Electrical stimulation of superior colliculus affects strabismus angle in monkey models for strabismus.

Disruption of binocular vision during the critical period for development leads to eye misalignment in humans and in monkey models. We have previously suggested that disruption within a vergence circuit could be the neural basis for strabismus. Electrical stimulation in the rostral superior colliculus (rSC) leads to vergence eye movements in normal monkeys. Therefore, the purpose of this study was to investigate the effect of SC stimulation on eye misalignment in strabismic monkeys. Electrical stimulation was delivered to 51 sites in the intermediate and deep layers of the SC (400 Hz, 0.5-s duration, 10-40 µA) in 3 adult optical prism-reared strabismic monkeys. Scleral search coils were used to measure movements of both eyes during a fixation task. Staircase saccades with horizontal and vertical components were elicited by stimulation as predicted from the SC topographic map. Electrical stimulation also resulted in significant changes in horizontal strabismus angle, i.e., a shift toward exotropia/esotropia depending on stimulation site. Electrically evoked saccade vector amplitude in the two eyes was not significantly different (P > 0.05; paired t-test) but saccade direction differed. However, saccade disconjugacy accounted for only ~50% of the change in horizontal misalignment while disconjugate postsaccadic movements accounted for the other ~50% of the change in misalignment due to electrical stimulation. In summary, our data suggest that electrical stimulation of the SC of strabismic monkeys produces a change in horizontal eye alignment that is due to a combination of disconjugate saccadic eye movements and disconjugate postsaccadic movements.NEW & NOTEWORTHY Electrical stimulation of the superior colliculus in strabismic monkeys results in a change in eye misalignment. These data support the notion of developmental disruption of vergence circuits leading to maintenance of eye misalignment in strabismus.

Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters.

Immunization programs against SARS-CoV-2 with commercial intramuscular vaccines prevent disease but are less efficient in preventing infections. Mucosal vaccines can provide improved protection against transmission, ideally for different variants of concern (VOCs) and related sarbecoviruses. Here, we report a multi-antigen, intranasal vaccine, NanoSTING-SN (NanoSTING-Spike-Nucleocapsid), eliminates virus replication in both the lungs and the nostrils upon challenge with the pathogenic SARS-CoV-2 Delta VOC. We further demonstrate that NanoSTING-SN prevents transmission of the SARS-CoV-2 Omicron VOC (BA.5) to vaccine-naïve hamsters. To evaluate protection against other sarbecoviruses, we immunized mice with NanoSTING-SN. We showed that immunization affords protection against SARS-CoV, leading to protection from weight loss and 100% survival in mice. In non-human primates, animals immunized with NanoSTING-SN show durable serum IgG responses (6 months) and nasal wash IgA responses cross-reactive to SARS-CoV-2 (XBB1.5), SARS-CoV and MERS-CoV antigens. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to reducing transmission of respiratory viruses, and (2) eliciting immunity against multiple antigens can be advantageous in engineering pan-sarbecovirus vaccines.

An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models.

Respiratory viral infections cause morbidity and mortality worldwide. Despite the success of vaccines, vaccination efficacy is weakened by the rapid emergence of viral variants with immunoevasive properties. The development of an off-the-shelf, effective, and safe therapy against respiratory viral infections is thus desirable. Here, we develop NanoSTING, a nanoparticle formulation of the endogenous STING agonist, 2'-3' cGAMP, to function as an immune activator and demonstrate its safety in mice and rats. A single intranasal dose of NanoSTING protects against pathogenic strains of SARS-CoV-2 (alpha and delta VOC) in hamsters. In transmission experiments, NanoSTING reduces the transmission of SARS-CoV-2 Omicron VOC to naïve hamsters. NanoSTING also protects against oseltamivir-sensitive and oseltamivir-resistant strains of influenza in mice. Mechanistically, NanoSTING upregulates locoregional interferon-dependent and interferon-independent pathways in mice, hamsters, as well as non-human primates. Our results thus implicate NanoSTING as a broad-spectrum immune activator for controlling respiratory virus infection.

Muscimol inactivation of caudal fastigial nucleus and posterior interposed nucleus in monkeys with strabismus.

Previously, we showed that neurons in the supraoculomotor area (SOA), known to encode vergence angle in normal monkeys, encode the horizontal eye misalignment in strabismic monkeys. The SOA receives afferent projections from the caudal fastigial nucleus (cFN) and the posterior interposed nucleus (PIN) in the cerebellum. The objectives of the present study were to investigate the potential roles of the cFN and PIN in 1) conjugate eye movements and 2) binocular eye alignment in strabismic monkeys. We used unilateral injections of the GABAA agonist muscimol to reversibly inactivate the cFN (4 injections in exotropic monkey S1 with ≈ 4° of exotropia; 5 injections in esotropic monkey S2 with ≈ 34° of esotropia) and the PIN (3 injections in monkey S1). cFN inactivation induced horizontal saccade dysmetria in all experiments (mean 39% increase in ipsilesional saccade gain and 26% decrease in contralesional gain). Also, mean contralesional smooth-pursuit gain was decreased by 31%. cFN inactivation induced a divergent change in eye alignment in both monkeys, with exotropia increasing by an average of 9.8° in monkey S1 and esotropia decreasing by an average of 11.2° in monkey S2 (P < 0.001). Unilateral PIN inactivation in monkey S1 resulted in a mean increase in the gain of upward saccades by 13% and also induced a convergent change in eye alignment, reducing exotropia by an average of 2.7° (P < 0.001). We conclude that cFN/PIN influences on conjugate eye movements in strabismic monkeys are similar to those postulated in normal monkeys and cFN/PIN play important and complementary roles in maintaining the steady-state misalignment in strabismus.

Investigation of Selective Innervation of Extraocular Muscle Compartments.

Purpose: Recent magnetic resonance imaging studies have suggested that extraocular muscles (EOM) are further divided into transverse compartments that behave differentially and often unexpectedly during eye movements. Selective innervation of EOM compartments may explain the observation that certain horizontal recti compartments contribute to specific vertical eye movements and that some cyclovertical EOM compartments do not contribute to vertical vergence. We investigated the discharge characteristics of extraocular motoneurons during these eye movement tasks where EOM compartments behaved differentially for evidence of selective innervation. Methods: We recorded from all six extraocular motoneuron populations in the abducens, oculomotor, and trochlear nuclei as two non-human primates performed vertical vergence and vertical smooth-pursuit. The relationship between motoneuron firing rate, horizontal and vertical eye parameters of the innervated eye during each task was determined using multiple linear regression. Results: All 26 medial rectus motoneurons recorded showed no significant modulation during vertical smooth-pursuit and vertical vergence. Twenty-eight of 30 abducens motoneurons showed no significant modulation during vertical vergence, and all 30 cells did not modulate during vertical smooth-pursuit. For the cyclovertical motoneurons, 147 of the 149 cells (44/46 inferior rectus, 27/27 superior oblique, 41/41 superior rectus and 35/35 inferior oblique) modulated significantly during vertical vergence. Conclusions: Extraocular motoneuron activity during vertical vergence and vertical smooth-pursuit does not support the theory that EOM compartments are selectively innervated. The observed differential behavior of EOM compartments is likely not driven by oculomotor control and could be due to passive change in EOM cross-sectional area.

A competition framework for fixation-preference in strabismus.

Strabismic subjects often develop the ability to fixate on a target with either eye. Previous studies have shown that fixation-preference behavior varies systematically depending on spatial location of the target. We hypothesized that, when an eccentric target is presented, oculomotor fixation-preference in strabismus may be accounted for in a competitive decision framework wherein the brain must choose between two possible retinal errors to prepare a conjugate saccade that results in one of the eyes acquiring the eccentric target. We tested this framework by recording from visuo-motor neurons in the superior colliculus (SC) of two strabismic rhesus macaque monkeys as they performed a delayed saccade task under binocular viewing conditions. In one experiment, visual targets were presented at one of two locations corresponding to the neuronal receptive field location with respect to either the viewing or the deviated eye. Robust visual sensory responses were observed when targets were presented at either location indicating the presence of competing sensory signals for eye-choice. In a second experiment, a single visual target was placed at the neuronal receptive field location where the animal switched fixation on some trials and did not on other trials. At such target locations where either eye could acquire the target, both visual and build-up activity was greater in trials when the saccade encoded by the neuron "won." These findings provide evidence for the influence of visual suppression within SC sensory activity and support the possible utilization of a competition framework, one that has been previously described for when a binocularly aligned animal chooses from among multiple targets, to drive fixation-preference behavior in strabismus.

Human deprivation amblyopia: treatment insights from animal models.

Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system. Among the subtypes of amblyopia, the most debilitating and recalcitrant to treatment is deprivation amblyopia. Nevertheless, human studies focused on advancing the standard of care for amblyopia have largely avoided recruitment of patients with this rare but severe impairment subtype. In this review, we delineate characteristics of deprivation amblyopia and underscore the critical need for new and more effective therapy. Animal models offer a unique opportunity to address this unmet need by enabling the development of unconventional and potent amblyopia therapies that cannot be pioneered in humans. Insights derived from studies using animal models are discussed as potential therapeutic innovations for the remediation of deprivation amblyopia. Retinal inactivation is highlighted as an emerging therapy that exhibits efficacy against the effects of monocular deprivation at ages when conventional therapy is ineffective, and recovery occurs without apparent detriment to the treated eye.

Unreferenced spatial localization under monocular and dichoptic viewing conditions.

Knowledge of eye position in the brain is critical for localization of objects in space. To investigate the accuracy and precision of eye position feedback in an unreferenced environment, subjects with normal ocular alignment attempted to localize briefly presented targets during monocular and dichoptic viewing. In the task, subjects' used a computer mouse to position a response disk at the remembered location of the target. Under dichoptic viewing (with red (right eye)-green (left eye) glasses), target and response disks were presented to the same or alternate eyes, leading to four conditions [green target-green response cue (LL), green-red (LR), red-green (RL), and red-red (RR)]. Time interval between target and response disks was varied and localization errors were the difference between the estimated and real positions of the target disk. Overall, the precision of spatial localization (variance across trials) became progressively worse with time. Under dichoptic viewing, localization errors were significantly greater for alternate-eye trials as compared to same-eye trials and were correlated to the average phoria of each subject. Our data suggests that during binocular dissociation, spatial localization may be achieved by combining a reliable versional efference copy signal with a proprioceptive signal that is unreliable perhaps because it is from the wrong eye or is too noisy.

Muscimol inactivation caudal to the interstitial nucleus of Cajal induces hemi-seesaw nystagmus.

Hemi-seesaw nystagmus (hemi-SSN) is a jerk-waveform nystagmus with conjugate torsional and disjunctive vertical components. Halmagyi et al. in Brain 117(Pt 4):789-803 (1994), reported hemi-SSN in patients with unilateral lesions in the vicinity of the Interstitial Nucleus of Cajal (INC) and suggested that an imbalance in projections from the vestibular nuclei to the INC was the source of the nystagmus. However, this hypothesis was called into question by Helmchen et al. in Exp Brain Res 119(4):436-452 (1998), who inactivated INC in monkeys with muscimol (a GABA(A) agonist) and induced failure of vertical gaze-holding (neural integrator) function but not hemi-SSN. We injected 0.1-0.2 microl of 2% muscimol into the supraoculomotor area, 1-2 mm dorso-lateral to the right oculomotor nucleus and caudal to the right INC. A total of seven injections in two juvenile rhesus monkeys were performed. Hemi-SSN was noted within 5-10 min after injection for six of the injections. Around the time the hemi-SSN began, a small skew deviation also developed. However, there was no limitation of horizontal or vertical eye movements, suggesting that the nearby oculomotor nucleus was not initially compromised. Limitations in eye movement range developed about (1/2)-1 h following the injections. Clinical signs that were observed after the animal was released to his cage included a moderate to marked head tilt toward the left (contralesional) side, consistent with an ocular tilt reaction. We conclude that hemi-SSN can be caused by lesions just caudal to the INC, whereas lesions of the INC itself cause down-beat nystagmus and vertical gaze-holding failure, as demonstrated by Helmchen et al. Combined deficits may be encountered with lesions that involve several midbrain structures.

Fixation Preference for Visual and Auditory Targets in Monkeys with Strabismus.

Purpose: During binocular viewing, many strabismic subjects choose the eye of fixation depending on the retinotopic location of a visual target. Here, we compare eye choice behavior when orienting to visual and non-visual (auditory) targets. Methods: Eye movements were measured in two head-fixed exotropic strabismic monkeys in a saccadic task involving either a visual or an auditory stimulus (no visual target information or feedback) during monocular or binocular viewing. The stimulus was one of 21 visual or auditory targets arranged 10° apart in a 7 × 3 array at a distance of 57 cm in an otherwise dark room. Fixation preference was calculated by recording the incidence of using a specific eye to acquire the target at any location. Results: Spatial patterns of fixation preference were observed in both monkeys for both visual and auditory stimuli; targets to the far right were acquired by the right eye, and targets to the far left were acquired by the left eye. For visual targets, the border for a change in fixation preference occurred in between the visual axes of the fixating and deviated eyes (variable in the two animals). In contrast, the border for fixation change remained near the cranio-center during the auditory task. During monocular viewing, fixation switching was observed only at the extremities during visual tasks; during the auditory task, fixation preference was similar to that observed during binocular viewing. Conclusions: Fixation preference persists for invisible auditory targets. Our data suggest that visual suppression could modify underlying eye choice behavior that functions independently from vision.

Longitudinal Development of Ocular Misalignment in Nonhuman Primate Models for Strabismus.

Purpose: To investigate the longitudinal change in horizontal and vertical ocular alignment in normal and prism-reared infant monkeys during the critical developmental period. Methods: Ocular alignment was measured using Hirschberg photographic methods in 6 infant monkeys reared under prism-viewing from day 1 after birth to 4 months, and 2 monkeys reared with normal visual experience. Photographs were acquired twice a week for the first 6 months of life and analyzed to identify pupil center and the first Purkinje image from which eye positions and strabismus angle were calculated. Results: At 3 weeks after birth, prism monkeys presented with significant horizontal ocular misalignment. A gradual change in alignment was seen in all prism-reared monkeys stabilizing at approximately 11 weeks, at which time 5 monkeys were exotropic (mean, 16° XT; range, 13°-24°) and 1 monkey was esotropic (5° ET). A reduction in ocular misalignment was observed after exposure to normal visual environment at 16 weeks, but at 34 weeks of age, that is, 18 weeks after removal of prisms, prism-reared monkeys displayed a mean horizontal strabismus of 7° XT (range, 2° ET to 20° XT), which was still significantly different from normal monkeys. Conclusions: Prism-rearing disrupts binocular fusion mechanisms, and horizontal and vertical strabismus is seen to develop as early as 3 weeks of age in monkey models, equivalent to approximately 3 months in humans. The time course of change in alignment overlaps with disruption in various visual sensory functions, suggesting a causal temporal link between sensory and motor mechanisms for alignment.

Vertical vergence in nonhuman primates depends on horizontal gaze position.

The goal of this study was to compare vertical fusion capability at different orbital eye positions in normal nonhuman primates and attempt to use this information to isolate the extraocular muscles (EOMs) that mediate vertical vergence. Scleral search coils were used to record movements of both eyes as two normal nonhuman primates (M1, M2) performed a vertical vergence task at different horizontal eye positions. In a control experiment, M1 was also tested at different angles of horizontal vergence. To elicit vertical vergence, a 50° x 50° stimulus comprising a central fixation cross and random dots elsewhere was presented separately to each eye under dichoptic viewing conditions. Vertical disparity was introduced by slowly displacing the stimulus for one eye vertically. Vertical fusion amplitude (maximum disparity that the monkey was able to fuse) and vertical vergence (maximum difference in vertical position of the two eyes) were measured. Vertical fusion capability differed at different orbital eye positions. Monkey M1 had significantly smaller vertical fusion capabilities when the right eye (RE) was abducted than left eye (LE) while M2 had significantly smaller vertical fusion capabilities when the RE was adducted and LE abducted. M1 also showed greater vertical fusion capability for near gaze. M1 data suggested that the vertical recti mediated vertical vergence in the RE and the oblique muscles in the LE while M2 data suggested that the oblique muscles mediated vertical vergence in the RE and the vertical recti in the LE. The variable results within the same animal and across animals suggest that EOM involvement during vertical fusional vergence is idiosyncratic and likely a weighted combination of multiple cyclovertical muscles.

Response Properties of Cells Within the Rostral Superior Colliculus of Strabismic Monkeys.

Purpose: The superior colliculus (SC) is an important oculomotor structure which, in addition to saccades and smooth-pursuit, has been implicated in vergence. Previously we showed that electrical stimulation of the SC changes strabismus angle in monkey models. The purpose of this study was to record from neurons in the rostral SC (rSC) of two exotropic (XT; divergent strabismus) monkeys (M1, M2) and characterize their response properties, including possible correlation with strabismus angle. Methods: Binocular eye movements and neural data were acquired as the monkeys performed fixation and saccade tasks with either eye viewing. Results: Forty-two cells with responses likely related to eye misalignment were recorded from the rSC of the strabismic monkeys of which 29 increased firing for smaller angles of exotropia and 13 increased firing for larger exotropia. Twenty-six of thirty-five cells showed a pause (decrease in firing rate) during large amplitude saccades. Blanking the target briefly during fixation did not reduce firing responses indicating a lack of visual sensitivity. A bursting response for nystagmus quick phases was identified in cells whose topographic location matched the direction and amplitude of quick phases. Conclusions: Certain cells in the rSC show responses related to eye misalignment suggesting that the SC is part of a vergence circuit that plays a role in setting strabismus angle. An alternative interpretation is that these cells display ocular preference, also a novel finding, and could potentially act as a driver of downstream oculomotor structures that maintain the state of strabismus.

Neural Plasticity Following Surgical Correction of Strabismus in Monkeys.

Purpose: Although widely practiced, surgical treatment of strabismus has varying levels of success and permanence. In this study we investigated adaptive responses within the brain and the extraocular muscles (EOM) that occur following surgery and therefore determine long-term success of the treatment. Methods: Single cell responses were collected from cells in the oculomotor and abducens nuclei before and after two monkeys (M1, M2) with exotropia (divergent strabismus) underwent a strabismus correction surgery that involved weakening of the lateral rectus (LR) and strengthening of the medial rectus (MR) muscle of one eye. Eye movement and neuronal data were collected for up to 10 months after surgery during a monocular viewing smooth-pursuit task. These data were fit with a first-order equation and resulting coefficients were used to estimate the population neuronal drive (ND) to each EOM of both eyes. Results: Surgery resulted in a ∼70% reduction in strabismus angle in both animals that reverted toward presurgical misalignment by approximately 6 months after treatment. In the first month after surgery, the ND to the treated MR reduced in one animal and ND to the LR increased in the other animal, both indicating active neural plasticity that reduced the effectiveness of the treatment. Adaptive changes in ND to the untreated eye were also identified. Conclusions: Active neural and muscle plasticity corresponding to both the treated and the untreated eye determines longitudinal success following surgical correction of strabismus. Outcome of surgical treatment could be improved by identifying ways to enhance "positive" adaptation and limit "negative" adaptation.

Correlation of cross-axis eye movements and motoneuron activity in non-human primates with "A" pattern strabismus.

PURPOSE: The authors showed earlier that animals reared with certain types of visual sensory deprivation during their first few months of life develop large horizontal strabismus, A/V patterns, and dissociated vertical deviation (DVD). Cross-axis eye movements were observed in the nonfixating eye that reflected pattern strabismus and DVD. The purpose of this study was to investigate whether neuronal activity within the oculomotor nucleus could be driving the abnormal cross-axis eye movements observed in the nonfixating eye. METHODS: Burst-tonic activity was recorded from oculomotor nucleus neurons in three animals with A-pattern exotropia as they performed horizontal or vertical smooth pursuit during monocular viewing. Two animals were reared by alternate monocular occlusion for 4 months, and one animal was reared by binocular deprivation for 3 weeks. RESULTS: In this study, efforts were focused on neurons modulated for vertical eye movements. Vertical burst-tonic motoneurons were strongly correlated with vertical eye movements regardless of whether the movement was purposeful, as in vertical smooth pursuit, or whether it was inappropriate, as in a vertical component observed in the nonfixating eye during horizontal smooth pursuit. Quantitative analysis of position and velocity sensitivities of the cells measured during the different tracking conditions suggested that motoneuron activity was sufficient to account for most of the inappropriate vertical cross-axis component. CONCLUSIONS: Results suggest that, in animals with sensory-induced strabismus, innervation to extraocular muscles from motor nuclei produce the inappropriate cross-axis eye movements, resulting in change in ocular misalignment with gaze position associated with pattern strabismus and DVD.

Horizontal saccade disconjugacy in strabismic monkeys.

PURPOSE: Previous studies have shown that binocular coordination during saccadic eye movement is affected in humans with large strabismus. The purpose of this study was to examine the conjugacy of saccadic eye movements in monkeys with sensory strabismus. METHODS: The authors recorded binocular eye movements in four strabismic monkeys and one unaffected monkey. Strabismus was induced by first occluding one eye for 24 hours, switching the occluder to the fellow eye for the next 24 hours, and repeating this pattern of daily alternating monocular occlusion for the first 4 to 6 months of life. Horizontal saccades were measured during monocular viewing when the animals were 2 to 3 years of age. RESULTS: Horizontal saccade testing during monocular viewing showed that the amplitude of saccades in the nonviewing eye was usually different from that in the viewing eye (saccade disconjugacy). The amount of saccade disconjugacy varied among animals as a function of the degree of ocular misalignment as measured in primary gaze. Saccade disconjugacy also increased with eccentric orbital positions of the nonviewing eye. If the saccade disconjugacy was large, there was an immediate postsaccadic drift for less than 200 ms. The control animal showed none of these effects. CONCLUSIONS: As do humans with large strabismus, strabismic monkey display disconjugate saccadic eye movements. Saccade disconjugacy varies with orbital position and increases as a function of ocular misalignment as measured in primary gaze. This type of sensory-induced strabismus serves as a useful animal model to investigate the neural or mechanical factors responsible for saccade disconjugacy observed in humans with strabismus.

Recovery of dynamic visual acuity in bilateral vestibular hypofunction.

OBJECTIVE: To determine the effect of vestibular exercises on the recovery of visual acuity during head movement in patients with bilateral vestibular hypofunction (BVH). DESIGN: Prospective, randomized, double-blinded study. SETTING: Outpatient clinic, academic setting. PATIENTS: Thirteen patients with BVH, aged 47 to 73 years. INTERVENTION: One group (8 patients) performed vestibular exercises designed to enhance remaining vestibular function, and the other (5 patients) performed placebo exercises. MAIN OUTCOME MEASURES: Measurements of dynamic visual acuity (DVA) during predictable head movements using a computerized test; measurement of intensity of oscillopsia using a visual analog scale. RESULTS: As a group, patients who performed vestibular exercises showed a significant improvement in DVA (P = .001), whereas those performing placebo exercises did not (P = .07). Only type of exercise (ie, vestibular vs placebo) was significantly correlated with change in DVA. Other factors examined, including age, time from onset, initial DVA, and complaints of oscillopsia and disequilibrium, were not significantly correlated with change in DVA. Change in oscillopsia did not correlate with change in DVA. CONCLUSIONS: Use of vestibular exercises is the main factor involved in recovery of DVA in patients with BVH. We theorize that exercises may foster the use of centrally programmed eye movements that could substitute for the vestibulo-ocular reflex. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00411216.

Comparison of Naso-temporal Asymmetry During Monocular Smooth Pursuit, Optokinetic Nystagmus, and Ocular Following Response in Strabismic Monkeys.

PURPOSE: Under monocular viewing conditions, humans and monkeys with infantile strabismus exhibit asymmetric naso-temporal (N-T) responses to motion stimuli. The goal of this study was to compare and contrast these N-T asymmetries during 3 visually mediated eye tracking tasks-optokinetic nystagmus (OKN), smooth pursuit (SP) response, and ocular following responses (OFR). METHODS: Two adult strabismic monkeys were tested under monocular viewing conditions during OKN, SP, or OFR stimulation. OKN stimulus was unidirectional motion of a 30°x30° random dot pattern at 20°, 40°, or 80°/s for 1 minute. OFR stimulus was brief (200 ms) unidirectional motion of a 38°x28°whitenoise at 20°, 40°, or 80°/s. SP stimulus consisted of foveal step-ramp target motion at 10°, 20°, or 40°/s. RESULTS: Mean nasalward steady state gain (0.87±0.16) was larger than temporalward gain (0.67±0.19) during monocular OKN (P<0.001). In monocular OFR, the asymmetry is manifested as a difference in OFR velocity gain (nasalward: 0.33±0.19, temporalward: 0.22±0.12; P=0.007). During monocular SP, mean nasal gain (0.97±0.2) was larger than temporal gain (0.66±0.14; P<0.001) and the mean nasalward acceleration during pursuit initiation (156±61°/s2) was larger than temporalward acceleration (118±77°/s2; P=0.04). Comparison of N-T asymmetry ratio across the 3 conditions using ANOVA showed no significant difference. CONCLUSIONS: N-T asymmetries are identified in all 3 visual tracking paradigms in both monkeys with either eye viewing. Our data are consistent with the current hypothesis for the mechanism for N-T asymmetry that invokes an imbalance in cortical drive to brainstem circuits.