Effects of neonatal hemispherectomy on location and number of corticospinal neurons in the rat

Corticospinal neurons in the rat normally project to the contralateral spinal cord only. After neonatal hemispherectomy, the remaining single hemisphere forms both ipsilateral and contralateral projections. The distribution and number of corticospinal neurons projecting to the contralateral and to the ipsilateral spinal cord were studied in the hemispherectomized rat. The method used was that of retrograde labelling of corticospinal neurons by unilateral spinal cord injection of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP). The establishment of both crossed and uncrossed corticospinal projections by one cerebral hemisphere is accomplished in two ways. (1) Some neurons located within the confines of normal motor cortex send axons to ipsilateral spinal cord, where normally only contralateral projections occur. (2) There is expansion of the areas of cerebral cortex that contain corticospinal neurons. This expansion is most pronounced near the frontal pole, but it occurs at all borders of motor cortex except at its posterior limit, where the border with visual cortex persists unchanged. Only corticospinal neurons forming uncrossed projections occur in aberrant sites, while both cells with crossed and those with uncrossed spinal axons are intermingled in cortex that normally contains corticospinal neurons. The findings suggest that plasticity of the corticospinal motor system in the rat occurs to some extent at the expense of impaired localization of functions in cerebral cortex, and that following focal brain injury there may be an increase in areas that subserve multiple functions.     

A ventral uncrossed corticospinal tract in the rat

By studying cross-section autoradiograms of the spinal cord with dark field microscopy we demonstrated a ventral uncrossed corticospinal tract in the rat. Corticospinal fibers were labeled by the slow axoplasmic flow of a minute volume of high specific activity tritiated proline injected directly into the motor sensory cortex. The uncrossed ventral corticospinal tract was small but easily identifiable in the cervical region. More caudally the tract became less distinct and could not be traced below midthoracic levels. Only two corticospinal tracts were identified in this study: the well-known crossed dorsal corticospinal tract and the ventral uncrossed corticospinal tract described in this study.     

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 of the motor cortex in a patient with congenital hemiparesis and mirror movements

Abnormal branching of corticospinal fibers from the unaffected motor cortex is responsible for mirror movements in patients with congenital hemiparesis, but it is unknown which mechanisms enable these patients to lateralize motor activity. Using multiunit electromyographic analysis and transcranial magnetic stimulation, the authors provide evidence for nonbranched crossed and uncrossed corticospinal projections and intracortical inhibition of the mirror hand. They propose that this remarkable reorganization of the unaffected motor cortex helps these patients to reduce mirror movements.     

Motor cortex activation is preserved in patients with chronic hemiplegic stroke

Many central nervous system conditions that cause weakness, including many strokes, injure corticospinal tract but leave motor cortex intact. Little is known about the functional properties of surviving cortical regions in this setting, in part because many studies have used probes reliant on the corticospinal tract. We hypothesized that many features of motor cortex function would be preserved when assessed independent of the stroke-affected corticospinal tract. Functional MRI was used to study 11 patients with chronic hemiplegia after unilateral stroke that spared regions of motor cortex. Activation in stroke-affected hemisphere was evaluated using 3 probes independent of affected corticospinal tract: passive finger movement, a hand-related visuomotor stimulus, and tapping by the nonstroke index finger. The site and magnitude of cortical activation were similar when comparing the stroke hemisphere to findings in 19 control subjects. Patients activated each of 8 cortical regions with similar frequency as compared to controls, generally with a smaller activation volume. In some cases, clinical measures correlated with the size or the site of stroke hemisphere activation. The results suggest that, despite stroke producing contralateral hemiplegia, surviving regions of motor cortex actively participate in the same proprioceptive, visuomotor, and bilateral movement control processes seen in control subjects.     

Neurophysiology of unimanual motor control and mirror movements.

In humans, execution of unimanual motor tasks requires a neural network that is capable of restricting neuronal motor output activity to the primary motor cortex (M1) contralateral to the voluntary movement by counteracting the default propensity to produce mirror-symmetrical bimanual movements. The motor command is transmitted from the M1 to the contralateral spinal motoneurons by a largely crossed system of fast-conducting corticospinal neurons. Alteration or even transient dysfunction of the neural circuits underlying movement lateralization may result in involuntary mirror movements (MM). Different models exist, which have attributed MM to unintended motor output from the M1 ipsilateral to the voluntary movement, functionally active uncrossed corticospinal projections, or on a combination of both. Over the last two decades, transcranial magnetic stimulation (TMS) proved as a valuable, non-invasive neurophysiological tool to investigate motor control in healthy volunteers and neurological patients. The contribution of TMS and other non-invasive electrophysiological techniques to characterize the neural network responsible for the so-called 'non-mirror transformation' of motor programs and the various mechanisms underlying 'physiological' mirroring, and congenital or acquired pathological MM are the focus of this review.     

Crossed corticothalamic and thalamocortical connections of macaque prefrontal cortex

We have conducted a systematic comparison of the ipsilateral (uncrossed) and contralateral (crossed) thalamic connections of prefrontal cortex in macaque monkeys, using cortical implants of horseradish peroxidase pellets and tetramethyl benzidine histochemistry to demonstrate anterograde and retrograde thalamic labeling. Contrary to the prevailing belief that thalamocortical projections are entirely uncrossed, our findings indicate that a modest crossed projection to prefrontal cortex arises from the mesial thalamus, principally the anteromedial and midline nuclei. Also, while confirming that corticothalamic projections are bilateral, we found that the pattern of crossed projections differs from that of uncrossed projections. Projections to mesial thalamic nuclei, specifically to the anteromedial nucleus, the midline nuclei, and the magnocellular part of the mediodorsal nucleus are bilateral, the contralateral projection being nearly as dense as the ipsilateral projection. Projections to the parvicellular part of the mediodorsal and ventral anterior nuclei are also bilateral, but the contralateral projection is much weaker than the ipsilateral projection. Prefrontal projections to the reticular nucleus, medial pulvinar, suprageniculate nucleus, and limitans nucleus appear to be exclusively ipsilateral. These results indicate that prefrontal cortex has prominent bilateral and reciprocal connections with the nuclei of the mesial thalamic region. As this region of the diencephalon has been implicated by anatomical and behavioral studies in memory functions, our findings suggest that prefrontal cortex, through its connections with this region, may be involved in the bilateral integration of mnemonic systems.     

Cognitive development in benign focal epilepsies of childhood

Benign focal epilepsy of childhood (BFEC) is the most common form of epilepsy, in children from 3 to 12 years. Its prognosis is always favourable as far as the epilepsy is concerned. Nevertheless, recent clinical data suggest that children affected by BFEC are more likely to show learning difficulties and behavioural disturbances than their peers. We report here the preliminary findings of a prospective study of 22 children affected with BFEC. Electroclinical and neuropsychological changes observed during the first 18 months of the follow-up strengthen the conclusion of recent neuropsychological studies stressing the correlation between epilepsy and cognitive performances. The cognitive deficits affecting mainly non-verbal functions were significantly correlated with the frequency of seizures and spike-wave discharges and to the lateralization of the epileptic focus in the right hemisphere, whereas frontal functions like attention control, response organization and fine motor speed, were impaired in the presence of active BFEC independently of the lateralization of the epileptic focus. Our results indicate that maturing cognitive functions subserved by a cortical area distant from the epileptic focus are susceptible to interference with epilepsy. Copyright Copyright 1999 S. Karger AG, Basel     

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.     

Language Lateralization in Children with Benign Partial Epilepsy

To investigate the relationship between epilepsy and hemispheric asymmetries for language, a dual-task procedure was used to assess language lateralization in children with benign rolandic childhood epilepsy. In the sample selection, care was taken to include factors believed to influence both the mental capabilities of epileptic patients and the individual functional cerebral organization. Results suggest that the interhemispheric prevalence pattern is related to the focus site. Controls as well as epileptic patients with a right hemispheric focus showed the expected left language lateralization; conversely, children with a left unilateral focus showed a different pattern of functional representation, suggesting an involvement of the right hemisphere in language mechanisms. It is emphasized that this atypical cerebral organization is found in subjects with no structural lesion and no therapy. It seems likely that the presence of a focal epileptic activity itself can alter the cerebral mechanisms underlying cognitive functions. A relationship between this modified hemispheric specialization and subtle neuropsychological dysfunctions observed in the children with focal epilepsy is suggested.     

Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci.

Bilateral synchronous epileptiform discharges registered in patients with partial epilepsies may be generated by different pathophysiological mechanisms. Differentiation between underlying mechanisms is often crucial for correct diagnosis and adequate treatment in clinical epileptology. The aim of this study was to model in rats two possible mechanisms--secondary bilateral sychrony and interaction between multiple epilepic foci. Furthermore, to describe in detail semiology, laterality and differences in motor phenomena. Secondary bilateral synchrony was modeled by unilateral topical application of bicuculline methiodide (BMI) over the sensorimotor cortex. Bilateral symmetric application of BMI was used as a model of multiple epileptic foci. Electrographic and behavioural phenomena were recorded for 1h following the application of BMI. Electroencephalogram in both groups was characterized by presence of bilateral synchronous discharges. Myoclonic and clonic seizures involving forelimb and head muscles represented the most common motor seizure pattern in both groups. Significant differences were found in the laterality of motor phenomena. Motor seizures in unilateral foci always started in the contralateral limbs whereas symmetrical foci exhibited bilateral independent onset of convulsions. Similar lateralization was observed in interictal motor phenomena (myoclonic jerks). An important influence of posture on epileptic motor phenomena was demonstrated. Active or passive changes in animal posture (verticalization to bipedal posture) caused conversion from unilateral myoclonic jerks or clonic seizures to bilaterally synchronous (generalized) motor phenomena in both groups.     

Functional Plasticity of the Motor Cortical Structures Demonstrated by Navigated TMS in Two Patients with Epilepsy

BackgroundRecently, navigated transcranial magnetic stimulation (nTMS) has been suggested to be useful in preoperative functional localization of motor cortex in patients having tumors close to the somatomotor cortex. Resection of tumors in anatomically predicted eloquent areas without adverse effects have emphasized functional plasticity elicited by intracranial pathology.ObjectiveTo describe functional plasticity of motor cortex indicated by nTMS in two patients with epilepsy.MethodsnTMS, functional MRI (fMRI), diffusion-tensor (DT)-tractography and magnetoencephalography (MEG) were utilized to preoperatively localize motor cortical areas in the workup for epilepsy surgery. The localizations were compared with each other, with the cortical anatomical landmarks, and in one patient with invasive electrical cortical stimulation (ECS).ResultsIn two out of 19 studied patients, nTMS identified motor cortical sites that differed from those indicated by anatomical landmarks. In one patient, nTMS activated preferentially premotor cortex rather than pathways originating from the precentral gyrus. MEG and fMRI localizations conformed with nTMS whereas ECS localized finger motor function into the precentral gyrus. Resection of the area producing motor responses in biphasic nTMS did not produce a motor deficit. In the other patient, nTMS indicated abnormal ipsilateral hand motor cortex localization and confirmed the functionality of aberrant motor cortical representations of the left foot also indicated by fMRI and DT-tractography.ConclusionnTMS may reveal the functional plasticity and shifts of motor cortical function. Epileptic foci may modify cortical inhibition and the nTMS results. Therefore, in some patients with epilepsy, the nTMS results need to be interpreted with caution with regard to surgical planning.     

Effects of changes in the periphery on development of the corticospinal motor system in the rat

Effects of changes in the periphery on development of the corticospinal (CS) motor system were studied in the rat. Unilateral forelimb restraint between ages 5 and 30 days resulted in an increase in the number of CS neurons which persisted in the adult. The effect was most marked ipsilateral to limb restraint where both crossed and uncrossed CS connections were increased, but it also occurred to a lesser extent on the contralateral side. Animals with limb restraint had enlargement of the areas of cerebral cortex in which CS neurons occurred. The enlargement of motor cortex regions and increase in CS neurons closely resembled the changes found in the remaining cerebral hemisphere after neonatal hemispherectomy. The findings in animals with forelimb restraint differed markedly from those after forelimb amputation, where little change occurred in either number or location of CS neurons. Limb restraint initiated at the time of postnatal hemispherectomy had no effects on location or number of CS neurons beyond those of hemispherectomy alone. It is proposed that transient CS axons that occur normally in the postnatal rat may be recruited for formation of permanent connections under very diverse conditions, i.e. hemispherectomy and limb restraint. Failure to observe an additional effect of limb restraint in hemispherectomized animals may be due to the fact that after hemispherectomy all available transient fibers in the remaining hemisphere are recruited for innervation of the side of the spinal cord that has lost its cortical input.     

Verbal dichotic listening performance and its relationship with EEG features in benign childhood epilepsy with centrotemporal spikes

PURPOSE: Benign epilepsy of childhood with centrotemporal spikes (BECTS) is the most common form of idiopathic partial epilepsy in children from 3 to 12 years old. Little and far from conclusive information is available on its chronic impact on the organization of higher cognitive functions during development. The aim of this study was to assess the effect of interictal EEG discharges in the peri-sylvian regions on language lateralization in BECTS. METHODS: Twenty-four 7-12-year-old children with BECTS were compared with a control group of 16 healthy children matched for age, gender and schooling. Hemispheric speech lateralization was determined with the vowel-consonant dichotic listening (DL) test. RESULTS: DL data showed that BECTS children lacked the typical right ear/left hemisphere functional advantage. The side of the interictal spikes had no specific influence on DL performance, while a multifocal location of the discharges had a particularly significant effect on the laterality index, as shown by the complete loss of the right-ear advantage in favor of a symmetrical performance with the overall level of accuracy remaining constant. No correlation was found between spike frequency and DL data. CONCLUSIONS: BECTS coincides with an atypical performance in DL test with the loss of the usual right ear/left hemisphere advantage, suggesting that interictal activity may induce a reorganization of speech perception lateralization, with a bilateral representation of the phonological processing of auditory and verbal stimuli. This was particularly evident in the group with multifocal spikes, which may mean that a widespread hyperexcitability can affect the network underlying DL performance more severely.     

Use of functional MRI in epilepsy]

For the purpose of examining pathophysiological mechanisms of a memory function in epileptic patients or an utility of fMRI for a presurgical assessment in neurosurgical treatment of epilepsy, activated areas in fMRI during verbal or visual memory task were investigated in patient group of temporal lobe epilepsy and normal subject group. Patient group of temporal lobe epilepsy consisted of 7 cases, of which 3 and 3 cases had left and right temporal foci, respectively, except 1 case having undetermined laterality of temporal foci. Normal subjects were 16 cases. All the epileptic and normal subjects were right-handed except for 1 lefty normal subject. Verbal memory tasks were composed of covert and overt recall tasks of 10 words given auditorily, while visual ones were recall tasks of 6 figures given visually. Eventually, in normal subjects, the left side-dominant medial frontal lobes including the superior frontal and anterior cingulate gyri were mainly activated in fMRI during the covert recall tasks of verbal memory, while the left side-dominant inferior frontal and precentral gyri as the motor language areas were chiefly activated in addition to the medial frontal lobe during the overt recall tasks. Further, the bilateral occipital lobes were activated in fMRI during the recall tasks of visual memory. Also in patient groups of temporal lobe epilepsy, the activated areas in fMRI during these tasks were the same as in normal subject group, regardless of the laterality of epileptic temporal foci. These results suggest that fMRI is useful for the determination of the lateralization of the cerebral hemisphere contributing to verbal memory function and therefore for the presurgical assessment of memory function in neurosurgical treatment of epilepsy.     

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.     

Uncrossed cortico-muscular projections in humans are abundant to facial muscles of the upper and lower face,but may differ between sexes

It is a popular concept in clinical neurology that muscles of the lower face receive predominantly crossed cortico-bulbar motor input, whereas muscles of the upper face receive additional ipsilateral, uncrossed input. To test this notion, we used focal transcranial magnetic brain stimulation to quantify crossed and uncrossed cortico-muscular projections to 6 different facial muscles (right and left Mm. frontalis, nasalis, and orbicularis oris) in 36 healthy right-handed volunteers (15 men, 21 women, mean age 25 years). Uncrossed input was present in 78% to 92% of the 6 examined muscles. The mean uncrossed: crossed response amplitude ratios were 0.74/0.65 in right/left frontalis, 0.73/0.59 in nasalis, and 0.54/0.71 in orbicularis oris; ANOVA p>0.05). Judged by the sizes of motor evoked potentials, the cortical representation of the 3 muscles was similar. The amount of uncrossed projections was different between men and women, since men had stronger left-to-left projections and women stronger right-to-right projections. We conclude that the amount of uncrossed pyramidal projections is not different for muscles of the upper from those of the lower face. The clinical observation that frontal muscles are often spared in central facial palsies must, therefore, be explained differently. Moreover, gender specific lateralization phenomena may not only be present for higher level behavioural functions, but may also affect simple systems on a lower level of motor hierarchy.     

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.     

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.     

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.