Smooth Pursuit–Related Information Processing in Frontal Eye Field Neurons that Project to the NRTP

The cortical pursuit system begins the process of transforming visual signals into commands for smooth pursuit (SP) eye movements. The frontal eye field (FEF), located in the fundus of arcuate sulcus, is known to play a role in SP and gaze pursuit movements. This role is supported, at least in part, by FEF projections to the rostral nucleus reticularis tegmenti pontis (rNRTP), which in turn projects heavily to the cerebellar vermis. However, the functional characteristics of SP-related FEF neurons that project to rNRTP have never been described. Therefore, we used microelectrical stimulation (ES) to deliver single pulses (50–200 μA, 200-μs duration) in rNRTP to antidromically activate FEF neurons. We estimated the eye or retinal error motion sensitivity (position, velocity, and acceleration) of FEF neurons during SP using multiple linear regression modeling. FEF neurons that projected to rNRTP were most sensitive to eye acceleration. In contrast, FEF neurons not activated following ES of rNRTP were often most sensitive to eye velocity. In similar modeling studies, we found that rNRTP neurons were also biased toward eye acceleration. Therefore, our results suggest that neurons in the FEF–rNRTP pathway carry signals that could play a primary role in initiation of SP

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

Conjugate Adaptation of Smooth Pursuit during Monocular Viewing in Strabismic Monkeys with Exotropia

Purpose: Humans and monkeys are able to adapt their smooth pursuit output when challenged with consistent errors in foveal/parafoveal image motion during tracking. Visual motion information from the retina is known to be necessary for guiding smooth pursuit adaptation. The purpose of this study is to determine whether retinal motion signals delivered to one eye during smooth pursuit produce adaptation in the fellow eye. We tested smooth pursuit adaptation during monocular viewing in strabismic monkeys with exotropia. Methods: To induce smooth pursuit adaptation experimentally, we used a step-ramp tracking with two different velocities (adaptation paradigm), where the target begins moving at one speed (25°/s) for first 100 ms and then changes to a lower speed (5°/s) for the remainder of the trial. Typically, 100 to 200 trials were used to adapt the smooth pursuit response. Control trials employing single speed step-ramp target motion (ramp speed = 25°/s) were used before and after adaptation paradigm to estimate adaptation. Results: The magnitude of adaptation as calculated by percentage change was not significantly different (P = 0.53) for the viewing (mean, 40.3% ± 5.9%) and the nonviewing (mean, 39.7% ± 6.2%) eyes during monocular viewing conditions, even in cases with large angle (18°–20°) strabismus. Conclusions: Our results indicate that animals with strabismus retain the ability to produce conjugate adaptation of smooth pursuit. Therefore, we suggest that a single central representation of retinal motion information in the viewing eye drives adaptation for both eyes equally

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)

Signal Processing and Distribution in Cortical?Brainstem Pathways for Smooth Pursuit Eye Movements

Smooth pursuit (SP) eye movements are used to maintain the image of a moving object relatively stable on the fovea. Even when tracking a single target over a dark background, multiple areas including frontal eye fields (FEF) and middle temporal (MT) and medial superior temporal (MST) cortex contribute to converting visual signals into initial commands for SP. Signals in the cortical pursuit system reach the oculomotor cerebellum through brainstem centers including the dorsolateral pontine nucleus (DLPN), nucleus reticularis tegmenti pontis (NRTP), and pretectal nucleus of the optic tract (NOT). The relative information carried in these parallel pathways remains to be fully defined. We used multiple linear?regression modeling to estimate the relative sensitivities of cortical (MST, FEF), pontine (NRTP, DLPN), and NOT neurons to eye? and retinal?error parameters (position, velocity, and acceleration) during step?ramp SP of macaques (Macaca mulatta). We found that a large proportion of pursuit?related MST and DLPN neurons were most sensitive to eye?velocity or retinal error velocity. In contrast, a large proportion of FEF and rostral NRTP neurons were most sensitive to eye acceleration. Visual neurons in MST, DLPN, and NOT were most sensitive to retinal image velocity

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 a suitable model to study 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 the 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

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. Maethods: 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

Transmitter inputs to different motoneuron subgroups in the oculomotor and trochlear nucleus in monkey

In all vertebrates the eyes are moved by six pairs of extraocular muscles enabling horizontal, vertical and rotatory movements. Recent work showed that each extraocular muscle is controlled by two motoneuronal groups: (1) Motoneurons of singly-innervated muscle fibers (SIF) that lie within the boundaries of motonuclei mediating a fast muscle contraction: and (2) motoneurons of multiply-innervated muscle fibers (MIF) in the periphery of motonuclei mediating a tonic muscle contraction. Currently only limited data about the transmitter inputs to the SIF and MIF motoneurons are available. Here we performed a quantitative study on the transmitter inputs to SIF and MIF motoneurons of individual muscles in the oculomotor and trochlear nucleus in monkey. Pre-labeled motoneurons were immunostained for GABA, glutamate decarboxylase, GABA-A receptor, glycine transporter 2, glycine receptor 1, and vesicular glutamate transporters 1 and 2. The main findings were: (1) the inhibitory control of SIF motoneurons for horizontal and vertical eye movements differs. Unlike in previous primate studies a considerable GABAergic input was found to all SIF motoneuronal groups, whereas a glycinergic input was confined to motoneurons of the medial rectus (MR) muscle mediating horizontal eye movements and to those of the levator palpebrae (LP) muscle elevating the upper eyelid. Whereas SIF and MIF motoneurons of individual eye muscles do not differ numerically in their GABAergic, glycinergic and vGlut2 input, vGlut1 containing terminals densely covered the supraoculomotor area (SOA) targeting MR MIF motoneurons. It is reasonable to assume that the vGlut1 input affects the near response system in the SOA, which houses the preganglionic neurons mediating pupillary constriction and accommodation and the MR MIF motoneurones involved in vergence

An Information-Theoretic Approach for Evaluating Probabilistic Tuning Functions of Single Neurons

Neuronal tuning functions can be expressed by the conditional probability of observing a spike given any combination of explanatory variables. However, accurately determining such probabilistic tuning functions from experimental data poses several challenges such as finding the right combination of explanatory variables and determining their proper neuronal latencies. Here we present a novel approach of estimating and evaluating such probabilistic tuning functions, which offers a solution for these problems. By maximizing the mutual information between the probability distributions of spike occurrence and the variables, their neuronal latency can be estimated, and the dependence of neuronal activity on different combinations of variables can be measured. This method was used to analyze neuronal activity in cortical area MSTd in terms of dependence on signals related to eye and retinal image movement. Comparison with conventional feature detection and regression analysis techniques shows that our method offers distinct advantages, if the dependence does not match the regression model