Normal correspondence of tectal maps for saccadic eye movements in strabismus

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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confidence: 80%

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

Upadhyaya

Das

2019

“…Eye muscle surgery has been used to experimentally induce strabismus in monkeys for many years. 10,11,[21][22][23][38][39][40][41][42][43][44] Nonetheless, one might wonder whether the pattern strabismus in these animals might be due to an abnormal pulling direction for the medial rectus muscles. To further test this possibility, we performed two additional analyses: First, we recorded 15 medial rectus motoneurons from monkey XT1 and plotted the preferred directions using the same procedure described above for the NPH neurons.…”

Section: Consideration Of Alternative Explanationsmentioning

confidence: 99%

Abnormal Tuning in Nucleus Prepositus Hypoglossi of Monkeys With “A” Pattern Exotropia

Pallus

Walton

2020

In many individuals with pattern strabismus, the vertical misalignment varies with horizontal eye position. It has been proposed that these cross-axis effects result from abnormal cross-talk between brainstem structures that would normally encode horizontal and vertical eye position and velocity. The nucleus prepositus hypoglossi (NPH) is an ideal structure to test this overarching hypothesis. Neurons in the NPH are believed to mathematically integrate eye velocity signals to generate a tonic signal related to horizontal eye position. We hypothesized that, in monkeys with A-pattern exotropia and vertical inconcomitance, these neurons would show an abnormally large sensitivity to vertical eye position. METHODS. Three rhesus monkeys (1 normal and 2 with A-pattern exotropia) were trained to maintain fixation on a visual target as it stepped to various locations on a tangent screen. Extracellular neural activity was recorded from neurons in the NPH. Each neuron's sensitivity to horizontal and vertical eye position was estimated using multiple linear regression and preferred directions computed for each eye. RESULTS. Unexpectedly, the mean preferred directions for the left eye were normal in the monkeys with A-pattern exotropia. For the right eye, there was a clear upward deviation for the right NPH and a downward deviation for the left NPH. In addition, the R 2 values were significantly lower for model fits for neurons recorded from the exotropic monkeys. CONCLUSIONS. We suggest that vertical inconcomitance results from inappropriate verticalto-horizontal cross-talk that affects the two eyes differently.

“…For a subset of patients, the horizontal and vertical misalignments vary with eye position along the orthogonal axis 1. When the horizontal and vertical eye positions are plotted simultaneously in these patients, the misalignments form a pattern that often resembles the letters “A” or “V.”2–6 Thus, this condition is referred to as “pattern strabismus.”…”

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confidence: 99%

“…Numerous studies employing nonhuman primate models of the infantile strabismus syndrome have shown that, when binocular vision is disturbed for a prolonged period in infancy, both visual and oculomotor areas of the brain develop abnormally 7,8. Most of these monkeys develop at least a mild “A” or “V” pattern, and some show a strong pattern strabismus 3,5,6. In human patients, pattern strabismus is typically described, and treated, as overaction or underaction of the oblique muscles 1,9.…”

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confidence: 99%

“…For example, single unit recordings from oculomotor nucleus have shown that modulation of the firing rates of superior rectus, inferior rectus, and medial rectus motoneurons could account for most of the contextually inappropriate cross-axis movement of the ipsilateral eye when the contralateral eye pursues a visual target moving along the orthogonal axis 4,6. Indeed, we10–12 and other groups5,13,14 have suggested that pattern strabismus has a more complex, neurological origin involving abnormal cross-talk between brainstem areas that normally would encode signals related to either the horizontal or vertical component of eye movements. At present very little is known about where in the brainstem this might occur but, since both saccades and smooth pursuit show similar patterns of directional disconjugacy,2–4,6,14 it is reasonable to hypothesize that the cross-talk is occurring at the level of structures that are shared by multiple oculomotor subsystems.…”

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confidence: 99%

See 1 more Smart Citation

Abnormal Eye Position Signals in Interstitial Nucleus of Cajal in Monkeys With “A” Pattern Strabismus

Pallus

Mustari

Walton

2019

PurposePattern strabismus is characterized by a cross-axis pattern of horizontal and vertical misalignments. In A-pattern strabismus, for example, a divergent change in the horizontal misalignment occurs on downgaze. Work with nonhuman primate models has provided evidence that this disorder is associated with abnormal cross-talk between brainstem pathways that normally encode horizontal and vertical eye position and velocity. Neurons in the interstitial nucleus of Cajal (INC) are normally sensitive to vertical eye position; in the present study, we test the hypothesis that, in monkeys with pattern strabismus, some INC neurons will show an abnormal sensitivity to horizontal eye position.MethodsMonkeys were rewarded for fixating a visual target that stepped to various locations on a tangent screen. Single neurons were recorded from INC in one normal monkey, and two with A-pattern strabismus. Multiple linear regression analysis was used to estimate the preferred direction for each neuron.ResultsIn the normal monkey, all INC neurons had preferred directions within 20° of pure vertical (either up or down). The preferred directions were significantly more variable in the monkeys with pattern strabismus, with a minority being more sensitive to horizontal eye position than vertical eye position. In addition, the vertical eye position sensitivity was significantly less in the monkeys with strabismus.ConclusionsIn pattern strabismus, neurons in INC show neurophysiological abnormalities consistent with a failure to develop normal tuning properties. Results were consistent with the hypothesis that, in pattern strabismus, INC receives an abnormally strong signal related to horizontal eye position.