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Biomedical subjects

C H Markham

Publications and source records attributed to C H Markham.

At least 73 records · Page 4Linked to original sources

Direct projection of pause neurons to nystagmus-related excitatory burst neurons in the cat pontine reticular formation.

Brain-stem pause neurons (PNs) are inhibitory neurons which cease their tonic firing about 20 ms prior to the quick phase of horizontal vestibular nystagmus in either direction. One group of nystagmus-related burst neurons just rostral to the abducens nucleus exhibits a burst of spikes before and during the quick phase to the ipsilateral side--excitatory burst neurons (EBNs). The present study supported the conclusion that PNs project to, and tonically inhibit EBNs during the slow phase and that the burst of activity of EBNs at the quick phase is partly caused by the abrupt release from pauser inhibition. The evidence leading to this conclusion is: simultaneous recording of PNs and EBNs showed close alternation of firing; PNs were antidromically activated from the EBN region; systematic microstimulation tracks within the EBN region showed an antidromic activation pattern of low threshold sites separated by high threshold sites consistent with PN axonal branching in the EBN region; during the nystagmus slow phase there were positive field potentials in the EBN region, followed by an abrupt negative deflection whose onset was synchronous with the last pauser spike; when single PN spikes were used to trigger averages of extracellular field potentials in the EBN region (postspike averaging), a consistent short-latency positivity was observed. This study shows an additional connection in the premotor neural network responsible for the generation of the quick phase of horizontal vestibular nystagmus.

Action Potentials↗

Ocular counterrolling as an indicator of vestibular otolith function.

Sixteen normal subjects, 8 patients with unilateral vestibular nerve section, and 11 patients with acoustic neuromas underwent dynamic ocular counterrolling (OCR) testing. Both eyes were photographed at every 10 degrees as the subject was tilted about the naso-occipital axis at a constant velocity of 3 degrees/sec. Normal subjects differed from patients in four characteristics: (1) The binocular OCR patterns of normal subjects were consistent from one trial to the next. (2) The two eyes were mostly conjugate in movement. (3) The patterns were smooth. (4) OCR was approximately symmetric to right and left tilts. In the patients, patterns were abnormal when tilted to the side opposite the lesion. In quantified measures of the four characteristics, differences between the normal group and the group of patients with unilateral vestibular nerve sections were significant in consistency and total scores. In the patients with acoustic neuromas, OCR abnormalities corresponded to the size and location of the tumors and the extent to which they impinged on the utricular nerve and brainstem.

Adult↗

Evaluating the evaluations: or how to weigh the scales of parkinsonian disability.

We used four disability scales to evaluate eight patients with Parkinson's disease who were treated with pergolide mesylate for 1 year. Disability was rated on all four scales by the same neurologist at each of 11 visits. Prior ratings were not available to the examiner, who did not know that the scales themselves were an object of study. Disability scores, converted to percentage improvement relative to baseline, varied considerably between scales; for instance, at 5 months, one showed 13% improvement and another 58%. At 9 months, one showed worsening of 6% and another showed improvement of 34%. The four disability scales clearly measure different aspects of parkinsonism, and comparing results of different studies may not be valid if the disability scales are not the same.

Drug Evaluation↗

Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan.

Patterns of local cerebral glucose utilization were measured with positron emission, computed tomography using the 18F-fluorodeoxyglucose method in 13 patients with Huntington's disease (HD), 15 subjects at risk for HD, and 40 normal control subjects. These data were compared with computed tomographic measures of cerebral atrophy, with age, and with duration and severity of symptoms. The results indicate that in HD there is a characteristic decrease in glucose utilization in the caudate and putamen and that this local hypometabolism appears early and precedes bulk tissue loss. In contrast to patients with senile dementia, in these HD patients glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite apparent shrinkage of brain tissue. Our results suggest the possibility that the caudate may be hypometabolic in some asymptomatic subjects who are potential carriers of the autosomal dominant gene for HD.

Adolescent↗

Cat medial pontine reticular neurons related to vestibular nystagmus: firing pattern, location and projection.

In alert cats, extracellular spikes of neurons in the medial pontine tegmentum were recorded simultaneously with whole nerve discharges of the abducens and medial rectus nerves during horizontal vestibular nystagmus. Nystagmus-related neurons were classified by their firing patterns in relation to the abrupt cessation of the slow phase nerve activity of abducens or medial rectus nerves. The ipsilateral abducens nucleus was electrically stimulated to examine the axonal projections of physiologically identified examples of each category of neurons. Anatomically, pause units clustered near the midline at the rostral pole of the abducens nucleus. Long- and medium-lead burst units were 1-4 mm rostral to the area for pause units. Most burst-tonic units, clearly distinguished from nearby axons of passage, were found close to the MLF. Physiologically, it was concluded that: (1) some long-lead burst units terminate in the abducens nucleus and may excite motoneurons and/or internuclear neurons; (2) pause units directly inhibit burst inhibitory neurons which terminate slow phase activities of contralateral abducens motoneurons; (3) burst-tonic units fire in a manner very similar to contralateral abducens motoneurons; and (4) some medium-lead burst, long-lead burst and burst-tonic neurons (but not pause neurons) project to the cerebellar flocculus.

Abducens Nerve↗

Arborization of axons in oculomotor nucleus identified by vestibular stimulation and intra-axonal injection of horseradish peroxidase.

Axons in the medial rectus (MR) subdivisions of the oculomotor nucleus were identified by horizontal rotation and by electrical stimulation of the vestibular nerves and abducens nuclei. Three types of axons (vestibular type I and II and abducens interneurons) were then injected intra-axonally with horseradish peroxidase (HRP). Each injected axon was reconstructed under the microscope in the frontal and horizontal planes and terminal arborization and boutons contacting with MR motoneurons were studied. The MR motoneurons were identified by retrograde uptake of HRP, HRP being injected in the MR muscle prior to the intra-axonal experiment. The main types of horizontal canal-related axons were as follows: (1) ATD-unilateral termination axons: Most type I axons were of this type. Axons ascended in ascending tract of Deiters (ATD) to the oculomotor nucleus and terminated in ipsilateral MR area. (2) ATD-bilateral termination axons: Very few secondary canal responsive axons were in this group. Axon ascended in ATD to the oculomotor nucleus and terminated in MR motoneuron areas bilaterally and in Edinger-Westphal nucleus. (3) MLF-bilateral termination axons: Most type II neurons were in this group. Axons went up in the contralateral MLF and into both oculomotor nuclei. Their branches distributed to several motoneuron areas but only infrequently to the MR area; and to the Edinger-Westphal nucleus. (4) AB interneuron axons: Axons ascended in the MLF contralateral to cells of origin and terminated in the contralateral MR motoneuron area.

Abducens Nerve↗

Evidence to support early levodopa therapy in Parkinson disease.

To see whether duration of disease or of levodopa treatment was responsible for gradual worsening of parkinsonian patients, 58 persons treated with levodopa were classified into three groups based on predopa disease duration. Data over 6 years of treatment showed that disease duration was the determining factor. Patients matched for disease duration had similar disability scores regardless of duration of therapy. Matched for therapy duration, patients with longer disease duration had consistently higher disability scores. Side effects showed no differences between groups and did not increase over time. In sum, delaying therapy fails to improve disability in the early years of disease and does not confer any benefit in later years.

Athetosis↗

Eye movement related neurons in the cat pontine reticular formation: projection to the flocculus.

This study examines projection to the cerebellar flocculus of eye movement-related neurons in the median and paramedian part of the cat pontine tegmentum between the trochlear and the abducens nucleus. They were identified by rhythmic activity related to horizontal vestibular nystagmus induced by sinusoidal rotation. These neurons were classified into several groups by their discharge patterns during nystagmus, using criteria of earlier studies on saccadic eye movements and vestibular nystagmus in the monkey. Electrical stimulation of the ipsilateral flocculus elicited antidromic spike responses in a number of burst-tonic neurons and long-lead and medium-lead burst neurons. These neurons were located in and around the medial longitudinal fasciculus, the nucleus raphe pontis and the nucleus reticularis tegmenti pontis. A few neurons tested were also activated antidromically by stimulation of the contralateral flocculus. In contrast, no pauser neurons were activated from the ipsilateral flocculus. It is concluded that eye movement-related neurons in the medial pontine tegmentum, except for pauser neurons, directly project to the flocculus and may convey information about eye movements of visual and vestibular origins to the flocculus.

Abducens Nerve↗

Direct inhibitory projection of pause neurons to nystagmus-related pontomedullary reticular burst neurons in the cat.

Brainstem pause neurons (PNs) exhibit a tonic discharge during the slow phase of horizontal vestibular nystagmus and pause prior to and during the quick phase in both directions. One type of pontomedullary burst neurons, burst inhibitory neurons (BINs), show a high frequency burst of spikes before and during the quick phase to the ipsilateral side and this burst directly inhibits contralateral abducens motoneurons, terminating the slow phase firing of these motoneurons. The present study focused on synaptic relations between PNs and BINs. The following data supported the conclusion that PNs probably make direct inhibitory connections with BINs and produce IPSPs in BINs during the slow phase of horizontal vestibular nystagmus: (a) there were positive field potentials in the BIN area during the slow phase; (b) PNs were antidromically activated from BIN areas bilaterally; (c) systematic microstimulation of the BIN area revealed a pattern consistent with axonal branching in the BIN area; (d) repetitive microstimulation of the PN area induced a positive shift in the field potential in the BIN area and suppressed both the characteristic bursts of BINs and nystagmic activity of the contralateral abducens nerve; (e) microstimulation of the PN area during intracellular recording of BINs induced monosynaptic latency hyperpolarizing potentials which could be reversed by C1- injection; (f) during intracellular recording from BINs during vestibular nystagmus in either direction, the membrane potential during the slow phases had a tonic hyperpolarization which was shown to be due to IPSPs by means of C1- injection. This study suggests that burst activity of BINs during the quick phase is caused by abrupt release from PN IPSPs (disinhibition), besides some excitatory inputs from other sources.

Afferent Pathways↗

Cat primary canal neurons: relation of conduction velocity to resting and dynamic firing characteristics.

Spontaneous discharge patterns of first-order canal afferents were analyzed in cats anethetized with pentobarbital sodium with particular emphasis on the relationship of regularity of resting discharge, sensitivity to angular acceleration and adaptation to the time delay between electrical labyrinthine stimulation and recording from afferents near Scarpa's ganglion. Regular units were found to have a high resting rate, low sensitivity to angular acceleration, were mostly nonadapting during prolonged acceleration and showed relatively long latency to electrical stimulation. Irregular units tended to have a low resting rate, high sensitivity, frequently showed adaptation and had short latencies. Intermediate neurons had mixed characteristics of regular and irregular units. In medulated nerve fibers, a direct relation exists between conduction velocity and fiber diameter. As latency is due primarily to conduction in the first-order axon, we may speculate that regular neurons have thin fibers which innervate the slope of the crista, irregular neurons have thick fibers which innervate the summit, and intermediate units have medium caliber fibers which innervate both the slope and summit of the crista ampullaris.

Animals↗