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Sites of action of segmental and descending control of transmission on pathways mediating PAD of Ia- and Ib-afferent fibers in cat spinal cord.

The present series of investigations was aimed to disclose the possible sites of action of excitatory and inhibitory inputs on tho-interneuron pathway mediating the primary afferent depolarization (PAD) of group I afferents of extensor muscles in the cat spinal cord. To this end we compared the effects produced by stimulation of segmental and descending pathways on the PAD generated either by stimulation of group I fibers of flexor muscles or by intraspinal microstimulation. It was assumed that under the appropriate conditions the PAD produced by intraspinal microstimulation results from the activation of the last-order interneurons in the PAD pathway and may, therefore, allow detection pathway. The PAD of single group I afferent fibers was determined in barbiturate-anesthetized preparations by measuring the test stimulus current required to maintain a constant probability of antidromic firing. This was achieved by means of a feedback system that continuously adjusted the test stimulus current to the required values. The PAD of individual group Ia gastrocnemius soleus (GS) fibers that is produced by activation of the low-threshold afferents of the posterior biceps and semitendinosus nerve was found to be inhibited by conditioning stimulation of the relatively low-threshold cutaneous fibers and also by stimulation of supraspinal structures such as the ipsilateral brain stem reticular formation, the contralateral red nucleus, and the contralateral pyramidal tract. In contrast, the PAD of group Ia fibers produced by microstimulation applied in the intermediate nucleus could be inhibited only by stimulation of the brain stem reticular formation but not by stimulation of the other descending inputs presently tested or by stimulation of cutaneous nerves. PAD of group Ia fibers was produced also by microstimulation applied within the motor nucleus. However, in most fibers the resulting PAD could not be inhibited either by stimulation of the brain stem reticular formation, the red nucleus, the pyramidal tract, or cutaneous nerves. Stimulation of cutaneous and of flexor muscle nerves of the brain stem reticular formation, the red nucleus, and the pyramidal tract all produced PAD of the group Ib GS fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Globoid cell leukodystrophy: distinguishing early-onset from late-onset disease using a brain MR imaging scoring method.

BACKGROUND AND PURPOSE: Our purpose was to determine the characteristic MR features of early-onset (before age 2 years) versus late-onset (after age 2 years) globoid cell leukodystrophy (GLD). METHODS: Thirty-four brain MR images in 22 patients with GLD were reviewed. A severity score (0 to 32), based on a point system derived from the location and extent of disease and the presence of focal and/or global atrophy, was calculated for each examination. RESULTS: Of the 22 patients, three were asymptomatic and 19 were symptomatic. Ten patients had early-onset disease, whereas nine had late-onset disease. MR images of all patients showed abnormalities. In the early-onset group (n = 10; mean maximum MR score, 8.1; range, 3-18), 90% had pyramidal tract involvement, 80% had cerebellar white matter involvement, 70% had deep gray matter involvement, 60% had posterior corpus callosal involvement, 50% had parietooccipital white matter involvement, and 40% had cerebral atrophy. Serial MR imaging in four of these patients revealed progressive disease. In the late-onset group (n = 9; mean maximum MR score, 5.6; range, 4-10), 100% had pyramidal tract involvement, 100% had parietooccipital white matter involvement, 89% had posterior corpus callosal involvement, and none had cerebellar white matter involvement, deep gray matter involvement, or cerebral atrophy. Serial MR imaging in one patient with late-onset GLD did not reveal any change. A spectrum of findings was observed in the three patients who were asymptomatic. CONCLUSION: Cerebellar white matter and deep gray matter involvement are present only in early-onset GLD. Pyramidal tract involvement is a characteristic finding in both early- and late-onset GLD. This scoring method for brain MR observations will assist in the objective assessment of the impact of hematopoietic stem cell transplantation in patients with GLD.

Adolescent↗

White matter injury in amyotrophic lateral sclerosis (ALS).

Microscopic examination of 6 brains and spinal cords of patients deceased of amyotrophic lateral sclerosis reveals as follows: 1) White matter changes considerably exceeding those found in motor neurons structures. 2) They involve white matter of frontal, temporal and parietal lobes including long association fibers. 3) Pyramidal tracts are extremely damaged within spinal cord and medulla. 4) Within spinal cord besides pyramidal tracts majority of ascending and descending pathways are damaged. 5) Pathomechanism of white matter changes seems to be complex. Within brain hemispheres predominate nonspecific changes, 6) Imaging methods in ALS bring a diagnostic progress but at present the conclusions on specificity of changes encountered in various imaging methods in different diseases seem to be precautions.

Adult↗

Functional properties of monkey motor cortex neurones receiving afferent input from the hand and fingers.

1. Records have been made from area 4 of the cerebral cortex in five conscious monkeys. The properties of 216 neurones responsive to natural stimulation of the hand and fingers have been investigated.2. 46% of these neurones responded only to cutaneous stimulation (especially light brushing across the glabrous skin) and a further 38% responded only to movement of the digits. 4% responded to brief prods of the hand. 12% of the sample responded to more than one stimulus modality.3. Many hand-input neurones, including pyramidal tract neurones, responded at short-latency (8-15 msec) to light mechanical stimulation of the hand and to weak electrical stimulation of the median nerve.4. Responsive neurones were found at all depths of the cortical grey matter. Responses of shortest latency were encountered in neurones probably located in layers IV and V.5. The behaviour of eighty hand-input neurones was analysed during a simple, stereotyped task which involved pulling a lever and collecting a food reward from a small well. For comparison, the activity of 117 neurones with inputs from the wrist, elbow or shoulder was also analysed.6. Nearly all hand-input neurones modulated their activity either before (48/80) or during (29/80) the retrieval of the reward which required precision grip between index finger and thumb. Many were silent during proximal arm movements and some displayed activity patterns independent of these movements.7. By contrast, the activity of many neurones with proximal arm (elbow, shoulder) inputs was unrelated to food retrieval and manipulation, but well related to arm movements.8. Forty-three of the eighty neurones had cutaneous input from the hand. Twenty-seven were active before hand contact. Thirty-five modulated their discharge when contact was made (twenty-one excitation, fourteen inhibition).9. Most hand-input neurones were more active during fractionated movements of the hand or fingers than during power or ball grips requiring simultaneous flexion of all digits. Neurones with glabrous inputs often showed intense activity during small, precise finger movements and during active tactile exploration without the aid of vision.10. Analysis of the discharge frequency of twenty-five hand-input neurones revealed that some (mainly non-pyramidal tract neurones) had a similar mean frequency and range of modulation during both active movement and passive stimulation. Others (mainly pyramidal tract neurones) had a greater frequency range and higher mean frequency during active than during passive movements.

Action Potentials↗

[Surface negative waves in penicillin-induced epileptogenesis in cats].

The "surface negative (SN) wave" produced by pyramidal tract stimulation and recorded at the cortical surface has been identified as a reflection of postsynaptic potentials generated through recurrent inhibitory pathways (Humphrey, et al.). We studied changes in SN wave in an attempt to examine inhibitory mechanisms underlying epileptogenesis in immobilized cats. 1) A single shock applied to the cerebral peduncle evoked alpha and beta wave at the surface of ipsilateral anterior sigmoid gyrus (Fig.1 A). A train of 4 shocks with 4 msec shock-interval elicited SN wave which had a peak latency of 20 msec and decayed in 60-80 msec (Fig. 1 B,C,D). 2) The spindle-like after-discharges elicited by direct cortical shock were markedly suppressed with conditioning stimulation of the ipsilateral pyramidal tract (Fig. 2). Spike-and-wave complexes and other ECoG paroxysms produced by intramuscular administration of penicillin (Pc) were also depressed by repeated stimulation of the cerebral peduncle (Fig. 3). These facts revealed that the inhibitory effects of pyramidal tract stimulation caused to suppress the occurrence of epileptic discharges. 3) SN wave gradually diminished in amplitude after topical application of Pc at the anterior sigmoid gyrus (Fig. 4 A-D). It disappeared completely when tonic-clonic sustained paroxysms occurred at the focus (Fig. 4 E). These effects are due presumably to depression of recurrent postsynaptic inhibition caused by topical penicillin. 4) SN wave observed at the contralateral secondary focus was almost unchanged during interictal and ictal stage (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway of the cat. II. Responses of single cells in the pontine nuclei.

Extracellular and intracellular recordings were made from single cells in the pontine nuclei (PN) of the cat. PN cells were identified by antidromic invasion from the cerebellum by stimulating either the brachium pontis (BP) or the white matter near the cerebellar nuclei. The cerebrally-induced impulses excited PN cells postsynaptically with a monosynaptic latency. Both fast and slow conducting cortical fibres contributed to the corticopontine excitation, so that the latency varied over a wide range. Measurements of the latencies for antidromic and corticopontine excitation and of the distances between stimulated sites permitted the calcuation of conduction velocities of PN cell axons and of their cortical input fibres. PN cells with fast conducting axons received convergence from both fast and slow cortical fibres, whereas PN cells with slow axons were innervated only by slow cortical fibres. The majority of PN cells were also excited by stimulating the medullary pyramid through collaterals of the pyramidal tract. Evidence of abundant pyramidal collaterals was provided by the collision technique. The functional role of the PN is discussed in connection with the cerebro-cerebellar loop circuits.

Animals↗

Repetitive sleep starts in neurologically impaired children: an unusual non-epileptic manifestation in otherwise epileptic subjects.

Sleep starts, also called hypnagogic or hypnic jerks, are bilateral, sometimes asymmetric, usually single, brief body jerks that coincide with sleep onset. We describe sleep starts occurring repetitively in three epileptic children with spastic-dystonic diplegia and mental retardation. Repetitive sleep starts began at age 18 months in two children and at 9 months in the third. All three children had had feto-neonatal asphyxia; two presented with spastic and one with dystonic tetraparesis. One had West syndrome and two had partial motor seizures in the first year of life. Seizures were controlled in all three patients by antiepileptic drug therapy. Video/EEG recordings of all the children during the afternoon nap revealed clusters of sleep starts during the transition between wakefulness and sleep. Cluster lasted 4-15 min and comprised from twenty to twenty-nine contractions. The EEG counterpart of the event sometimes showed an arousal response, at times inducing complete awakening. Repetitive sleep starts should be recognized and clearly differentiated from epileptic seizures, especially if they appear in epileptic subjects. In neurologically compromised patients, they could represent an intensification of an otherwise normal event, due to the lack of strong inhibitory influence of the pyramidal tract resulting from the pyramidal lesion.

Cerebral Cortex↗

Motor evoked potentials elicited from pyramidal stimulation and recorded from the spinal cord in the rat.

This study investigated the spinal evoked response to focal electrical stimulation of the sensorimotor cortex in 32 rats. The results demonstrate a long-latency response (beginning at 8 milliseconds) elicited by electrical stimulation, which is distinct from the short-latency motor evoked potential previously reported. The conduction velocity of this later response is similar to that reported for the pyramidal tract in the rat. Experiments confirm that the longer latency response depends upon the integrity of the pyramidal system. Focal stimulation outside the sensorimotor cortex failed to elicit a response. Experimental lesions of the pyramidal tract or ablating the sensorimotor cortex eliminated the spinal cord evoked response. The results demonstrate that focal stimulation of the sensorimotor cortex results in a spinal cord evoked response that represents activity within the pyramidal system. The utility of this response in the rat model for assessing experimental cord injury is discussed.

Animals↗

Transient spinal inhibition induced by electrical stimulation of the rat brain.

Intracortical electrical stimulation of the rat brain using single pulse induced motor evoked potentials (MEPs) with shorter onset latencies in the bilateral extremity muscles. The MEPs appeared in the stimulation of cortical areas outside the motor cortex (MI) and subcortical areas. Train-pulse stimulation of the MI at a stimulus intensity just above the threshold induced MEPs with longer onset latency in muscles corresponding to the somatotopy of the MI stimulated. This implies that the potential characterizing shorter onset latency is equal to responses induced via the extrapyramidal tract, and responses with longer onset latency originate in the pyramidal tract. Corresponding to MEPs, we recorded two types of spinal potentials (SPs) via extrapyramidal and pyramidal tracts. In paired-pulse stimulation of the extrapyramidal tract, second MEPs showed a long-lasting inhibition up to 3 s after the first MEPs, while the changes in second SPs were not remarkable. Extrapyramidal tract stimulation inhibited H-reflex in the same manner as MEPs. These results suggest that the electrical stimulation of rat brain has a long-lasting effect in inhibiting lower motoneuron excitabilities. Our method may be a useful experimental model to induce the transient inhibition of spinal motoneuron excitabilities caused by supraspinal structures.

Animals↗

Neural correlates of the results-of-action acceptor in a functional biotechnical complex.

This report presents data illustrating the neurophysiological features of efferent-afferent convergence on cortical neurons. During combination of stimulus of pyramidal tract axons with electrocutaneous reinforcement, some of the study neurons were found to change the parameters of their activity evoked by stimulation of this tract: evoked responses started to reproduce the structure of responses to the reinforcement. The most dynamic rearrangements of pyramidal tract responses were obtained in experiments in which the study neurons were included in a biotechnical complex with feedback, the complex consisting of "neuron-computer-stimulator-animal" and actually being an analog of a natural functional system. The role of efferent-afferent convergence on CNS neurons in the development of the results-of-action acceptor of a functional system for a voluntary behavioral act is discussed.

Afferent Pathways↗

The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway of the cat. I. Responses in the brachium pontis.

Cerebrally-induced responses of pontine nuclei cells (PN cells) were studied in cats anesthetized with pentobarbitone sodium and with the midbrain transected bilaterally sparing only the cerebral penuncles. After stimulating the subcortical white matter, the internal capsule or the cerebral peduncle, mass potentials were recorded from the cut end of fibres in the brachium pontis (BP) and in the pyramid at the level of the trapezoid body. These potentials were regarded as indicating, respectively, the size of an output volley of PN cells and the size of its causative input volley through the pyramidal tract. BP responses consisted of short- and long-latency potentials which were caused by fast and slow conducting pyramidal tract volleys, respectively. The input-output relations for fast component responses took a characteristic S-shaped form resembling those obtained from the monosynaptic spinal reflex. The input-output relations for slow component responses were almost linear. Both fast and slow BP responses were remarkably potentiated after single or relatively brief repetitive peduncular stimulation, but were depressed after long-lasting high-frequency activation. During repetitive stimulation with varied frequencies, fast and slow BP responses showed different patterns of frequency-dependence of their amplitudes. These results suggest the existence of two separate transmission lines with different properties in cerebro-ponto-cerebellar pathways.

Animals↗

Projection from area 3a to the motor cortex by neurons activated from group I muscle afferents.

Two receiving areas in the pericruciate cortex are known for inputs from group I muscle afferents of forelimb nerves. One focus is near the postcruciate dimple of area 3a, and the other in the lateral sigmoid gyrus of the motor cortex (area 4gamma). The cortico-cortical projection of area 3a to 4gamma, and the relay by this projection of group I muscle afferent input to the motor cortex were investigated in cats. The following results were obtained. 1. Seventy-four neurons within area 3a were antidromically activated by intracortical microstimulation of the motor cortex. 2. Although excitation evoked by stimulation of group I muscle afferents could be demonstrated for only a few (8 of 48) cortico-cortical neurons in extracellular recordings, due to the methodological limitations discussed, this input evoked EPSPs in 8 of 9 cortico-cortical neurons recorded intracellularly. Therefore, it is likely that the majority of neurons projecting from area 3a to the motor cortex have an excitatory synaptic input from group I afferents. 3. Neurons projecting from area 3a to the motor cortex were most commonly found in cortical layer III, although some were found in layer V. 4. Five of nine pyramidal tract neurons of area 3a had a strong excitatory synaptic input from group I muscle afferents. 5. A new type of pyramidal tract neuron was found which has cortico-cortical axon collaterals connecting the two cytoarchitectonic regions. These various neurons may be part of a feedback system from muscle afferents to the motor cortex.

Afferent Pathways↗

[Features of the antidromal and synaptic activation of neurons of the Bekhterev nucleus reticularis tegmenti pontis induced by cortico- and cerebello-fugal spiking].

Antidromic activation on the Bechterew nucleus neurons with stimulation of brachia pontis and conjunctivum as well as cerebellar central nuclei and pyramidal tract, was studied in anesthetized cats. The Bechterew nucleus neurons were found to receive direct activating inputs from brachium conjunctivum, cerebellar central nuclei and the pyramidal tract. Convergence of the inputs in single neurons was shown to exist.

Animals↗

A morphometric comparison of central and peripheral hypomyelination induced by postnatal undernourishment of rats.

Developing Long-Evans rats were undernourished to produce a body-weight deficit of 39% at the age of weaning. Well-nourished litter mates were used as controls. Morphometric analyses were made of pyramidal tracts and posterior tibial nerves of each animal. In measuring pyramidal tract, we observed that axonal circumferences of myelinated fibers were smaller in the undernourished rats and that the number of myelin lamellae per axon appeared reduced by a small amount. The most striking observation in the undernourished rats compared to the controls was that the proportion of myelinated fibers was decreased by 40% at 20 days of age. Axon circumferences of nonmyelinated axons were not measured. Similar decreases were observed in myelinated axon circumference and myelin lamellae of posterior tibial nerves of undernourished rats. Because of sampling problems, we did not attempt to compare the proportion of myelinated and nonmyelinated fibers in posterior tibial nerves of undernourished and well-nourished rats. These morphometric data, particularly the reduction of myelinated fibers, are consistent with biochemical studies of brain hypomyelination in undernourished rats. The data indicate that the mechanism of hypomyelination in nutritionally deprived rats involves a failure of the "trigger" by which myelin-forming cells begin to sheath axons in myelin.

Animals↗

Dysarthria in acute ischemic stroke: lesion topography, clinicoradiologic correlation, and etiology.

BACKGROUND AND PURPOSE: Although dysarthria is a frequent symptom in cerebral ischemia, there is little information on its anatomic specificity, spectrum of associated clinical characteristics, and etiologic mechanisms. METHODS: An investigation of 68 consecutive patients with sudden onset of dysarthria due to a single infarction confirmed by MRI or CT was conducted. RESULTS: Dysarthria was associated with a classic lacunar stroke syndrome in 52.9% of patients. Isolated dysarthria and dysarthria-central facial and lingual paresis occurred in 2.9% (n = 2) and 10.3% (n = 7), respectively. Dysarthria-clumsy hand syndrome was observed in 11.7% (n = 8) of patients and associated with pure motor hemiparesis and/or ataxic hemiparesis in 27.9% (n = 19). The lesions were due to small-vessel disease in 52.9% (n = 36), to cardioembolism in 11.8% (n = 8), and to large-vessel disease in only 4.4% (n = 3) of cases. Infarctions were located in the lower part of the primary motor cortex (5.9%; n = 4), middle part of the centrum semiovale (23.5%; n = 16), genu and ventral part of the dorsal segment of the internal capsule (8.8%; n = 6), cerebral peduncle (1.5%; n = 1), base of the pons (30.9%; n = 21), and ventral pontomedullary junction (1.5%; n = 1). Isolated cerebellar infarctions affected the rostral paravermal region in the superior cerebellar artery territory. CONCLUSIONS: Extracerebellar infarcts causing dysarthria were located in all patients along the course of the pyramidal tract. This finding correlates with the frequent occurrence of associated pyramidal tract signs in 90.7% (n = 62) of patients. Isolated cerebellar infarcts leading to dysarthria were in all cases located in the territory of the superior cerebellar artery.

Adult↗

Non-myelinated axons are rare in the medullary pyramids of the macaque monkey.

Previous electron microscopic studies of the medullary pyramids have concluded that non-myelinated axons constitute about 30-60% of all axons in the pyramid of the rat, and about 8-15% in the cat and monkey. Physiological studies of pyramidal tract axons have not found fibers conducting in the range predicted for non-myelinated axons, less than 1 m/s. This present study of the primate pyramid demonstrates that most of the profiles which could be interpreted as being non-myelinated axons when viewed in cross-section, are actually astroglial processes when examined in longitudinal section. We conclude that non-myelinated axons constitute less than 1% of the pyramidal tract axons in the old world adult primate.

Animals↗

Conduction properties of identified neural pathways in the central nervous system of mice in vivo.

Various lines of transgenic or knockout mice are now available that have abnormalities in neuron, glial cells or neuron-glial interaction. However, the techniques for quantitative analysis of their pathophysiological functions are still limited. We established an experimental model system to measure the properties of nerve conduction of identified neural pathways in the CNS using anesthetized and immobilized mice. Dorsal column (DC), vestibulospinal/reticulospinal tracts (VRST) and pyramidal tract (PT) were stimulated by inserting stimulating electrodes into the dorsal column nuclei, medial longitudinal fasciculus, and the medullary pyramid, respectively. Volleys were recorded at various segments in the cervical spinal cord with surface electrodes, and their conduction velocities (CVs) and relative refractory periods (RRPs) were measured. The CVs of the DC, VRST and PT were 26.25 +/- 4.96 m/s (n = 7), 51.55 +/- 4.65 m/s (n = 7), 8.89 +/- 1.81 m/s (n = 7), respectively. Data from paired stimulation indicated that the median values of RRPs of the DC, VRST and PT were 10, 2 and 4 ms, respectively, which suggested marked difference among individual tracts. This is the first attempt to measure the conduction properties of the central tracts in mice in vivo. This experimental procedure will give us a physiological measure of CNS functions in normal and genetically manipulated mice and contribute to clarifying the molecular mechanisms and pathophysiology of neurodegenerative diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).

Animals↗

Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids.

OBJECTIVE: To provide clinical, MRI, and histopathologic findings in a rare white matter disorder with autosomal dominant inheritance, so-called hereditary diffuse leukoencephalopathy with spheroids (HDLS). BACKGROUND: Progressive leukoencephalopathies often constitute a diagnostic dilemma in both children and adults. In some cases, histopathologic examination of brain tissue is required for a classifying diagnosis. METHODS: Clinical history, MRI, and autopsy findings were reviewed in three patients with HDLS: a father, his daughter, and an unrelated patient. RESULTS: Clinical history consisted of an adult-onset neurologic deterioration with signs of frontal lobe dysfunction, epilepsy, spasticity, ataxia, and mild extrapyramidal disturbances. MRI findings included cerebral atrophy and patchy white matter changes, most pronounced in the frontal and frontoparietal area with extension through the posterior limb of the internal capsule into the pyramidal tracts of the brainstem. Autopsy in two patients revealed a leukoencephalopathy with frontoparietal and frontal preponderance and numerous neuroaxonal spheroids in the abnormal white matter. The pyramidal tracts were affected throughout the brainstem. CONCLUSION: Similar clinical and histopathologic findings have been reported in members of a Swedish pedigree. The homogeneity of the findings strongly suggests that HDLS is a distinct disease entity. In the absence of a biochemical or genetic marker, a definitive diagnosis requires histopathologic confirmation in one of the affected family members. Neuroaxonal spheroids.

Adult↗