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J S Stahl

Publications and source records attributed to J S Stahl.

At least 19 recordsLinked to original sources

Increased noise level of purkinje cell activities minimizes impact of their modulation during sensorimotor control.

While firing rate is well established as a relevant parameter for encoding information exchanged between neurons, the significance of other parameters is more conjectural. Here, we show that regularity of neuronal spike activities affects sensorimotor processing in tottering mutants, which suffer from a mutation in P/Q-type voltage-gated calcium channels. While the modulation amplitude of the simple spike firing rate of their floccular Purkinje cells during optokinetic stimulation is indistinguishable from that of wild-types, the regularity of their firing is markedly disrupted. The gain and phase values of tottering's compensatory eye movements are indistinguishable from those of flocculectomized wild-types or from totterings with the flocculus treated with P/Q-type calcium channel blockers. Moreover, normal eye movements can be evoked in tottering when the flocculus is electrically stimulated with regular spike trains mimicking the firing pattern of normal simple spikes. This study demonstrates the importance of regularity of firing in Purkinje cells for neuronal information processing.

Action Potentials↗

Simple spike and complex spike activity of floccular Purkinje cells during the optokinetic reflex in mice lacking cerebellar long-term depression.

Cerebellar long-term depression (LTD) at parallel fibre-Purkinje cell (P-cell) synapses is thought to embody neuronal information storage for motor learning. Transgenic L7-protein kinase C inhibitor (PKCI) mice in which cerebellar LTD is selectively blocked do indeed exhibit impaired adaptation in the vestibulo-ocular reflex (VOR) while their default oculomotor performance is unaffected. Although supportive, these data do not definitively establish a causal link between memory storage required for motor learning and cerebellar LTD. As the L7-PKCI transgene is probably activated from the early stages of P-cell development, an alternative could be that P-cells develop abnormal signals in L7-PKCI mutants, disturbing mechanisms of motor learning that rely on proper P-cell outputs. To test this alternative hypothesis, we studied simple spike (SS) and complex spike (CS) activity of vertical axis P-cells in the flocculus of L7-PKCI mice and their wild-type littermates during sinusoidal optokinetic stimulation. Both SS and CS discharge dynamics appeared to be very similar in wild-type and transgenic P-cells at all stimulus frequencies (0.05-0.8 Hz). The CS activity of all vertical axis cells increased with contralateral stimulus rotation and lagged ipsiversive eye velocity by 165-180 degrees. The SS modulation was roughly reciprocal to the CS modulation and lagged ipsiversive eye velocity by approximately 15 degrees. The baseline SS and CS discharge characteristics were indistinguishable between the two genotypes. We conclude that the impaired VOR learning in L7-PKCI mutants does not reflect fundamental aberrations of the cerebellar circuitry. The data thus strengthen the evidence that cerebellar LTD is implicated in rapid VOR learning but not in the development of normal default response patterns.

Action Potentials↗

The torsional component of "horizontal" congenital nystagmus.

OBJECTIVES: To study the relationship between the major horizontal and minor torsional components of congenital nystagmus to elucidate the diagnostic importance, effects on vision, and pathogenetic implications of the torsional components. METHODS: We recorded the eye movements of 13 subjects with congenital nystagmus using a three-dimensional magnetic search coil technique over a 15-year period. The subjects fixated on stationary targets straight ahead and along the horizontal and vertical meridians. Six of the 10 subjects with horizontal congenital nystagmus were asymptomatic; the remaining 4 (plus two with a vertical component to their congenital nystagmus) had adult-onset symptoms. An additional subject without symptoms had a vertical congenital nystagmus component plus seesaw nystagmus; one of the symptomatic subjects also had seesaw nystagmus. RESULTS: In all 13 subjects, the horizontal and torsional cycles were phase-locked, and positive horizontal (rightward), vertical (upward, if any), and torsional (clockwise) motion coincided in 10 subjects. That is, rightward horizontal eye rotation coincided with clockwise curvilinear motion (rightward and downward) of the upper pole of each eye. During the horizontal foveation periods, torsional motion was also of low velocity. In 2 of 13 subjects, the torsional waveforms differed from those in the horizontal plane; in others, the direction or the variation with gaze angle differed from that predicted by Listing. In each of the 13 subjects, the torsional components ranged from 8.16% to 94.42% (median, 32.94%) of the peak-to-peak magnitudes of the congenital nystagmus. In most cases, the measured torsion was far greater than that predicted by Listing's law for a worst-case analysis (range, 0.69-11.83%; median, 4.91%). The torsional components of the two subjects with seesaw nystagmus were 60.48% and 264.02%. CONCLUSIONS: The manner in which the horizontal and torsional components of "horizontal" congenital nystagmus were phase-locked made clinical detection of the torsional component difficult. Most "horizontal" congenital nystagmus is actually horizontal-torsional congenital nystagmus. Visual acuity during horizontal foveation periods is not significantly diminished by torsional motion. In only one subject did the torsional component of the congenital nystagmus have an amplitude equivalent to Listing torsion; in the other 12 subjects, torsion exceeded our estimate of what Listing's law would predict. The torsional components of the seesaw nystagmus in two subjects also greatly exceeded the torsion predicted by Listing torsion. The most parsimonious explanation for our data is that the cyclic torsion in congenital nystagmus was generated centrally and not a result of Listing torsion, mechanical crosstalk, or normal or abnormal extraocular-muscle (plant) dynamics. Further measurements are needed to confirm this hypothesis.

Adult↗

The dynamic characteristics of the mouse horizontal vestibulo-ocular and optokinetic response.

In the present study the optokinetic reflex, vestibulo-ocular reflex and their interaction were investigated in the mouse, using a modified subconjunctival search coil technique. Gain of the ocular response to sinusoidal optokinetic stimulation was relatively constant for peak velocities lower than 8 degrees /s, ranging from 0.7 to 0.8. Gain decreased proportionally to velocity for faster stimuli. The vestibulo-ocular reflex acted to produce a sinusoidal compensatory eye movement in response to sinusoidal stimuli. The phase of the eye movement with respect to head movement advanced as stimulus frequency decreased, the familiar signature of the torsion pendulum behavior of the semicircular canals. The first-order time constant of the vestibulo-ocular reflex, as measured from the eye velocity decay after a vestibular velocity step, was 660 ms. The response of the vestibulo-ocular reflex changed with stimulus amplitude, having a higher gain and smaller phase lead when stimulus amplitude was increased. As a result of this nonlinear behavior, reflex gain correlated strongly with stimulus acceleration over the 0.1-1.6 Hz frequency range. When whole body rotation was performed in the light the optokinetic and vestibular system combined to generate nearly constant response gain (approximately 0.8) and phase (approximately 0 degrees ) over the tested frequency range of 0.1-1.6 Hz. We conclude that the compensatory eye movements of the mouse are similar to those found in other afoveate mammals, but there are also significant differences, namely shorter apparent time constants of the angular VOR and stronger nonlinearities.

Animals↗

Eye-head coordination and the variation of eye-movement accuracy with orbital eccentricity.

Different humans vary widely in the tendency to move the head during saccadic shifts in gaze. The reasons for this variation are unknown. Because combined eye-head movements are associated with a recentering of the eyes in the orbits, humans who are "head movers" tend to maintain the eyes within a narrower range than do non-head movers. We explored the possibility that variations in the ability to control eye movements at eccentric positions lead to variations in customary ocular motor range and, by extension, explain the variations in head-movement tendencies. We studied ten normal adults. In each, we measured the full-scale ocular motor range and customary ocular motor range (the eccentricity range within which the eye was found at the conclusion of eye- or eye-head saccades). We also determined the eye-only range, the orbital range within which the probability of a head movement accompanying a gaze shift was low. Customary, eye-only, and full-scale ranges spanned (mean +/-SD) 41.1+/-16.9 degrees, 30.2+/-18.8 degrees, and 92.8+/- 9.1 degrees, respectively. We then assessed variations in kinematics of several ocular motor behaviors as functions of eye eccentricity. The stable fixation range, defined by the range over which drift velocities were below 1 degree/s, spanned 81.1+/-11.2 degrees in the light and 69.5+/-21.5 degrees in the dark. The range over which the gains of the vestibulo-ocular reflex in the light and smooth pursuit approached their values at zero eccentricity spanned 66.3+/-7.1 degrees and 69.0+/-10.0 degrees, respectively. Small centrifugal saccades (5-10 degrees) tended to become either slowed or hypometric with increasing eccentricity. Sensitive to both slowing and hypometria, the ratio of peak gaze velocity to target shift amplitude was flat over a range spanning 65.7+/-14.9 degrees. Finally, the ranges over which the initial saccade placed the fovea upon the target averaged 35.5+/-10.7 degrees for eye-only saccades and 36.6+/-15.0 degrees for eye-head saccades. With the exception of the range of stable fixation in the light, the kinematic ranges were either unrelated or inconsistently related to full-scale range, indicating that the deterioration of eye movements with increasing ocular eccentricity is not a simple consequence of the eyes encountering the limits of their excursion. None of the kinematic ranges correlated positively with customary or eye-only range. Thus, while head movements may be orchestrated so as to maintain the eyes within a desired range, that range (and thus head movement tendencies) is not predicated upon the range of ocular eccentricity over which eye movements are accurately controlled.

Adult↗

Adaptive plasticity of head movement propensity.

Individual humans exhibit differing propensity to move the head in association with saccadic shifts in gaze. We assessed whether this tendency can be modified in normal subjects by either reducing neck mobility with a cervical collar or restricting the field of view using aperture spectacles. We quantified head movement propensity in terms of the range of orbital eccentricity within which the eyes are customarily maintained (customary ocular motor range), and the range of final eye-in-head eccentricity for which a planned saccade is likely to be executed without a concomitant head movement (eye-only range). Three subjects wore rigid collars during waking hours for periods of up to 9 days. We measured customary and eye-only ranges with the collar removed, at various times during the adaptation and recovery periods. Collar adaptation reduced head movement propensity in all three subjects, increasing the average customary ocular range from 27.6 +/- 8.9 degrees (mean +/- SD) to 66.1 +/- 4.5 degrees and the eye-only range from 24.6 +/- 17.0 degrees to 67.6 +/- 7.4 degrees. In two subjects the modifications persisted for weeks following final collar removal. In parallel with the reduction in head movement propensity, all subjects improved in their ability to maintain eccentric gaze, suggesting that neck restriction led to effects at the level of the brainstem. Three subjects were adapted to spectacles, masked to restrict the field of view to approximately 20 degrees. The aperture spectacles were worn for periods of up to 9 days. When tested without the apertures, one subject exhibited a definite increase in head movement propensity; in the other two, the data were equivocal, indicating either a small increase in head movement propensity or no effect. Averaged across subjects, customary ocular motor range decreased from 35.1 +/- 12.8 degrees to 25.4 +/- 13.4 degrees and eye-only range decreased from 35.1 +/- 7.5 degrees to 23.0 +/- 4.0 degrees. The marked difference in the magnitudes of collar- and spectacle-induced changes suggests that the responses to the two restrictive appliances are mediated by different mechanisms. Collar adaptation may involve parametric modulation of circuits mediating reflex recruitment of head movements, while aperture adaptation may primarily reflect substitution of an alternative mode of head control triggered by the presence of the restricted field of view, with only minor parametric modulation of the underlying head recruitment circuit. The enduring effects of restricting neck mobility upon head movement tendencies may relate to the common clinical association between neck injury and persistent dysequilibrium.

Adaptation, Physiological↗

Nystagmus.

Advances in understanding the organization of the ocular motor system, including its anatomy and pharmacology, have provided new insights into the pathogenesis of various forms of nystagmus. The discoveries of fibromuscular pulleys that govern the pulling directions of the extraocular muscles has provided a new conceptual framework to account for the different axes of rotation of vestibular and other types of movements that may contribute to nystagmus. Theoretical and experimental evidence has suggested that acquired pendular nystagmus, which is commonly due to multiple sclerosis, arises from the neural network that normally guarantees steady gaze by integrating premotor signals. Pharmacologic inactivation studies have implicated both gamma-aminobutyric acid (GABA) and glutamate as important transmitters in the neural integrator and suggested new drug therapies. New electro-optic devices may eventually prove to be effective treatment for the visual symptoms cause by acquired nystagmus. The demonstration of proprioceptive mechanisms in the distal extraocular muscles has provided a rationale for new operative treatments for congenital nystagmus.

Humans↗

A comparison of video and magnetic search coil recordings of mouse eye movements.

Interest in connecting molecular biology and behavior is motivating research into the eye movements of mice. Unfortunately, recording eye movements in this diminutive animal is technically difficult. We present the first method for obtaining calibrated video oculography, and contrast the results with simultaneously obtained scleral search coil recordings in C57BL/6 pigmented mice. We determined the distance of the pupil from the center of corneal curvature, based upon relative motions of the pupil and corneal reflections during camera movements, and used the distance to convert subsequent video measurements of pupil motion to eye rotation. We recorded responses during sinusoidal rotation (0.1-1.6 Hz) in the light, by video prior to search coil implantation, and by video and search coil simultaneously following implantation. Pre-implantation, video-derived gains ranged from 0.86+/-0.03 (mean+/-SD) at 0.1 Hz to 0.95+/-0.03 at 0.8 Hz. Phase progressed monotonically from -3.1+/-2. 6 degrees (eye leads head) at 0.1 Hz to +5.9+/-1.1 degrees at 1.6 Hz. Coil implantation reduced the range of video-derived gains to 0. 64-0.79. This reduction reflects disruption of normal behavior by the coil. Coil data confirmed the video results. Video and search coil techniques each have advantages. Specific precautions are required when designing and interpreting experiments using the coil technique.

Animals↗

Acquired nystagmus.

Traditionally, acquired forms of nystagmus have been classified in descriptive terms based on their clinical features and recorded waveforms. In the past 20 years, the mechanisms of several major forms of nystagmus have been elucidated; animal and mathematical models for these ocular oscillations have been developed. These advances, which owe much to modern anatomical, physiological, and pharmacological techniques, have enhanced the diagnostic value of nystagmus and provide the basis for developing rational therapy.

Eye Movements↗

Prospects for treating acquired pendular nystagmus with servo-controlled optics.

PURPOSE: To determine whether a device featuring electronically controlled motor-driven prisms can reduce oscillopsia and improve acuity in patients with acquired pendular nystagmus (APN). METHODS: A device was developed that senses eye movements and, by the use of motor-driven prisms, oscillates the image of the world in lockstep with the pathologic nystagmus, to negate its deleterious visual effects. Unlike existing optical and surgical treatments for nystagmus, the device negates only the pathologic movements. Voluntary and normal reflex eye movements required for normal vision are unaffected. The benefits of the device were assessed by its impact on acuity in five patients with medication-refractory APN. RESULTS: All patients reported decreases in oscillopsia when the device was in operation. Averaged across patients, the device increased the percentage of time in which retinal image velocity was within +/-4 degrees/sec from 12.8% to 33.3%. Acuities improved in four of five patients, by an average of 0.21 logMAR units. CONCLUSIONS: The symptoms of pendular nystagmus can be treated with a servomechanical device. Further refinements in the device should result in greater improvements in acuity, and a portable, wearable version is feasible using existing technologies.

Adult↗

Vertical nystagmus in normal subjects: effects of head position, nicotine and scopolamine.

We measured gaze stability in darkness of four normal humans using the search coil technique. Subjects were tested first with their heads erect, and then with their heads positioned 180 degrees upside-down. In each position, subjects held their head stationary for one minute, and then actively performed pitch rotations for 20 sec. All subjects showed sustained chin-beating nystagmus in the upside-down position. Each subject showed a significant increase of slow-phase velocity directed towards their brow after 40 sec in the inverted versus erect position. Pitch head rotation had little effect on subsequent nystagmus, except for transient reversal in one subject. The sustained changes of vertical eye drifts induced by 180 deg change of head position suggest that otolithic factors may contribute to vertical nystagmus in normals. The subjects were retested after wearing a nicotine patch for 2 hours. In three subjects, nicotine induced brow-beating nystagmus; adopting a head-hanging position increased this nystagmus in two subjects. In a third session, subjects were tested after wearing a scopolamine patch for 2 hours; results were generally similar to the control condition. We conclude that normal subjects may show chin-beating ("downbeating") nystagmus in a head-hanging position in darkness, reflecting a normal, physiological change in otolithic inputs brought about by the head orientation.

Adult↗

Square-wave jerks induced by pallidotomy in parkinsonian patients.

Square-wave jerks (SWJs) are small, inappropriate saccades that intrude on steady fixation by taking the eye away from the target and then returning it after approximately 200 msec. The pathophysiology of SWJs is unknown; they have not been attributed to any specific lesion. We found that unilateral pallidotomy substantially increased the frequency of SWJs in three patients with Parkinson's disease. This effect is likely due to imbalance in the fixation system caused by asymmetric reactivation of prefrontal cortex via ascending thalamocortical projections. Alternatively, disruption of nigral projections to the superior colliculus might be responsible.

Adult↗

Amplitude of human head movements associated with horizontal saccades.

Human saccades may or may not be associated with head movements. To date, little attention has been devoted to the mechanisms determining head movement recruitment and scaling. Normal human subjects made horizontal, centrifugal saccades along an encircling array of light-emitting diodes. Measurements of gaze, head, and eye-in-head angle were made at the conclusion of the head movement (or at the end of the eye movement in eye-only saccades). We found that head movement amplitude (deltaH) related in a simple fashion to the eye eccentricity that would have resulted if the gaze shift had been performed without a head movement. Plots of deltaH vs this predicted eye eccentricity (E(PRED)) had a central flat region in which gaze shifts were unaccompanied by head movements (the eye-only range) and two flanking lobes in which deltaH was a linear function of E(PRED) (the eye-head ranges). DeltaH correlated with EPRED better than with gaze shift amplitude, as would be expected if head movements were controlled so as to keep eye eccentricity within a particular range. Head movement tendencies were quantified by the width of the eye-only range, the slope of the eye-head range, and the width of the region within which the eye was likely to be found at the conclusion of the completed gaze-shifting behavior (the customary ocular motor range). The measures ranged widely in these normal subjects: 35.8+/-31.9 degrees for the eye-only range (mean+/-SD), 0.77+/-0.16 for the slope of the eye-head range, and 44.0+/-23.8 degrees for the customary ocular motor range. Yet for a given subject, the measurements were reproducible across experimental sessions, with the customary ocular motor range being the most consistent measure of the three. The form of the deltaH vs E(PRED) plots suggests that the neural circuitry underlying eye-head coordination carries out two distinct functions--gating the head movement and scaling the head movement. The reason for the large intersubject variability of head movement tendencies is unknown. It does not parallel intersubject differences in full-scale eye (in orbit) range or full-scale neck range.

Adult↗

Clinical evidence of extraocular muscle fiber-type specificity of botulinum toxin.

OBJECTIVE: To compare the effects of botulinum toxin on static and dynamic aspects of eye movements, and thereby elucidate the mechanisms of its action on eye muscles. BACKGROUND: Laboratory evidence indicates that static alignment and saccades are subserved by different extraocular muscle fiber types, and botulinum toxin may cause specific dysfunction of the fibers controlling static alignment. Diplopia is a well-known side effect of periorbital botulinum toxin injections in humans, and may be a clinical correlate of the laboratory findings. METHODS: Search coil recording of eye movements was performed in one patient with systemic botulism, and in three patients with diplopia following periorbital injection of botulinum toxin A. RESULTS: In the patient with acute botulism, eye movement alignment, range, and saccadic velocity profiles were abnormal. In three patients with iatrogenic diplopia, static alignment was abnormal but movement range and saccadic velocities were within normal limits. Edrophonium improved the range of movements and saccadic velocities in the patient with systemic botulism but was ineffective in reversing ocular misalignment in the one iatrogenic patient to whom it was administered. CONCLUSIONS: Precise alignment is subserved by orbital singly innervated muscle fibers, and the effects of botulinum toxin are greatest on these fibers. This predilection is apparent when the toxin dose is very small, as must have been the case in our patients with iatrogenic diplopia. The lack of a response to edrophonium probably reflects structural damage to muscle fibers. In contrast, larger doses of toxin produce an acute dysfunction of all extraocular muscle fiber types, which is responsive to edrophonium and consequently reflects partial blockade at the neuromuscular junction.

Adult↗

Bilateral ptosis and upgaze palsy with right hemispheric lesions.

Bilateral ptosis is reported with unilateral hemispheric lesions, suggesting partial lateralization of the control of the levator palpebrae superioris. There is a tight synkinesis between vertical eye and eyelid movements, but a similar, lateralized control of vertical gaze has not been previously described. We report 3 patients with right hemispheric infarctions, in whom bilateral ptosis was accompanied by impaired upward gaze. We postulate that this lateralization of ocular motor function reflects the special contribution that the nondominant hemisphere makes to attention.

Aged↗

A pilot study of gabapentin as treatment for acquired nystagmus.

The effects of the anticonvulsant gabapentin were measured on vision and eve movements in three patients with acquired pendular nystagmus. In two patients, the nystagmus was associated with multiple sclerosis and, in the other, it followed brainstem stroke. A single oral 600 mg dose of gabapentin produced improvement of vision due to changes in ocular oscillations in all three patients. The effect was sustained after five weeks of treatment in two patients who elected to continue taking gabapentin 900-1500 mg/day. The results of this pilot study suggest that a controlled trial of gabapentin should be conducted to evaluate its role in the treatment of acquired forms of nystagmus.

Acetates↗

Dynamics of abducens nucleus neurons in the awake rabbit.

1. We recorded abducens neurons, identified by electrical stimulation as internuclear neurons or motoneurons, in awake rabbits. The relationship of firing rate to eye movement was determined from responses during stable fixations, sinusoidal rotation in the light (0.05-0.8 Hz), and triangular optokinetic stimulation at 0.1 Hz. 2. All abducens neurons were excited during temporal movement of the ipsilateral eye. Temporal and nasal saccades were associated with bursts or pauses, respectively, in the firing rate. 3. Motoneurons and internuclear neurons are qualitatively indistinguishable. There was no significant quantitative difference between the phase and sensitivity of the two groups for 0.2-Hz sinusoidal rotation in the light. 4. On the basis of the response to stable eye positions, we determined static eye position sensitivity of the abducens neuron pool to be 8.2 +/- 2.5 (SD) spikes.s-1/0, with a static hysteresis of 8.9 spikes/s (1.14 +/- 0.37 degrees). 5. We determined apparent eye position sensitivity (k) and apparent eye velocity sensitivity (r) from the responses to sinusoidal rotation in the light. k increases and r decreases with stimulus frequency, which indicates that the simplest transfer function mediating conversion of abducens nucleus (VI) firing rate to eye position (E) has two poles and one zero. 6. The VI-->E relationship has an "amplitude nonlinearity," manifest as a tendency for k, r, and firing rate phase lead to decrease as eye movement amplitude increases at a fixed frequency. On a percentage basis, phase is less affected than are the sensitivities. The nonlinearity becomes less pronounced for stimulus amplitudes > 2.5 degrees, and consequently a linear model of the VI-->E transformation remains useful, provided that consideration is restricted to the appropriate range of stimulus/response amplitudes. 7. We determined time constants of the linear two-pole, one-zero transfer function from the variation of r/k versus stimulus frequency. The pole time constants were T1 = 3.4 s and T2 = 0.28 s, and the zero time constant (Tz) = 1.6 s. The magnitude of Tz was corroborated by measuring the time constant of the exponential decay in firing rate after step changes in eye position. This transient method yielded a Tz of 1.1 s. 8. The time constants of the VI-->E transfer function are roughly 10 times larger than those reported for the rhesus macaque. The difference is attributable to the reported 10-fold lower stiffness of the rabbit oculomotor plant, which may in turn relate to rabbits postulated lower degree of activation of extraocular muscles at any given position.(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗