Ocular Motor System Research Articles

Cervical dystonia: a neural integrator disorder

Ocular motor neural integrators ensure that eyes are held steady in straight-ahead and eccentric positions of gaze. Abnormal function of the ocular motor neural integrator leads to centripetal drifts of the eyes with consequent gaze-evoked nystagmus. In 2002 a neural integrator, analogous to that in the ocular motor system, was proposed for the control of head movements. Recently, a counterpart of gaze-evoked eye nystagmus was identified for head movements; in which the head could not be held steady in eccentric positions on the trunk. These findings lead to a novel pathophysiological explanation in cervical dystonia, which proposed that the abnormalities of head movements stem from a malfunctioning head neural integrator, either intrinsically or as a result of impaired cerebellar, basal ganglia, or peripheral feedback. Here we briefly recapitulate the history of the neural integrator for eye movements, then further develop the idea of a neural integrator for head movements, and finally discuss its putative role in cervical dystonia. We hypothesize that changing the activity in an impaired head neural integrator, by modulating feedback, could treat dystonia.

Symptom Provocation More Likely Following Vestibular/Ocular Motor Screening in Athletes with Attention Deficit Hyperactivity Disorder

Vestibular and ocular-motor impairments are routinely reported in patients with a sports-related concussion (SRC) and may result in delayed return to play. The Vestibular/Ocular Motor Screening (VOMS), a brief clinical assessment for vestibular and ocular-motor impairments, has been shown to be a sensitive clinical assessment for identifying patients with a concussion. However, in athletes with attention deficit hyperactivity disorder (ADHD), the VOMS may not be indicated as these patients exhibit impairment of the ocular-motor system in the absence of concussive injury. Thus, VOMS findings in an athlete with ADHD may be overstated and a higher proportion of athletes reporting symptom provocation are likely. PURPOSE: To determine if differences exist between those athletes with and without ADHD in relation to symptom provocation during VOMS. METHODS: A retrospective chart review of patient (n = 223; 80 girls, 143 boys) records (age range: 11-19 yr; mean ± SD; 15±2) of those presenting with SRC from Jan - Dec 2014 was conducted. As part of the initial visit a VOMS assessment was performed by trained medical personnel who documented symptom provocation using a dichotomous scale (0=not present, 1=present). The VOMS used in this clinic consisted of the following domains: smooth pursuits (SMO_PUR), horizontal (HOR_) and vertical saccades (VER_SAC), horizontal (HOR_) and vertical vestibular ocular reflex (VER_VOR), convergence (CONV), and accommodation (ACCOM). Diagnostic history of ADHD was self-reported. χ2 analyses for categorical variables was used to examine relationship between ADHD and VOMS symptom provocation. RESULTS: ADHD was present in 14.3% of patients. A greater proportion of patients with ADHD reported symptom provocation in the following VOMS domains: SMO_PUR (57.6% vs. 36.6%; p = 0.023), HOR_SAC (69.7% vs. 48.7%; p =0.026), HOR_VOR (64.5% vs. 41.8%; p = 0.019). VER_SAC (69.7% vs. 53.8%; p = 0.089) approached significance. No difference was observed in proportion presenting with or without ADHD in domains of VER_VOR, ACCOM, or CONV. CONCLUSION: Athletes with ADHD may report symptom provocation during specific domains of the VOMS assessment more often than those athletes without ADHD. These findings may have important implications in the diagnosis and treatment of concussions in athletes with ADHD.

Effects of preparation time and trial type probability on performance of anti- and pro-saccades

Cognitive control optimizes responses to relevant task conditions by balancing bottom-up stimulus processing with top-down goal pursuit. It can be investigated using the ocular motor system by contrasting basic prosaccades (look toward a stimulus) with complex antisaccades (look away from a stimulus). Furthermore, the amount of time allotted between trials, the need to switch task sets, and the time allowed to prepare for an upcoming saccade all impact performance. In this study the relative probabilities of anti- and pro-saccades were manipulated across five blocks of interleaved trials, while the inter-trial interval and trial type cue duration were varied across subjects. Results indicated that inter-trial interval had no significant effect on error rates or reaction times (RTs), while a shorter trial type cue led to more antisaccade errors and faster overall RTs. Responses following a shorter cue duration also showed a stronger effect of trial type probability, with more antisaccade errors in blocks with a low antisaccade probability and slower RTs for each saccade task when its trial type was unlikely. A longer cue duration yielded fewer errors and slower RTs, with a larger switch cost for errors compared to a short cue duration. Findings demonstrated that when the trial type cue duration was shorter, visual motor responsiveness was faster and subjects relied upon the implicit trial probability context to improve performance. When the cue duration was longer, increased fixation-related activity may have delayed saccade motor preparation and slowed responses, guiding subjects to respond in a controlled manner regardless of trial type probability.

Chapter 22 - Vestibular migraine

During the last decades a new vestibular syndrome has emerged that is now termed vestibular migraine (VM). The main body of evidence for VM is provided by epidemiologic data demonstrating a strong association between migraine and vestibular symptoms. Today, VM is recognized as one of the most common causes of episodic vertigo. The clinical presentation of VM is heterogeneous in terms of vestibular symptoms, duration of episodes, and association with migrainous accompaniments. Similar to migraine, there is no clinical or laboratory confirmation for VM and the diagnosis relies on the history and the exclusion of other disorders. Recently, diagnostic criteria for VM have been elaborated jointly by the International Headache Society and the Bárány Society. Clinical examination of patients with acute VM has clarified that the vast majority of patients with VM suffer from central vestibular dysfunction. Findings in the interval may yield mild signs of damage to both the central vestibular and ocular motor system and to the inner ear. These interictal clinical signs are not specific to VM but can be also observed in migraineurs without a history of vestibular symptoms. How migraine affects the vestibular system is still a matter of speculation. In the absence of high-quality therapeutic trials, treatment is targeted at the underlying migraine.

Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets.

ObjectivePerineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements – saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy.MethodsTogether with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin-embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses.ResultsExcitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.InterpretationOur findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.

Relationship of ocular accommodation and motor skills performance in developmental coordination disorder

Ocular accommodation provides a well-focussed image, feedback for accurate eye movement control, and cues for depth perception. To accurately perform visually guided motor tasks, integration of ocular motor systems is essential. Children with motor coordination impairment are established to be at higher risk of accommodation anomalies. The aim of the present study was to examine the relationship between ocular accommodation and motor tasks, which are often overlooked, in order to better understand the problems experienced by children with motor coordination impairment. Visual function, gross and fine motor skills were assessed in children with developmental coordination disorder (DCD) and typically developing control children. Children with DCD had significantly poorer accommodation facility and amplitude dynamics compared to controls. Results indicate a relationship between impaired accommodation and motor skills. Specifically, accommodation anomalies correlated with visual motor, upper limb and fine dexterity task performance. Consequently, we argue accommodation anomalies influence the ineffective coordination of action and perception in DCD. Furthermore, reading disabilities were related to poorer motor performance. We postulate the role of the fastigial nucleus as a common pathway for accommodation and motor deficits. Implications of the findings and recommended visual screening protocols are discussed.

Saccadic palsy following cardiac surgery: a review and new hypothesis.

The ocular motor system provides several advantages for studying the brain, including well-defined populations of neurons that contribute to specific eye movements. Generation of rapid eye movements (saccades) depends on excitatory burst neurons (EBN) and omnipause neurons (OPN) within the brainstem, both types of cells are highly active. Experimental lesions of EBN and OPN cause slowing or complete loss of saccades. We report a patient who developed a permanent, selective saccadic palsy following cardiac surgery. When she died several years later, surprisingly, autopsy showed preservation of EBN and OPN. We therefore considered other mechanisms that could explain her saccadic palsy. Recent work has shown that both EBN and OPN are ensheathed by perineuronal nets (PN), which are specialized extracellular matrix structures that may help stabilize synaptic contacts, promote local ion homeostasis, or play a protective role in certain highly active neurons. Here, we review the possibility that damage to PN, rather than to the neurons they support, could lead to neuronal dysfunction-such as saccadic palsy. We also suggest how future studies could test this hypothesis, which may provide insights into the vulnerability of other active neurons in the nervous system that depend on PN.

Ocular motor tests in relapsing remitting multiple sclerosis

Background Multiple sclerosis (MS) is the quintessential neurologic disorder from which one can gain insights into the principles of afferent and efferent neuro-ophthalmology. The popularity of eye movements as an experimental tool can be partly attributed to the fact that they can be conveniently and accurately measured and analyzed, and also because much is known about their neural substrate. It is therefore no surprise that eye movements have been commonly applied to better understand the visual and motor disorders in patients with MS. Objectives The aim of this study was to demonstrate the vast ocular motor abnormalities that occur in this disease using videonystagmography as our tool of description and determine the relationship with Expanded Disability Status Scale (EDSS) and MRI findings. Materials and methods The current study included 76 patients who were divided into two groups. Group I comprised 54 patients with relapsing-remitting multiple sclerosis who fulfilled the Revised Mcdonald's criteria for diagnosis of MS. The age of the patients in group I ranged from 20 to 68 years, with a mean of 35.13 ± 9.42 SD (23 men and 31 women). Group II comprised 22 healthy age-matched and sex-matched individuals who were recruited from the general population and were not relatives of the patients. Their ages ranged from 19 to 54 years, with a mean of 33.81 years ± 10.07 SD (11 men and 11 women). Video-nystagmography, saccadic tracking, random horizontal saccades, optokinetic tracking (at 20, 40, and 60΀/s), smooth pursuit (0.2, 0.3, 0.4, 0.5, 0.6, and 0.7 Hz), and gaze-evoked nystagmus were examined in both groups. Group I, in addition, was subjected to a thorough neurological history and neurological examination, EDSS assessment, ophthalmologic examination (visual acuity and ocular motility), and radiological assessment by MRI with and without contrast. Results The eye movement disorders most commonly noted are saccadic dysmetria, followed by gaze-evoked nystagmus and pendular nystagmus. They are caused by disease affecting the brain stem and cerebellar circuits. Reduced pursuit gain and saccadic pursuit were also noted. A strong correlation between brainstem and cerebellar MRI lesions and the affection of the ocular motor system was well noted. A high EDSS score was well correlated with abnormal ocular motor test findings. Conclusion Ocular motor system tests are more sensitive than conventional clinical examinations in identifying abnormalities in MS.

Fusion Maldevelopment (Latent/Manifest Latent) Nystagmus Syndrome: Effects of Four-Muscle Tenotomy and Reattachment

To examine the waveform and clinical effects of the four-muscle tenotomy and reattachment procedure in fusion maldevelopment nystagmus syndrome (FMNS) and to compare them to those documented in infantile nystagmus syndrome (INS) and acquired nystagmus. Both infrared reflection and high-speed digital video systems were used to record the eye movements in a patient with FMNS (before and after tenotomy and reattachment). Data were analyzed using the eXpanded Nystagmus Acuity Function (NAFX) that is part of the OMtools software. Model simulations and predictions were performed using the authors' behavioral ocular motor system model in MATLAB Simulink (The MathWorks, Inc., Natick, MA). The model predicted, and the patient's data confirmed, that the tenotomy and reattachment procedure produces improvements in FMN waveforms across a broader field of gaze and decreases the Alexander's law variation. The patient's tenotomy and reattachment plots of NAFX after surgery versus gaze angle were higher and had lower slope than before surgery. Clinically, despite moderate improvements in both peak measured acuity and stereoacuity, dramatic improvements in the patient's abilities and lifestyle resulted. The four-muscle tenotomy and reattachment nystagmus surgery produced beneficial therapeutic effects on FMN waveforms that are similar to those demonstrated in INS and acquired nystagmus. These results support the authors' prior recommendation that tenotomy and reattachment nystagmus should be added to required strabismus procedures in patients who also have FMNS (ie, perform tenotomy and reattachment on all unoperated muscles in the plane of the nystagmus). Furthermore, when strabismus surgery is not required, four-muscle tenotomy and reattachment may be used to improve FMN waveforms and visual function.

Different topological organization of human brain functional networks with eyes open versus eyes closed

Opening and closing the eyes are fundamental behaviors for directing attention to the external versus internal world. However, it remains unclear whether the states of eyes-open (EO) relative to eyes-closed (EC) are associated with different topological organizations of functional neural networks for exteroceptive and interoceptive processing (processing the external world and internal state, respectively). Here, we used resting-state functional magnetic resonance imaging and neural network analysis to investigate the topological properties of functional networks of the human brain when the eyes were open versus closed. The brain networks exhibited higher cliquishness and local efficiency, but lower global efficiency during the EO state compared to the EC state. These properties suggest an increase in specialized information processing along with a decrease in integrated information processing in EO (vs. EC). More importantly, the “exteroceptive” network, including the attentional system (e.g., superior parietal gyrus and inferior parietal lobule), ocular motor system (e.g., precentral gyrus and superior frontal gyrus), and arousal system (e.g., insula and thalamus), showed higher regional nodal properties (nodal degree, efficiency and betweenness centrality) in EO relative to EC. In contrast, the “interoceptive” network, composed of visual system (e.g., lingual gyrus, fusiform gyrus and cuneus), auditory system (e.g., Heschl's gyurs), somatosensory system (e.g., postcentral gyrus), and part of the default mode network (e.g., angular gyrus and anterior cingulate gyrus), showed significantly higher regional properties in EC vs. EO. In addition, the connections across sensory modalities were altered by volitional eye opening. The synchronicity between the visual system and the motor, somatosensory and auditory systems, characteristic of EC, was attenuated in EO. Further, the connections between the visual system and the attention, arousal and subcortical systems were increased in EO. These results may indicate that EO leads to a suppression of sensory modalities (other than visual) to allocate resources to exteroceptive processing. Our findings suggest that the topological organization of human brain networks dynamically switches corresponding to the information processing modes as we open or close our eyes.

Velocity storage mechanism in zebrafish larvae

The optokinetic reflex (OKR) and the angular vestibulo-ocular reflex (aVOR) complement each other to stabilize images on the retina despite self- or world motion, a joint mechanism that is critical for effective vision. It is currently hypothesized that signals from both systems integrate, in a mathematical sense, in a network of neurons operating as a velocity storage mechanism (VSM). When exposed to a rotating visual surround, subjects display the OKR, slow following eye movements frequently interrupted by fast resetting eye movements. Subsequent to light-off during optokinetic stimulation, eye movements do not stop abruptly, but decay slowly, a phenomenon referred to as the optokinetic after-response (OKAR). The OKAR is most likely generated by the VSM. In this study, we observed the OKAR in developing larval zebrafish before the horizontal aVOR emerged. Our results suggest that the VSM develops prior to and without the need for a functional aVOR. It may be critical to ocular motor control in early development as it increases the efficiency of the OKR.

α2-Chimaerin Regulates a Key Axon Guidance Transition during Development of the Oculomotor Projection

The ocular motor system consists of three nerves which innervate six muscles to control eye movements. In humans, defective development of this system leads to eye movement disorders, such as Duane Retraction Syndrome, which can result from mutations in the α2-chimaerin signaling molecule. We have used the zebrafish to model the role of α2-chimaerin during development of the ocular motor system. We first mapped ocular motor spatiotemporal development, which occurs between 24 and 72 h postfertilization (hpf), with the oculomotor nerve following an invariant sequence of growth and branching to its muscle targets. We identified 52 hpf as a key axon guidance "transition," when oculomotor axons reach the orbit and select their muscle targets. Live imaging and quantitation showed that, at 52 hpf, axons undergo a switch in behavior, with striking changes in the dynamics of filopodia. We tested the role of α2-chimaerin in this guidance process and found that axons expressing gain-of-function α2-chimaerin isoforms failed to undergo the 52 hpf transition in filopodial dynamics, leading to axon stalling. α2-chimaerin loss of function led to ecotopic and misguided branching and hypoplasia of oculomotor axons; embryos had defective eye movements as measured by the optokinetic reflex. Manipulation of chimaerin signaling in oculomotor neurons in vitro led to changes in microtubule stability. These findings demonstrate that a correct level of α2-chimaerin signaling is required for key oculomotor axon guidance decisions, and provide a zebrafish model for Duane Retraction Syndrome.

The Founding of the International Neuro-Ophthalmology Society

The Founding of the International Neuro-Ophthalmology Society

Ocular Motor Dysfunction due to Multiple Sclerosis

Ocular motor disorders are common in patients afflicted by multiple sclerosis. We present a particularly complex case of multifaceted ocular motor dysfunction as it illustrates the arcane associated neuroanatomy and the interplay between ocular motor systems in the brainstem, midbrain, and cerebellum.

Vertical Vergence Adaptation Produces an Objective Vertical Deviation That Changes With Head Tilt

To document the cyclovertical ocular motor mechanism used for vertical fusion in healthy subjects, and to explore whether vertical vergence training in healthy individuals can produce objectively confirmed vertical deviations that change with head tilt, revealing a basic mechanism that can produce a pattern of misalignment in an otherwise normal ocular motor system that is similar to superior oblique muscle paresis (SOP). Seven subjects with normal orthoptic examinations were adapted to vertical image disparities using our tilting haploscopic eye-tracking apparatus presenting concentric circle targets without torsional cues. Static eye positions were recorded with head straight and when tilted 45 degrees to the left and right, during both binocular and monocular viewing. Vertical fusional vergence was accompanied by a cycloversion, with the downward-moving eye intorting and the upward-moving eye extorting, implicating primary involvement of the oblique extraocular muscles. After adaptation to the slowly increasing vertical target separation, all subjects developed a temporary vertical deviation in the straight ahead position that increased with head tilt to one side and decreased with head tilt to the other side. These results not only show that head-tilt-dependent changes in vertical deviation are not necessarily pathognomonic for SOP, but also, and more importantly, suggest mechanisms that can mimic SOP and suggest a possible role for vertical vergence training in reducing deviations and thus the amount of head tilt required for fusion. Ultimately, vertical vergence training may provide an adjunct or alternative to extraocular muscle surgery in selected cases.

Albinism: particular attention to the ocular motor system.

The purpose of this report is to summarize an understanding of the ocular motor system in patients with albinism. Other than the association of vertical eccentric gaze null positions and asymmetric, (a) periodic alternating nystagmus in a large percentage of patients, the ocular motor system in human albinism does not contain unique pathology, rather has “typical” types of infantile ocular oscillations and binocular disorders. Both the ocular motor and afferent visual system are affected to varying degrees in patients with albinism, thus, combined treatment of both systems will maximize visual function.

Covert oculo-manual coupling induced by visually guided saccades

Hand pointing to objects under visual guidance is one of the most common motor behaviors in everyday life. In natural conditions, gaze and arm movements are commonly aimed at the same target and the accuracy of both systems is considerably enhanced if eye and hand move together. Evidence supports the viewpoint that gaze and limb control systems are not independent but at least partially share a common neural controller. The aim of the present study was to verify whether a saccade execution induces excitability changes in the upper-limb corticospinal system (CSS), even in the absence of a manual response. This effect would provide evidence for the existence of a common drive for ocular and arm motor systems during fast aiming movements. Single-pulse TMS was applied to the left motor cortex of 19 subjects during a task involving visually guided saccades, and motor evoked potentials (MEPs) induced in hand and wrist muscles of the contralateral relaxed arm were recorded. Subjects had to make visually guided saccades to one of 6 positions along the horizontal meridian (±5°, ±10°, or ±15°). During each trial, TMS was randomly delivered at one of 3 different time delays: shortly after the end of the saccade or 300 or 540 ms after saccade onset. Fast eye movements toward a peripheral target were accompanied by changes in upper-limb CSS excitability. MEP amplitude was highest immediately after the end of the saccade and gradually decreased at longer TMS delays. In addition to the change in overall CSS excitability, MEPs were specifically modulated in different muscles, depending on the target position and the TMS delay. By applying a simple model of a manual pointing movement, we demonstrated that the observed changes in CSS excitability are compatible with the facilitation of an arm motor program for a movement aimed at the same target of the gaze. These results provide evidence in favor of the existence of a common drive for both eye and arm motor systems.

Diagnose von Schwindel mit besonderem Blick auf Augenbewegungsstörungen

With specialist knowledge ophthalmologists can make a valuable contribution to the interdisciplinary work-up of patients with vertigo as the leading symptom. The neuro-ophthalmological examination of eye movements by an ophthalmologist and/or orthoptist is an important contribution because the various vertigo syndromes can only be correctly evaluated by a combined examination of the vestibular and ocular motor systems. If the ophthalmologist is the first doctor to examine a patient suspected disorders from other specialist fields can be indicated, in particular neurology and otorhinolaryngology. When taking the patient history the ophthalmologist should inquire about the type and duration of the vertigo, triggering or modifying factors and accompanying symptoms. This is followed by a systematic examination of the eye position and the different types of eye movements, the head-impulse test and a special examination to check for the presence of nystagmus.

Ischaemic stroke: the ocular motor system as a sensitive marker for motor and cognitive recovery

ObjectiveTo evaluate the sensitivity of measuring cognitive processing in the ocular motor system as a marker for recovery of deficit in post stroke patients.Methods15 patients (mean age 60.6 years, mean...

A dynamic model for eye‐position‐dependence of spontaneous nystagmus in acute unilateral vestibular deficit (Alexander's Law)

Spontaneous nystagmus (SN) is a symptom of acute vestibular tone asymmetry. Alexander's Law (AL) states that slow-phase velocity of SN is higher when looking in the direction of fast-phases of nystagmus and lower in the slow-phase direction. Earlier explanations for AL predict that during SN, slow-phase eye velocity is a linear function of eye position, increasing linearly as eye deviates towards the fast-phase direction. Recent observations, however, show that this is often not the case; eye velocity does not vary linearly with eye position. Such new findings necessitate a re-evaluation of our understanding of AL. As AL may be an adaptive response of the vestibular system to peripheral lesions, understanding its mechanism could shed light on early adaptation strategies of the brain. Here, we propose a physiologically plausible mechanism for AL that explains recent experimental data. We use a dynamic control system model to simulate this mechanism and make testable predictions. This mechanism is based on the known effects of unilateral vestibular deficit on the response of the ipsi- and contralesional vestibular nuclei (VN) of the brainstem. This hypothesis is based on the silencing of the majority of ipsilesional VN units, which creates an asymmetry between the responses of the ipsi- and contralesional VN. Unlike former explanations, the new hypothesis does not rely on lesion detection strategies or signals originating in higher brain structures. The proposed model demonstrates possible consequences of acute peripheral deficits for the function of the velocity-to-position neural integrator of the ocular motor system and the vestibulo-ocular reflex.