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PubMed2006

Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures.

Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD.

Adult↗
PubMed1975

Bilateral effects of vestibular nerve stimulation on activity in the lumbar spinal cord.

These experiments were designed to study the effects of vestibular nerve stimulation on the activity of hindlimb motoneuron pools. Two techniques were used to stimulate the vestibular nerves of precollicularly decerebrated cats. In one set of experiments the individual semicircular canals were stimulated via bipolar electrodes placed near the canal nerves. In the second series of experiments the whole vestibular nerve was stimulated with an electrode placed on the intradural nerve. Activity in the hindlimb motoneuron pools was ascertained by evoking monosynaptic reflexes in the various hindlimb nerves. Stimulation of the individual semicircular canals produced response patterns that varied with both the vestibular branch being stimulated and the hindlimb nerve being conditioned. Intradural stimulation of the vestibular nerve, on the other hand, evoked similar response patterns in the antagonist ankle flexor and extensor nerves. The most common pattern consisted of facilitation followed by a period of inhibition. Lesions of descending fiber tracts produced results which suggest the presence of a diffuse pathway, involving the recitular formation, which mediates the observed responses. It is suggested that the biphasic response pattern is analogous to the startle response and the function of the responses is discussed in that context.

Animals↗
PubMed1975

Reticulospinal neurons with and without monosynaptic inputs from cerebellar nuclei.

An account is given of the responses of 557 medial reticular neurons with axons projecting down the spinal cord. All 30 experiments were on decerebrated unanesthetized cats paralyzed by Flaxedil. Recording from single neurons was by extracellular glass microelectrodes. Identification was first by location (confirmed by subsequent histology) in the medial reticular nucleus of medulla or pons, and second by antidromic activation from cord stimulation at C2 and L2 segmental levels. Axonal conduction velocities were calculated from the latency differential between L2 and C2 antidromic responses, and were usually in the range of 90-140 m/s; but about 25% were slower, ranging down to 30 m/s. Stimulation by electrodes in the ipsilateral and contralateral fastigial nuclei differentiated reticulospinal neurons into two classes according to whether they did or did not receive monosynaptic inputs, the respective populations of fully investigated neurons being 270 and 174. The fastigioreticular neurons were distinguished by a higher background frequency with mean values of 28 as against 15/s. There were also significant diffences in both the excitatory and inhibitory responses to afferent volleys from forelimb and hindlimb nerves. Comparison of the respective latency histograms showed that the responses of neurons with a fastigial input had an excess of latencies in the ranges that can be correlated with the latency histograms observed for fastigial responses. Thus, there is evidence for the effectiveness of the fastigial input and so for the pathway with monosynaptic linkage: Purkinje cells of cerebellar vermis yields fastigial neurons yields medial reticular neurons projecting down the spinal cord. Adequate stimulation of cutaneous receptors by pad taps and air-jet stimulation of hairy skin in a disppointingly small action when compared with fastigical responses. Explanations of this deficiency are suggested. Another discrpancy from the fastigial responses is that the medial reticular neurons have much wider receptive fields with little discrimination between ipsilateral and contralateral and between forelimb and hindlimb. Stimulation of the ipsilateral tegmental tract was tested on 183 reticulospinal neurons, 112 being with fastigial inputs. In about half there was a powerful monosynaptic excitation, which would identify such neurons as being on the pathway from mesencephalic and diencephalic centers to the spinal cord. There is a general discussion of transmission across successive synaptic relays, where specificity is sacrificed to integration.

Action Potentials↗
PubMed2005

[Parakinesia brachialis oscitans].

INTRODUCTION: In some cases of hemiplegia the onset of yawning is associated with an involuntary raising of the paralyzed arm. PATIENTS AND METHOD: Four observations of this movement, which is seldom described probably because it is mostly neglected, were made in the neurology unit of the University Hospital of Poitiers. The descriptions were compared with other cases that have been published in the medical literature of the last 150 years. Cerebral imagery shows a lesion that is most often localized on the internal capsule. After comparison with experimental models in cats, it is proposed that the section of the cortico-neocerebellum tract of the extra-pyramidal system disinhibits the spino-archeocerebellum tract, enabling a motor stimulation of the arm by the lateral reticular nucleus, which harmonises central respiratory and locomotor rhythms. RESULTS AND CONCLUSION: Some subcortical structures, that are phylogenetically more ancient, thus disinhibit regained autonomy in the homeostasis process associating the massive inspiration of yawning--a form of reflex behavior that stimulates vigilance--with a motor control that is active during locomotion. For this phenomenon we coined the term "parakinesia brachialis oscitans".

Adult↗
PubMed1999

Pursuit of the origin of the large myelinated fibers of the anterolateral funiculus in the spinal cord in humans in relation to the pathomechanism in amyotrophic lateral sclerosis.

To determine the origin of the large myelinated fibers in the anterolateral funiculus (ALF) in the spinal cord of humans, myelinated fibers in the ALF of the mid-cervical spinal cord were examined quantitatively. Five groups of subjects were examined, consisting of control subjects, patients with cerebral lesions and showing complete degeneration of the unilateral/bilateral pyramis of the medulla oblongata, those with lesions of the pontine tegmentum, those with lesions of the lower cervical spinal cord, and those with thoracic/lumbar lesions. The results indicate that the large myelinated fibers in the ALF of the mid-cervical spinal cord of humans originate from the tegmentum of the brain stem and the lower cervical spinal cord, and not from the cerebrum, or the thoracic or lumbar spinal cord. Thus, they are descending fibers from the brain stem tegmentum and ascending fibers from the lower cervical cord, and not corticospinal tracts or long-ascending fibers from the thoracic or lumbar spinal cord. The origin of the large myelinated fibers in the ALF of the spinal cord in humans, the number of which was severely decreased in patients with amyotrophic lateral sclerosis, is considered to be the long-descending neurons in the brain stem tegmentum and the propriospinal neurons in the spinal cord.

Adult↗
PubMedDate not supplied

[The activity of rubrospinal neurons in Macaca mulatta monkeys].

Action potentials of single cells in nucleus ruber have been recorded extracellularly inresponse to antidromic activation of the rubro-spinal tract and stimulation of contralateral interpositus nucleus of the cerebellum in the monkey M. mulatta. The analysis of the data obtained indicates that both large cells of the caudal portion and neurons of small-cell part of n. ruber send their axons to the spinal cord. Conduction velocity along the axons of rubro-spinal neurons in monkeys veries within 17.4--108.8 m/sec (peak velocity 60--90 m/sec). Experiments with stimulation of the interpositus nucleus of the cerebellum confirm the presence of monosynaptic interposito-rubral connections in monkeys.

Action Potentials↗
PubMed2006

Deterioration of hemiparesis after recurrent stroke in the unaffected hemisphere: Three further cases with possible interpretation.

BACKGROUND: The concept of neural reorganization after brain damage is already well established, and many previous studies have successfully reported the translocation of the neural activation in the motor-related cortices during motor tasks using functional imaging modalities. Several primate and human studies have suggested the formation of newly reorganized tracts in the ipsilesional or contralesional hemisphere, but the mechanism for the formation of these tracts is still largely unknown. METHODS: Three acute stroke patients who presented with abrupt deterioration of their right-sided hemiparesis due to the infarcts following a recurrent stroke in the originally unaffected hemisphere were studied using magnetic resonance imaging (MRI), MR angiography and single-photon emission CT. The relationship between the neurological symptom on admission and the precise location of the new infarct was carefully investigated from the perspective of reorganization. RESULTS: Diffusion-weighted MRI showed a new subcortical infarct in the right hemisphere contralateral to the initial stroke in all patients. These new lesions involved the thalamus, globus pallidus or corona radiata, sparing the area of the internal capsule. T2-weighed MRI on admission showed an old infarct in the left middle cerebral artery territory, which had caused the original right-sided hemiparesis. CONCLUSION: It is proposed that the 'extrapyramidal' motor pathway in the unaffected hemisphere is associated with poststroke neural reorganization.

Acute Disease↗
PubMed1984

Integration in descending motor pathways controlling the forelimb in the cat. 10. Inhibitory pathways to forelimb motoneurones via C3-C4 propriospinal neurones.

A further analysis has been made of inhibitory pathways to motoneurones via C3-C4 propriospinal neurones (PNs). Intracellular recording was made from triceps brachi motoneurones and effects from higher centres and forelimb afferents on corticospinal IPSPs were investigated after transection of the corticospinal tract at the C5/C6 border. The shortest latencies of the IPSPs evoked by stimulation of the pyramid were as brief as those of the pyramidal EPSPs (Illert et al. 1977). It is postulated that the minimal linkage of the pyramidal IPSPs is disynaptic via inhibitory C3-C4 PNs projecting directly to motoneurones. It was confirmed that pyramidal IPSPs usually are depressed by volleys in forelimb motor axon collaterals (Illert and Tanaka 1978). A quantitative comparison was made of the recurrent depression of pyramidal IPSPs and of IPSPs caused by activation of the Ia inhibitory interneurones. The result support the hypothesis of two parallel inhibitory cortico-motoneuronal pathways via C3-C4 PNs, one disynaptic via the inhibitory PNs and the other trisynaptic via excitatory PNs and Ia inhibitory interneurones. Pyramidal volleys also evoked late IPSPs which in some cases were not depressed from forelimb motor axon collaterals. It is postulated that the late IPSPs are partly due to activation of inhibitory C3-C4 PNs. Disynaptic pyramidal IPSPs were effectively facilitated by volleys in rubro-, tecto- and reticulospinal fibres - but not from vestibulospinal fibres - showing a convergence from the former descending tracts on common inhibitory C3-C4 PNs. Projection from forelimb afferents and corticospinal fibres on common inhibitory C3-C4 PNs was revealed by strong facilitation of disynaptic pyramidal IPSPs from cutaneous forelimb afferents. No corresponding effect was evoked from C2 neck afferents. Stimulation in the lateral reticular nucleus (LRN) evoked monosynaptic IPSPs in some motoneurones. The results of threshold mapping in and around the LRN suggest that the IPSPs are caused by antidromic stimulation of ascending collaterals of inhibitory neurones also projecting to motoneurones, possibly the inhibitory C3-C4 PNs.

Animals↗
PubMed1976

Inhibitory potentials produced in cortical cells by stimulation of the lateral hypothalamus in rabbits.

(1) Intracellular potentials were recorded from pyramidal tract (PT) and non-pyramidal tract (non-PT) cells of the frontal cortex in urethane-anesthetized rabbits and the effects of electrical stimulation of the lateral hypothalamus (LH) were examined on the ipsilateral side. (2) Latencies of antidromic spikes of PT cells evoked by stimulation of the medullary pyramidal tract (PYR) had a unimodal distribution with the mean at 4.0 msec. The mean conduction velocity of the pyramidal tract fibers was 10.5 m/sec. (3) Prolonged IPSPs were produced in PT and non-PT cells by single shock stimulation of LH (LH-IPSP). They were significantly longer lasting than those produced by PYR stimulation (PYR-IPSP). (4) The latencies of LH-IPSPs ranged from 1.7 to 25.0 msec and were divided into two groups. The latencies of PYR-IPSPs had a unimodal distribution ranging from 2.5 to 30 msec. (5) In a few non-PT cells, a sequence of brief depolarization and prolonged hyperpolarization occurred in response to LH stimulation. (6) In some non-PT cells, EPSPs which occasionally resulted in spike discharges were observed after LH stimulation. However, no excitation of PT cells was observed by LH stimulation.

Animals↗
PubMed1983

Origin of the rubrospinal tract in neonatal, developing, and mature rats.

This investigation describes the origin of the rubrospinal tract in neonatal (1-10 days old), developing (15-20 days old), and mature (2-4 months old) rats studied by using the horseradish peroxidase (HRP) method of tracing neuronal connections. HRP was administered in the cervical or lumbosacral segments of the spinal cord either in the crystal or solution form. The results showed that the rubrospinal tract extended to the lumbosacral part of the spinal cord at birth. There appeared to be no difference in the pattern of labelled rubrospinal (RS) neurons following the administration of HRP in the cervical or the lumbosacral cord segment of the neonatal, developing, and mature rats. In rats of these three age groups, labelled neurons were found bilaterally in the red nucleus, with a contralateral predominance, and they were found in both the parvicellular and magnocellular portions of the red nucleus. There was a somatotopic arrangement in the labelled RS neurons: Those projecting to the cervical cord segments were located in the dorsal and dorsomedial regions of the red nucleus and those projecting to the lumbosacral cord segments were located in the ventral and ventrolateral regions of the nucleus.

Age Factors↗
PubMed1975

Pipotiazine palmitate: an evaluation of a new long acting intramuscular antipsychotic agent in severely ill schizophrenic patients.

Findings in this study support earlier investigations in attesting to the antipsychotic efficacy and relatively low toxicity of pipotiazine palmitate. Results with all efficacy measures utilized were consistent in indicating a high level of efficacy for this investigational compound. Pipotiazine palmitate apparently has an average duration of action that extends beyond 4 weeks in severely ill schizophrenic patients. This particular long acting IM antipsychotic preparation appears to have an even longer duration of activity than some of the other available standard long acting agents. The optimal dosage range for severely ill schizophrenic patients appears to be between 100 and 600 mg once monthly. While this type of drug (as is the case with many antipsychotic drugs) does reduce the psychotic symptomatology and improves the thought associations sufficient to enable the patient to leave the hospital, it should be re-emphasized that socioeconomic and guidance counseling services are necessary to maintain the patient in the community. The availability of this type of long acting preparation is not only economical in terms of nursing care and hospital cost but it should also increase the efficacy of psychopharmacologic treatment of schizophrenics by reducing both patient errors and staff errors in administration of medication. In addition, this IM preparation should prove to be of invaluable help in maintaining the schizophrenic patient in his community by reducing the relapse and the rehospitalization rates. It should be noted that there are schizophrenic patients who either absorb compounds from the gastrointestinal tract in a very poor manner or too rapidly metabolize the antipsychotic agents with resultant suboptimal blood levels and these subjects may be called "drug refractory." This type of long acting medication is an ideal preparation for the schizophrenic patient who has these types of absorption or metabolic problems since the "circulatory pass" through the liver is minimal after IM medication as compared to that encountered by an orally administered agent. The clinical disadvantage of pipotiazine palmitate is the delay in onset of therapeutic activity after injection. Significant improvement is first noted after 3 to 4 days after the highest IM dosage administration. Therefore, it may be necessary to use an oral or IM preparation of a neuroleptic with a more rapid onset of activity or utilize an oral dosage of the pipotiazine salt during the first week following IM administration of pipotiazine palmitate.

Administration, Oral↗
PubMed2000

Organization of nonprimary motor cortical inputs on pyramidal and nonpyramidal tract neurons of primary motor cortex: An electrophysiological study in the macaque monkey.

To elucidate the functions of nonprimary motor cortical (nPMC) areas whose afferents synapse onto output neurons of the primary motor cortex (PMC), we examined the responses of pyramidal tract neurons (PTNs) and non-PTNs (nPTNs) to electrical stimulation in the three nPMCs, the supplementary motor area (SMA) and the dorsal and ventral divisions of the premotor cortex (PMd and PMv), with extracellular unit recording in alert monkeys. Typical responses of PTNs to nPMC stimulation were early orthodromic excitatory responses followed by inhibitory responses. Among 27 PTNs tested by constructing peri-stimulus time histograms, 19 (70.4%) showed inhibitory responses to stimulation in all of the nPMC areas. In contrast, 5/33 PTNs (15.2%) and 10/72 nPTNs (13.9%) showed excitatory responses to stimulation in all of the nPMCs. The inhibitory responses of PTNs were mediated by inhibitory interneurons, some of which may correspond to nPTNs in the superficial layers of the PMC. These interneurons probably possess widely extended axons and nonspecifically inhibit multiple PTNs in layer V. The excitatory and inhibitory influences, and the patterns of convergence of inputs from the nPMCs onto the PTNs, are important to understand motor control by the nPMC-PMC-spinal cord pathway.

Animals↗
PubMed1984

Glucose utilization is unchanged in red nucleus after axotomy.

Separate series of adult rats were subjected to unilateral high cervical and low thoracic section of the rubrospinal tract and sacrificed 1-30 (cervical series) and 3-100 days (thoracic series) later. Local cerebral glucose utilization ([14C]2-DG method of Sokoloff et al.) was determined in the red nucleus and in the inferior colliculus, nucleus interpositus and sensorimotor cortex of both sides in operates and controls. Although severe atrophy of rubral neurons follows cervical tractotomy while reversible chromatolytic alterations occur after thoracic lesions, glucose utilization did not differ in the red nucleus of operated and control rats. However, glucose utilization increased slightly in the inferior colliculus of all operated animals, a finding of indeterminate significance. The failure of axotomized intrinsic neurons of red nucleus and their surround to show altered glucose utilization stands in sharp contrast to the marked increase which occurs in cranial nerve nuclei after axotomy of their contained extrinsic neurons. The data are held to constitute another indication that there is a fundamental difference in the metabolic responses of extrinsic and intrinsic mammalian neurons to axotomy and may support the contention that, in mammals, the axon reaction of intrinsic neurons is fundamentally different from that of extrinsic nerve cells. This difference may have significance for failure of axon regeneration in mammalian CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death.

Rubrospinal tract cells undergo massive retrograde degeneration following spinal cord damage in newborn rats (Prendergast and Stelzner, J. Comp. Neurol. 166:163-172, '76b). In the current study, fetal spinal cord tissue (E12-14) was grafted into midthoracic spinal cord lesions in newborn rats (less than 72 hours old) in order to determine whether such transplants could modify the response of the immature host central nervous system (CNS) to axotomy. These transplants grew, differentiated, and formed extensive areas of apposition with the recipient spinal cords. Counts of red nucleus (RN) neurons indicated a significant loss of RN neurons in animals with lesion alone, but a rescuing of most of these cells if a transplant was placed into the lesion site. In fact, the number of neurons in animals with lesions and transplants was not significantly different from control animals. Horseradish peroxidase injected 10-15 mm caudal to the transplant (at 1-12 months post-transplantation) labeled neurons within the transplant and RN neurons contralateral to the spinal cord lesions and transplant. In animals with spinal cord lesion but no transplant, only the unaxotomized RN was labeled. Thus, spinal cord transplants prevented the massive retrograde cell death of immature axotomized rubrospinal neurons. Some of these rescued neurons projected to the host spinal cord caudal to the transplant.

Animals↗
PubMed1984

Integration in descending motor pathways controlling the forelimb in the cat. 11. Inhibitory pathways from higher motor centres and forelimb afferents to C3-C4 propriospinal neurones.

Intracellular recording was made in the C3-C4 segments from cell bodies of a previously described system of propriospinal neurones (PNs), which receive convergent monosynaptic excitation from different higher motor centres and mediate disynaptic excitation and inhibition from them to forelimb motoneurones. Inhibitory effects in these PNs have now been investigated with electrical stimulation of higher motor centres and forelimb nerves. Short-latency IPSPs were evoked by volleys in the cortico-, rubro- and tectospinal tracts and from the reticular formation. Latency measurements showed that those IPSPs which required temporal summation were disynaptically mediated. After transection of the corticospinal tract in C2, only small and infrequent disynaptic IPSPs were evoked from the pyramid. It is postulated that disynaptic pyramidal IPSPs only to a small extent are evoked by monosynaptic excitation of reticulospinal inhibitory neurones known to project directly to the PNs, and that they are mainly mediated by inhibitory interneurones in the C3-C4 segments. Tests with spatial facilitation revealed monosynaptic excitatory convergence from tecto-, rubro- and probably also from reticulospinal fibres on inhibitory interneurones monosynaptically excited from corticospinal fibres (interneuronal system I). Disynaptic IPSPs were also evoked in the great majority of the PNs by volleys in forelimb muscle and skin nerves. A short train of volleys was usually required to evoke these IPSPs from group I muscle afferents. In the case of cutaneous nerves and mixed nerves single volleys were often effective, and the lack of temporal facilitation of IPSPs produced by a train of volleys showed strong linkage from these nerves. The results obtained after transection of the dorsal column at different levels show that the relay is almost entirely rostral to the forelimb segments. Test with spatial facilitation revealed that interneurones monosynaptically activated from forelimb afferents receive convergent excitation from corticospinal but not or only weakly so from tecto- or rubrospinal fibres. There was also convergence from group I muscle afferents and low threshold cutaneous afferents on common interneurones. It is postulated that the disynaptic IPSPs from forelimb afferents are mediated by inhibitory interneurones (interneuronal system II) other than those receiving convergent descending excitation. Volleys in corticospinal fibres, in addition to the disynaptic IPSPs, evoke late IPSPs in the PNs. Similar late IPSPs were evoked from the ipsilateral forelimb by stimulation of the FRA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Integration in descending motor pathways controlling the forelimb in the cat. 12. Interneurones which may mediate descending feed-forward inhibition and feed-back inhibition from the forelimb to C3-C4 propriospinal neurones.

Extra- and intracellular recording was made from cells in the C3-C4 segments with the aim of finding interneurones of previously described inhibitory pathways to the C3-C4 propriospinal neurones, which may mediate descending feed-forward inhibition and feed-back inhibition from the forelimb, respectively. The lateral interneurones were found in the lateral part of lamina VII interspersed among the C3-C4 PNs and like them they receive convergent monosynaptic EPSPs and disynaptic IPSPs from the cortico-, rubro-, tecto- and reticulospinal tracts. Disynaptic IPSPs, but only rarely monosynaptic EPSPs, are evoked in them from forelimb nerves. The lateral interneurones do not project to the lateral reticular nucleus (LRN). The medial interneurones were found medially in laminae V and VI in a region where volleys in forelimb nerves evoke extracellular monosynaptic focal potentials (Rosén 1969). There is somatotopic organization of the projection from the forelimb to this region. Many neurones are strongly monosynaptically excited from group I muscle or/and cutaneous forelimb afferents. In addition, late discharges are evoked in many cells from cutaneous afferents and high threshold muscle afferents. Corticospinal volleys evoked monosynaptic excitation in the great majority of these cells and usually also late EPSPs or IPSPs. Typically, rubrospinal and tectospinal volleys evoked neither monosynaptic excitation nor late effects as those elicited from corticospinal fibres. In some of the interneurones, IPSPs were evoked from forelimb nerves. About 20% of the medial "interneurones" have an ascending projection to the caudal brain stem. Threshold mapping for antidromic stimulation revealed termination in the main cuneate nucleus, the external cuneate nucleus and/or the LRN and also a branch projecting to more rostral levels in the brain. A few of the neurones in the medial region are PNs projecting to the forelimb segments. It is postulated that interneurones both of the lateral and medial type are inhibitory and project to the C3-C4 PNs. It is further postulated that the former are intercalated in the descending feed-forward inhibitory pathway to the C3-C4 PNs and the latter in the feed-back inhibitory pathway from the forelimb to these PNs. The role of feed-forward and feed-back inhibition of transmission from the brain to forelimb motoneurones via the C3-C4 PNs is discussed.

Afferent Pathways↗