. Pastorm, J. F. Albucher, F. Chollet, I. Loubinoux, (2008, 2008Neural correlates of proprioceptive integration in the contralesional hemisphere of very impaired patients shortly after a subcortical stroke: an fMRI study. Neurorihab. Neural Repair, 22154165
15 - R. P. Dum, P. L. Strick, 1996Spinal cord terminations of the medial wall motor areas in macaque monkeys. J. Neurosci., 1665136525
16 - R. P. Dum, P. L. Strick, 2005Frontal lobe inputs to the digit representations of the motor areas on the lateral surface of the hemisphere. J. Neurosci., 2513751386
17 - P. W. Duncan, L. B. Goldstein, D. Matchar, G. W. Divine, J. Feussner, 1992Measurement of motor recovery after stroke: outcome measures and sample size requirements. Stroke, 2310841089
18 - A. Feydy, R. Carlier, A. Rody-Brami, B. Bussel, F. Cazalis, L. Pierot, Y. Burnod, M. A. Maier, 2002Longitudinal study of motor recovery after stroke: recruitment and focusing of brain activation. Stroke,3316101617
19 - T. Field, M. Hernandez-Reif, M. Diego, S. Schanberg, C. Kuhn, 2005Cortisol decreases and serotonin and dopamine increase following massage therapy. Int. J. Neurosci., 11513971413
20 - C. Fromm, E. V. Evarts, 1982Pyramidal tract neurons in somatosensory cortex: central and peripheral inputs during voluntary movement. Brain Res., 238186191
21 - S. B. Frost, S. Barbay, K. M. Friel, E. J. Plautz, R. J. Nudo, 2003Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. J. Neurophysiol., 8932053214
22 - J. Grezes, J. Decety, 2001Functional anatomy of execution, mental simulation, observation, and verb generation of actions: a meta-analysis. Hum. Brain Mapp., 12119
23 - U. Halsband, R. K. Lange, 2006Motor learning in man: a review of functional and clinical studies. J. Physiol. Paris,99414424
24 - S. Q. He, R. P. Dum, P. L. Strick, 1995Topographic organization of corticospinal projections from the frontal lobe: motor areas on the medial surface of the hemisphere. J. Neurosci., 1512843306
25 - A. Herholz, W. Heiss, D. , 2000Functional imaging correlates of recovery after stroke in humans. J. Cereb. Blood Flow Metab.,2016191631
26 - S. H. Jang, 2007A review of motor recovery mechanisms in patients with stroke. Neurorehabilitation,22253259
27 - S. H. Jang, S. H. Ahn, D. S. Yang, D. K. Lee, D. K. Kim, S. M. Son, 2005Cortical reorganization of hand motor function to primary sensory cortex in hemiparetic patients with a primary motor cortex infarct. Arch. Phys. Med. Rehabil.,8617061708
28 - E. G. Jones, J. D. Coulter, S. H. Hendry, 1978Intracortical connectivity of architectonic fields in the somatic sensory, motor and parietal cortex of monkeys. J. Comp. Neurol., 181291347
29 - U. Juergens, 1984The efferent and afferent connections of the supplementary motor area. Brain Res., 3006381
30 - A. Kaelin-Lang, A. R. Luft, L. Sawaki, A. H. Burstein, Y. H. Sohn, L. G. Cohen, 2002Modulation of human corticomotor excitability by somatosensory input. J. Physiol., 540(Pt 2), 623 EOF33 EOF
31 - H. Kato, M. Izumiyama, 2010Restorative and compensatory changes in the brain during early motor recovery from hemiparetic stroke: a functional MRI study, Neuroimaging, Cristina Marta Del-Ben (Ed.), 978-9-53307-127-5Sciyo, Available from: http://sciyo.com/articles/show/title/restorative-and-compensatory-changes-in-the-brain-during-early-motor-recovery-from-hemiparetic-strok
32 - H. Kato, M. Izumiyama, H. Koizumi, A. Takahashi, Y. Itoyama, 2002Near-infrared spectroscopic topography as a tool to monitor motor reorganization after hemiparetic stroke. A comparison with functional MRI. Stroke, 3320322036
33 - T. J. Kimberley, S. M. Lewis, E. J. Auerbach, L. L. Dorsey, J. M. Lojovich, J. R. Carey, (2004, 2004Electrical stimulation driving functional improvements and cortical changes in subjects with stroke. Exp. Brain Res., 154450460
34 - R. N. Lemon, 1999Neural control of dexterity: what has been achieved? Exp.Brain Res., 128612
35 - R. N. . Lemon, R. Porter, 1976Afferent input to movement-related precentral neurons in conscious monkeys. Proc. R. Soc. Lond. B. Biol. Sci., 194313339
36 - Y. Liu, E. M. Rouiller, (1999, 1999Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys. Exp. Brain Res.,128149159
37 - I. Loubinoux, C. Carel, J. Pariente, S. Dechaumont, J. Albucher, F. , C. Marque, F. Chollet, (2003, 2003Correlation between cerebral reorganization and motor recovery after subcortical infarcts. Neuroimage, 2021662180
38 - F. Mc Glone, E. F. Kelly, M. Trusson, S. T. Francis, G. Westling, R. Bowtell, 2002Functional neuroimaging studies of human somatosensory cortex. Behav. Brain Res., 135147158
39 - R. S. Marshall, G. M. Perera, R. M. Lazar, J. W. Krakauer, R. C. Constantine, R. L. De La Paz, 2000Evolution of cortical activation during recovery from corticospinal tract infarction. Stroke, 31656661
40 - K. Maruyama, R. Shimojo, M. Ohkubo, H. Maruyama, M. Kurosawa, 2012Tactile skin stimulation increases dopamine release in the nucleus accumbens in rats. J. Physiol. Sci., 62259266
41 - K. C. Mazzetto-Betti, R. F. Leoni, O. M. Pontes-Neto, A. C. Santos, J. P. Leite, A. C. Silva, D. B. de Araujo, 2010The stability of the BOLD fMRI response to motor tasks is altered in patients with chronic ischemic stroke. Stroke, 4119211926
42 - Moore,C.I.;Stern,C.E.;Corkin,S.;Fischi,B.;Gray,A.C.;Rosen,B.R.&Dale,A.M.2000Segregation of somatosensory activation in the human rolandic cortex using fMRI. J. Neurophysiol., 84558569
43 - Y. Murata, K. Sakatani, T. Hoshino, N. Fujiwara, T. Kano, S. Nakamura, Y. Katayama, 2006Effects of cerebral ischemia on evoked cerebral blood oxygenation responses and BOLD contrast functional MRI in stroke patients. Stroke, 3725142520
44 - G. Nelles, W. Jentzen, M. Jueptner, S. Mueller, H. C. Diener, (2001, 2001Arm training induced brain plasticity in stroke studied with serial positron emission tomography. Neuroimage, 1311461154
45 - G. Nelles, G. Spiekermann, M. Jueptner, G. Leonhardt, S. Mueller, H. Gerhard, C. Diener, 1999Reorganization of sensory and motor systems in hemiplegic stroke patients. A positron emission tomography study. Stroke, 3015101516
46 - Y. Nii, S. Uematsu, R. P. Lesser, B. Gordon, (1996, 1996Does the central sulcus divide motor and sensory functions? Cortical mapping of human hand areas as revealed by electrical stimulation through subdural grid electrodes. Neurology, 46360367
47 - C. Pavlides, E. Miyashita, H. Asanuma, 1993Projection from the sensory to the motor cortex is important in learning motor skills in the monkey. J. Neurophysiol., 70733741
48 - R. Pineiro, S. Pendlebury, H. Johansen-Berg, P. M. Matthews, 2001Functional MRI detects posterior shifts in primary sensorimotor cortex activation after stroke.Evidence of local adaptive reorganization? Stroke,3211341139
49 - M. C. Ridding, B. Brouwer, T. S. Miles, J. B. Pitcher, P. D. Thompson, 2000Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects.Exp. Brain Res., 131135143
50 - P. M. Rossini, C. Calautti, F. Pauri, J. C. Baron, (2003, 2003Post-stroke plastic reorganization in the adult brain. Lancet Neurol.,2493502
51 - E. M. Rouiller, A. Babalian, O. Kazennikov, V. Moret, X. H. Yu, M. Wiesendanger, 1994Transcallosal connections of the distal forelimb representations of the primary and supplementary motor cortical areas in macaque monkeys. Exp. Brain Res., 102227243
52 - T. . Sakamoto, K. Arissian, H. Asanuma, 1989Functional role of the sensory cortex in learning motor skills in cats. Brain Res., 503258264
53 - L. Sawaki, C. W. Wu, A. Kaelin-Lang, L. G. Cohen, 2006Effects of somatosensory stimulation on use-dependent plasticity in chronic stroke. Stroke, 37246247
54 - J. D. Schaechter, C. A. van Oers, B. N. Groisser, S. S. Salles, M. G. Vangel, C. I. Moore, R. M. Dijkhuizen, 2012Increase in sensorimotor cortex response to somatosensory stimulation over subacute poststroke period correlates with motor recovery in himipareric patients. Neurorehabil. Neural Repair, 26325334
55 - M. Silvestrini, L. M. Cupini, F. Placidi, M. Diomedi, G. Bernardi, 1998Bilateral hemispheric activation in the early recovery of motor function after stroke. Stroke,2913051310
56 - A. L. Small, P. Hlustik, D. C. Noll, C. . Genovese, A. Solodkin, 2002Cerebellar hemispheric activation ipsilateral to the paretic hand correlates with functional recovery after stroke. Brain,12515441557
57 - I. Stepniewska, T. M. Preuss, J. H. Kaas, 2006Ipsilateral cortical connections of dorsal and ventral premotor areas in New World owl monkeys. J. Comp. Neurol., 495691708
58 - K. Takeda, Y. Gomi, I. Imai, N. Shimoda, M. Hiwatari, H. Kato, 2007Shift of motor activation areas during recovery from hemiparesis after cerebral infarction: a longitudinal study with near-infrared spectroscopy. Neurosci. Res.,59136144
59 - D. Tombari, I. Loubinoux, J. Pariente, A. Gerdelat, J. Albucher, F. , J. Tardy, E. Cassol, F. Chollet, (2004, 2004A longitudinal fMRI study: in recovering and then in clinically stable subcortical stroke patients. Neuroimage, 23827839
60 - R. Traversa, P. Cicinelli, A. Bassi, P. M. Rossini, G. Bernardi, (1997, 1997Mapping of motor cortical reorganization after stroke. A brain stimulation study with focal magnetic pulses. Stroke, 28110117
61 - E. D. Vidoni, N. E. Acerra, E. Dao, S. K. Meehan, L. A. Boyd, 2010Role of the primary somatosensory cortex in motor learning: An rTMS study. Neurobiol. Learn. Mem., 93532539
62 - E. D. Vidoni, L. A. Boyd, 2009Preserved motor learning after stroke is related to the degree of proprioceptive deficit. Behav. Brain Funct., 5,36 EOF
63 - N. S. Ward, M. M. Brown, A. J. Thompson, R. S. J. Frackowiak, 2003aNeural correlates of outcome after stroke: a cross-sectional fMRI study. Brain, 12614301448
64 - N. S. Ward, M. M. Brown, A. J. Thompson, R. S. J. Frackowiak, 2003bNeural correlates of motor recovery after stroke: a longitudinal fMRI study. Brain,12624762496
65 - N. S. Ward, L. G. Cohen, 2004Mechanisms underlying recovery of motor function after stroke. Arch. Neurol.. 6118441848
66 - N. S. Ward, J. M. Newton, O. B. Swayne, L. Lee, A. J. Thompson, R. J. Greenwood, J. C. Rothwell, R. S. Frackowiak, 2006Motor system activation after subcortical stroke depends on corticospinal system integrity. Brain,129(Pt. 3), 809 EOF819 EOF
67 - C. Weiller, F. Chollet, K. J. Fristo, R. J. Wise, R. S. Frackowiak, 1992Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann.Neurol., 315463472
68 - C. W. Wu, H. J. Seo, L. G. Cohen, 2006Influence of electric somatosensory stimulation on paretic-hand function in chronic stroke. Arch. Phys. Med. Rehabil., 87351357
69 - C. W. Wu, P. van Gelderen, T. Hanakawa, Z. Yaseen, L. G. Cohen, 2005Enduring representational plasticity after somatosensory stimulation. Neuroimage, 27872884
70 - N. Yozbtiran, B. Donmez, N. Kayak, O. Bozan, 2006Electrical stimulation of wrist and fingers for sensory and functional recovery in acute hemiplegia. Clin. Rehabil., 20411
71 - A. C. Zemke, P. J. Heagerty, C. Lee, S. C. Cramer, 2003Motor cortex organization after stroke is related to side of stroke and level of recovery. Stroke,34, e2328