Cortical neuromodulation by constraint-induced movement therapy in congenital hemiparesis: an FMRI study

OBJECTIVE: The aim of this study was to assess neuromodulative effects of CIMT in congenital hemiparesis. PATIENTS AND METHODS: Ten patients (age range: 10-30 years) with congenital hemiparesis due to unilateral cortico-subcortical infarctions in the middle cerebral artery territory, and with preserved cortico-spinal projections from the affected hemisphere to the paretic hand, were included. After a twelve-day period of constraint-induced movement therapy (CIMT), all showed a significant improvement of paretic hand function. Immediately before and after therapy, functional MRI during active and passive hand movements was performed to monitor cortical activation. RESULTS: Four patients showed consistent increases in cortical activation during movements of the paretic hand in the primary sensorimotor cortex of the affected hemisphere. Of the remaining six patients, three showed similar changes, but these results were potentially contaminated by an improved task performance after therapy. No significant alteration in activation was observed in two patients, and one showed movement artifacts. CONCLUSIONS: Even a short period of CIMT can induce changes of cortical activation in congenital hemiparesis. In our sample, increases in fMRI activation were consistently observed in the primary sensorimotor cortex of the affected hemisphere. Thus, the potential for neuromodulation is preserved in the affected hemisphere after early brain lesions.     

Functional relevance of ipsilateral motor activation in congenital hemiparesis as tested by fMRI-navigated TMS

Many, but not all patients with congenital hemiparesis (i.e., hemiparesis due to a pre-, peri- or neonatally acquired brain lesion) control their paretic hands via ipsilateral cortico-spinal projections from the contra-lesional hemisphere (CON-H). Patients who still control their paretic hands via preserved crossed cortico-spinal projections from the damaged hemisphere nevertheless show increased fMRI activation during paretic hand movements in the CON-H. We used fMRI-navigated rTMS induced functional lesions over the primary motor cortex (M1) hand area, the dorsal premotor cortex (dPMC) and the superior parietal lobe (SPL) of the CON-H in four of these patients to investigate whether this increased ipsilateral activation during finger movements of the paretic hand contributes to movement performance. Functional lesions of the dPMC and M1 but not SPL of the CON-H induced decreased temporal preciseness of finger sequences. The present results argue for a possible role of dPMC and M1 of the CON-H on complex motor behavior even in those patients with congenital hemiparesis who control their paretic hands via crossed cortico-spinal projections from the damaged hemisphere.     

Predicting hand function after hemispherotomy: TMS versus fMRI in hemispheric polymicrogyria

Patients with hemispheric malformations of cortical development (such as polymicrogyria) often develop medically intractable epilepsies for which hemispherotomy can be an excellent treatment option. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are noninvasive methods used to evaluate the sensorimotor system in adults and children before surgery. Preoperative results of both methods and their predictive values regarding hand function after hemispherotomy are described in four boys with hemispheric polymicrogyria, pharmacoresistent epilepsy, and hemiparesis with preserved grasp function of the paretic hand. TMS showing ipsilateral projections from the contralesional hemisphere but no evidence of crossed corticospinal projections from the lesioned hemisphere correctly predicted preserved postoperative grasp function in all four patients. In contrast, the interpretation of sensorimotor fMRI in patients with congenital hemiparesis is more difficult, as ipsilesional activation can occur as it was the case in three of four patients in the current study. This activation might represent contralaterally preserved primary somatosensory (S1) and not primary motor (M1) representation and is apparently not necessary for the paretic hand to still perform grasp movements.     

Reduced integrity of sensorimotor projections traversing the posterior limb of the internal capsule in children with congenital hemiparesis

There is reduced integrity of corticospinal projections that traverse the posterior limb of the internal capsule (PLIC) in children with unilateral cerebral palsy (CP). It remains unclear whether there are changes in integrity of other projections traversing the PLIC. Forty children with congenital hemiparesis and 15 typically developing children underwent structural and diffusion-weighted MRI. All children with congenital hemiparesis showed lesions to the periventricular white matter. Structural images were parcellated into 34 cortical regions per hemisphere and posterior limb of the internal capsule was identified. PLIC connections to each cortical region were extracted using probabilistic tractography. Differences between hemispheres for each cortical projection (asymmetry index (AI)) and tract microstructure (fractional anisotropy (FA), mean diffusivity (MD)) were assessed. The results showed that 17 children (42.5%) with congenital hemiparesis showed bilateral lesions on structural MRI. Projections to the primary motor cortex (precentral gyrus and paracentral lobule) showed greater asymmetry in unilateral CP group compared to typically developing children and indicate reduced projections on the hemisphere contralateral to the impaired limb (i.e., contralateral hemisphere). Reduced FA and increased MD were also observed for connections with the primary motor cortex, primary sensory cortex (postcentral gyrus) and precuneus on the contralateral hemisphere in children with congenital hemiparesis. Similar changes were observed between children with unilateral and bilateral lesions on structural MRI. Notably, microstructural changes were associated with deficits in both sensory and motor function. The findings further unravel the underlying neuroanatomical correlates of sensorimotor deficits in children with congenital hemiparesis.     

Do patients with congenital hemiparesis and ipsilateral corticospinal projections respond differently to constraint‐induced movement therapy?

This study investigates whether the type of corticospinal reorganization (identified by transcranial magnetic stimulation) influences the efficacy of constraint-induced movement therapy (CIMT). Nine patients (five males, four females; mean age 16y [SD 6y 5mo], range 11-30y) controlling their paretic hand via ipsilateral corticospinal projections from the contralesional hemisphere and seven patients (three males, four females; mean age 17y [SD 7y], range 10-30y) with preserved crossed corticospinal projections from the affected hemisphere to the paretic hand underwent 12 consecutive days of CIMT. A Wolf motor function test applied before and after CIMT revealed a significant improvement in the quality of upper extremity movements in both groups. Only in patients with preserved crossed projections, however, was this amelioration accompanied by a significant gain in speed, whereas patients with ipsilateral projections tended to show speed reduction. These data, although preliminary, suggest that patients with congenital hemiparesis and ipsilateral corticospinal projections respond differently to CIMT.     

Evolution of cortical activation during recovery from corticospinal tract infarction

BACKGROUND AND PURPOSE: Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is known about the time course of cortical activation in these regions as recovery proceeds. METHODS: Eight patients with first-ever corticospinal tract lacunes causing hemiparesis had serial fMRIs within the first few days after stroke and at 3 to 6 months. Six healthy subjects were used as controls. Statistically significant voxels during a finger-thumb opposition task were identified with an automated image processing program. An index of ipsilateral versus contralateral activity was used to compare relative contributions of the 2 hemispheres to motor function in the acute and chronic phases after stroke. RESULTS: Controls showed expected activation in the contralateral sensorimotor cortex (SMC), premotor, and supplementary motor areas. Stroke patients differed from control patients in showing greater activation in the ipsilateral SMC, ipsilateral posterior parietal, and bilateral prefrontal regions. Compared with the nonparetic hand, the ratio of contralateral to ipsilateral SMC activity during movement of the paretic hand increased significantly over time as the paretic hand regained function. CONCLUSIONS: The evolution of activation in the SMC from early contralesional activity to late ipsilesional activity suggests that a dynamic bihemispheric reorganization of motor networks occurs during recovery from hemiparesis.     

Sensorimotor organization in patients who have undergone hemispherectomy: a study with (15)O-water PET and somatosensory evoked potentials

To identify cortical structures that subserve residual motor and sensory function in patients with congenital hemiparesis due to a porencephalic cyst, we examined, using [(15)O]H2O, PET and somatosensory evoked potentials (SEPs) in three patients with left-sided hemiparesis who had undergone hemispherectomy. Motor stimulation of the affected hand produced ipsilateral activation in the premotor area in all patients, the SMA in two patients, and SII in two patients. Vibrotactile stimulation resulted in activation of the ipsilateral SII in all subjects. Median nerve stimulation of the affected hand produced ipsilateral long-latency SEPs in fronto-centro-parietal areas, whereas stimulation of the non-affected hand produced normal early cortical potentials in the contralateral hemisphere. Our results suggest that residual function in the paretic hand is warranted through non-primary motor and sensory areas, and higher order associative areas in the intact hemisphere.     

Contribution of the ipsilateral motor cortex to recovery after chronic stroke

It has been proposed that the intact (ipsilateral) motor cortex play a significant role mediating recovery of motor function in the paretic hand of chronic stroke patients, but this hypothesis has not been tested experimentally. Here, we evaluated the effects of transcranial magnetic stimulation (TMS) on motor performance of the paretic hand of chronic stroke patients and healthy controls. We hypothesized that, if activity in the intact hemisphere contributes to functional recovery, TMS should result in abnormal motor behavior in the paretic hand. We found that stimulation of the intact hemisphere resulted in delayed simple reaction times (RTs) in the contralateral healthy but not in the ipsilateral paretic hand, whereas stimulation of the lesioned hemisphere led to a marked delay in RT in the contralateral paretic hand but not in the ipsilateral healthy hand. RT delays in the paretic hand correlated well with functional recovery. Finger tapping in the paretic hand was affected by TMS of the lesioned but not the intact hemisphere. These results are consistent with the idea that recovered motor function in the paretic hand of chronic stroke patients relies predominantly on reorganized activity within motor areas of the affected hemisphere.     

Congenital hemiparesis: different functional reorganization of somatosensory and motor pathways.

OBJECTIVES: To investigate the reorganization of somatosensory and motor cortex in congenital brain injury. METHODS: We recorded motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) in a 41 year old man with severe congenital right hemiparesis but only mild proprioceptive impairment. Brain magnetic resonance imaging showed a large porencephalic cavitation in the left hemisphere mainly involving the frontal and parietal lobes. RESULTS: TMS showed fast-conducting projections from the undamaged primary motor cortex to both hands, whereas MEPs were not elicited from the damaged hemisphere. Left median nerve stimulation evoked normal short-latency SEPs in the contralateral undamaged somatosensory cortex. Right median nerve stimulation did not evoke any SEP in the contralateral damaged hemisphere, but a middle-latency SEP (positive-negative-positive, 39-44-48 ms) in the ipsilateral undamaged hemisphere, with a fronto-central scalp distribution. CONCLUSIONS: Our data show that somatosensory function of the affected arm is preserved, most likely through slow-conducting non-lemniscal connections between the affected arm and ipsilateral non-primary somatosensory cortex. In contrast, motor function was poor despite fast-conducting ipsilateral cortico-motoneuronal output from the primary motor cortex of the undamaged hemisphere to the affected arm. This suggests that different forms of reorganization operate in congenital brain injury and that fast-conducting connections between primary cortex areas and ipsilateral spinal cord are not sufficient for preservation or recovery of function.     

Interhemispheric reorganization of motor hand function to the primary motor cortex predicted with functional magnetic resonance imaging and transcranial magnetic stimulation

The objective of this study was presurgical assessment of reorganization of motor hand function in an 11-year-old girl with intractable epilepsy and a right-sided hemiplegia resulting from an extensive perinatal left hemispheric stroke. Prior to a left functional hemispherectomy, functional magnetic resonance imaging (MRI) showed that both nonparetic and paretic motor hand function predominantly activated the right primary motor cortex, whereas no activation was found in the left hemisphere. Transcranial magnetic stimulation of the right central area yielded responses in both the nonparetic and the paretic hand, whereas no responses were obtained after stimulation of the affected hemisphere. Both techniques indicated that motor function was mediated by corticospinal fibers originating from the undamaged (primary) motor cortex and predicted no further loss of motor hand function after surgery. Indeed, subsequent functional hemispherectomy induced no new sensorimotor deficits. Functional MRI was repeated 22 months after surgery and matched preoperative sensorimotor functional MRI findings, confirming reorganization of the primary motor cortex. No additional reorganization was introduced by surgery.     

Corticospinal tract development and its plasticity after perinatal injury

The final pattern of the origin and termination of the corticospinal tract is shaped during development by the balance between projection and withdrawal of axons. In animals, unilateral inhibition of the sensorimotor cortex during development results in a sparse contralateral projection from this cortex and retention of a greater number of ipsilateral projections from the more active cortex. Similarly in subjects with hemiplegic cerebral palsy if transcranial magnetic stimulation (TMS) of the damaged motor cortex fails to evoke responses in the paretic upper limb, TMS of the undamaged ipsilateral motor cortex evokes abnormally large and short-onset responses. Rather than representing a “reparative plasticity in response to injury”, this review presents evidence that increased ipsilateral projections from the non-infarcted motor cortex arise from perturbation of ongoing developmental processes, whereby reduced activity in the damaged hemipshere, leads to increased withdrawal of its surviving contralateral corticospinal projections because their terminals have been displaced by the more active ipsilateral projections of the undamaged hemisphere and thereby adding to the degree of long-term motor impairment.     

Hand motor cortical area reorganization following cerebral infarction evaluated with functional MRI, near infrared spectroscopic imaging, and transcranial magnetic stimulation]

A 60-year-old, right-handed man suffered from left hemiparesis with upper limb dominance. CT and MRI revealed cerebral infarction of the entire right middle cerebral artery territory. His hemiparesis recovered excellently and residual neurological deficits 6 years later were left hand weakness(grasping power 9 kg vs. 35 kg in the right) and clumsiness. Functional MRI was performed. During right(normal) hand grasping, activation was seen in the left sensorimotor cortex and supplementary motor area. During left(paretic) hand grasping, activation was seen in the left (ipsilateral) sensorimotor cortex, right parietal cortex, and bilateral supplementary motor areas. Near infrared spectroscopic imaging showed similar results. During right hand grasping, left sensorimotor cortex was activated, and during left hand grasping, bilateral sensorimotor cortices were activated with ipsilateral predominance. Transcranial magnetic stimulation of the left motor hand area evoked right hand movement and stimulation of a point near that area evoked ipsilateral left hand muscle movement. Thus, the findings of the three techniques consistently suggest that the recovery of left hemiparesis of this patient was promoted by motor cortical area reorganization including the ipsilateral motor cortex.     

Ipsilateral corticospinal pathways in congenital hemiparesis on routine magnetic resonance imaging

Several transcranial magnetic stimulation studies have demonstrated that patients with congenital hemiparesis can possess ipsilateral corticospinal pathways projecting from the contralesional hemisphere to the paretic hand. This study reports on signal abnormalities in the pons (focal areas of hyperintensity on T(2)-weighted magnetic resonance imaging), which were observed in the course of the corticospinal tract of the contralesional hemisphere in 6 of 10 patients with evidence for ipsilateral corticospinal projections on transcranial magnetic stimulation, but in none of 13 patients without such projections. Thus this magnetic resonance imaging abnormality seems to be related to the presence of ipsilateral corticospinal projections from the contralesional hemisphere in congenital hemiparesis.     

Intraoperative brain mapping to identify corticospinal projections during resective epilepsy surgery in children with congenital hemiparesis

Purpose

The purpose of the study is to determine corticospinal organization using intraoperative neurophysiologic monitoring (IONM) during resective epilepsy surgery for patients with congenital hemiparesis and intractable epilepsy.

Methods

Ten patients, aged 3–17, with intractable epilepsy underwent resective surgery. Transcranial stimulation (TCS) was achieved using a pair of cork screws at Cz and C3/C4, respectively. A 1?×?4 stimulating electrode strip was placed on the presumed motor cortex of the affected hemisphere for direct cortical stimulation (DCS) after craniotomy. Multipulse TCS and DCS train stimulation was delivered, with simultaneous recordings from bilateral abductor pollicis brevis and abductor halluces, to determine the corticospinal projection pattern of the paretic limbs.

Results

The above mapping techniques revealed ipsilateral corticospinal projections from the contralesional hemisphere to target muscles in the paretic limbs in three patients, projections from both hemispheres to target muscles in three, and preserved crossed projections from the affected hemisphere in four. Nine patients were seizure free after surgery. Five had unchanged postoperative functional status, and three showed minimally improved use of the paretic hand. Two developed new motor deficits after surgery, which may have been due to a premotor syndrome in one patient, since it completely resolved within 2 weeks. The other experienced increased weakness of the paretic lower limb because a small part of the eloquent cortex was removed for better seizure control.

Conclusions

Using IONM to define the corticospinal projection pattern is a valuable technique that can potentially replace preoperative fMRI and transcranial magnetic stimulation in resective epilepsy surgery, particularly for younger patients.     

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.     

Reorganization in congenital hemiparesis acquired at different gestational ages

It is well established that the reorganizational potential of the developing human brain is superior to that of the adult brain, but whether age-dependent differences exist already in the prenatal and perinatal period is not known. We have studied sensorimotor reorganization in 34 patients with congenital hemiparesis (age range, 5-27 years), using transcranial magnetic stimulation and functional magnetic resonance imaging during simple hand movements. Underlying pathologies were brain malformations (first and second trimester lesions; n = 10), periventricular brain lesions (early third trimester lesions; n = 12), and middle cerebral artery infarctions (late third trimester lesions; n = 12). Of this cohort, eight patients with malformations and all patients with periventricular lesions have been published previously. In all three groups of pathologies, transcranial magnetic stimulation identified patients in whom the paretic hand was controlled via ipsilateral corticospinal projections from the contralesional hemisphere (n = 16). In these patients, the motor dysfunction of the paretic hand correlated significantly with the timing period of the underlying brain lesion. This demonstrates that the efficacy of reorganization with ipsilateral corticospinal tracts indeed decreases during pregnancy.     

Differences in sensory and motor cortical organization following brain injury early in life

There have been a number of physiological studies of motor recovery in hemiplegic cerebral palsy which have identified the presence of novel ipsilateral projections from the undamaged hemisphere to the affected hand. However, little is known regarding the afferent projection to sensory cortex and its relationship to the reorganized cortical motor output. We used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the affected and unaffected hands in a group of subjects with hemiplegic cerebral palsy, and also performed functional magnetic resonance imaging (fMRI) studies of the patterns of activation in cortical motor and sensory areas following active and passive movement of the hands. Both TMS and fMRI demonstrated a normal contralateral motor and sensory projection between the unaffected hand and the cerebral hemisphere. However, in the case of the affected hand, the TMS results indicated either a purely ipsilateral projection or a bilateral projection in which the ipsilateral pathway had the lower motor threshold, whereas passive movement resulted in fMRI activation in the contralateral hemisphere. These results demonstrate that there is a significant fast-conducting corticomotor projection to the affected hand from the ipsilateral hemisphere in this group of subjects, but that the predominant afferent projection from the hand is still directed to the affected contralateral hemisphere, resulting in an interhemispheric dissociation between afferent kinesthetic inputs and efferent corticomotor output. The findings indicate that there can be differences in the organization of sensory and motor pathways in cerebral palsy, and suggest that some of the residual motor dysfunction experienced by these subjects could be due to an impairment of sensorimotor integration at cortical level as a result of reorganization in the motor system.     

Changes in motor cortex activation after recovery from spinal cord inflammation.

Diseases of the spinal cord are associated with reactive changes in cerebral cortex organization. Many studies in this area have examined spinal cord conditions not associated with recovery, making it difficult to consider the value of these cortical events in the restoration of neurological function. We studied patients with myelitis, a syndrome of transient spinal cord inflammation, in order to probe cortical changes that might contribute to recovery after disease of the spinal cord. Seven patients, each of whom showed improvement in hand motor function after a diagnosis of myelitis involving cervical spinal cord, were clinically evaluated then studied with functional MRI. During right and left index finger tapping, activation volumes were assessed in three cortical motor regions within each hemisphere. Results were compared with findings in nine control subjects. Compared to the control group, myelitis patients had larger activation volumes within contralateral sensorimotor as well as contralateral premotor cortex. The degree of daily hand use showed a significant correlation with the volume of activation in contralateral sensorimotor cortex. Recovery from myelitis is associated with an enlarged activation volume in contralateral motor cortices. This change in motor cortex function is related to behavioral experience, and thus may contribute to motor improvement. The expanded activation in motor cortex, seen with several forms of spinal cord insult may have maximal utility when corticospinal tract axons are preserved.     

Ipsilateral motor pathway without contralateral motor pathway in a stroke patient

The ipsilateral motor pathway from the unaffected motor cortex to the affected extremity is one of the mechanisms of motor recovery following stroke. We report on a stroke patient who showed the ipsilateral motor pathway without the contralateral motor pathway on functional MRI and diffusion tensor tractography. A 53-year-old left hemiparetic patient with an infarct in the right middle cerebral artery territory was evaluated. During a period of three months after onset, motor function of the affected (left) hand had recovered slowly, to the extent that the patient was able to overcome gravity. FMRI showed that only the unaffected (left) primary sensorimotor cortex was activated by movements of the unaffected (right) hand or of the affected (left) hand. On diffusion tensor tractography, the corticospinal tract of the left hemisphere originated from the primary sensori-motor cortex and descended through the known corticospinal tract pathway. By contrast, the right corticospinal tract showed a disruption with Wallerian degeneration to the upper medulla. We conclude that the motor function of the affected (left) hand appeared to be controlled only by the ipsilateral motor pathway from the left motor cortex to the left hand. Motor function of the affected hand appeared to have been reorganized to the ipsilateral motor pathway from the unaffected motor cortex to the affected hand.     

Functional relevance of abnormal fMRI activation pattern after unilateral schizencephaly

Brain plasticity was investigated in a child with a hemiplegia due to unilateral schizencephaly involving the sensorimotor cortex. This focal lesion led to a dramatic functional reorganization of the undamaged hemisphere, as evidenced by the unusual pattern of fMRI activation during paretic finger movements. The functional relevance of the activation in the undamaged motor cortex was supported by the finding that TMS of this area yielded a response in the paretic hand, indicating that it controls both hands. However, this reorganization was not restricted to the primary motor cortex, but also concerned other structures involved in the control of movements, as shown by the activation of contralesional SMA and thalamus. In contrast, the fMRI activation in the damaged sensorimotor cortex during paretic hand movements appears functionally irrelevant.