Réorganisation du cortex sensorimoteur dans le cadre de la paralysie cérébrale unilatérale : apports des neurosciences

Cerebral palsy (CP) is a non-progressive injury to the developing central nervous system and defines as permanent disorders of the development of movement and posture, causing activity limitation. This neurodevelopmental disorder may lead to spastic unilateral cerebral palsy after early unilateral brain lesions. Physical and rehabilitation medicine has a particular interest in the study of organization and reorganization of the sensorimotor cortex following early brain injury. From neuroscience standpoint, early brain lesions have been shown to induce substantial neural reorganization owing to the higher plasticity in the developing brain. Unilateral injuries either to the motor cortex or the corticospinal tract can lead to different patterns of reorganization of the sensorimotor cortex. Many patients develop ipsilateral corticospinal pathways to control the paretic hand with the non-lesioned hemisphere. This type of reorganization is often observed following unilateral periventricular brain lesions, which damage the corticospinal tracts in the periventricular white matter. In this group of patients, the primary motor cortex has been found to be represented in the non-lesioned precentral gyrus ipsilateral to the paretic side. Inversely, in patients with perinatal unilateral middle cerebral artery stroke, primary motor cortex remains organised in the lesioned precentral gyrus contralateral to the paretic hand. However, regardless of these inter- or intrahemispheric motor representations, the primary somatosensory cortex representation remains in the lesioned hemisphere in both groups. These two types of corticospinal reorganization could influence the efficacy of rehabilitation.     

Changes in serial optical topography and TMS during task performance after constraint-induced movement therapy in stroke: a case study

The authors examined serial changes in optical topography in a stroke patient performing a functional task, as well as clinical and physiologic measures while undergoing constraint-induced therapy (CIT). A 73-year-old right hemiparetic patient, who had a subcortical stroke 4 months previously, received 2 weeks of CIT. During the therapy, daily optical topography imaging using near-infrared light was measured serially while the participant performed a functional key-turning task. Clinical outcome measures included the Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and functional key grip test. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were also used to map cortical areas and hemodynamic brain responses, respectively. Optical topography measurement showed an overall decrease in oxy-hemoglobin concentration in both hemispheres as therapy progressed and the laterality index increased toward the contralateral hemisphere. An increased TMS motor map area was observed in the contralateral cortex following treatment. Posttreatment fMRI showed bilateral primary motor cortex activation, although slightly greater in the contralateral hemisphere, during affected hand movement. Clinical scores revealed marked improvement in functional activities. In one patient who suffered a stroke, 2 weeks of CIT led to improved function and cortical reorganization in the hemisphere contralateral to the affected hand.     

Reorganization of sensory and motor systems in hemiplegic stroke patients. A positron emission tomography study.

BACKGROUND AND PURPOSE: Cortical reorganization of motor systems has been found in recovered stroke patients. Reorganization in nonrecovered hemiplegic stroke patients early after stroke, however, is less well described. We used positron emission tomography to study the functional reorganization of motor and sensory systems in hemiplegic stroke patients before motor recovery. METHODS: Regional cerebral blood flow (rCBF) was measured in 6 hemiplegic stroke patients with a single, subcortical infarct and 3 normal subjects with the [(15)O]H(2)O injection technique. Brain activation was achieved by passive elbow movements driven by a torque motor. Increases of rCBF comparing passive movements and rest were assessed with statistical parametric mapping. Significant differences were defined at P<0.01. RESULTS: In normal subjects, significant increases of rCBF were found in the contralateral sensorimotor cortex, supplementary motor area, cingulate cortex, and bilaterally in the inferior parietal cortex. In stroke patients, significant activation was observed bilaterally in the inferior parietal cortex and in the contralateral sensorimotor cortex, ipsilateral prefrontal cortex, supplementary motor area, and cingulate cortex. Significantly larger increases of rCBF in patients compared with normal subjects were found bilaterally in the sensorimotor cortex, stronger in the ipsilateral, unaffected hemisphere, and in both parietal lobes, including the ipsilateral precuneus. CONCLUSIONS: Passive movements in hemiplegic stroke patients before clinical recovery elicit some of the brain activation patterns that have been described during active movements after substantial motor recovery. Changes of cerebral activation in sensory and motor systems occur early after stroke and may be a first step toward restoration of motor function after stroke.     

Arm function after stroke: from physiology to recovery

There are varying degrees of spontaneous improvement in arm paresis over the first 6 months after stroke. The degree of improvement at 6 months is best predicted by the motor deficit at 1 month despite standard rehabilitative interventions in the ensuing 5 months. Animal studies indicate that the loss of fine motor control, especially individuation of the digits, is due to interruption of monosynaptic corticomotoneuronal connections. Spasticity occurs because of loss of cortical modulatory control on descending brain stem pathways and spinal segmental circuits but is not a major cause of motor dysfunction. Quantitative studies of reaching movements in patients suggest that arm paresis consists of higher-order motor planning and sensorimotor integration deficits that cannot be attributed to weakness or presence of synergies. Cortical stimulation experiments in animals and functional imaging studies in humans indicate that motor learning and recovery after stroke share common brain reorganization mechanisms. Rehabilitation techniques enhance learning-related changes after stroke and contribute to recovery. Future research will benefit from using quantitative methods to characterize the motor impairment after stroke and by applying concepts in motor learning to devise more physiologically based rehabilitation techniques.     

Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats

We investigated axonal plasticity in the bilateral motor cortices in rats after unilateral stroke and bone marrow stromal cell (BMSC) treatment. Rats were subjected to permanent right middle cerebral artery occlusion followed by intravenous administration of phosphate-buffered saline or BMSCs 1 day later. Adhesive-removal test and modified neurologic severity score were performed weekly to monitor limb functional deficit and recovery. Anterograde tracing with biotinylated dextran amine injected into the right motor cortex was used to assess axonal sprouting in the contralateral motor cortex and ipsilateral rostral forelimb area. Animals were killed 28 days after stroke. Progressive functional recovery was significantly enhanced by BMSCs. Compared with normal animals, axonal density in both contralateral motor cortex and ipsilateral rostral forelimb area significantly increased after stroke. Bone marrow stromal cells markedly enhanced such interhemispheric and intracortical connections. However, labeled transcallosal axons in the corpus callosum were not altered with either stroke or treatment. Both interhemispheric and intracortical axonal sprouting were significantly and highly correlated with behavioral outcome after stroke. This study suggests that, after stroke, cortical neurons surviving in the peri-infarct motor cortex undergo axonal sprouting to restore connections between different cerebral areas. Bone marrow stromal cells enhance axonal plasticity, which may underlie neurologic functional improvement.     

Cortical reorganization after modified constraint-induced movement therapy in pediatric hemiplegic cerebral palsy

Constraint-induced movement therapy improves motor function in the affected hand of children with hemiplegic cerebral palsy and results in cortical changes in adults with stroke. This study measured clinical improvement and cortical reorganization in a child with hemiplegia who underwent modified constraint-induced movement therapy for 3 weeks. Clinical, functional magnetic resonance imaging and magnetoencephalography measurements were done at baseline, after therapy, and 6 months after therapy. Modified constraint-induced movement therapy resulted in clinical improvement as measured by the Pediatric Motor Activity Log. Functional magnetic resonance imaging showed bilateral sensorimotor activation before and after therapy and a shift in the laterality index from ipsilateral to contralateral hemisphere after therapy. Magnetoencephalography showed increased cortical activation in the ipsilateral motor field and contralateral movement evoked field after therapy. Cortical reorganization was maintained at the 6-month follow-up. This is the first study to demonstrate cortical reorganization after any version of constraint-induced movement therapy in a child with hemiplegia.     

Functional reorganization of the cerebral motor system after stroke

PURPOSE OF REVIEW: Recovery of function after stroke is now widely considered to be a consequence of central nervous system reorganization. Non-invasive techniques such as functional magnetic resonance imaging, transcranial magnetic stimulation, electroencephalography and magnetoencephalography now allow the study of the working human brain. Studies in stroke patients can now address how cerebral networks in the human brain respond to focal injury and whether these changes are related to functional recovery. This understanding may in turn lead to the development of techniques that will drive cerebral reorganization in a way that promotes functional improvement. RECENT FINDINGS: The relationship between cerebral reorganization and functional recovery has been examined in both cross-sectional and longitudinal studies. It appears that the motor system reacts to damage in a way that attempts to generate motor output through surviving brain regions and networks. There are changes in cortical excitability after stroke that may provide the substrate whereby the effects of motor practice or experience can be more effective in driving long lasting changes in motor networks. This will be particularly important in intact portions of neural networks subserving motor skills learning. SUMMARY: Functionally relevant adaptive changes occur in the human brain following focal damage. A greater understanding of how these changes are related to the recovery process will allow the development of novel therapeutic techniques that are based on neurobiological principles and which are designed to minimize impairment in appropriately targeted patients suffering from stroke.     

Plasticity and reorganization of the brain post stroke

Reorganization of the cortex post stroke is dependent not only on the lesion site but also on remote brain areas that have structural connections with the area damaged by the stroke. Motor recovery is largely dependent on the intact cortex adjacent to the infarct, which points out the importance of preserving the penumbral areas. There appears to be a priority setting with contralateral and ipsilateral motor pathways, with ipsilateral (unaffected hemisphere) pathways only becoming prominent after more severe strokes where functional contralateral (affected hemisphere) pathways are unable to recover. Ipsilateral or unaffected hemisphere motor pathway activation is therefore associated with a worse prognosis.     

A review of diffusion tensor imaging studies on motor recovery mechanisms in stroke patients

For the past decade, diffusion tensor imaging (DTI) has been used in elucidation of the motor recovery mechanisms in stroke patients. In the current study, I reviewed the DTI studies with regard to the motor recovery mechanisms in stroke patients, according to the following classification of motor recovery mechanisms; recovery of a damaged lateral corticospinal tract (CST), subcortical peri-lesional reorganization, ipsilateral motor pathway from the unaffected motor cortex to the affected extremities, and other motor recovery mechanisms. In addition, I discussed the characteristics of DTI as an evaluation tool for motor recovery mechanisms and future direction. DTI has a unique advantage in identification and estimation of neural tracts at the subcortical level. Therefore, it could contribute much to research on the motor recovery mechanisms of stroke patients, especially, in terms of recovery of a damaged CST and subcortical peri-lesional reorganization. In spite of the advantages of DTI, fewer DTI studies on this topic have been conducted compared to studies using transcranial magnetic stimulation or functional MRI. Therefore, the total number of DTI studies on this topic should be increased. Moreover, further studies on various topics related to brain plasticity of motor function, as well as the motor recovery mechanism itself, should be encouraged; for example, DTI changes with passage of time, with rehabilitative intervention, or with motor recovery.     

High-resolution EEG in poststroke hemiparesis can identify ipsilateral generators during motor tasks

BACKGROUND AND PURPOSE: Multimodal neuroimaging with positron emission tomography (PET) scanning or functional MRI can detect and display functional reorganization of the brain's motor control in poststroke hemiplegia. We undertook a study to determine whether the new modality of 128-electrode high-resolution EEG, coregistered with MRI, could detect changes in cortical motor control in patients after hemiplegic stroke. METHODS: We recorded movement-related cortical potentials with left and right finger movements in 10 patients with varying degrees of recovery after hemiplegic stroke. All patients were male, and time since stroke varied from 6 to 144 months. All patients were right-handed. There was also a comparison group of 20 normal control subjects. RESULTS: Five of 8 patients with left hemiparesis had evidence of ipsilateral motor control of finger movements. There were only 2 cases of right hemiparesis; in addition, 1 patient had a posteriorly displaced motor potential originating behind a large left frontal infarct (rim). CONCLUSIONS: Reorganization of motor control takes place after stroke and may involve the ipsilateral or contralateral cortex, depending on the site and size of the brain lesion and theoretically, the somatotopic organization of the residual pyramidal tracts. Our results are in good agreement with PET and functional MRI studies in the current literature. High-resolution EEG coregistered with MRI is a noninvasive imaging technique capable of displaying cortical motor reorganization.     

Cortical reorganization--effects of intensive therapy

Recovery from hemiparesis after stroke largely depends on widespread functional and structural neuronal plasticity. Based on animal studies of rehabilitative and pharmacological interventions on recovery, recent neuroscientific findings suggest that new rehabilitative interventions may also have benefits by modulating neuroplastic mechanisms in stroke patients. Neurofunctional imaging methods such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) as well as transcranial magnetic stimulation (TMS) now permit direct studies of training-induced plasticity in stroke patients. Prospectively conducted studies using these techniques have investigated how plasticity relates to recovery of motor function and how intensive training modulates cortical reorganization. Despite technical and methodological differences, consistent neuroanatomic findings on training-induced reorganization of the motor system have been reported. These discoveries have important implications for the future development of neurorehabilitative training methods. With continuously improving methods to study cortical reorganization and over 100 randomized clinical trials on stroke rehabilitation published during the past five years, this promises to be an exciting time in stroke rehabilitation research.     

Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis

Using functional magnetic resonance imaging (fMRI), we investigated whether movement-associated functional changes of the brain are present in patients who are, most likely, at the earliest stage of multiple sclerosis (MS). Functional MRI exams were obtained from 16 patients at presentation with clinically isolated syndromes (CIS) suggestive of MS and 15 sex- and age-matched healthy volunteers during the performance of three simple and one more complex motor tasks with fully normal functioning extremities. fMRI analysis was performed using statistical parametric mapping (SPM99). Compared to healthy volunteers, CIS patients had increased activations of the contralateral primary sensorimotor cortex (SMC), secondary somatosensory cortex (SII), and inferior frontal gyrus (IFG), when performing a simple motor task with the dominant hand. The increased recruitment of the contralateral primary SMC was also found during the performance of the same motor task with the non-dominant hand and with the dominant foot. In this latter case, an anterior shift of the center of activation of this region was detected. During the performance of a complex motor task with the dominant upper and lower limbs, CIS patients had an increased recruitment of a widespread network (including the frontal lobe, the insula, the thalamus), usually considered to function in motor, sensory, and multimodal integration processing. The comparison of brain activations during the performance of simple vs. complex motor tasks showed that the movement-associated somatotopic organization of the cerebral and cerebellar cortices was retained in patients with CIS. Cortical reorganization occurs in patients at presentation with CIS highly suggestive of MS. Local synaptic reorganization, recruitment of parallel existing pathways, and reorganization of distant sites are all likely to contribute to the observed functional changes. Hum. Brain Mapping 21:106-115, 2004.     

Resting state alpha-band functional connectivity and recovery after stroke

After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. However, the unpredictable timing and extent of sensorimotor recovery reflects a gap in understanding of these underlying neural mechanisms. We aimed to identify the plasticity of alpha-band functional neural connections within the perilesional area and the predictive value of functional connectivity with respect to motor recovery of the upper extremity after stroke. Our results show improvements in upper extremity motor recovery in relation to distributed changes in MEG-based alpha band functional connectivity, both in the perilesional area and contralesional cortex. Motor recovery was found to be predicted by increased connectivity at baseline in the ipsilesional somatosensory area, supplementary motor area, and cerebellum, contrasted with reduced connectivity of contralesional motor regions, after controlling for age, stroke onset-time and lesion size. These findings support plasticity within a widely distributed neural network and define brain regions in which the extent of network participation predicts post-stroke recovery potential.     

Cortical plasticity and motor activity studied with transcranial magnetic stimulation

For decades cortical representations of the parts of the body have been considered to be unchangeable. This view has changed radically during the past 20 years using new tools designed to study plasticity in the adult human brain. Transcranial magnetic stimulation (TMS) is a valuable non-invasive technique for exploring the ability of the motor cortex to change during motor skill acquisition. Results obtained with TMS in neurological patients as well as in normal subjects demonstrate that cortical plasticity is a necessity for correct adaptation to the continuously changing environment. Topographical reorganization of the motor cortex depends on the types of movements performed by the subjects. During simple training, the cortical representation is enlarged, and it returns to its initial size when the task is overlearned. These transient modifications characterize simple motor training. Motor skills in which coordination of distal and proximal muscles, precision of the task and spatio-temporal constraints are associated, has a different impact on cortical reorganization. We propose that years of practice of a complex motor skill induces a new cortical topography that must be interpreted as structural plasticity which provides the capacity to execute a plastic behaviour instead of a stereotypical movement. We review the neuronal mechanisms underlying plasticity in different types of movement. We stress new emerging notions, such as overlap of cortical maps, and system dynamics at single neuron and network levels, to explain the reorganization of movement representations that encode motor skill. Dendritic arborizations as functional computing elements, newly generated neurons in adult brain, and plastic architectures of cortical networks operating as distributed functional modules are new hypotheses for structural plasticity.     

Non-invasive brain mapping of motor-related areas of four limbs in patients with clinically isolated syndrome compared to healthy normal controls

Functional MRI studies on patients with multiple sclerosis (MS) have demonstrated widespread cortical reorganization of the motor network. However, few functional studies have addressed cortical plasticity in patients with clinically isolated syndrome (CIS). The activity of the lower limb motor system, despite its highlighted involvement in patients with CIS and MS, has been little studied. Thus, brain activation was compared in CIS patients with clinically intact motor systems with that in healthy control participants while they were performing motor tasks with four limbs. A total of 26 right-handed patients with CIS with clinically intact motor systems and 28 right-handed age and sex-matched controls participated in the functional MRI (fMRI) motor task. Patients with CIS showed greater activation in the ipsilateral secondary somatosensory cortex, cingulate gyrus and precuneus cortex while performing the ankle movement task compared to healthy controls. In the finger-tapping task, patients with CIS showed greater activity in the contralateral thalamus, ipsilateral premotor and superior temporal gyrus. In addition, the left inferior frontal gyrus was activated more in patients with CIS, regardless of the hand used. Therefore, despite having clinically intact motor systems, patients with CIS had different motor networks. All novel recruited regions were adjacent to the somatotopy of the primary motor areas of the limbs. Our finding confirm that brain reorganization precedes clinical manifestation, as no patient had any clinical manifestation that suggested involvement of the motor system.     

Motor network reorganization after motor imagery training in stroke patients with moderate to severe upper limb impairment

Background

Motor imagery training (MIT) has been widely used to improve hemiplegic upper limb function in stroke rehabilitation. The effectiveness of MIT is associated with the functional neuroplasticity of the motor network. Currently, brain activation and connectivity changes related to the motor recovery process after MIT are not well understood. Aim: We aimed to investigate the neural mechanisms of MIT in stroke rehabilitation through a longitudinal intervention study design with task-based functional magnetic resonance imaging (fMRI) analysis.

Methods

We recruited 39 stroke patients with moderate to severe upper limb motor impairment and randomly assigned them to either the MIT or control groups. Patients in the MIT group received 4 weeks of MIT therapy plus conventional rehabilitation, while the control group only received conventional rehabilitation. The assessment of Fugl-Meyer Upper Limb Scale (FM-UL) and Barthel Index (BI), and fMRI scanning using a passive hand movement task were conducted on all patients before and after treatment. The changes in brain activation and functional connectivity (FC) were analyzed. Pearson's correlation analysis was conducted to evaluate the association between neural functional changes and motor improvement.

Results

The MIT group achieved higher improvements in FM-UL and BI relative to the control group after the treatment. Passive movement of the affected hand evoked an abnormal bilateral activation pattern in both groups before intervention. A significant Group × Time interaction was found in the contralesional S1 and ipsilesional M1, showing a decrease of activation after intervention specifically in the MIT group, which was negatively correlated with the FM-UL improvement. FC analysis of the ipsilesional M1 displayed the motor network reorganization within the ipsilesional hemisphere, which correlated with the motor score changes.

Conclusions

MIT could help decrease the compensatory activation at both hemispheres and reshape the FC within the ipsilesional hemisphere along with functional recovery in stroke patients.     

Cortical plasticity after stroke: implications for rehabilitation.

While adaptive processes in the cerebral cortex have long been thought to contribute to functional recovery after stroke, the precise neuronal structures and mechanisms underlying these processes have been difficult to identify. Over the past 15 years, a large number of studies conducted in human stroke patients and in experimental animal models have contributed to a more coherent picture of the brain's adaptive capacity after injury. These studies suggest that the cerebral cortex undergoes significant and functional structural plasticity for at least several weeks to months following injury. Adaptive changes have been demonstrated in the intact tissue surrounding the lesion, as well as in other cortical motor areas remote from the site of injury. Recent results from non-human primate studies of cortical reorganization after stroke demonstrate marked functional changes in the intact cortical tissue adjacent to the infarct in the weeks following an ischemic lesion. Further, intensive task-specific practice with the impaired limb has a modulatory effect on the inevitable cortical plasticity. Taken together with parallel studies of forced use in human stroke patients, it is likely that use of the impaired limb can influence adaptive reorganizational mechanisms in the intact cerebral cortex, and thus, promote functional recovery.     

Functional neuroimaging of dressing-related skills

Restoration of motor function following stroke involves reorganization of motor output through intact pathways, with compensatory brain activity likely variable by task. One class of motor tasks, those involved in self-care, is particularly important in stroke rehabilitation. Identifying the brain areas that are engaged in self-care and how they reorganize after stroke may enable development of more effective rehabilitation strategies. We piloted a paradigm for functional MRI assessment of self-care activity. In two groups, young adults and older adults, two self-care tasks (buttoning and zipping) produce activation similar to a bimanual tapping task, with bilateral activation of primary and secondary motor cortices, primary sensory cortex, and cerebellum. Quantitative differences include more activation of sensorimotor cortex and cerebellum in buttoning than bimanual tapping. Pilot subjects with stroke showed greater superior parietal activity across tasks than controls, potentially representing an increased need for sensorimotor integration to perform motor tasks.     

Movement disorders in stroke

Dyskinesias are infrequent presentations in acute stroke (1%). They can be found more frequently as delayed presentations after a stroke, but the prevalence is not available from the literature. The full spectrum of hyper- and hypo-akinetic syndromes has been described, but three main pictures are rather specific of an acute stroke: limb shaking, hemichorea-hemiballism and unilateral asterixis. Besides limb shaking, that seems to reflect a transient diffuse ischemia of the frontosubcortical motor pathway, lesions are described at all levels of the frontosubcortical motor circuit including the sensorimotor frontoparietal cortex, the striatum, the pallidum, the thalamic nuclei, the subthalamic nucleus, the substantia nigra, the cerebellum, the brainstem and their interconnecting pathways, as ischemic or hemorrhagic strokes. The preferentially late development of dyskinesia could reflect the return to a more ancestral motor control level, the most functional possible with the remaining configuration of structures, elaborated by brain plasticity after stroke.