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.     

Immediate improvement of motor function after epilepsy surgery in congenital hemiparesis

Hemispherectomy often leads to a loss of contralateral hand function. In some children with congenital hemiparesis, however, paretic hand function remains unchanged. An immediate improvement of hand function has never been reported. A 17‐year‐old boy with congenital hemiparesis and therapy‐refractory seizures due to a large infarction in the territory of the middle cerebral artery underwent epilepsy surgery. Intraoperatively, electrical cortical stimulation of the affected hemisphere demonstrated preserved motor projections from the sensorimotor cortex to the (contralateral) paretic hand. A frontoparietal resection was performed, which included a complete disconnection of all motor projections originating in the sensorimotor cortex of the affected hemisphere. Surprisingly, the paretic hand showed a significant functional improvement immediately after the operation. This observation demonstrates that, in congenital hemiparesis, crossed motor projections from the affected hemisphere are not always beneficial, but can be dysfunctional, interfering with ipsilateral motor control over the paretic hand by the contralesional hemisphere.     

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.     

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.     

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.     

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.     

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.     

Functional MRI and motor behavioral changes obtained with constraint‐induced movement therapy in chronic stroke

Background: The clinical benefits of intensive stroke rehabilitation vary individually. We used multimodal functional imaging to assess the relationship of clinical gain and imaging changes in patients with chronic stroke whose voluntary motor control improved after constraint‐induced movement therapy (CIMT). Methods: Eleven patients (37.6 ± 36.8 months from stroke) were studied by functional MRI (fMRI), transcranial magnetic stimulation (TMS), and behavioral assessment of hand motor control (Wolf Motor Function Test) before and after 2 weeks of CIMT. Individual and group‐level changes in imaging and behavioral parameters were investigated. Results: Increase in fMRI activation in the sensorimotor areas was greater amongst those subjects who had poor hand motor behavior before therapy and/or whose motor behavior improved notably because of therapy than amongst subjects with relatively good motor behavior already before therapy. The magnitude of CIMT‐induced changes in task‐related fMRI activation differed between lesioned and non‐lesioned hemispheres, and the fMRI laterality index was different for paretic and non‐paretic hand tasks. The corticospinal conduction time in TMS was significantly decreased after CIM therapy. Conclusions: Alterations in sensorimotor cortical activations (fMRI) and corticospinal conductivity (TMS) were observed after intensive rehabilitation in patients with chronic stroke. Activation and functional changes in fMRI and TMS correlated significantly with the degree of clinical improvement in hand motor behavior. The present data advance the understanding of the functional underpinnings of motor recovery, which may be obtained even years after the stroke.     

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.     

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.     

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.     

Congenital mirror movement: a study of functional MRI and transcranial magnetic stimulation

Two male patients (a child and an adult) with congenital mirror movement were studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Bilateral primary sensorimotor cortices were activated during unilateral hand gripping on fMRI when the child patient was 8 years old andthe adult was 37 years old. Bilateral motor evoked potentials were induced from the hand and forearm muscles after TMS of each hemisphere. Bilateral motor responses were also induced from the arm muscles in the adult patient. Bilateral motor responses had short and similar latencies. Contralateral motor responses to TMS were smaller than ipsilateral ones in the hand muscles, while contralateral responses were larger than ipsilateral ones in the arm muscles. Contralateral hand motor responses reduced in amplitude or disappeared with increasing age while in the child patient, mirror movements decreased gradually. Our results suggest that bilateral activation of the primary sensorimotor cortices during intended unilateral hand movement and bilateral motor responses to TMS account, at least in part, for the pathophysiology of congenital mirror movement. Reduction of contralateral hand motor responses may be related to the decrease in mirror movements during development.     

Exceptional verbal intelligence after hemispherotomy in a child with Rasmussen encephalitis

We report a longitudinal case study of a left-handed girl who underwent left hemispherotomy at 7 years for Rasmussen encephalitis (RE). Presurgical evaluation showed mild hemiparesis, no visual defect, and light neuropsychological impairment with short-term memory weakness. Language fMRI showed a right hemispheric dominance. Postoperatively, the patient exhibited right hemiplegia and hemianopsia but preserved intellectual capacities. She became seizure-free, and antiepileptic medication was discontinued. Long-term follow-up showed very high verbal intelligence at 11 years of age (VCI of 155) and improvement in working memory as well as language and reading abilities. Furthermore, a significant visuoverbal discrepancy became increasingly pronounced. Thus, early surgical treatment of epilepsy avoided the global cognitive deterioration usually associated with RE. Finally, such a high level of verbal functioning combined with low spatial reasoning with a single hemisphere provides additional information on the neurocognitive profile of children with RE after hemispherotomy.     

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis

OBJECTIVE: To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours. METHODS: Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation-that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI. RESULTS: The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy. CONCLUSION: In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.     

Motor cortex localization using functional MRI and transcranial magnetic stimulation.

OBJECTIVE: Congenital brain lesions producing focal seizures may be accompanied by reorganization of the areas responsible for motor and sensory functions within the brain due to a phenomenon that has been termed "neuronal plasticity." This can be studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Using either method, the motor cortex can be localized noninvasively, but to date there have been few studies correlating the level of agreement between the two techniques. METHODS: We used fMRI and TMS to localize the motor cortex in a young woman with intractable focal seizures, congenital left arm weakness, and a dysplastic right hemisphere on MRI. RESULTS: There was excellent agreement in the localization of motor representation for each hand. Both were predominantly located in the left hemisphere. fMRI also showed an area of posterior activation in the right hemisphere, but there was no evidence of descending corticospinal projections from this site using TMS, direct cortical stimulation, and Wada testing. CONCLUSIONS: Functional MRI (fMRI) and transcranial magnetic stimulation (TMS) were successfully used to localize cortical motor function before epilepsy surgery. Each technique demonstrated migration of motor function for the left hand to the left motor cortex. After resection of the dysplastic right precentral gyrus there was no permanent increase in weakness or disability. The two techniques are complementary; fMRI indicates all cortical areas activated by the motor task, whereas TMS identifies only those areas giving rise to corticospinal projections.     

Functional MRI in a 6-year-old boy with unilateral cortical malformation: concordant representation of both hands in the unaffected hemisphere

Functional magnetic resonance imaging (fMRI) was performed in a 6-year-old boy with a complex malformation of the right hemisphere who suffered from pharmaco-refractory epilepsy. Clinical examination revealed left-sided hemiparesis and marked mirror movements of the opposite hand both during paretic and non-paretic hand movements. Functional MRI of repetitive unimanual grasping demonstrated that the two hands share a common cortical representation located in the central motor region of the unaffected left hemisphere. The affected right hemisphere did not show any activation during either task. This case study demonstrates the feasibility and usefulness of motor fMRI in young children before they undergo epilepsy surgery.     

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.     

Selectively disrupted sensorimotor circuits in chronic stroke with hand dysfunction

AimTo investigate the directional and selective disconnection of the sensorimotor cortex (SMC) subregions in chronic stroke patients with hand dysfunction.MethodsWe mapped the resting‐state fMRI effective connectivity (EC) patterns for seven SMC subregions in each hemisphere of 65 chronic stroke patients and 40 healthy participants and correlated these patterns with paretic hand performance.ResultsCompared with controls, patients demonstrated disrupted EC in the ipsilesional primary motor cortex_4p, ipsilesional primary somatosensory cortex_2 (PSC_2), and contralesional PSC_3a. Moreover, we found that EC values of the contralesional PSC_1 to contralesional precuneus, the ipsilesional inferior temporal gyrus to ipsilesional PSC_1, and the ipsilesional PSC_1 to contralesional postcentral gyrus were correlated with paretic hand performance across all patients. We further divided patients into partially (PPH) and completely (CPH) paretic hand subgroups. Compared with CPH patients, PPH patients demonstrated decreased EC in the ipsilesional premotor_6 and ipsilesional PSC_1. Interestingly, we found that paretic hand performance was positively correlated with seven sensorimotor circuits in PPH patients, while it was negatively correlated with five sensorimotor circuits in CPH patients.ConclusionSMC neurocircuitry was selectively disrupted after chronic stroke and associated with diverse hand outcomes, which deepens the understanding of SMC reorganization.     

Asymmetry in corticomotor facilitation revealed in right-handers in the context of haptic discrimination

In this study we asked whether asymmetries related to handedness in right-handers (n=10) and left-handers (n=10) could influence hemispheric motor facilitation when the preferred or less-preferred hand is engaged in haptic sensing. Transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability when young participants performed a precision grip under two conditions, i.e., with or without a haptic sensing component. In the grip condition participants were required to grasp a 5-mm thick plate between thumb and index fingers, whereas in the haptic condition they performed the same action but were also required to make judgements about the plate's thickness, i.e., either thin (5 mm) or thick (10 mm). Analysis of task-related variations in motor evoked potentials (MEP) amplitude recorded in hand muscles revealed a significant task×hand/hemisphere interaction only in the group of right-handers when the left hand/right hemisphere was engaged in haptic sensing as opposed to simply gripping. Collectively, these results are congruent with other TMS reports describing a greater degree of hemispheric asymmetry in right-handers, who are typically more strongly lateralised than left-handers. Our results with regard to a rightward hemispheric asymmetry for MEP facilitation with haptic sensing are also congruent with the predominant role ascribed to the right sensorimotor cortex in the processing of proprioceptive information.