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Biomedical subjects

W M King

Publications and source records attributed to W M King.

At least 19 recordsLinked to original sources

Attentional sensitivity and asymmetries of vertical saccade generation in monkey.

The first goal of this study was to systematically document asymmetries in vertical saccade generation. We found that visually guided upward saccades have not only shorter latencies, but higher peak velocities, shorter durations and smaller errors. The second goal was to identify possible mechanisms underlying the asymmetry in vertical saccade latencies. Based on a recent model of saccade generation, three stages of saccade generation were investigated using specific behavioral paradigms: attention shift to a visual target (CUED paradigm), initiation of saccade generation (GAP paradigm) and release of the motor command to execute the saccade (DELAY paradigm). Our results suggest that initiation of a saccade (or "ocular disengagement") and its motor release contribute little to the asymmetry in vertical saccade latency. However, analysis of saccades made in the CUED paradigm indicated that it took less time to shift attention to a target in the upper visual field than to a target in the lower visual field. These data suggest that higher attentional sensitivity to targets in the upper visual field may contribute to shorter latencies of upward saccades.

Animals↗

Neural basis of disjunctive eye movements.

New evidence has challenged a widely accepted interpretation of Hering's law of equal innervation, which states that disjunctive saccades are produced by the linear addition of conjugate and vergence innervation commands produced by independent oculomotor subsystems. We hypothesize, instead, that saccades are produced by a monocular premotor control network. A model, based on this hypothesis and consistent with known brain-stem anatomy, simulates realistic disjunctive saccades including initial and late slow vergence movements.

Animals↗

Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy.

BACKGROUND/OBJECTIVES: Animal and human studies suggest that beta(2)-adrenergic agonists exert anabolic effects on muscles, inducing and preventing atrophy after a variety of insults. Based on data from an open-label trial of albuterol in 15 patients with facioscapulohumeral dystrophy (FSHD), the authors conducted a randomized, double-blind, placebo-controlled trial of sustained-release albuterol in this disease. METHODS: Ninety patients were randomized to three groups: placebo; 8.0 mg albuterol twice daily; or 16.0 mg albuterol twice daily. Patients were treated for 1 year with assessments at baseline and weeks 13, 26, and 52. The primary outcome was the 52-week change in global strength by maximum voluntary isometric contraction testing (MVICT). Secondary outcomes included changes at 52 weeks in strength by manual muscle testing (MMT), grip strength, functional testing, and muscle mass assessed by dual energy x-ray absorptiometry (DEXA). RESULTS: Eighty-four patients completed the study. The mean changes in composite MVICT scores were not significantly different between the groups (mean +/- SD: placebo 0.20 +/- 0.91; low dose -0.04 +/- 0.84; high dose 0.08 +/- 0.98). Similarly, there were no differences in the mean MMT change (placebo 0.04 +/- 0.16; low dose -0.03 +/- 0.13; high dose 0.00 +/- 0.15). Grip improved in both treatment groups compared to placebo (placebo -0.53 +/- 4.13, low dose +1.90 +/- 3.34 [p = 0.02], high dose +1.70 +/- 4.13 [p = 0.03]). The high-dose group had a significant increase in lean mass by DEXA (+1.57 +/- 1.71 kg) compared to placebo (0.25 +/- 2.24; p = 0.007). Albuterol was well tolerated; side effects included cramps, tremors, insomnia, and nervousness. CONCLUSIONS: Although albuterol did not improve global strength or function in patients with FSHD, it did increase muscle mass and improve some measures of strength.

Adrenergic beta-Agonists↗

A randomized efficacy and safety trial of oxandrolone in the treatment of Duchenne dystrophy.

BACKGROUND: A pilot study suggested that oxandrolone, an anabolic steroid, improved strength in boys with Duchenne dystrophy (DD) and indicated the need for a more definitive study. METHODS: A 6-month, randomized, double-blind, placebo-controlled study of oxandrolone in boys with an established diagnosis of DD, using the change from baseline to 6 months in the average muscle strength score (MMT) as the primary efficacy measure. RESULTS: The mean change from baseline for the oxandrolone group was +0.035 and that for the placebo group was -0.140. Although the oxandrolone group did not get worse and the placebo patients showed some deterioration in strength, the difference was not significant (p = 0.13). The average of the four quantitative muscle tests (QMT) showed a significant improvement in the oxandrolone-treated boys as compared with placebo. No adverse reactions attributable to oxandrolone were recorded. CONCLUSIONS: Although oxandrolone did not produce a significant change in the average manual muscle strength score as compared with placebo, the mean change in QMT was significant. Because oxandrolone is safe, accelerates linear growth, and may have some beneficial effect in slowing the progress of weakness, it may be useful before initiating corticosteroid therapy.

Anabolic Agents↗

Responses of rostral fastigial neurons to linear acceleration in an alert monkey.

Vestibular-only neuronal responses to angular acceleration have been systematically characterized in the rostral fastigial nucleus (FN) by several studies. However, responses of these neurons to linear acceleration have not been examined. In this study, we recorded single-unit activity of vestibular-only neurons in an alert monkey during pure sinusoidal linear acceleration along different directions in the horizontal plane. Spatiotemporal response properties were quantified by computing two-dimensional response ellipses in the horizontal plane. Based on this analysis, neurons were classified as narrowly or broadly tuned. About 29% (5/17) of neurons were broadly tuned. The other 71% (12/17) were narrowly tuned. Unlike vestibular nuclei neurons, all recorded FN neurons exhibited irregular resting discharge rates (CV*0.2). Based on studies of linear motion-sensitive neurons in the vestibular nuclei, the data suggest that irregular neurons in the rostral FN and the vestibular nuclei have similar responses to linear acceleration in behaving monkeys.

Acceleration↗

Anatomical risk factors for phonological dyslexia.

Successful behavioral genetic studies require precise definition of a homogenous phenotype. This study searched for anatomical markers that might restrict variability in the reading disability phenotype. The subjects were 15 college students (8 male/7 female) diagnosed with a reading disability (RD) and 15 controls (8 males/7 females). All subjects completed a cognitive and reading battery. Only 11 of the RD subjects had a phonological deficit [phonological dyslexia (PD): pseudo word decoding scores < 90 (27th percentile)]. Thirteen RD (9 PD) and 15 controls received a volumetric MRI scan. Four anatomical measures differentiated the PD group from the remainder of the subjects: (i) marked rightward cerebral asymmetry, (ii) marked leftward asymmetry of the anterior lobe of the cerebellum, (ii) combined leftward asymmetry of the planum and posterior ascending ramus of the sylvian fissure, and (iv) a large duplication of Heschl's gyrus on the left. When these four measures were normalized and summed, the resulting variable predicted short- and long-term phonological memory. By contrast, oral and written comprehension skills were predicted by a different anatomical variable: low cerebral volume. These findings provide neurobiological support for an RD phenotype characterized by phonological deficits in the presence of normal or superior comprehension. The study of individual variation in cortical structure may provide a useful link between genotype and behavior.

Adult↗

New ideas about binocular coordination of eye movements: is there a chameleon in the primate family tree?

Many animals with laterally placed eyes, such as chameleons, move their eyes independently of one another. In contrast, primates with frontally placed eyes and binocular vision must move them together so that both eyes are aimed at the same point in visual space. Is binocular coordination an innate feature of how our brains are wired, or have we simply learned to move our eyes together? This question sparked a controversy in the 19(th) century between two eminent German scientists, Ewald Hering and Hermann von Helmholtz. Hering took the position that binocular coordination was innate and vigorously challenged von Helmholtz's view that it was learned. Hering won the argument and his hypothesis, known as Hering's Law of Equal Innervation, became generally accepted. New evidence suggests, however, that similar to chameleons, primates may program movements of each eye independently. Binocular coordination is achieved by a neural network at the motor periphery comprised of motoneurons and specialized interneurons located near or in the cranial nerve nuclei that innervate the extraocular muscles. It is assumed that this network must be trained and calibrated during infancy and probably throughout life in order to maintain the precise binocular coordination characteristic of primate eye movements despite growth, aging effects, and injuries to the eye movement neuromuscular system. Malfunction of this network or its ability to adaptively learn may be a contributing cause of strabismus.

Animals↗

Forthcoming topics

Explore the source record for details and available documents.

Journal Article↗

Influence of speech stimuli intensity on the activation of auditory cortex investigated with functional magnetic resonance imaging.

Understanding the impact of variations in the acoustic signal is critical for the development of auditory and language fMRI as an experimental tool. We describe the dependence of the BOLD signal and speech intelligibility on the intensity of auditory stimuli. Eighteen subjects were imaged on a 1.5-T MRI scanner. Speech stimuli were English monosyllabic words played at five intensity levels. Intrasubject reproducibility was measured on one subject by presenting the stimulus five times at the same intensity level. Intelligibility was measured during data acquisition as subjects signaled when hearing two targets. Each functional trial consisted of four cycles (30 s off-30 s on). Five oblique slices covering primary and association auditory areas were imaged. Activated voxels were identified by cross-correlation analysis and their percent signal change (delta S) was measured. Intersubject differences in activation extent, asymmetry, and dependence on intensity were striking. Volume of activation was significantly greater in the left than in the right hemisphere. Intrasubject reproducibility for delta S was higher than for volume of activation. delta S and intelligibility showed a similar dependence on intensity suggesting that not only intensity but also intelligibility affect the fMRI signal.

Adult↗

Stereotactic posterioventral pallidotomy improves balance control as assessed by computerized posturography.

Postural instability is arguably the most debilitating symptom of Parkinson's disease (PD). Recently, posterioventral pallidotomy/pallidoansotomy (PVP) has been advocated to improve a multitude of symptoms associated with PD. Dyskinesias, rigidity and bradykinesia are the most talked about improved symptoms, but posture and gait are also affected after PVP. To analyze the effect of PVP on postural control, 14 patients with PD were prospectively studied using a computerized dynamic posturography machine. Seven males and 7 females underwent a total of 18 procedures, 6 left PVP, 6 right PVP, 2 bilateral and 2 had Vim thalamotomies in addition to PVP. Data were collected pre- and postoperatively after a 12-hour drug-free interval ('off' period) and 1-2 h after medications ('on' period). Postoperative analyses were performed between 1 and 3 months postoperatively. As a group, patients' balance, in the off period, improved after surgery in a dynamic setting. Prior to surgery, patients' anterior-posterior sway exceeded their stability limits (patient fell) on 31% of the trials. After surgery, the fall rate decreased to 23%. Anterior-posterior sway decreased significantly (p < 0.05) postoperatively when the platform was sway referenced. In comparing the effect of surgery in decreasing sway with that of medication preoperatively, improvement after surgery (off period) was better than the preoperative on period (p < 0.05). Patients also improved in ostoperative off state when compared to preoperative off state with the platform sway referenced (p < 0.05), controlling for improvement in dyskinesia-induced imbalance. In conclusion, PVP improves standing balance performance better than that achieved with medications preoperatively. Since central input parameters were improved, the mechanism of PVP may be centralized.

Aged↗

Premotor commands encode monocular eye movements.

Binocular coordination of eye movements is essential for stereopsis (depth perception) and to prevent double vision. More than a century ago, Hering and Helmholtz debated the neural basis of binocular coordination. Helmholtz believed that each eye is controlled independently and that binocular coordination is learned. Hering believed that both eyes are innervated by common command signals that yoke the eye movements (Hering's law of equal innervation). Here we provide evidence that Hering's law is unlikely to be correct. We show that premotor neurons in the paramedian pontine reticular formation that were thought to encode conjugate velocity commands for saccades (rapid eye movements) actually encode monocular commands for either right or left eye saccades. However, 66% of the abducens motor neurons, which innervate the ipsilateral lateral rectus muscle, fire as a result of movements of either eye. The distribution of sensitivity to ipsilateral and contralateral eye movements across the abducens motor neuron pool may provide a basis for learning binocular coordination in infancy and adapting it throughout life.

Abducens Nerve↗

Pilot trial of albuterol in facioscapulohumeral muscular dystrophy. FSH-DY Group.

BACKGROUND/OBJECTIVE: Facioscapulohumeral muscular dystrophy (FSHD) is currently untreatable, and there have been few therapeutic trials of any agent in the disease. Animal studies have demonstrated that beta2-adrenergic agonists induce muscle hypertrophy and prevent atrophy after a variety of physical and biochemical insults, and two human studies have shown that these agents increase certain measures of strength in healthy volunteers. We conducted an open-label pilot trial of a beta2-agonist (albuterol) in patients with FSHD. METHODS: Fifteen FSHD patients were given sustained-release albuterol (16.0 mg/day) for 3 months. The primary outcome measure was lean body mass, which was assessed through dual energy X-ray absorptiometry (DEXA). Strength was evaluated through maximal voluntary isometric contraction testing (MVICT) and manual muscle testing. RESULTS: Albuterol significantly increased DEXA lean body mass (the skeletal muscle compartment) by 1.29 +/- 1.18 kg (mean +/- SD, p = 0.001). Strength assessed through composite MVICT scores also increased by an average of 0.33 +/- 0.60 (p = 0.05), representing an overall 12% improvement in strength. CONCLUSIONS: These encouraging results suggest that beta2-agonists may have a role in treating FSHD and possibly other neuromuscular diseases. The effects of albuterol in FSHD are currently being evaluated in a larger, randomized, double-blind, placebo-controlled trial lasting 1 year.

Absorptiometry, Photon↗

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↗