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PubMed1990

Electrophysiological and histological follow-up study in 15 Friedreich's ataxia patients.

A clinical and electrophysiological follow-up was carried out for 3 to 7 years on 15 patients with Friedreich's ataxia (FA). Sural nerve biopsy was performed once in all patients, and a second time 6-7 years later in three of them. Clinical worsening and progression of disturbance were evaluated according to IAP and IACR scales. Sensory orthodromic conduction along median and tibial nerves was typical of FA and did not change between first and last examinations, nor were there morphological changes between the first and the second sural nerve biopsies. Peripheral nerve involvement is thought to be a result of defective development of the largest neurons and to remain stable from a very early stage of the disease; the clinical worsening may then be due to a progressive involvement of the pyramidal tracts and the cerebellar pathways.

Adolescent↗
PubMed1994

Suppression and long latency excitation of single spinal motoneurons by transcranial magnetic stimulation in health, multiple sclerosis, and stroke.

Whether or not suppression at the level of the spinal motoneuron plays a role in motor deficits such as central paresis is unknown. In this study suppression in the firing of tonically active low threshold single motoneurons following low intensity transcranial magnetic stimulation is described in health and disease. Changes in firing probability in the absence of an early excitatory response were studied in a total of 14 motor units from 4 healthy subjects, 5 patients with multiple sclerosis, and 1 patient with stroke. Firing probability began to fall 18-59 ms after the stimulus and remained low for a period of 27-133 ms. There were no obvious differences between the three subject groups. The change in firing probability was not associated with specific physical signs. Late rises in firing probability were seen in 7 of the 14 motor units at latencies that were similar to the secondary peak which is known to occur with higher stimulus intensities. It is argued that the mechanism of partial suppression is not dependent on the full integrity of the pyramidal tract and is likely to involve a transient withdrawal of descending excitatory drive rather than an inhibitory postsynaptic potential at the spinal motoneuron.

Adult↗
PubMed1996

Effect of fatiguing maximal voluntary contraction on excitatory and inhibitory responses elicited by transcranial magnetic motor cortex stimulation.

Vertex transcranial magnetic stimulation (TMS) elicited tibialis anterior motor evoked potentials (MEPs) and silent periods (SPs) that were recorded during and following isometric maximal volitional contraction (MVC). During MVC in 6 healthy subjects, MEP amplitudes in the exercised muscle showed an increasing trend from an initial value of 4539 +/- 809 muV (mean +/- SE) to 550 +/- 908 muV (P < 0.13) while force and EMG decreased (P < 0.01). Also, SP duration increased from 165 +/- 37 ms to 231 +/- 32 ms (P < 0.01). Thus, during a fatiguing MVC both excitatory and inhibitory TMS-induced responses increased. TMS delivered during repeated brief 10% MVC contractions before and after a fatiguing MVC in 5 subjects, showed no change in MEP amplitude but SP duration was prolonged after MVC. This SP prolongation was focal to the exercised muscle. Silent periods recorded after pyramidal tract stimulation were unchanged following the MVC. These results suggest that MEP and SP might have common sources of facilitation during an MVC and that inhibitory mechanisms remain focally augmented following a fatiguing MVC.

Adult↗
PubMed1993

Effect of rat subarachnoid hemorrhage on serotonin innervation of the cerebral ventricular wall and serotonin neurons of the ventral surface of the brain stem: an immunohistochemical study.

The effect of subarachnoid hemorrhage on serotonin (5-HT) innervation of the cerebral ventricles and on 5-HT neurons in the ventral surface of the brain stem was studied immunohistochemically in the rat. Subarachnoid hemorrhage (SAH) was induced by injection of autologous arterial blood into the cisterna magna. In normal and sham-operated animals, the entire ependyma of the ventricles was supplied with 5-HT-immunoreactive supraependymal nerves. The ependyma in the dorsal third ventricle received the most dense innervation. 5-HT neurons on the surface of the brain stem were found in the median fissure and on the ventral surface of the pyramidal tract. A marked reduction in supraependymal 5-HT immunostaining was observed in animals sacrificed as early as 6 h post-SAH and this change continued until 14 days and recovered by 28 days following SAH. 5-HT neurons on the ventral surface of the brain stem were visible even in the rat with SAH. The results suggest that SAH caused a transient depletion of 5-HT immunoreactivity in the supraependymal nerves but 5-HT neurons on the ventral surface of the brain stem were unchanged. Depletion of 5-HT immunoreactive nerves on the cerebral ventricular wall might be involved in the pathophysiology after SAH.

Animals↗
PubMed2002

Traumatic brain injury in the immature mouse brain: characterization of regional vulnerability.

We characterized the regional and temporal patterns of neuronal injury and axonal degeneration after controlled cortical impact of moderate severity in mice at postnatal day 21. Animals were euthanized at 1, 3, or 7 days after injury or sham operation. The brains were removed and prepared for immunolocalization of neurons and microglia/macrophages or subjected to Fluoro-Jade and silver stains, indicators of irreversible neuronal cell injury and axonal degeneration. There was significant neuronal loss in both the ipsi- and the contralateral cortices, ipsilateral hippocampus, and ipsilateral thalamus by 7 days post injury compared to sham-operated animals. Activated microglia/macrophages were most prominent in regions of neuronal loss including the ipsilateral cortex, hippocampus, and thalamus. Neuronal injury, as evidenced by Fluoro-Jade labeling, was not apparent in sham-operated animals. In injured animals, labeling was identified in the ipsilateral cortex and hippocampus at 1 and 3 days post injury. Silver- and Fluoro-Jade-labeled degenerating axons were observed in the ipsilateral subcortical white matter by 1 day post injury, in the ipsilateral external capsule, caudate putamen, and contralateral subcortical white matter by 3 days post injury, and in the internal capsule, pyramidal tracts, and cerebellar peduncles by 7 days post injury. Our findings demonstrate that controlled cortical impact in the developing brain generates neuronal loss in both the ipsilateral and the contralateral cortex, a temporally distinct pattern of subcortical neuronal injury/death, and widespread white matter damage. These observations serve as an important baseline for studying human brain injury and optimizing therapies for the brain-injured child.

Age Factors↗
PubMed2001

Fatigue in multiple sclerosis is associated with abnormal cortical activation to voluntary movement--EEG evidence.

Converging evidence is consistent with the view that fatigue in Multiple Sclerosis is independent from pyramidal tract involvement, suggesting a possible involvement of frontal areas. During voluntary movement, changes of the EEG rhythms can be observed over sensorimotor areas. Event-related desynchronization (ERD) of the 10 and 20 Hz frequency bands occurs during motor planning and execution and is followed after movement termination by event-related synchronization (ERS), expressing cortical idling or inhibition. We evaluated the pattern of cortical activation to voluntary movement in MS patients complaining of fatigue assessed using the Fatigue Severity Scale. Fifteen MS patients complaining of fatigue, 18 MS patients without fatigue, and 14 normal controls were studied. The two patients groups were similar for age, sex, disease duration, and were not disabled (score <1.5 at the Expanded Disability Status Scale). Twenty-nine channel EEG was recorded during about 60 self-paced extensions of the right thumb. The onset latency and amount of the contralateral sensorimotor (C3 electrode) 10 and 18--22 Hz ERD were similar in the three groups. ERD was more widespread anteriorly in the fatigue group compared with normal controls (P < 0.01 over Fz electrode). Postmovement contralateral sensorimotor 18--22 Hz ERS was significantly lower in fatigue MS patients compared with normal subjects (P < 0.005) and with nonfatigue MS patients (P = 0.02). These findings are consistent with a central origin of fatigue in MS and indicate cortical dysfunction even during a simple motor task, resulting in hyperactivity during movement execution and failure of the inhibitory mechanisms intervening after movement termination.

Adult↗
PubMed1981

Pallido-luyso-nigral atrophy and amyotrophic lateral sclerosis.

Clinical and neuropathological studies of a case of pallido-luyso-nigral atrophy and amyotrophic lateral sclerosis (ALS) in a young woman with a strong likelihood of a similar familial past medical history have been presented. Microscopic examination revealed neuronal loss and gliosis of globus pallidus, corpus luysii and substantia nigra. Pallor of the pyramidal tracts and neuronal loss in hypoglossal nuclei and anterior horns with gliosis were present. The rarity of the association of a pallido-luyso-nigral atrophy and an ALS, the occurrence of an ALS at such a young age and the fact that her grandmother died of Parkinson disease at age 30 suggest that this association may represent more than a coincidental occurrence.

Adult↗
PubMed1996

Delayed neuronal damage following focal ischemic injury in stroke-prone spontaneously hypertensive rats.

We detected the delayed accumulation of 45Ca in the lateral part of the striatum 3 days after distal middle cerebral artery (MCA) occlusion in stroke-prone spontaneously hypertensive rats (SHRSP). However, the mechanism of delayed neuronal damage in the striatum, which is not supplied by the occluded MCA, remains unknown. The aim of this study was to evaluate whether the delayed damage involves alterations in the extracellular release of neurotransmitter monoamines and amino acids. Chronological changes in the distribution of neuronal damage were determined by 45Ca autoradiography. The microdialysis probes were inserted into either the medial or lateral part of the striatum. The dialysate content of monoamines, their metabolites and amino acids was determined by analytical techniques. 45Ca accumulation was detected only in the cortex and corpus callosum by 24 hours postischemia and extended to the pyramidal tract, thalamus and lateral portion of the striatum by 3 days. A 3-fold increase in glutamate content, and a 2-fold increase in dopamine content were observed only in the lateral part of the striatum following ischemia. The results suggest that excessive release of glutamate and dopamine is related to delayed neuronal damage that occurs in the lateral part of the striatum in this ischemic model.

Amino Acids↗
PubMed1995

Postnatal development of the human primary motor cortex: a quantitative cytoarchitectonic analysis.

The postnatal development of the human primary motor cortex (area 4) was analyzed in 54 individuals ranging in age from birth to 90 years. Three parameters defining major cytoarchitectonic features (areal fraction, numerical density and mean area of cells) were measured in vertical columns extending from the pial surface to the border between cortex and underlying white matter. The data were compiled in profile curves that reveal or more detailed laminar pattern than the classical cytoarchitectonic descriptions. The most pronounced decreases in numerical density and areal fraction of Nissl-stained cells profiles during early postnatal ontogeny are observed in layer II. A clearly delineable layer IV, which is still recognizable in the newborn, disappears gradually during the first postnatal months. Although the width of the cortex as a whole increases during this period, layer V, the main source of pyramidal tract fibers, is the only lamina that also increases in relative thickness. The other layers remain stable or become relatively thinner. These results reveal specific laminar growth processes in area 4, which take place in parallel with the functional maturation of the cortical motor system.

Adolescent↗
PubMedDate not supplied

Pharmacological evidence that protein kinase C modulates monosynaptic excitations in the olfactory cortex.

The possible occurrence and role of protein kinase C at the lateral olfactory tract (LOT)-pyramidal cell synapse of the rat olfactory cortex slice has been investigated by determining the effects of both activators (4-beta-phorbol-12,13,diacetate [PDAc] and 1,2-dioctanoyl-sn-glycerol) and inhibitors (5-isoquinolinylsulphonyl)-2-methylpiperazine [H-7], sangivamycin and polymyxin B) of the enzyme on the surface field potential known as the N-wave. PDAc (0.3 to 20 mumol/l) and 1,2-dioctanoyl-sn-glycerol (25 to 250 mumol/l) increased the area and amplitude of the potential. In control slices in which a population spike was recorded, PDAc also triggered the appearance of multiple spikes. In a series of input-output experiments, PDAc (2.5 or 5 mumol/l) increased the area and amplitude of the N-wave relative to that of the action potential but did not significantly affect pyramidal cell excitability. The effects of PDAc on the N-wave were antagonised by all three protein kinase C inhibitors but not by the calmodulin antagonist calmidazolium and were greater in slices perfused with solution containing 10 rather than 1 mmol/l Mg2+ or 1.25 rather than 5 mmol/l Ca2+. The effect of PDAc on the amplitude but not area of the N-wave was blocked by the potassium channel blocker tetraethylammonium (10 mmol/l) but not by 4-aminopyridine (0.25 mmol/l). In a series of conditioning experiments, PDAc (1 to 5 mumol/l) reduced the amplitude of the N-wave evoked by a second stimulus compared to that evoked by the first conditioning pulse.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Static firing rates of premotor and primary motor cortical neurons associated with torque and joint position.

Single cell activity was studied in the postarcuate premotor area (PMA) and primary motor cortex (MI) of two monkeys performing a load-bearing task with the contralateral hand. Steady-state discharge rates were examined in relation to positional maintenance of the wrist which was held in one of three given positions against graded torques directed towards flexion or extension. Significant and monotonic relationships between tonic firing rate and static torque were found in 41% of 477 MI cells and in only 26% of 470 units studied in PMA. However, for specific cell groups in the PMA the proportion of load-related neurons reached that of the MI samples; this was true for pyramidal tract neurons (PTNs) and for 'non-PTNs' if recorded in their vicinity. The most interesting difference pertains to the range of load over which cells in both areas modulated activity. MI neurons showed steepest change of firing rates over a limited range of small torques around zero external load; the population average displayed a sigmoidal relationship. Proportionally more PMA neurons increased their activity over the entire range of torques examined or showed the highest increase with stronger torques; the population average best fitted a quadratic function. The mean firing rate-torque slope of the PMA population was significantly smaller than that of MI. Many cells in either area were related to both torque and joint position and displayed correlates of length-tension properties of muscle. Change of position sensitivity with torque was found to parallel the rate-torque characteristics in individual neurons. Mean position sensitivity of PMA neurons increased with increasing torques in the 'preferred' direction. In contrast, greatest position sensitivity of the MI population occurred over the range of low torques, which means a clear quantitative dissociation from the muscular activities. The results suggest differential roles of MI and PMA in the control of 'fine' versus 'gross' muscular forces. Undoubtedly, some PMA cell elements (possibly certain output neurons) are involved in aspects of postural control of EMG adjustment to load and joint position.

Animals↗
PubMed1993

Disynaptic excitation from the medial longitudinal fasciculus to lumbosacral motoneurons: modulation by repetitive activation, descending pathways, and locomotion.

Short-latency excitatory postsynaptic potentials (EPSPs) evoked by stimulation in the medial longitudinal fasciculus (MLF) were recorded intracellularly from motoneurons in the cat lumbosacral spinal cord. Monosynaptic and disynaptic EPSPs occurred in most flexor and extensor motoneurons studied. These EPSPs resulted from the activation of fast (> 100 m/s) descending axons from the MLF to the spinal cord. Several features distinguished monosynaptic and disynaptic MLF EPSPs. Disynaptic EPSPs exhibited temporal facilitation during short trains of stimulation, whereas monosynaptic EPSPs did not. Disynaptic EPSPs, but not monosynaptic EPSPs, were also facilitated by stimulation of the pyramidal tract and the mesencephalic locomotor region. However, disynaptic MLF EPSPs exhibited little or no facilitation when conditioned by short-latency cutaneous pathways. During fictive locomotion, the amplitude of disynaptic MLF EPSPs was modulated, with maximal amplitudes during the step cycle phase when the recorded motoneuron was active, resulting in reciprocal patterns of modulation of flexors and extensors. No comparable change was seen in the amplitude of monosynaptic MLF EPSPs during fictive stepping. These data suggest that the central pattern generator for locomotion modulates disynaptic MLF excitation at a premotoneuronal level in a phase-dependent manner. The effects of lesions made in the MLF and thoracic cord suggest that the interneurons in the disynaptic pathway from the MLF to motoneurons reside in the lumbosacral cord.

Animals↗
PubMed1982

Supraspinal facilitation of cutaneous polysynaptic EPSPs in cat medical gastrocnemius motoneurons.

We examined the characteristics of postsynaptic potentials (PSPs) produced in antidromically-identified medical gastrocnemius (MG) alpha-motoneurons by electrical stimulation of low threshold (less than 3 x T) distal limb cutaneous afferents in the sural (SUR) nerve in adult cats anesthetized with alpha-chloralose, together with the effects of SUR PSPs of supraspinal conditioning stimulation of the contralateral red nucleus (RN) and pyramidal tract (PT). In the majority of MG motoneurons, SUR afferents with electrical thresholds less than 1.5 x T produced early excitatory synaptic potentials (EPSPs) with minimum central latency of about 2.0 ms, suggesting activation of a trisynaptic segmental pathway with two interposed interneurons. Such early EPSPs were often detectable with stimuli less than 1.2 x T, as determined by recording the compound action potential in the sciatic nerve and from the first appearance of the N1 wave of the cord dorsum potential. Inhibitory synaptic potentials (IPSPs) were regularly produced by SUR volleys of only slightly greater strength (often as low as 1.3 x T) and these had minimum central latencies of about 3.0 ms (about 1.0 ms longer than the earliest EPSPs), suggesting a three interneuron central pathway. Repetitive stimulation of RN and PT regularly produced facilitation of both EPSP and IPSP components in the SUR response, suggesting that these supraspinal systems directly or indirectly excite some of the same interneurons that convey the SUR effects to MG motoneurons. When using very low strength SUR stimuli, PT conditioning produced relatively pure facilitation of the SUR EPSPs but with larger SUr volleys, PT clearly facilitated both EPSPs and IPSPs. RN conditioning produced more parallel facilitation of SUR EPSPs and IPSPs. Supraspinal control of the polysynaptic pathway producing SUR EPSPs is of particular interest because of earlier evidence that this pathway is differentially distributed to motoneurons of fast twitch versus slow twitch MG motor units.

Animals↗
PubMed1981

Intracellular studies on cortical synaptic plasticity. Conditioning effect of antidromic activation on test-EPSPs.

1. An intracellular study on pyramidal tract (PT) neurons in the cat's motor cortex was carried out to examine whether their antidromic activation would be able to induce plastic changes in the efficacy of the synapses situated on their membrane. 2. The experimental paradigm was based on the principles of classical conditioning. It included habituation, pseudoconditioning, conditioning and extinction procedures. The antidromic spike was regarded as an unconditioned stimulus while excitatory postsynaptic potentials (EPSPs) evoked by thalamic (n. ventralis lateralis), callosal and somatosensory afferents served as conditioned stimuli. Stimulus pairs were given, consisting of EPSPs and antidromic spikes with various time intervals, and the stimulus sequences were at a 0.2--1.0/s frequency. 3. Reversible, short-term (3--28 min) enhancement of synaptic excitability was observed in 27% of the PT cells after conditioning with 60--150 stimulus pairs. 4. EPSP-spike and spike-EPSP sequences were equally effective, but plastic changes were induced only by stimulus pairs with less than 100 ms interstimulus intervals. 5. Facilitated EPSP states were frequently accompanied by changes in membrane potential, membrane resistance and firing activity. 6. In repeated conditioning series, the temporal parameters of conditioning changes, the number of stimuli necessary for full development of facilitation, and some membrane parameters showed marked alterations. 7. Conditioned plastic changes in synaptic efficacy showed analogies with associative learning: (a) they were specific to the pairing procedure, because randomized presentation of EPSPs and antidromic spikes never produced synaptic facilitation; (b) unpaired spike trains used as unconditioned stimuli (of 10--200/s frequency and 1--20 s duration) caused only a minor degree of facilitation as compared with EPSP-spike pairings; (c) changes in synaptic efficacy were subject to extinction. 8. The present findings indicate that the plastic changes in synaptic transmission may be localized to the postsynaptic membrane of the conditioned PT cells.

Action Potentials↗
PubMed1985

The responses of cat motor cortical units to electrical cutaneous stimulation during locomotion and during lifting, falling and landing.

Experiments were performed to examine the influence of cutaneous information on motor cortical cells during movement in intact, awake cats. The movements investigated were locomotion and a sequence in which the animal was repeatedly lifted and dropped. Electrical stimuli to distal skin areas were delivered periodically during the movements and responses of motor cortical cells were examined. The animals used in these experiments were chronically implanted with cortical microelectrodes, a pyramidal tract stimulating electrode, cutaneous stimulating electrodes in the forepaw, and a recording cuff electrode around the median nerve. EMG electrodes were implanted in several forelimb muscles and a length gauge was implanted across the elbow joint. Results included in this report were obtained from three cats. The twenty-two cortical units analysed in this study (seven were PT units) were selected from a larger sample by the following criteria: cutaneous receptive fields which included the distal part of the limb, consistent short latency responses to electrical cutaneous stimulation and spontaneous activity modulated in consistent patterns during the movement investigated. Sixteen units were recorded during locomotion, 12 during the lifting and dropping cycle and 6 of these during both conditions. Most of the cells were influenced by the cutaneous input during locomotion. Three units had no response to peripheral stimulation during locomotion though they were responsive to this stimulus when the animal was sitting quietly. All the cells were responsive to the cutaneous input during the lifting and dropping cycle. The responses to cutaneous stimuli were found to be modulated in relation to phases of the step cycle and the lifting and dropping cycle. In 13 units this modulation did not parallel the modulation of the unit's spontaneous firing during these activities. For these units a common finding during locomotion was that the response to cutaneous stimuli increased throughout stance, reached maximum during the flexion part of the swing, and then declined to a minimum during the beginning of the next stance. During the lifting and dropping cycle, the responses were greatest when the animal was held in the air and when starting to fall, and minimal just prior to and after landing. In both movements, cutaneous responses were reduced when the limb was used to support the animal's weight. There is apparently a movement phase-related modulation of cutaneous input to some motor cortical cells. This modulation of cutaneous input resembled the modulation of cutaneous reflexes during locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Sustained excitatory synaptic input to motor cortex neurons in awake animals revealed by intracellular recording of membrane potentials.

1. Most of the intracellular electrophysiological data on cortical neurons has been obtained in anesthetized or reduced preparations, and differs from observations in awake, intact animals. To determine whether these differences are due to experimental techniques or physiological factors, we recorded membrane potentials intracellularly from motor cortex neurons in chronically prepared cats and monkeys under Nembutal-anesthetized, Halothane-anesthetized, and unanesthetized conditions, or during transitions between anesthetized and awake conditions. 2. Resting membrane potentials were found to depend on the anesthetic state of the animal. Membrane potentials of neurons recorded in awake animals were more depolarized than those recorded in the anesthetized state. In the awake state membrane potentials were all less than -65 mV. 3. The input resistance of neurons recorded in awake animals were significantly smaller than those measured in the anesthetized state. Action potentials recorded in awake animals typically showed an undershoot (i.e. negative values at peak), implying that voltage-dependent conductances may be altered. Undershoot of the action potential was more prominent in pyramidal tract neurons (PTNs) than non-PTNs. 4. These data suggested that in awake animals motor cortex neurons, especially PTNs, receive sustained excitatory synaptic input or neuro-modulatory activities.

Action Potentials↗
PubMed1989

Short latency somaesthetic responses in motor cortex, transmitted through the spino-thalamic system, in the cat.

Evidence is presented that in the cat, the spinothalamic system contributes to short latency somaesthetic responses in motor cortex efferent cells. Intracellular recordings performed on identified pyramidal tract cells and corticospinal cells show that these cells are still activated and/or inhibited from the periphery after a set of central nervous lesions leaving intact only the ventral half of the spinal cord. The responses were attributed to the spinothalamic system. The ascending system is activated through collaterals of afferent fibres running in the dorsal columns of the spinal cord. This peripheral link to the motor cortex might participate in updating the motor command on the basis of information feedback from the periphery.

Action Potentials↗
PubMed1996

Intra-axial endophytic primitive neuroectodermal tumors in the pons: clinical, radiological, and immunohistochemical aspects in four children.

We present the clinical findings, radiological aspects, operative results, and histopathological features of four typical primitive neuroectodermal tumors (PNET) located in the pontine region in children. All the tumors had an endophytic intra-axial growth pattern. All the children had a short history of severe neurological deficits with involvement of the cranial nerves and pyramidal tract. MRI did not reveal any common feature of malignancy. Compared to our successful experience in operations of intra-axial endophytic brainstem tumors in a total of 32 children, the outcome was poor: all 4 children died within 13 months. We conclude that PNET occurring in the pons is not as rare as was believed, and, compared to PNET in other areas the prognosis is worse.

Actins↗