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Biomedical subjects

Vallabh E Das

Publications and source records attributed to Vallabh E Das.

9 recordsLinked to original sources

Incomitance in monkeys with strabismus.

PURPOSE: Rhesus monkeys reared with restricted visual environment during their first few months of life develop large ocular misalignment (strabismus). The purpose of this study was to describe 'A and V' patterns and DVD in these animals during fixation and eye movements and suggest that this form of rearing produces animals that are suitable model to study the mechanisms that might cause 'A/V' pattern incomitant strabismus and dissociated vertical deviation (DVD) in humans. METHODS: Eye movements were recorded during fixation, smooth-pursuit and saccades using binocular search coils in one monkey with esotropia, three monkeys with exotropia and one normal monkey. RESULTS: 1) Monkeys reared with Alternating Monocular Occlusion or Binocular deprivation (tarsal plates intact) showed both horizontal and vertical misalignment during monocular and binocular viewing. 2) Large 'A' patterns were evident in 2 out of 3 exotropes while a 'V' pattern was observed in the esotrope. 3) Similar 'A/V' patterns were observed with either eye viewing and during fixation or eye movements. 4) The vertical misalignment, which consisted of the non-viewing eye being higher than the fixating eye, appeared to constitute a DVD. CONCLUSION: Visual sensory deprivation methods that induce large strabismus also induce 'A/V' patterns and DVD similar to certain types of human strabismus. The source of pattern strabismus could be central, i.e., altered innervation to extraocular muscles from motor nuclei, or peripheral, i.e., altered location of extraocular muscle pulleys.

Animals↗

Modeling of smooth pursuit-related neuronal responses in the DLPN and NRTP of the rhesus macaque.

The dorsolateral pontine nucleus (DLPN) and nucleus reticularis tegmenti pontis (NRTP) comprise obligatory links in the cortico-ponto-cerebellar system supporting smooth pursuit eye movements. We examined the response properties of DLPN and rNRTP neurons during step-ramp smooth pursuit of a small target moving across a dark background. Our neurophysiological studies were conducted in awake, behaving juvenile macaques (Macaca mulatta). We used multiple linear-regression modeling to estimate the relative sensitivities of neurons to eye parameters (position, velocity, and acceleration) and retinal-error parameters (position, velocity, and acceleration). We found that a large proportion of pursuit-related DLPN neurons primarily code eye-velocity information, whereas a large proportion of rNRTP neurons primarily code eye-acceleration information. We calculated the relative decrease in variance found when using a six-component model that included both eye- and retinal-error parameters compared with three-component models that include either eye or retinal error. These comparisons show that a majority of DLPN (14/20) and rNRTP (17/19) neurons have larger contributions from eye compared with retinal-error parameters (P < 0.001, paired t-test). Even though eye-motion parameters provide the strongest contributions in a given model, a significant contribution from retinal error was often present (i.e., >20% reduction in variance in 6-component model compared with 3-component models). Thus our results indicate that the DLPN plays a larger role in maintaining steady-state smooth pursuit eye velocity, whereas rNRTP contributes to both the initiation and maintenance of smooth pursuit.

Acceleration↗

Gaze-related response properties of DLPN and NRTP neurons in the rhesus macaque.

The dorsolateral pontine nucleus (DLPN) and nucleus reticularis tegmenti pontis (NRTP) are basilar pontine nuclei important for control of eye movements. The aim of this study was to compare the response properties of neurons in DLPN and rostral NRTP (rNRTP) during visual, oculomotor, and vestibular testing. We tested 51 DLPN neurons that were modulated during smooth pursuit (23/51) or during motion of a large-field visual stimulus (28/51). Following vestibular testing, we found that the majority of smooth pursuit-related neurons in DLPN were best classified as gaze (13/23) or eye velocity (7/23) related. Only a small percentage (3/51) of DLPN neurons responded during vestibular ocular reflex in the dark (VORd). We tested rNRTP neurons as described above and found the majority of neurons (35/43) were modulated during smooth pursuit or during motion of a large-field stimulus only (4/43). A significant proportion of our rNRTP gaze velocity neurons (10/18) were also modulated during VORd. We found that the majority of smooth pursuit related neurons in rNRTP were best classified as gaze velocity (18/35) or gaze acceleration (11/35) sensitive. The remaining neurons were classified as eye position or eye/head related. We used multiple linear-regression modeling to determine the relative contributions of eye, head and visual inputs to the responses of DLPN and rNRTP neurons. Our results support the suggestion that both DLPN and rNRTP play significant roles not only in control of smooth pursuit but also in control of gaze.

Action Potentials↗

Conjugate adaptation of saccadic gain in non-human primates with strabismus.

In this study, we have used the double-step paradigm to test saccadic gain adaptation during monocular viewing in one normal monkey, two monkeys with exotropia, and one monkey with esotropia. In this paradigm, the target for the saccade is displaced during the saccade, resulting in a consistent visual error. Studies in normal humans and monkeys have shown that the brain responds to this consistent visual error by gradually changing saccade gain. Using this technique, we were able to elicit adaptation in both the viewing eye and the nonviewing eye in the normal monkey and in monkeys with strabismus. The rate of adaptation was not significantly different in the viewing and nonviewing eyes in the normal and strabismic monkeys. The magnitude of adaptation as calculated by a percentage change in gain was also not significantly different in the viewing and the nonviewing eyes in the normal and strabismic monkeys. Our data show that animals with strabismus retain the ability to elicit a conjugate adaptation of saccades using this mechanism. We also suggest that the double-step paradigm elicits a conjugate adaptation of saccades whether the animal is viewing monocularly (our studies) or binocularly (data published in literature).

Adaptation, Physiological↗

Recovery of dynamic visual acuity in unilateral vestibular hypofunction.

OBJECTIVE: To determine the effect of vestibular exercises on the recovery of visual acuity during head movement in patients with unilateral vestibular hypofunction. STUDY DESIGN: Prospective, randomized, double-blind study. SETTING: Ambulatory referral center. PATIENTS: Twenty-one patients with unilateral vestibular hypofunction, aged 20 to 86 years. INTERVENTION: One group (13 patients) performed vestibular exercises designed to enhance the vestibulo-ocular reflex, and the other group (8 patients) performed placebo exercises. The placebo group was switched to vestibular exercises after 4 weeks. OUTCOME MEASURES: Measurements of dynamic visual acuity (DVA) during predictable (DVA-predictable) and unpredictable (DVA-unpredictable) head movements by means of a computerized test and measurement of intensity of oscillopsia by means of a visual analog scale. RESULTS: As a group, patients who performed vestibular exercises showed a significant improvement in DVA-predictable (P<.001) and DVA-unpredictable (P<.001), while those performing placebo exercises did not (P =.07). On the basis of stepwise regression analysis, the leading factor contributing to improvement was vestibular exercises. This reached significance for DVA-predictable (P =.009) but not DVA-unpredictable (P =.11). Other factors examined included age, time from onset, initial DVA, oscillopsia, and duration of treatment. Changes in oscillopsia did not correlate with DVA-predictable or DVA-unpredictable. CONCLUSIONS: Use of vestibular exercises is the main factor involved in recovery of DVA-predictable and DVA-unpredictable in patients with unilateral vestibular hypofunction. Exercises may foster the use of centrally programmed eye movements that could substitute for the vestibulo-ocular reflex. The DVA-predictable would benefit more from this than would DVA-unpredictable.

Adult↗

Role of the dorsolateral pontine nucleus in short-term adaptation of the horizontal vestibuloocular reflex.

The dorsolateral pontine nucleus (DLPN) is a major component of the cortico-ponto-cerebellar pathway that carries signals essential for smooth pursuit. This pathway also carries visual signals that could play a role in visually guided motor learning in the vestibular ocular reflex (VOR). However, there have been no previous studies that tested this possibility directly. The aim of this study was to determine the potential role of the DLPN in short-term VOR gain adaptation produced by viewing a scene through lenses placed in front of both eyes. In control experiments, adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz, 30 degrees /s) for 2 h while the monkey viewed a stationary visual surround through either magnifying (x2) or minifying (x0.5) lenses. This led to increases (23-32%) or decreases (22-48%) of VOR gain as measured in complete darkness (VORd). We used injections of muscimol, a potent GABA(A) agonist (0.5 microl; 2%), to reversibly inactivate the DLPN, unilaterally, in three monkeys. After DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit was reduced by 35-68%, and steady-state gain was reduced by 32-61%. Despite these significant deficits (P < 0.01) in ipsilesional smooth pursuit, the VOR during lens viewing was similar to that measured in preinjection control experiments. Similarly, after 2 h of adaptation, VORd gain was not significantly different (P > 0.61) from control adaptation values for either ipsi- or contralesional directions of head rotation. This was the case even though a stable ipsilesional smooth pursuit deficit persisted throughout the full adaptation period. Our results suggest that visual error signals for short-term adaptation of the VOR are derived from sources other than the DLPN perhaps including other basilar pontine nuclei and the accessory optic system.

Adaptation, Physiological↗

Role of the dorsolateral pontine nucleus in visual-vestibular behavior.

Visual-vestibular behavior depends on signals traveling in climbing and mossy fiber pathways. Our study examined the role of the dorsolateral pontine nucleus (DLPN), a major component of the cortico-ponto-cerebellar mossy fiber pathway. DLPN neurons discharge in relation to smooth pursuit and during visual stimulation, indicating a potential role in visually guided motor learning in the vestibulo-ocular reflex (VOR). We used unilateral muscimol injections to determine the potential role of the DLPN in short-term VOR gain adaptation. Preinjection adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz, 30 degrees /s) for 2 h while the monkey viewed a stationary visual surround through either magnifying (x2) or minifying (x0.5) lenses. VOR gain increases (23-32%) or decreases (22-48%) as measured in complete darkness (VORd) were achieved. Following DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit was reduced by 35-68%, and steady state gain was reduced by 32-61%. Furthermore, the monkey's ability to cancel the VOR was impaired. In contrast to these significant deficits in ipsilesional smooth pursuit, the VOR during lens viewing was similar to that measured in preinjection control experiments. Similarly, following 2 h of adaptation, VORd gain adaptation was indistinguishable from control adaptation values for either ipsilesional or contralesional directions of head rotation. Our results suggest that visual error signals for short-term adaptation of the VOR are derived from sources other than the DLPN, such as those from the accessory optic system.

Animals↗

Animal models for visual deprivation-induced strabismus and nystagmus.

The development of gaze-stabilizing systems depends on normal vision during infancy. Monkeys reared with binocular lid suture (BLS) for the first 25-40 days of life have strabismus, optokinetic nystagmus deficits, latent nystagmus, and decreased binocular cells in the visual cortex and nucleus of the optic tract. When BLS is extended to 55 days, pendular and congenital nystagmus also occurs. Eyelids in infant monkeys are hairless and thin, but BLS still degrades sensory fusion, motion, and form perception. To determine to what extent these visual properties are critical in the development of normal gaze stabilization, we examined infant monkeys reared with one opaque contact lens over one eye, alternated to the fellow eye every other day (AMO); and monkeys reared in a 3-Hz strobe environment. Monkeys reared with AMO develop strabismus, but have normal optokinetic nystagmus and no spontaneous nystagmus. Area 17 is monocular, but the medial temporal area and the nucleus of the optic tract are binocular. Monkeys reared in strobe light develop pendular nystagmus but not strabismus. We were puzzled by the results of the AMO monkeys until we examined infant monkeys with BLS that were prevented from seeing form through the lids. This was done by leaving the tarsal plate intact behind the eyelid. They developed similar to the AMO monkeys. These results suggest that disruption of sensory fusion during infancy (BLS, AMO) causes strabismus. If strabismus occurs while the monkeys have some form vision from each eye (BLS without tarsal plate), then the nucleus of the optic tract becomes monocular, which causes optokinetic nystagmus deficits and latent nystagmus. Infant monkeys reared without visual motion develop pendular nystagmus.

Animals↗

A neurobiological approach to acquired nystagmus.

The development of animal and mathematical models for several forms of acquired nystagmus has led to more comprehensive knowledge of these disorders. In the best understood forms, such as periodic alternating nystagmus, our range of knowledge includes an animal model, the neurotransmitters involved, and effective treatment. For some other forms, such as downbeat nystagmus, we have an animal model, but reliable treatment is lacking. In other cases, exemplified by acquired pendular nystagmus, we have only a provisional hypothesis for pathogenesis to account for the oscillations, without an animal model, but effective treatment is possible in some patients. The present trend of studying all aspects of the neurobiology of nystagmus, from molecules to behavior, seems to be the best approach to extend our knowledge and to identify new treatments, but much remains to be done.

Animals↗