Contralateral Corticospinal Tract Research Articles

A DTI study of the contralateral corticospinal tract modeled through simulated intracranial space-occupying lesions in macaque brain motor areas

Recent studies found that a loss of motor function following corticospinal tract (CST) damage can, to some extent, be restored. Few studies, however, examine how space-occupying lesions in the brain motor area may affect the contralateral CTS structure and function. We performed a simulation of intracranial space-occupying lesions in the brain motor area by implanting of balloons into the brains of the two healthy macaques. Diffusion tensor imaging (DTI) was performed on the macaques' brains four times to measure the FA values of the contralateral CST operative area. The results showed that on the day of balloon implantation, the FA values had no obvious effect, but with time the effect increased, becoming increasingly apparent one week after removing the balloons. Experimental results demonstrated that this model was both feasible and reliable. After the simulated space-occupying lesions occurred in the brain motor area, DTI showed a compensatory response of the contralateral CTS, which remained for a short period of time even after the lesions were removed. This result suggests that the contralateral CST may then also contribute to recovery of limb function.

Selective corticospinal tract injury in the rat induces primary afferent fiber sprouting in the spinal cord and hyperreflexia.

The corticospinal tract (CST) has dense contralateral and sparse ipsilateral spinal cord projections that converge with proprioceptive afferents on common spinal targets. Previous studies in adult rats indicate that the loss of dense contralateral spinal CST connections after unilateral pyramidal tract section (PTx), which models CST loss after stroke or spinal cord injury, leads to outgrowth from the spared side into the affected, ipsilateral, spinal cord. The reaction of proprioceptive afferents after this CST injury, however, is not known. Knowledge of proprioceptive afferent responses after loss of the CST could inform mechanisms of maladaptive plasticity in spinal sensorimotor circuits after injury. Here, we hypothesize that the loss of the contralateral CST results in a reactive increase in muscle afferents from the impaired limb and enhancement of their physiological actions within the cervical spinal cord. We found that 10 d after PTx, proprioceptive afferents sprout into cervical gray matter regions denervated by the loss of CST terminations. Furthermore, VGlut1-positive boutons, indicative of group 1A afferent terminals, increased on motoneurons. PTx also produced an increase in microglial density within the gray matter regions where CST terminations were lost. These anatomical changes were paralleled by reduction in frequency-dependent depression of the H-reflex, suggesting hyperreflexia. Our data demonstrate for the first time that selective CST injury induces maladaptive afferent fiber plasticity remote from the lesion. Our findings suggest a novel structural reaction of proprioceptive afferents to the loss of CST terminations and provide insight into mechanisms underlying spasticity.

Can cerebral palsy impairments be minimized in infants at risk? Potential insights from basic neuroscience research

As a clinician or clinical researcher, it is all too tempting to jump on board and try the latest ⁄ greatest treatments, especially those derived from adult stroke rehabilitation. Although such ‘best-guess’ approaches could work, one would miss important details that could take some of the guesswork out by developing theoretically driven treatments that are derived from basic research. In an elegant review, Martin et al. 1 demonstrate the importance of basic neuroscience research in providing a strong theoretical basis for pediatric rehabilitation efforts. They chronicle a decade of work establishing and testing an animal (feline) model of cerebral palsy (CP). The model focuses on the developing corticospinal tract (CST), the primary pathway underlying skilled behaviors. They review a series of studies in which they demonstrate a protracted period of CST development, with the maturity of CST terminations in the spinal cord closely paralleling skill acquisition. Specifically, they show that as in humans, cats initially have bilateral CST terminations, with ipsilateral projections subsequently eliminated and contralateral projections maintained during development. Their studies also show that this early rewiring is activity dependent, with competition between the two cortices playing an important role. Importantly, they further show that early damage to the brain may alter the development of these connections. These findings imply that perinatal damage to the developing CST as occurs in CP may be exacerbated by reduced activity in the contralateral motor cortex, associated with the emerging developmental disregard of the affected extremity. Thus there is a vicious cycle whereby lesions reduce movement, which in turn prohibits normal neural development of the circuitry underlying movement. More recently, Martin et al. have demonstrated that increasing the competitiveness of the contralateral CST after cortical inactivation can reestablish normal development of the damaged system. This was demonstrated separately by electrical stimulation of the affected cortex, as well as silencing the unaffected cortex. Similarly, constraining the unaffected limb as done in constraintinduced movement therapy has a similar effect, and in all of these approaches, rebalancing activity between the two cortices results in restoration of motor function. Of course, it should be realized that chemical inactivation of the motor cortex is not identical to the heterogeneous damage found in children with CP, which often involves gray and white matter. Never

Harnessing activity-dependent plasticity in the developing corticospinal system to restore motor function after perinatal brain injury

The corticospinal tract (CST) is the principal motor contr ol pathway for skilled movements. The CST, as well as the motor behaviors that it is important for controlling, has a p rotracted postnatal development in humans and many animals. We first discuss our experiments in the cat, showing that CST neu ronal activity is important for normal development of the tract; especially for development of the proper pattern of connections between CST axons and neurons in spinal cord motor circuits. We compare our results in the cat using neural pathway tracing techniques with research on development of the CST in humans using transcranial magnetic stimulation, showing that the cat model captures key features of normal human CST development. In the human, damage to the CST during development produces cerebral palsy, a debilitating motor control disorder. Cerebr al palsy research suggests that the motor signs of this condition refl ect both the loss of development of a strong contralateral CST, together with development of aberrant dense ipsilateral connections between the CST and spinal motor circuits. We have developed a cat model of unilateral (i.e., hemiplegic) cerebral palsy that both captures these key defects in CST connections and exhibits motor control impairments. We discuss our work, showing that harnessing activity-dependent processes later in development is capable of both restoring the proper connections of the CST in this model and restoring normal motor function.

Sprouting of corticospinal tract axons from the contralateral hemisphere into the denervated side of the spinal cord is associated with functional recovery in adult rat after traumatic brain injury and erythropoietin treatment

Erythropoietin (EPO) promotes functional recovery after traumatic brain injury (TBI). This study was designed to investigate whether EPO treatment promotes contralateral corticospinal tract (CST) plasticity in the spinal cord in rats after TBI. Biotinylated dextran amine (BDA) was injected into the right sensorimotor cortex to anterogradely label the CST. TBI was induced by controlled cortical impact over the left parietal cortex immediately after BDA injections. EPO (5000 U/kg) or saline was administered intraperitoneally at Days 1, 2, and 3 post-injury. Neurological function was assessed using a modified neurological severity score (mNSS) and footfault tests. Animals were sacrificed 35 days after injury and brain sections stained for histological analysis. Compared to the saline treatment, EPO treatment significantly improved sensorimotor functional outcome (lower mNSS and reduced footfaults) from Days 7 to 35 post-injury. TBI alone significantly stimulated contralateral CST axon sprouting toward the denervated gray matter of the cervical and lumbar spinal cord; however, EPO treatment further significantly increased the axon sprouting in TBI rats although EPO treatment did not significantly affect axon sprouting in sham animals. The contralesional CST sprouting was highly and positively correlated with sensorimotor recovery after TBI. These data demonstrate that CST fibers originating from the contralesional intact cerebral hemisphere are capable of sprouting into the denervated spinal cord after TBI and EPO treatment, which may at least partially contribute to functional recovery.

Extensive spinal decussation and bilateral termination of cervical corticospinal projections in rhesus monkeys.

To examine neuroanatomical mechanisms underlying fine motor control of the primate hand, adult rhesus monkeys underwent injections of biotinylated dextran amine (BDA) into the right motor cortex. Spinal axonal anatomy was examined using detailed serial-section reconstruction and modified stereological quantification. Eighty-seven percent of corticospinal tract (CST) axons decussated in the medullary pyramids and descended through the contralateral dorsolateral tract of the spinal cord. Eleven percent of CST axons projected through the dorsolateral CST ipsilateral to the hemisphere of origin, and 2% of axons projected through the ipsilateral ventromedial CST. Notably, corticospinal axons decussated extensively across the spinal cord midline. Remarkably, nearly 2-fold more CST axons decussated across the cervical spinal cord midline (approximately 12,000 axons) than were labeled in all descending components of the CST (approximately 6,700 axons). These findings suggest that CST axons extend multiple segmental collaterals. Furthermore, serial-section reconstructions revealed that individual axons descending in either the ipsilateral or contralateral dorsolateral CST can: 1) terminate in the gray matter ipsilateral to the hemisphere of origin; 2) terminate in the gray matter contralateral to the hemisphere of origin; or 3) branch in the spinal cord and terminate on both sides of the spinal cord. These results reveal a previously unappreciated degree of bilaterality and complexity of corticospinal projections in the primate spinal cord. This bilaterality is more extensive than that of the rat CST, and may resemble human CST organization. Thus, augmentation of sprouting of these extensive bilateral CST projections may provide a novel target for enhancing recovery after spinal cord injury.

Ipsilateral actions from the feline red nucleus on hindlimb motoneurones

The main aim of the study was to investigate whether neurones in the ipsilateral red nucleus (NR) affect hindlimb motoneurones. Intracellular records from motoneurones revealed that both EPSPs and IPSPs were evoked in them via ipsilaterally located premotor interneurones by stimulation of the ipsilateral NR in deeply anaesthetized cats in which only ipsilaterally descending tract fibres were left intact. When only contralaterally descending tract fibres were left intact, EPSPs mediated by excitatory commissural interneurones were evoked by NR stimuli alone while IPSPs mediated by inhibitory commissural interneurones required joint stimulation of the ipsilateral NR and of the medial longitudinal fascicle (MLF, i.e. reticulospinal tract fibres). Control experiments led to the conclusion that if any inadvertently coactivated axons of neurones from the contralateral NR contributed to these PSPs, their effect was minor. Another aim of the study was to investigate whether ipsilateral actions of NR neurones, pyramidal tract (PT) neurones and reticulospinal tract neurones descending in the MLF on hindlimb motoneurones are evoked via common spinal relay neurones. Mutual facilitation of these synaptic actions as well as of synaptic actions from the contralateral NR and contralateral PT neurones showed that they are to a great extent mediated via the same spinal neurones. A more effective activation of these neurones by not only ipsilateral corticospinal and reticulospinal but also rubrospinal tract neurones may thus contribute to the recovery of motor functions after injuries of the contralateral corticospinal tract neurones. No evidence was found for mediation of early PT actions via NR neurones.

BRAINSTEM CORTICOSPINAL TRACT DIFFUSION TENSOR IMAGING IN PATIENTS WITH PRIMARY POSTERIOR FOSSA NEOPLASMS STRATIFIED BY TUMOR TYPE

Diffusion tensor imaging (DTI) allows in vivo delineation of brainstem white matter tracts. The purpose of this study was to determine whether or not abnormalities of DTI metrics and fiber tractography correlate with neurological deficits and clinical status in patients with primary posterior fossa tumors. A review of patients with primary posterior fossa tumors who underwent magnetic resonance imaging with DTI was performed. Patients were stratified by tumor type (well-circumscribed or infiltrating lesions). Fractional anisotropy (FA) color maps were used to localize the corticospinal tracts within the brainstem. FA, mean diffusivity, and eigenvalues were measured. Tractography was performed. Correlations between DTI metrics and clinical status and between DTI metrics and neurological examination findings were assessed within each patient group using Bonferroni correction for multiple comparisons. Comparisons of DTI metrics were also made between patient groups (infiltrating lesions versus well-circumscribed lesions). Thirty patients were studied (mean age, 14.1 yr; 16 male, 14 female). Eighteen patients had infiltrating lesions and 12 had well-circumscribed lesions. Twelve patients (four well-circumscribed and eight infiltrating) demonstrated motor weakness on physical examination (four right, three left, five bilateral). Patients with well-circumscribed lesions and weakness had higher mean diffusivity and lower FA in the contralateral corticospinal tract (P < 0.05). No such association was seen in patients with infiltrating tumors. In 102 total patient-years of follow-up (average follow-up period, 4.2 yr), 17 patients (six well-circumscribed and 11 infiltrating lesions) demonstrated complete response or stable disease and six patients (three well-circumscribed and three infiltrating lesions) demonstrated progressive disease or death. No differences were seen in terms of DTI metrics between patients with infiltrating lesions and those with well-circumscribed lesions. Patients with well-circumscribed tumors and a bad outcome had significantly lower transverse eigenvalue measures in the corticospinal tracts compared with those with a more favorable clinical status (P < 0.05). In patients with well-circumscribed primary posterior fossa masses, higher mean diffusivity and lower FA in the brainstem corticospinal tract are associated with contralateral motor deficits; lower transverse eigenvalue may be observed with an unfavorable clinical outcome.

Ipsilateral silent period: A marker of callosal conduction abnormality in early relapsing–remitting multiple sclerosis?

Objective The corpus callosum (CC) is commonly affected in multiple sclerosis (MS). The ipsilateral silent period (iSP) is a putative electrophysiological marker of callosal demyelination. The purpose of this study was to re-assess, under recently established optimised protocol conditions [Jung P., Ziemann U. Differences of the ipsilateral silent period in small hand muscles. Muscle Nerve in press.], its diagnostic sensitivity in MS, about which conflicting results were reported in previous studies. Methods ISP measurements (onset, duration, and depth) were obtained in the abductor pollicis brevis (APB) muscle of either hand in 49 patients with early relapsing–remitting MS (RRMS) (mean EDSS, 1.3). Standard central motor conduction times to the APB (CMCT APB) and tibial anterior muscles (CMCT TA), and magnetic resonance images (MRI) were also obtained. Results ISP measurements showed a similar diagnostic sensitivity (28.6%) as CMCT APB (24.5%), while diagnostic sensitivities of CMCT TA (69.4%) and MRI of the CC (78.6%) were much higher. Prolongation of iSP duration was the most sensitive single iSP measure. ISP prolongation occurred more frequently when CMCT APB to the same hand was also prolonged (40.0% vs. 8.4%, p < 0.0001). The correlation between iSP duration and CMCT APB was significant (Pearson's r = 0.24, p < 0.02), suggesting that iSP duration can be contaminated by demyelination of the contralateral corticospinal tract. ISP duration did not correlate with MRI abnormalities of the CC. Conclusions ISP measures are neither a sensitive nor a specific marker of callosal conduction abnormality in early RRMS.

Highly Functional Ipsilateral Motor Control After Extensive Left Hemispheric Damage During Gestation

In large early cortical lesions, one of the most devastating consequences is the impaired motor dexterity of the contralateral limb. We present the case of an 8-year-old girl with a large left hemispherical porencephaly. Unlike previous reports, the girl exhibited high dexterity of the contralateral hand with preserved independent finger movements. We performed functional MRI of hand motor functions and diffusion tensor imaging, which revealed activation of the ipsilateral motor cortex and absence of a contralateral corticospinal tract. These observations suggest that by intensive training in early life, a complete transhemispheric shift of motor control with high skills can be achieved.

Diffusion Tensor Imaging of the Corticospinal Tract Following Cerebral Hemispherectomy

Following cerebral hemispherectomy, the corticospinal tract is believed to undergo reorganizational changes, which can induce enhanced function of the contralateral motor pathway and mediate partial recovery of motor function. The aim of this study was to use diffusion tensor imaging to investigate the effects of hemispherectomy on the corticospinal tract, with particular attention to the corticospinal tract contralateral to the resection. Diffusion tensor imaging would presumably detect microstructural abnormalities through quantitative measurements of the fiber tract integrity and orientation. Four patients with anatomic hemispherectomy and three patients with subtotal hemispherectomy were examined and compared with age-matched normal controls. Apparent diffusion coefficient and fractional anisotropy values were measured in regions along the corticospinal tract: internal capsule, cerebral peduncle, rostral pons, midpons, and caudal pons. None of the patients with anatomic hemispherectomy or subtotal hemispherectomy showed significant changes in either apparent diffusion coefficient or fractional anisotropy values in the corticospinal tract contralateral to the resected hemisphere, whereas increased apparent diffusion coefficient and decreased fractional anisotropy were observed in the ipsilateral rostral pons, midpons, and caudal pons of all patients with anatomic hemispherectomy, as well as in the ipsilateral cerebral peduncle of one patient with subtotal hemispherectomy. Increased apparent diffusion coefficient values were also noted in the ipsilateral internal capsule of the same patient. This study revealed no evidence of significant reinforcement of the contralateral corticospinal tract in patients with hemispherectomy, at least from diffusion tensor imaging measurements, but suggests that wallerian degeneration most likely occurs in the ipsilateral motor pathway.

Central motor conduction in cervical dystonia with cervical spondylotic myelopathy

Objectives: It has been known that cervical dystonia develops secondarily to spinal cord injuries as secondary dystonia. However, little is known about the pathophysiological mechanism. Patients and methods: We examined motor and sensory conduction in six patients with symptomatic cervical dystonia by transcranial magnetic stimulation (TMS). All of the patients exhibited unilateral head rotation. They had symptoms corresponding to cervical myelopathy and felt discomfort in the neck, shoulders or arms before involuntary movement occurred. Results: Although the overall central motor conduction time (CMCT) was not different from that of normal controls, contralateral CMCT was significantly delayed compared to ipsilateral CMCT ( p < 0.05). The results of somatosensory evoked potential study demonstrated that contralateral central conduction time (CCT) was not significantly different from ipsilateral CCT. Conclusion: These findings indicate that there is a selective interference with the contralateral corticospinal tract in patients with symptomatic cervical dystonia.

Motor Recovery in Stroke Patients

Stroke is a leading cause of chronic physical disability. The recent randomized controlled trials have that motor function of chronic stroke survivors could be improved through physical or pharmacologic intervention in the stroke rehabilitation setting. In addition, several functional neuroimaging techniques have recently developed, it is available to study the functional topography of sensorimotor area of the brain. However, the mechanisms involved in motor recovery after stroke, are still poorly understood. Four motor recovery mechanisms have been suggested, such as reorganization into areas adjacent to the injured primary motor cortex (M1), unmasking of the motor pathway from the unaffected motor cortex to the affected hand, attribution of secondary motor areas, and recovery of the damaged contralateral corticospinal tract. Understanding the motor recovery mechanisms would provide neurorehabilitation specialists with more information to allow for precise prognosis and therapeutic strategies based on the scientific evidence; this may help promote recovery of motor function. This review introduces several methodologies for neuroimaging techniques and discusses theoretical issues that impact interpretation of functional imaging studies of motor recovery after stroke. Perspectives, for future research are presented.

The Evaluation of Wallerian Degeneration in Chronic Paediatric Middle Cerebral Artery Infarction Using Diffusion Tensor MR Imaging

Background: The long-term neuromotor outcome in paediatric strokes ranges from normal to varying degrees of hemiplegia. We evaluated the indices of diffusion tensor magnetic resonance imaging (DTI), fractional anisotropy and mean diffusivity to determine if these indices can identify and quantify the presence of Wallerian degeneration in paediatric patients with chronic middle cerebral artery infarction, and to determine if these quantitative parameters correlate with the neuromotor outcome. Methods: Eleven children (mean age 8.1 years) with evidence of unilateral middle cerebral artery stroke on magnetic resonance imaging and 10 control subjects (mean age 8.7 years) were studied. Neuromotor outcome was based on functions of the affected hand: mild (n = 3), moderate (n = 6), and severe (n = 2) hemiparesis. Fractional anisotropy and mean diffusivity of the ipsilateral corticospinal tract were compared with matched contralateral regions using the Mann-Whitney U test. Spearman’s test was performed to study the relationship between neuromotor outcome and the following: ipsilateral-to-contralateral ratio of fractional anisotropy, mean diffusivity and cerebral peduncle area, and the largest infarction size. Results: For control subjects, there were no significant differences in fractional anisotropy and mean diffusivity of the corticospinal tract between the right and left side. For patients, fractional anisotropy decreased by 18% and mean diffusivity increased by 8% in the ipsilateral compared to the contralateral corticospinal tract. Neuromotor outcome correlated with the ipsilateral-to-contralateral ratio of fractional anisotropy (r = –0.638, p = 0.035) but not with the mean diffusivity ratio, cerebral peduncle area ratio and largest infarction size. Conclusion: DTI can be used to detect and quantify Wallerian degeneration in chronic paediatric middle cerebral artery infarction. Our preliminary data show that loss of anisotropy in the corticospinal tract correlates with neuromotor outcome.

Bilateral corticospinal projections arise from each motor cortex in the macaque monkey: a quantitative study.

The corticospinal projection is considered to influence fine motor function through nearly exclusively contralateral projections from the cortex in primates. However, unilateral lesions to this system in various species are frequently followed by significant functional improvement, raising the possibility that bilateral projections of this pathway may exist or emerge after injury. To examine the detailed anatomy and projections of the corticospinal motor neurons in rhesus monkeys (n = 4), we injected the high-resolution anterograde tracer biotinylated dextran amine (BDA) into 126 sites centered about the right lower extremity (LE) primary motor cortex. Projection and termination patterns were quantified at lumbar levels L1, L4, and L7 and mapped by using serial-section reconstructions. Notably, a mean of 10.1 +/- 0.6% (+/- SEM) of corticospinal tract (CST) axons descended in the lateral CST ipsilateral to the cortical BDA injection, and 87.9 +/- 1.0% of total CST axons projected in the contralateral lateral CST. The ipsilateral ventral CST contained only 1.0 +/- 0% of all projecting CST axons, whereas the contralateral ventral CST contained 0.3 +/- 0.2% of all axons. In addition, a minor dorsal column CST projection was identified. Measurement of BDA-labeled terminals in the spinal cord gray matter revealed that 11.2 +/- 2.2% of CST axons terminated ipsilateral to the side of cortical injection, and the remainder terminated contralaterally. As previously reported, most CST axons terminated in spinal cord laminae V-VIII, as well as the laterodorsal motoneuronal group of lamina IX (which innervates distal extremity muscles). Notably, many CST axons crossed the spinal cord midline (mean 19.9 +/- 4.9 axons per 40-microm-thick section). Detailed single-axon reconstructions revealed that most ipsilaterally projecting lateral CST axons terminated in ipsilateral gray matter. Notably, we found that the bouton-like swellings of many ipsilateral CST axons descending in the dorsolateral tract were located within Rexed's lamina IX, in close proximity to motoneuronal somata. Thus, bilateral projections of corticospinal axons originating from a single motor cortex could contribute to bilateral control of spinal motor neurons and to the highly evolved degree of fine motor control in primates. Furthermore, bilateral CST projections from a single motor cortex could represent a potential source of plasticity after injury, as well as a target of therapeutic effort in neural regeneration strategies.

Estimation of localization of neural activity in the spinal cord using a biomagnetometer.

Spinal cord evoked potentials (SCEPs) measurement is widely used for level diagnosis of spondylotic myelopathy. However, because of the restriction of spatial resolution, SCEPs do not distinguish the neurophysiological activities among tracts in the spinal cord without invasive methods. Magnetic field measurement has the theoretical advantage of high spatial resolution, compared with electric measurement. We recorded spinal cord evoked magnetic fields (SCEFs) in the thoracic spinal cord after stimulation to the motor area in felines, and estimated the source of the magnetic fields. SCEFs showed a quadrupolar pattern, and conducted in a cranial-to-caudal direction at 55 m/sec. According to this result, we estimated that the SCEFs after stimulation to the motor area were generated by the contralateral corticospinal tract. Furthermore, the estimated dipole of the SCEFs after stimulation to the motor area was located on the contralateral side in the spinal cord. These results correspond with the anatomical location of the corticospinal tract of felines, and suggest that magnetic field recording can detect the magnetic source localization of each tract in the spinal cord.

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Glial Reaction after Pyramidotomy in Mice and Rats

Adult mice and rats were sacrificed by perfusion between 2 and 90 days after right pyramidotomy to study the microglial and astroglial response in the brain and spinal cord. The microglia were detected immunohistochemically with OX-42, OX-18 and OX-6 to assess respectively the expression of complement type 3 receptor, and major histocompatibility class I and class II antigens. Cell counting was also carried out in some animals to determine the possible proliferation of glial cells in the corticospinal tract and around layer V neurons in the cerebral cortex. Some operated animals were given rhodamine B isothiocyanate injection to investigate whether macrophages/monocytes could have migrated from the blood stream to the reactive area. The glial response around the cell bodies of layer V neurons in the ipsilateral cerebral cortex did not display any noticeable difference compared with that of the contralateral side and of the cerebral cortex of the sham-operated and normal control animals. In the cervical and lumbar cord segments of the operated animals, reactive microglial cells in the contralateral corticospinal tract appeared as early as 2 days post pyramidotomy (PP) in rats and 4 days PP in mice. Activation of microglial cells lasted up till 35 days PP, showing gradual increase in immunoreactive staining and hypertrophy. After that, the microglial immunoreactivity subsided and the cells assumed normal appearance by 90 days PP. Quantitative analysis showed a marked increase in the number of microglial cells in the contralateral CST up till 60 days PP. In mice, at 6 days PP, astroglial cells were hypertrophic and more intensely stained but showed no increase in number. No noticeable changes were noted in the astroglia of the rats throughout the period studied. Rhodamine-labelled cells were found at the lesion site, but not in layer V of the cerebral cortex, nor in the corticospinal tract. Though different glial reactions in the degenerating corticospinal tract were noted in mice and rats, there was the same apparent lack of glial reaction around the cell bodies of layer V neurons in the two animal species. Such lack of significant glial response is different from the vigorous glial response around the cell bodies of peripherally projecting neurons demonstrated in previous work. The possible mechanisms for such difference and the implication of the difference in axonal regeneration were discussed.

Concerning the Mechanism of Recovery in Stroke Hemiphegia

Two patients with pure motor hemiplegia were regaining strength in the affected limbs when a pure motor stroke developed on the opposite side. At the same time as the new hemiplegia appeared, the recovering side became re-paralyzed, suggesting that activity in the contralateral corticospinal tract had participated in the recovery process. Pathological studies were confirmatory. The literature pertaining to contralateral motor compensation is reviewed.

Descending pathways to the spinal cord, III: Sites of origin of the corticospinal tract

The somata of corticospinal neurons were labeled with horseradish peroxidase that had been applied to a hemisection of the spinal cord at the C1-C2 junction in 22 species of mammals. After tetramethylbenzidine processing, with and without counterstaining with cresyl violet or neutral red, the labeled cells in systematic sets of sections throughout the cerebral cortex were plotted and counted. Several morphological features of the corticospinal cells were examined including their cell type, number, density, concentration, laminar distribution, and their distribution across the cortical surface. The results show that the labeled corticospinal neurons were invariably layer V pyramidal cells. However, in many mammals they were found to be stacked one above the other within layer V, sometimes many neurons deep. Despite the concentration of corticospinal neurons within layer V, many unlabeled neurons were also present within the layer throughout the extent of the labeled region. The results also indicate that at least two spatially distinct regions of neocortex originate corticospinal fibers in each of the animals in the sample. In addition to these two regions, a third segregated region is present in the cortex of primates and an apparently different third region is present in the cortex of Glires (Rodentia and Lagomorpha). The third region of corticospinal cortex in primates is located on the lateral surface of the cortex in prosimians and New World monkeys and is buried in the caudal bank of the inferior arcuate sulcus in Old World monkeys. The results also show a predominantly contralateral corticospinal tract in all but 4 of the 22 mammals in the sample. Although these 4 mammals are each members of the order Insectivora, a less modified member of the same order possessed the predominantly contralateral projection of most mammals, hence denying the notion that a predominantly ipsilateral tract is a characteristic of Insectivora.