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Biomedical subjects

R John Leigh

Publications and source records attributed to R John Leigh.

At least 19 recordsLinked to original sources
PubMed2006

What clinical disorders tell us about the neural control of saccadic eye movements.

Saccades are rapid eye movements that redirect the fovea from one object to another. A great deal has been learned about the anatomy and physiology of saccades, making them an ideal system for studying the neural control of movement. Basic research on normal eye movements has greatly increased our understanding of saccadic performance, anatomy and physiology, and led to a large number of control system models. These models simulate normal saccades well, but are challenged by clinical disorders because they often do not incorporate the specific anatomical and physiological substrates needed to model clinically important abnormalities. Historically, studies of saccadic abnormalities in patients have played a critical role in understanding the neural control of saccades because they provide information that complements basic research and thus restricts hypotheses to those that are biologically plausible. This review presents four examples of clinical disorders (slow saccades, interrupted saccades, high-frequency saccadic oscillations and macrosaccadic oscillations) that have provided insights into the neurobiology of saccades, have driven the development of new models, and have suggested an explanation or treatment for these disorders. We raise general questions for both scientists and clinicians that will assist in their efforts to understand the neural control of movement, improve diagnostic criteria and develop new treatments.

Brain↗
PubMed2006

Tests of models for saccade-vergence interaction using novel stimulus conditions.

During natural activities, two types of eye movements - saccades and vergence - are used in concert to point the fovea of each eye at features of interest. Some electrophysiological studies support the concept of independent neurobiological substrates for saccades and vergence, namely saccadic and vergence burst neurons. Discerning the interaction of these two components is complicated by the near-synchronous occurrence of saccadic and vergence components. However, by positioning the far target below the near target, it is possible to induce responses in which the peak velocity of the vertical saccadic component precedes the peak velocity of the horizontal vergence component by approximately 75 ms. When saccade-vergence responses are temporally dissociated in this way, the vergence velocity waveform changes, becoming less skewed. We excluded the possibility that such change in skewing was due to visual feedback by showing that similar behavior occurred in darkness. We then tested a saccade-related vergence burst neuron (SVBN) model proposed by Zee et al. in J Neurophysiol 68:1624-1641 (1992), in which omnipause neurons remove inhibition from both saccadic and vergence burst neurons. The technique of parameter estimation was used to calculate optimal values for responses from human subjects in which saccadic and convergence components of response were either nearly synchronized or temporally dissociated. Although the SVBN model could account for convergence waveforms when saccadic and vergence components were nearly synchronized, it could not when the components were temporally dissociated. We modified the model so that the saccadic pulse changed the parameter values of the convergence burst units if both components were synchronized. The modified model accounted for velocity waveforms of both synchronous and dissociated convergence movements. We conclude that both the saccadic pulse and omnipause neuron inhibition influence the generation of vergence movements when they are made synchronously with saccades.

Action Potentials↗
PubMed2006

Contrast sensitivity, first-order motion and Initial ocular following in demyelinating optic neuropathy.

The ocular following response (OFR) is a measure of motion vision elicited at ultra-short latencies by sudden movement of a large visual stimulus. We compared the OFR to vertical sinusoidal gratings (spatial frequency 0.153 cycles/ degrees or 0.458 cycles/ degrees) of each eye in a subject with evidence of left optic nerve demyelination due to multiple sclerosis (MS). The subject showed substantial differences in vision measured with stationary low-contrast Sloan letters (20/63 OD and 20/200 OS at 2.5% contrast) and the Lanthony Desaturated 15-hue color test (Color Confusion Index 1.11 OD and 2.14 OS). Compared with controls, all of the subject's OFR to increasing contrast showed a higher threshold. The OFR of each of the subject's eyes were similar for the 0.153 cycles/ degrees stimulus, and psychophysical measurements of his ability to detect these moving gratings were also similar for each eye. However, with the 0.458 cycles/ degrees stimulus, the subject's OFR was asymmetric and the affected eye showed decreased responses (smaller slope constant as estimated by the Naka-Rushton equation). These results suggest that, in this case, optic neuritis caused a selective deficit that affected parvocellular pathways mediating higher spatial frequencies, lower-contrast, and color vision, but spared the field-holding mechanism underlying the OFR to lower spatial frequencies. The OFR may provide a useful method to study motion vision in individuals with disorders affecting anterior visual pathways.

Adult↗
PubMed2006

Motor neuronopathy with dropped hands and downbeat nystagmus: a distinctive disorder? A case report.

BACKGROUND: Eye movements are clinically normal in most patients with motor neuron disorders until late in the disease course. Rare patients are reported to show slow vertical saccades, impaired smooth pursuit, and gaze-evoked nystagmus. We report clinical and oculomotor findings in three patients with motor neuronopathy and downbeat nystagmus, a classic sign of vestibulocerebellar disease. CASE PRESENTATION: All patients had clinical and electrodiagnostic features of anterior horn cell disease. Involvement of finger and wrist extensors predominated, causing finger and wrist drop. Bulbar or respiratory dysfunction did not occur. All three had clinically evident downbeat nystagmus worse on lateral and downgaze, confirmed on eye movement recordings using the magnetic search coil technique in two patients. Additional oculomotor findings included alternating skew deviation and intermittent horizontal saccadic oscillations, in one patient each. One patient had mild cerebellar atrophy, while the other two had no cerebellar or brainstem abnormality on neuroimaging. The disorder is slowly progressive, with survival up to 30 years from the time of onset. CONCLUSION: The combination of motor neuronopathy, characterized by early and prominent wrist and finger extensor weakness, and downbeat nystagmus with or without other cerebellar eye movement abnormalities may represent a novel motor neuron syndrome.

Anterior Horn Cells↗
PubMed2005

Vestibular and non-vestibular contributions to eye movements that compensate for head rotations during viewing of near targets.

Geometry dictates that when subjects view a near target during head rotation the eyes must rotate more than the head. The relative contribution to this compensatory response by adjustment of the vestibulo-ocular reflex gain (Gvor), visual tracking mechanisms including prediction, and convergence is debated. We studied horizontal eye movements induced by sinusoidal 0.2-2.8 Hz, en-bloc yaw rotation as ten normal humans viewed a near target that was either earth-fixed (EFT) or head-fixed (HFT). For EFT, group median gain was 1.49 at 0.2 Hz declining to 1.08 at 2.8 Hz. For HFT, group median gain was 0.03 at 0.2 Hz increasing to 0.71 at 2.8 Hz. By applying transient head perturbations (peak acceleration >1,000 degrees s(-2)) during sinusoidal rotation, we determined that Gvor was similar during either EFT or HFT conditions, and contributed only approximately 75% to the compensatory response. We confirmed that retinal image slip contributed to the compensatory response by demonstrating reduced gain during EFT viewing under strobe illumination. Gain also declined during sum-of-sines head rotations, confirming the contribution of predictive mechanisms. The gain of compensatory eye movements was similar during monocular or binocular viewing, although vergence angle was greater during binocular viewing. Comparison with previous studies indicates that mechanisms for generation of eye rotations during near viewing depend on head stimulus type (rotation or translation), waveform (transient or sinusoidal), and the species being tested.

Adult↗
PubMed2005

Ocular oscillations generated by coupling of brainstem excitatory and inhibitory saccadic burst neurons.

The human saccadic system is potentially unstable and may oscillate if the burst neurons, which generate saccades, are not inhibited by omnipause neurons. A previous study showed that combined saccade vergence movements can evoke oscillations in normal subjects. We set out to determine: 1) whether similar oscillations can be recorded during other paradigms associated with inhibition of omnipause neurons; 2) whether lesions of the fastigial nuclei disrupt such oscillations; and 3) whether such oscillations can be reproduced using a model based on the coupling of excitatory and inhibitory burst neurons. We recorded saccadic oscillations during vergence movements, combined saccade-vergence movements, vertical saccades, pure vergence and blinks in three normal subjects, and in a patient with saccadic hypermetria due to a surgical lesion affecting both fastigial nuclei. During combined saccade-vergence, normal subjects and the cerebellar patient developed small-amplitude (0.1 - 0.5 degrees), high-frequency (27-35 Hz), conjugate horizontal saccadic oscillations. Oscillations of a similar amplitude and frequency occurred during blinks, pure vergence and vertical saccades. One normal subject could generate saccadic oscillations voluntarily (approximately 0.7 degrees amplitude, 25 Hz) during sustained convergence. Previous models proposed that high-frequency eye oscillations produced by the saccadic system (saccadic oscillations), occur because of a delay in a negative feedback loop around high-gain, excitatory burst neurons in the brainstem. The feedback included the cerebellar fastigial nuclei. We propose another model that accounts for saccadic oscillations based on 1) coupling of excitatory and inhibitory burst neurons in the brainstem and 2) the hypothesis that burst neurons show post-inhibitory rebound discharge. When omnipause neurons are inhibited (as during saccades, saccade-vergence movements and blinks), this new model simulates oscillations with amplitudes and frequencies comparable to those in normal human subjects. The finding of saccadic oscillations in the cerebellar patient is compatible with the new model but not with the recent models including the fastigial nuclei in the classic negative-feedback loop model. Our model proposes a novel mechanism for generating oscillations in the oculomotor system and perhaps in other motor systems too.

Adult↗
PubMed2005

Effects of retinal image slip on modulation of visual vestibulo-ocular reflex during near viewing.

During viewing of a near target, the gain of the visually modulated vestibulo-ocular reflex (vVOR) exceeds 1.0. We investigated whether retinal image slip contributes to this gain increase by measuring responses during strobe illumination. Subjects showed greater gain values during normal versus strobe illumination of the near target, even during rotation at frequencies above 1.0 Hz, indicating that retinal image velocity information is used to optimize vVOR.

Humans↗
PubMed2005

Tests of Hering- and Helmholtz-type models for saccade-vergence interactions by comparing visually guided and memory-guided movements.

We compared the dynamic properties of memory-guided and visually-guided saccade-vergence movements. For memory-guided responses, convergence components were slowed proportionally more than corresponding saccadic components, compared with visually-guided responses. This result is consistent with independent saccadic and vergence systems, and supports a Hering-type model for saccade-vergence interactions.

Convergence, Ocular↗
PubMed2005

Comparison of velocity waveforms of eye and head saccades.

We compared the velocity waveforms of head and eye-in-head movements during eye-head saccades over a range 5-50 degrees. The velocity waveforms of eye-in-head saccades showed a skew ratio (acceleration period/saccade duration) that varied as a function of saccade size and duration. The velocity waveforms of head saccades showed a more constant skew of approximately 0.5 for the range of movements tested. These results suggest independent system controllers for eye and head components of eye-head saccades.

Fixation, Ocular↗
PubMed2005

Abnormal eye movements predict disability in MS: two-year follow-up.

We conducted a two-year follow-up study of 40 patients with MS in whom we had reported that abnormal eye movements (AEM) were associated with greater general disability. AEM patients (17/40) remained significantly (p < .001) more disabled (median EDSS of 7.0) than those with normal eye movements (median EDSS of 5.0). AEM and great disability were associated with abnormal MRI signals in brainstem or cerebellum, where disease may involve control circuits for eye movements as well as descending motor pathways.

Adult↗
PubMed2005

Internuclear ophthalmoparesis in episodic ataxia type 2.

Two patients sharing a novel mutation of the CACNA1A gene for P/Q calcium channels showed significant slowing of adducting saccades compared with normal subjects or patients with cerebellar disease. Internuclear ophthalmoparesis (INO) was clinically evident in one. While these findings might be specific to this mutation, INO in our patients with episodic ataxia type 2 suggested involvement outside the cerebellum, either in the brain-stem internuclear pathway or at the neuromuscular junction.

Adult↗
PubMed2005

Studies of eccentric gaze stability: effects of pitch head position on horizontal gaze-holding in patients with cerebellar disease.

We studied the effects of change of head position in the pitch plane on the ability to hold horizontal eccentric gaze in five patients with cerebellar disorders. All patient showed a change in the time constant of horizontal centripetal drift when the head was pitched forward or back. This result suggests that otolithic inputs can influence the neural integrator for horizontal eye movements and indicates the value of testing horizontal gaze holding in different head positions.

Cerebellar Diseases↗
PubMed2004

Directional asymmetry during combined saccade-vergence movements.

We investigated relationships between saccadic and vergence components of gaze shifts as 10 human subjects switched visual fixation between targets aligned in the midsagittal plane that lay in different vertical directions and at different distances. When fixation was shifted between a higher distant target and a lower near target, peak convergence velocity followed peak vertical saccadic velocity by a median interval of 12 ms. However, when fixation was shifted between a lower distant target and a higher near target, peak convergence velocity followed peak vertical saccadic velocity by a median interval of 76 ms. For the 2 stimulus arrangements, the median intervals by which peak divergence velocity followed the peak vertical saccadic velocity were 4 and 20 ms, respectively. The dissociation interval between the peak velocities of convergence and upward saccades increased with vertical saccade size, required convergence angle, and elevation of the endpoint of the movement. Velocity waveforms of vergence responses were more skewed when peak velocity was closely associated with saccadic peak velocity than when the vergence responses were delayed. Convergence peak velocities did not vary in any consistent pattern, but divergence peak velocities were generally smaller with responses that were delayed. Vergence movements were accompanied by small, high-frequency conjugate oscillations, suggesting that omnipause neurons were inhibited for both types of responses. In conclusion, the present findings indicate that the dynamic properties of horizontal vergence movements depend on the direction and timing of vertical saccades; these findings suggest experimental tests for current models of saccade-vergence interaction.

Adult↗
PubMed2004

Effects of eyelid closure, blinks, and eye movements on the electroencephalogram.

OBJECTIVE: To characterize the effects of the eyeball and eyelid positions during eyeblinks on electroencephalographic (EEG) potentials. METHODS: Movements of the upper eyelids and eyes were measured in two healthy subjects using the magnetic search coil technique during horizontal and vertical eye rotations, eyeblinks, and lid closure. Corresponding signal changes were recorded simultaneously on the electroencephalogram (EEG). RESULTS: Spontaneous blinks produced small eye movements directed down and inward, whereas slow or forced blinks were associated with delayed upward eye rotations (i.e. Bell's phenomenon); both types of blinks caused positive EEG potentials with bifrontal distribution maximum at Fp1 and Fp2. CONCLUSIONS: In prior reports, these positive EEG artifacts have been attributed to upward eyeball rotation during blinks-Bell's phenomenon. By contrast, our findings indicate that movements of the eyelid contribute to a greater extent to these EEG potentials than do upward eyeball rotations. SIGNIFICANCE: Care is required in attributing EEG artifacts to movements of either eyeball or eyelid, since our findings suggest that they both contribute to these potentials.

Adult↗
PubMed2004

Sensorimotor recovery following spaceflight may be due to frequent square-wave saccadic intrusions.

Square-wave jerks (SWJs) are small, involuntary saccades that disrupt steady fixation. We report the case of an astronaut (approximately 140 d on orbit) who showed frequent SWJs, especially postflight, but who showed no impairment of vision or decrement of postflight performance. These data support the view that SWJs do not impair vision because they are paired movements, consisting of a small saccade away from the fixation position followed, within 200 ms, by a corrective saccade that brings the eye back on target. Since many returning astronauts show a decrement of dynamic visual function during postflight locomotion, it seems possible that frequent SWJs improved this astronaut's visual function by providing postsaccadic enhancement of visual fixation, which aided postflight performance. Certainly, frequent SWJs did not impair performance in this astronaut, who had no other neurological disorder.

Astronauts↗