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Biomedical subjects

W M King

Publications and source records attributed to W M King.

At least 37 records · Page 2Linked to original sources

Deficits in auditory temporal and spectral resolution in language-impaired children.

Between 3 and 6 per cent of children who are otherwise unimpaired have extreme difficulties producing and understanding spoken language. This disorder is typically labelled specific language impairment. Children diagnosed with specific language impairment often have accompanying reading difficulties (dyslexia), but not all children with reading difficulties have specific language impairment. Some researchers claim that language impairment arises from failures specific to language or cognitive processing. Others hold that language impairment results from a more elemental problem that makes affected children unable to hear the acoustic distinctions among successive brief sounds in speech. Here we report the results of psychophysical tests employing simple tones and noises showing that children with specific language impairment have severe auditory perceptual deficits for brief but not long tones in particular sound contexts. Our data support the view that language difficulties result from problems in auditory perception, and provide further information about the nature of these perceptual problems that should contribute to improving the diagnosis and treatment of language impairment and related disorders.

Analysis of Variance↗

Binocular eye movements not coordinated during REM sleep.

Rapid eye movements (REMs) are a defining characteristic of REM sleep during which vivid dreams occur. It has been suggested that REMs may be binocularly coordinated and related to "watching" dream images. For the first time, binocular eye movements were recorded during natural REM sleep in monkeys to test the conjugate nature of the oculomotor system and the "scanning hypothesis" of REMs during sleep. During REM sleep, the lines of sight of the two eyes are frequently misaligned up to 30 degrees horizontally and/or vertically. Since the lines of sight usually don't intersect, there is no fixation point. Instead, each eye is aimed at a different part of the visual field during REM sleep. Furthermore, REMs are not usually conjugate, but are disjunctive or even monocular in horizontal or vertical directions. These data argue against the idea that REMs actually "track" dream images, unless each eye is watching its own dream! Binocular misalignment and disjunctive (even monocular) REMs during sleep suggest that separate left eye and right eye pathways generate saccades in each eye and control the position of each eye. Binocular coordination cannot be the passive result of anatomical connectivity as has been argued previously, but instead must result from a high-level process associated with the awake state that coordinates activity in left-eye and right-eye pathways. Hering's law of equal innervation is not consistent with these data.

Animals↗

Behavior and physiology of the macaque vestibulo-ocular reflex response to sudden off-axis rotation: computing eye translation.

The vestibulo-ocular reflex (VOR) has historically been considered a computationally simple reflex: to stabilize images on the retina against imposed head rotation, the eyes must be counterrotated by an equal amount in the opposite direction. During almost any head rotation, however, the eyes are also translated. We show that the VOR compensates for 90% of this translation, and suggest a computational scheme by which this is done, based on a temporal dissection of the VOR response to sudden head rotation. An initial response that corrects only for imposed rotation is refined by a series of three temporally delayed corrections of increasing complexity. The first correction takes only head rotation and viewing distance into account; the second, head rotation, viewing distance, and otolith translation; and the third, head rotation, viewing distance, otolith translation, and translation of the eyes relative to the otoliths. Responses of type I gaze velocity Purkinje (GVP) cells in the cerebellar flocculus and ventral paraflocculus of rhesus monkeys were recorded during sudden head rotation. We show that cell discharge was modulated both by axis location and by viewing distance, suggesting that GVP cells play a role in the VOR response to rotation-induced eye translation.

Animals↗

Initiation of disjunctive smooth pursuit in monkeys: evidence that Hering's law of equal innervation is not obeyed by the smooth pursuit system.

Monkeys generated disjunctive smooth pursuit eye movements when they tracked visual targets that moved toward or away from them. Eye acceleration was computed during the initial 100 msec of pursuit (the open-loop interval) for various target trajectories. The initial acceleration of either eye was a function of the target's motion with respect to that eye, regardless of whether or not the pursuit was conjugate or disjunctive, or performed with one eye occluded. Eye movements produced by fusional vergence could be separated temporally from eye movements produced by smooth pursuit using step-ramp paradigms. The separation of the two responses demonstrates that the fusional vergence system operates in parallel with the smooth pursuit system, presumably to minimize disparity, but not to generate disjunctive components of smooth pursuit eye movements.

Animals↗

The role of glutamate reuptake in regulation of glutamate responses in Aplysia neurons.

Glutamate elicits several different responses on neurons of isolated ganglia of Aplysia, the most common of which is a hyperpolarization due to conductance increases to either chloride or potassium. We have investigated the actions of aspartate and cysteate on the responses to glutamate. Neither aspartate nor cysteate is potent in activation of glutamate receptors. However both aspartate and cysteate cause a dramatic increase in the response to glutamate when ionophoretically applied before the glutamate application. This potentiating effect of aspartate and cysteate is a result of competition with glutamate for the glutamate transport system, since the potentiation is blocked by cooling and by perfusion with sodium-free sea water. Blockade of glutamate re-uptake by perfusion of sodium-free sea water also causes a significant increase in the response to ionophoretically applied glutamate, which in some neurons may be very large. These results demonstrate that the glutamate reuptake system has an important role in regulation of the responses to glutamate which is similar to that of acetylcholinesterase in regulation of responses to acetylcholine. These observations may be of particular importance in mammalian systems where excess glutamate is associated with neuronal excitotoxicity and cell death.

Animals↗

Magnocellular or parvocellular lesions in the lateral geniculate nucleus of monkeys cause minor deficits of smooth pursuit eye movements.

The effects of unilateral LGN lesions, made with ibotenic acid, on smooth pursuit eye movements were studied in two monkeys (Macaca nemestrina). Both monkeys received unilateral magnocellular (M-) layer lesions 18 months before the study and one monkey received a parvocellular (P-) lesion during the study on the side opposite the magnocellular lesion. The lesions did not affect the accuracy of saccades to stationary or moving targets, but the latencies of saccades to targets in the M-layer lesioned hemifields were significantly longer. Neither M- nor P-layer lesions affected the earliest interval (0-50 msec) of pursuit initiation, but during later intervals (50-150 msec), eye acceleration was less for pursuit initiation in the lesioned hemifield compared to the control hemifield. M-layer lesions created larger deficits in ocular acceleration than P-layer lesions. All deficits, however, were relatively small and accurate pursuit speeds were achieved near the time of the initial "catch-up" saccade. If both M and P layers representing the same part of the visual field were destroyed, the monkey was unable to locate the target or initiate smooth pursuit eye movements. We conclude that smooth pursuit initiation receives contributions from both the M- and P-layers of the LGN and either of these inputs can support pursuit initiation.

Animals↗

Facioscapulohumeral dystrophy natural history study: standardization of testing procedures and reliability of measurements. The FSH DY Group.

BACKGROUND AND PURPOSE: The natural history of facioscapulohumeral muscular dystrophy (FSHD) has not been studied prospectively. Knowledge of the natural progression of any disease provides essential information for the design of clinical trials. We present a protocol for the study of the natural history of FSHD using quantitative muscle testing (QMT), manual muscle testing (MMT), and functional testing. SUBJECTS: Thirty-two persons with FSHD (mean age = 36.1 years, SD = 9.6, range = 17-49) and 32 age- and gender-matched volunteer controls (mean age = 35.8 years, SD = 8.0, range = 23-50) served as subjects. METHODS: Using standardized testing procedures, we examined intrarater reliability of the MMT, QMT, and functional testing measurements in both groups. We also examined interrater reliability in 7 subjects with FSHD. Eighteen muscle groups were tested for each subject using QMT and MMT. RESULTS: Intraclass correlation coefficient (ICC) values ranged from .86 to .99 for intrarater reliability and from .86 to .99 for interrater reliability of QMT measurements. Weighted kappa values of .81 to .98 for intrarater reliability and .50 to 1.00 for interrater reliability were obtained for MMT measurements. Intrarater ICCs for various functional testing measures ranged from .60 to .97. In addition, the comparability of the two QMT machines used in the study was demonstrated by testing the same set of volunteer controls on each machine's linear force transducer (ICC = .89-.98). CONCLUSION AND DISCUSSION: We conclude that this standardized testing protocol produces reliable measurements of muscle strength and functional ability in subjects with FSHD.

Adolescent↗

Quantitative longitudinal assessment of saccades in Huntington's disease.

While participating in a controlled study of baclofen as protective therapy, 39 Huntington's disease (HD) patients underwent measurements of horizontal saccade latency and velocity, repeated longitudinally over a 2-year period. Significant worsening of saccade latency and of mean velocity was detected in untreated patients. Although individual variation was great, initial velocity impairment was found to be more prominent in younger patients. Factors are identified that may affect the rate of decline in supranuclear oculomotor function, including age and the severity of illness at the time of initial assessment. We propose that serial quantitative measurement of saccade performance is a useful clinical marker of the rate of disease progression against which the efficacy of treatments may be tested.

Adult↗

Changes in vestibulo-ocular reflex (VOR) anticipate changes in vergence angle in monkey.

The axis of head rotation is usually different from the axis of eye rotation. Geometrical considerations show that the eyes translate with respect to visual targets located near the head. In order to accurately stabilize retinal images against this translation, the vestibulo-ocular reflex (VOR) must be modulated inversely with the target's distance. The neural correlate of viewing distance used to modulate the VOR is not known. Since vergence angle is related inversely to viewing distance, an efference copy of instantaneous vergence angle or proprioceptive afferent information from extraocular muscles could be used to adjust the VOR. To examine this hypothesis, we compared the time-course of changes in the VOR with the time-course of changes in vergence angle. The VOR was induced by briefly rotating monkeys about a vertical axis at different times during the execution of vergence eye movements. We found that the amplitude of the VOR changed systematically during the course of a vergence eye movement. On average, the changes in the amplitude of vestibular induced eye movements anticipated changes in vergence angle by 50 msec, but in some instances, up to 200 msec of anticipation was observed. These data suggest that a central command signal rather than an afferent or efferent copy of vergence eye position was used to modulate the VOR.

Animals↗

Intrarater reliability of manual muscle test (Medical Research Council scale) grades in Duchenne's muscular dystrophy.

The purpose of this study was to document the intrarater reliability of manual muscle test (MMT) grades in assessing muscle strength in patients with Duchenne's muscular dystrophy (DMD). Subjects were 102 boys, aged 5 to 15 years, who were participating in a double-blind, multicenter trial to document the effects of prednisone on muscle strength in patients with DMD. Four physical therapists participated in the study. Two identical (duplicate) evaluations were performed within 5 days of each other by the same examiner initially and after 6 and 12 months of treatment. A total of 18 muscle groups were tested on each patient, 16 of them bilaterally, using a modification of the Medical Research Council scale. Reliability of muscle strength grades obtained for individual muscle groups and of individual muscle strength grades was analyzed using Cohen's weighted Kappa. The reliability of grades for individual muscle groups ranged from .65 to .93, with the proximal muscles having the higher reliability values. The reliability of individual muscle strength grades ranged from .80 to .99, with those in the gravity-eliminated range scoring the highest. We conclude the MMT grades are reliable for assessing muscle strength in boys with DMD when consecutive evaluations are performed by the same physical therapist.

Adolescent↗

Effect of viewing distance and location of the axis of head rotation on the monkey's vestibuloocular reflex. I. Eye movement responses.

1. The vestibuloocular reflex (VOR) stabilizes images on the retina against movements of the head in space. Viewing distance, target eccentricity, and location of the axis of rotation may influence VOR responses because rotation of the head about most axes in space rotates and translates the eyes relative to visual targets. To study the VOR response to combined rotation and translation, monkeys were placed on a rate table and rotated briefly in the dark about a vertical axis that was located in front of or behind the eyes. The monkeys fixated a near or far visual target that was extinguished before the rotation. Eye movements were recorded from both eyes by the use of the search coil technique. 2. Peak eye velocity evoked by the VOR was linearly related to vergence angle for any axis of rotation. The percent change in the VOR with near target viewing relative to far target viewing at a vergence angle of 20 degrees was linearly related to the location of the axis of rotation. Axes located behind the eyes produced positive changes in VOR amplitude, and axes located in front of the eyes produced negative changes in VOR amplitude. An axis of rotation located in the coronal plane containing the centers of rotation of the eyes produced no modification of VOR amplitude. For any axis, the VOR compensated for approximately 90% of the translation of the eye relative to near targets. 3. The initial VOR response was not correct in magnitude but was refined by a series of three temporally delayed corrections of increasing complexity. The earliest VOR-evoked eye movement (10-20 ms after rotation onset) was independent of viewing distance and rotational axis location. In the next 100 ms, eye speed appeared to be sequentially modified three times: within 20 ms by viewing distance; within 30 ms by otolith translation; and within 100 ms by eye translation relative to the visual target. 4. These data suggest a formal model of the VOR consisting of four channels. Channel 1 conveys an unmodified head rotation signal with a pure delay of 10 ms. Channel 2 conveys an angular head velocity signal, modified by viewing distance with a pure delay of 20 ms, but invariant with respect to the location of the axis of rotation. Channel 3 conveys a linear head velocity signal, dependent on the location of the axis of rotation, that is modified by viewing distance with a pure delay of 30 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Dynamics and efficacy of saccade-facilitated vergence eye movements in monkeys.

1. Four macaque monkeys were trained to fixate visual targets. Eye movements were recorded binocularly using the search coil technique. Saccades, vergence movements, and combinations of the two were elicited by training the monkeys to alternate the gaze between real visual targets that differed in viewing distance and eccentricity with respect to the monkeys' heads. 2. When they shifted the gaze between targets that were at different viewing distances, the monkeys made vergence eye movements. For targets placed along the midsagittal plane, the monkeys often made binocularly symmetric vergence movements. The peak speed of symmetric divergence movements increased linearly with vergence amplitude by 5.7 deg/s per degree of vergence. The peak speed of symmetric convergence movements increased linearly with vergence amplitude by 7.9 deg/s per degree of vergence. 3. For gaze shifts between targets placed eccentrically with respect to the midsagittal plane and at different viewing distances, the monkeys made saccades in combination with vergence eye movements. When a saccade occurred during a vergence movement, peak vergence eye speed increased abruptly and reached a peak that was proportional to the speed of the saccade. For four monkeys, peak divergence speed ranged from 242 to 315 deg/s and peak convergence speed ranged from 257 to 340 deg/s for 16-deg vergence and 20-deg saccadic eye movements. 4. For gaze shifts between far targets at the same viewing distance but different eccentricities, saccadic eye movements were transiently disjunctive even though there was no vergence requirement. Initially, the eyes diverged and then converged to restore fixation to the correct depth plane. Divergence was followed by convergence regardless of the direction of the saccade. 5. The presence of transient saccade-related disjunctive eye movements suggested that the abrupt increase in peak vergence speed during combined saccadic and vergence eye movements was produced by the linear addition of a vergence eye movement and the saccade-related transients. Consistent with this hypothesis, the rate of change in peak vergence speed during various-sized saccades between far targets (no vergence required) was similar to the rate of change in peak vergence speed during combined saccadic and vergence movements. However, the peak vergence speeds during the combined movements were higher than predicted by the linear addition hypothesis, suggesting the presence of an additional mechanism. 6. The saccade-related increase in peak vergence speed during combined saccades and vergences led to a significant decrease in the amount of time required to complete vergence movements.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The long latency component of retinotectal transmission: enhancement by stimulation of nucleus isthmi or tectobulbar tract and block by nicotinic cholinergic antagonists.

The optic tectum of teleosts contains high concentrations of nicotinic and muscarinic acetylcholine receptors and receives putative cholinergic innervation from both nucleus isthmi in the tegmentum and a population of intrinsic tectal cells. Using in vitro preparations of goldfish brain, we have examined the effects of cholinergic antagonists and stimulation of nucleus isthmi on the tectal response to optic nerve stimulation. Our results show that: (1) a long latency component of the retinotectal field potential is polysynaptic in origin and occurs in isolated tectum; (2) this component can spread across the tectum from a beam of stimulated fibers and can appear in areas where the monosynaptic response is small or absent; (3) both monosynaptic and long latency components of the field potential are enhanced by prior stimulation of nucleus isthmi or the tectobulbar tract (15-300 ms); (4) both the long latency component of the field potential and the effects of stimulation of nucleus isthmic or tectobulbar tract are blocked by low concentrations of nicotinic antagonists; and (5) in deeper tectum a second polysynaptic response uncovered by pharmacological block of inhibition is not blocked by nicotinic antagonists. These results indicate that the cholinergic neurons intrinsic to tectum have a role in the spread of retinotectal excitation by nicotinic actions, and that stimulation of nucleus isthmi or tectobulbar tract facilitates activity in this system. There is in addition a separate recurrent excitatory circuit in tectum.

Alcuronium↗

Nicotinic depolarization of optic nerve terminals augments synaptic transmission.

The role of acetylcholine (ACh) as the neurotransmitter at the vertebrate neuromuscular junction has served as a model in the study of synaptic physiology throughout the nervous system, but its function in the brain has remained obscure. Nicotinic ACh receptors are found on afferent nerve terminals in several regions of vertebrate brain, and nicotinic agonists can cause transmitter release (as measured biochemically). Yet there is no direct evidence that activation of these receptors modulates synaptic function. Here I report that nicotinic agonists directly depolarize optic nerve terminals in goldfish tectum recorded via sucrose gap and simultaneously enhance synaptic transmission recorded via tectal field potentials. I also show that a recurrent cholinergic circuit in tectum, acting on these terminals, initiates antidromic impulses that cause repeated transmission at the retinotectal synapses.

Animals↗

Reliability of isokinetic measurements of hip muscle torque in young boys.

The purpose of this study was to determine the reliability of measurements of hip muscle torque obtained with the Cybex II isokinetic dynamometer from healthy young boys. Twenty-nine healthy boys, aged 6 to 10 years, were tested two times at one- to two-week intervals. Torque of the hip flexors and extensors and the hip abductors and adductors was assessed at angular velocities of 30 degrees and 90 degrees/sec. The torque generated by each muscle group at 30 degrees/sec was similar to the torque generated at 90 degrees/sec. Intraclass correlation coefficients (ICCs) were used to determine test-retest reliability for measurements of each of the muscle groups at both angular velocities. The ICCs were higher for hip flexion and extension than they were for hip abduction and adduction. The highest ICC (ICC = .84) was found for hip extension at 90 degrees/sec. The ICCs for hip abduction and adduction at both angular velocities were less than .60. Factors that possibly contributed to the relatively low reliability in hip abduction and adduction are discussed.

Biomechanical Phenomena↗

Voltage-clamp characterization of Cl- conductance gated by GABA and L-glutamate in single neurons of Aplysia.

1. Cl- conductance gated by gamma-aminobutyric acid (GABA) and L-glutamate in the medial pleural neurons of Aplysia was studied using conventional two-electrode voltage-clamp techniques and a continuous microperfusion system that allowed rapid and uniform agonist application. 2. Both GABA and glutamate elicited current responses that rapidly activated and then decayed (desensitized) during maintained presence of agonist. 3. Recovery from desensitization was rapid for both agonists. For intermediate concentrations of each agonist, recovery was approximately 90% complete within 1 min. 4. Dose-response experiments at a holding potential of -45 mV showed that 1) maximal peak responses to glutamate were on the average approximately 40% of those to GABA, 2) the dose-peak response curve for glutamate was steeper than that for GABA, and 3) time-to-peak (risetime) and desensitization half-time decreased monotonically with dose for GABA but were relatively insensitive to dose and more variable for glutamate. 5. Peak conductances elicited by GABA were voltage dependent, increasing with depolarization, whereas the Cl- conductance elicited by glutamate was voltage independent. Risetime and desensitization kinetics were insensitive to voltage for both agonists. 6. Lowering the temperature of the perfusion medium by 10 degrees C slowed activation and desensitization for both 0.1 mM GABA and 2 mM glutamate. The responses to the two agonists differed, however, in that the peak response to glutamate increased, whereas that to GABA decreased in amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗