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 ( > 0.05; paired -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. 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.

PurposeTo evaluate the contribution of fixational saccades toward fixation instability in strabismic monkeys.MethodsBinocular eye movements were measured as six experimental monkeys (five strabismic monkeys and one monkey with downbeat nystagmus) and one normal monkey fixated targets of two shapes (Optotype, Disk) and two sizes (0.5°, 2°) during monocular and binocular viewing. Fixational saccades were detected using an unsupervised clustering algorithm.ResultsWhen compared with the normal monkey, amplitude and frequency of fixational saccades in both the viewing and nonviewing eye were greater in 3 of 5 strabismic monkeys (1-way ANOVA on ranks P < 0.001; median amplitude in the normal monkey viewing eye: 0.33°; experimental animals: median amplitude range 0.20–0.82°; median frequency in the normal monkey: 1.35/s; experimental animals: median frequency range 1.3–3.7/s). Increase in frequency of fixational saccades was largely due to quick phases of ongoing nystagmus. Fixational saccade amplitude was increased significantly (3-way ANOVA; P < 0.001) but by small magnitude depending on target shape and size (mean difference between disk and optotype targets = 0.02°; mean difference between 2° and 0.5° targets = 0.1°). Relationship between saccade amplitude and the Bivariate Contour Ellipse Area (BCEA) was nonlinear, showing saturation of saccade amplitude. Fixation instability in depth was significantly greater in strabismic monkeys (vergence BCEA: 0.63 deg2–2.15 deg2) compared with the normal animal (vergence BCEA: 0.15 deg2; P < 0.001).ConclusionsIncreased fixational instability in strabismic monkeys is only partially due to increased amplitude and more frequent fixational saccades. Target parameter effects on fixational saccades are similar to previous findings of target effects on BCEA.

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.A pproximately 5% of all infants in the world have some form of strabismus (ocular misalignment). 1,2 This developmental disorder is treated mostly at the level of muscles using surgical methods where the position of eye muscles are altered to correct for the eye misalignment. 3 Recent data from animal models of strabismus acquired using neurophysiological methods such as electrical stimulation, muscimol inactivation, and single cell recording within numerous brain areas including the motor nuclei, supraoculomotor area (SOA), fastigial and posterior interposed nuclei of the cerebellum, paramedian pontine reticular formation (PPRF), and the superior colliculus (SC), have shown that various structures within a vergence neural circuit contributes toward maintenance of the state of strabismus. [4][5][6][7][8][9][10][11] The SC has been extensively studied for its involvement in saccadic eye movements, 12-14 and this structure also appears to have a role in vergence. Van Horn et al.,15 in a study in normal monkeys, have shown that the rostral SC (rSC) contains vergence related neurons (convergence and divergence), which modulate with eye movements made to sinusoidal target motion in depth. 15 It has also been shown that stimulation of the rSC during an asymmetric vergence task affects vergence eye movement in normal monkeys. 16,17 Vergence related neurons have also been recorded in rSC of cat. 18 In humans, a case ...

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