We studied the dependence of ocular torsion on eye position during horizontal optokinetic nystagmus (OKN) elicited by random-dot translational motion (tOKN) and prolonged rotation in the light (rOKN). For slow and quick phases, we fit the eye-velocity axis to vertical eye position to determine the tilt angle slope (TAS). The TAS for tOKN was 0.48 for both slow and quick phases, close to what is found during translational motion of the head. The TAS for rOKN was less for both slow (0.11) and quick phases (0.26), close to what is found during rotational motion of the head. Our findings are consistent with the notion that translational and rotational optic flow are processed differently by the brain and that they produce different 3-D eye movement commands that are comparable to the different commands generated in response to vestibular signals when the head is actually translating or rotating.

Subjective refraction is the gold-standard for prescribing refractive correction, but its accuracy is limited by patient's subjective judgment about their clarity of vision. We asked if an involuntary eye movement, optokinetic nystagmus (OKN), could serve as an objective measure of visual-clarity, specifically measuring the dependence of OKN-elicited by drifting spatial-frequency filtered noise-on mean spherical equivalent (MSE) refractive error. In Experiment 1 we quantified OKN score-a measure of consistency with stimulus-direction-for participants with different MSEs. Estimates of MSE based on OKN scores correlate well with estimates of MSE made using autorefraction (r = 0.878, p < 0.001, Bland-Altman analysis: mean difference of 0.00D (95% limits of agreement: - 0.85 to + 0.85D). In Experiment 2, we quantified the relationship between OKN gain (ratio of tracking eye-movement velocity to stimulus velocity) and MSEs (- 2.00, - 1.00, - 0.50, 0.00 and + 1.00D) induced with contact lenses for each participant. The mean difference between measures of MSE based on autorefraction or on OKN gain was + 0.05D (- 0.90 to + 1.01D), and the correlation of these measures across participants was r = 0.976, p < 0.001. Results indicate that MSE attenuates OKN gain so that OKN can be used as an objective proxy for patient response to select the best corrective lens.

Assessment of functional vision across the visual field is hampered by a reliance on patients' subjective judgement of the presence of a stimulus, and the accompanying demands (time and attention) this places on them. As a first step toward determining whether an objective measure of an involuntary eye movement (optokinetic nystagmus [OKN]) could provide an objective measure of field loss, we determined how various measures of OKN depend on the extent of simulated visual field loss (SVFL).

Modifying experimental conditions of optokinetic nystagmus (OKN) result in different outcomes and may not optimally translate into clinical testing. The purpose of this study was to assess the influence of subject instruction on the anatomical correlates of OKN. The instructions were to voluntarily look or stare at the same moving grating with fixed contrast and spatial and temporal frequencies. Look and stare OKN were generated under identical stimulus "ON" conditions (vertical sine wave grating of 1.14c/deg drifting right to left at 11.4c/s with binocular viewing). FMRI was undertaken utilizing a 3.0T GE system and the BOLD technique. Subjects included 6 normal adults ranging in age from 18 to 54 years with normal visual acuity (20/20 or better) and normal stereoacuity (40s of arc or better). The results reveal that look OKN generated significantly more cortical FMRI activation than stare OKN. Look OKN areas included the culmen, parahippocampal, lingual, middle temporal gyri, inferior and superior parietal lobules and precuneus, all of which were unilaterally activated in the left hemisphere. The middle occipital gyrus was unilaterally activated in the right hemisphere while the cuneus was bilaterally activated. These results show that the activation sites for OKN studies are dependent on subject instruction which influence the type of OKN generated. Specifically, voluntary look OKN involved more brain sites than stare OKN. In so doing, we illustrate the importance of subject instruction and recommend that FMRI investigators of OKN be cognizant of these effects. The anatomical correlates of the look versus stare are discussed.

To date, no systematic review or meta-analysis has critically evaluated the relevance of using optokinetic after-nystagmus (OKAN) in diagnosis of vestibular disorders. To assess the role of OKAN in diagnosis of vestibular disorders, the OKAN time constant (TC) between patients with vestibular disorders and healthy participants will be compared.

Neuromodulation serves as a cornerstone for brain sciences and clinical applications. Recent reports suggest that mid-infrared stimulation (MIRS) causes non-thermal modulation of brain functions. Current understanding of its mechanism hampers the routine application of MIRS. Here, we examine how MIRS influences the sensorimotor transformation in awaking-behaving pigeons, from neuronal signals to behavior. We applied MIRS and electrical stimulation (ES) to the pretectal nucleus lentiformis mesencephali (nLM), an essential retinorecipient structure in the pretectum, and examined their influences on the optokinetic nystagmus, a visually guided eye movement. We found MIRS altered eye movements by modulating a specific gain depending on the strength of visual inputs, in a manner different than the effect of ES. Simultaneous extracellular recordings and stimulation showed that MIRS could either excite and inhibit the neuronal activity in the same pretectal neuron depending on its ongoing sensory responsiveness levels in awake-behaving animals. Computational simulations suggest that MIRS modulates the resonance of a carbonyl group of the potassium channel, critical to the action potential generation, altering neuronal responses to sensory inputs and as a consequence, guiding behavior. Our findings suggest that MIRS could be a promising approach toward modulating neuronal functions for brain research and treating neurological diseases.

The aim of the current study was to develop and validate an automated contrast sensitivity (CS) test using a live- detection of optokinetic nystagmus (OKN) and an adaptive psychometric procedure. In addition, the study sought to replicate the known effect of defocus on CS for the OKN-based measurements in emmetropic participants.

Atypical eye movement patterns demonstrated by individuals with autism spectrum disorder (ASD) have the potential to serve as biomarkers for ASD diagnosis. However, instead of estimating individual differences in the degree of ASD from those patterns, many researchers have compared ASD groups with typical development groups. This study investigates the relationship between the Autism-spectrum Quotient (AQ) scores in typical adults, which can evaluate the degree of the traits associated with ASD, as well as the properties of optokinetic nystagmus (OKN), including the gain of the slow phase, the peak velocity and duration of the fast phase, the frequency, and the mean eye position of OKN. A random dot pattern that moved in one direction was presented on the display, and the participants' eye movements were measured. The results showed a negative correlation between subjects' AQ scores and the gain of slow-phase OKN. In addition, the correlations between subjects' AQ scores and the properties of OKN fast phase were not significant. These results indicate that the gain of slow-phase OKN could be a biomarker that estimates individual differences in the degree of ASD, reflected in our findings which considered AQ scores in typical adults.

Infantile nystagmus (IN) may result from aetiologies including albinism and FRMD7 mutations. IN has low prevalence, and twins with IN are rare. Whilst discordant presentation has been previously reported for IN, we present for the first time the comprehensive assessment of diagnostically discordant monozygotic twins. From a cohort of over 2000 patients, we identified twins and triplets discordant for nystagmus. Using next-generation sequencing, high-resolution infra-red pupil tracking and optical coherence tomography, we characterised differences in genotype and phenotype. Monozygotic twins (n = 1), dizygotic twins (n = 3) and triplets (n = 1) were included. The monozygotic twins had concordant TYR variants. No causative variants were identified in the triplets. Dizygotic twins had discordant variants in TYR, OCA2 and FRMD7. One unaffected co-twin demonstrated sub-clinical nystagmus. Foveal hypoplasia (FH) was noted in four of five probands. Both co-twins of the monozygotic pair and triplets displayed FH. In three families, at least one parent had FH without nystagmus. FH alone may be insufficient to develop nystagmus. Whilst arrested optokinetic reflex pathway development is implicated in IN, discordant twins raise questions regarding where differences in development have arisen. In unaffected monozygotes therefore, genetic variants may predispose to oculomotor instability, with variable expressivity possibly responsible for the discordance observed.

Observing a rotating visual pattern covering a large portion of the visual field induces optokinetic nystagmus (OKN). If the lights are suddenly switched off, optokinetic afternystagmus (OKAN) occurs. OKAN is hypothesized to originate in the velocity storage mechanism (VSM), a central processing network involved in multi-sensory integration. During a sustained visual rotation, the VSM builds up a velocity signal. After the lights are turned off, the VSM discharges slowly, with OKAN as the neurophysiological correlate. It has been reported that the initial afternystagmus in the direction of the preceding stimulus (OKAN-I) can be followed by a reversed one (OKAN-II), which increases with stimulus duration up to 15 min. In 11 healthy adults, we investigated OKAN following optokinetic stimulus lasting 30 s, 3-, 5-, and 10-min. Analysis of slow-phase cumulative eye position and velocity found OKAN-II in only 5/11 participants. Those participants presented it in over 70% of their trials with longer durations, but only in 10% of their 30 s trials. While this confirms that OKAN-II manifests predominantly after sustained stimuli, it suggests that its occurrence is subject-specific. We also did not observe further increases with stimulus duration. Conversely, OKAN-II onset occurred later as stimulus duration increased (p = 0.02), while OKAN-II occurrence and peak velocity did not differ between the three longest stimuli. Previous studies on OKAN-I, used negative saturation models to account for OKAN-II. As these approaches have no foundation in the OKAN-II literature, we evaluated if a simplified version of a rigorous model of OKAN adaptation could be used in humans. Slow-phase velocity following the trials with 3-, 5-, and 10-min stimuli was fitted with a sum of two decreasing exponential functions with opposite signs (one for OKAN-I and one for OKAN-II). The model assumes separate mechanisms for OKAN-I, representing VSM discharge, and OKAN-II, described as a slower adaptation phenomenon. Although the fit was qualitatively imperfect, this is not surprising given the limited reliability of OKAN in humans. The estimated adaptation time constant seems comparable to the one describing the reversal of the vestibulo-ocular reflex during sustained rotation, suggesting a possible shared adaptive mechanism.

The present study aimed to reveal the effects of age on the temporal profile of the positive blood-oxygen-level-dependent response (PBR) during low-velocity optokinetic nystagmus (OKN) in healthy subjects. We were specifically interested in comparing these effects with the effects of age on the PBR elicited by pure visual and motor tasks. Therefore, we conducted 2 additional control experiments: a checkerboard experiment (visual stimulation) and a finger-tapping (motor task) experiment. Whereas the oculomotor performance of the subjects remained unaltered, the temporal profile of the PBR changed significantly with increasing age in visual and oculomotor areas. None of the control experiments revealed significant age-related PBR changes. Thus, this study demonstrates that the PBR changes during OKN occur before any changes in the oculomotor performance can be detected. These effects of age are specific for the OKN task and probably reflect both changes in the neurovascular coupling and changes in the neural processing during OKN.

Optokinetic nystagmus (OKN) assists stabilization of the retinal image during head rotation. OKN is driven by ON direction selective retinal ganglion cells (ON DSGCs), which encode both the direction and speed of global retinal slip. The synaptic circuits responsible for the direction selectivity of ON DSGCs are well understood, but those sculpting their slow-speed preference remain enigmatic. Here, we probe this mechanism in mouse retina through patch clamp recordings, functional imaging, genetic manipulation, and electron microscopic reconstructions. We confirm earlier evidence that feedforward glycinergic inhibition is the main suppressor of ON DSGC responses to fast motion, and reveal the source for this inhibition-the VGluT3 amacrine cell, a dual neurotransmitter, excitatory/inhibitory interneuron. Together, our results identify a role for VGluT3 cells in limiting the speed range of OKN. More broadly, they suggest VGluT3 cells shape the response of many retinal cell types to fast motion, suppressing it in some while enhancing it in others.

The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed.

The decline in visual function due to normal aging impacts various aspects of our daily lives. Previous reports suggest that the aging retina exhibits mislocalization of photoreceptor terminals and reduced amplitudes of scotopic and photopic electroretinogram (ERG) responses in mice. These abnormalities are thought to contribute to age-related visual impairment; however, the extent to which visual function is impaired by aging at the organismal level is unclear. In the present study, we focus on the age-related changes of the optokinetic responses (OKRs) in visual processing. Moreover, we investigated the initial and late phases of the OKRs in young adult (2-3 months old) and aging mice (21-24 months old). The initial phase was evaluated by measuring the open-loop eye velocity of OKRs using sinusoidal grating patterns of various spatial frequencies (SFs) and moving at various temporal frequencies (TFs) for 0.5 s. The aging mice exhibited initial OKRs with a spatiotemporal frequency tuning that was slightly different from those in young adult mice. The late-phase OKRs were investigated by measuring the slow-phase velocity of the optokinetic nystagmus evoked by sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that optimal SF and TF in the normal aging mice are both reduced compared with those in young adult mice. In addition, we measured the OKRs of 4.1G-null (4.1G -/-) mice, in which mislocalization of photoreceptor terminals is observed even at the young adult stage. We found that the late phase OKR was significantly impaired in 4.1G - / - mice, which exhibit significantly reduced SF and TF compared with control mice. These OKR abnormalities observed in 4.1G - / - mice resemble the abnormalities found in normal aging mice. This finding suggests that these mice can be useful mouse models for studying the aging of the retinal tissue and declining visual function. Taken together, the current study demonstrates that normal aging deteriorates to visual motion processing for both the initial and late phases of OKRs. Moreover, it implies that the abnormalities of the visual function in the normal aging mice are at least partly due to mislocalization of photoreceptor synapses.

Myoblast determination protein 1 (MYOD) is a critical myogenic regulatory factor in muscle development, differentiation, myofiber repair, and regeneration. As the extraocular muscles significantly remodel their myofibers throughout life compared with limb skeletal muscles, we hypothesized that the absence of MYOD would result in their abnormal structure and function. To assess structural and functional changes in the extraocular muscles in MyoD-/- mice, fiber size and number and optokinetic nystagmus reflex (OKN) responses were examined.

Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled eye oscillations that can result in significant visual acuity loss. INS is often associated with albinism, but the mechanism is unclear. Albino mice have nystagmus; however, a pigmented mouse with a tyr mutation making it phenotypically albino, the B6(CG)-Tyr(c-2J)/J (B6 albino), had not been tested. We tested optokinetic response (OKR) in B6 albino and control mice. RNA-Seq was performed on extraocular muscles (EOM), tibialis anterior (TA) muscle, abducens (CN6), and oculomotor (CN3) neurons to uncover molecular differences that may contribute to nystagmus.

Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.

In this study, we seek to exclude other pathophysiological mechanisms by which Frmd7 knock-down may cause Idiopathic Infantile Nystagmus (IIN) using the Frmd7.tm1a and Frmd7.tm1b murine models. We used a combination of genetic, histological and visual function techniques to characterize the role of Frmd7 gene in IIN using a novel murine model for the disease. We demonstrate that the Frmd7.tm1b allele represents a more robust model of Frmd7 knock-out at the mRNA level. The expression of Frmd7 was investigated using both antibody staining and X-gal staining confirming previous reports that Frmd7 expression in the retina is restricted to starburst amacrine cells and demonstrating that X-gal staining recapitulates the expression pattern in this model. Thus, it offers a useful tool for further expression studies. We also show that gross retinal morphology and electrophysiology are unchanged in these Frmd7 mutant models when compared with wild-type mice. High-speed eye-tracking recordings of Frmd7 mutant mice confirm a specific horizontal optokinetic reflex defect. In summary, our study confirms the likely role for Frmd7 in the optokinetic reflex in mice mediated by starburst amacrine cells. We show that the Frmd7.tm1b model provides a more robust knock-out than the Frmd7.tm1a model at the mRNA level, although the functional consequence is unchanged. Finally, we establish a robust eye-tracking technique in mice that can be used in a variety of future studies using this model and others. Although our data highlight a deficit in the optiokinetic reflex as a result of the starburst amacrine cells in the retina, this does not rule out the involvement of other cells, in the brain or the retina where Frmd7 is expressed, in the pathophysiology of IIN.

Metabolic alterations, as they occur in Diabetes mellitus, have been mentioned in the development and maintenance of complaints related to the vestibular and auditory organs.

(1) Objectives: The evaluation of dizzy patients is difficult due to nonspecific symptoms that require a multi-specialist approach. The Dizziness Handicap Inventory (DHI) is widely used in the assessment of dizziness-related disability, but its clinical efficacy needs further expansion. The aim of this study was to identify the subscales of DHI that may correlate with some vestibular or nonvestibular dysfunctions. (2) Material and methods: This observational study included 343 dizzy patients with one of the following clinical conditions: Vestibular impairment noncompensated or compensated, central or bilateral, benign paroxysmal positional vertigo (BPPV), migraine and psychogenic dizziness. Principal component analysis was used to examine the factorial structure of the questionnaire. (3) Results: The DHI questionnaire total scoring and its vestibular subscale distinguished between patients with compensated and uncompensated vestibular dysfunction with positive predictive values of 76% and 79%, respectively. The DHI items composing the F3 (positional) subscale revealed the highest scoring in the BPPV group with 75% sensitivity and 92% negative predictive value (NPV) in reference to Dix-Hallpike tests. The DHI total score and the subscales scores correlated with anxiety-depression, and the highest correlation coefficients were calculated for vestibular (F2 0.56) and anxiety (F5 0.51) subscales. (4) Conclusions: Our analysis revealed that the DHI vestibular subscale distinguishes between patients with compensated and uncompensated vestibular dysfunction. The positional subscale showed the highest scoring in the BPPV group with high sensitivity and low specificity of the test. The DHI is highly correlated with patients' psychological status.