Optokinetic Nystagmus Research Articles

Depleting hypothalamic somatostatinergic neurons recapitulates diabetic phenotypes in mouse brain, bone marrow, adipose and retina.

Hypothalamic inflammation and sympathetic nervous system hyperactivity are hallmark features of the metabolic syndrome and type 2 diabetes. Hypothalamic inflammation may aggravate metabolic and immunological pathologies due to extensive sympathetic activation of peripheral tissues. Loss of somatostatinergic (SST) neurons may contribute to enhanced hypothalamic inflammation. The present data show that leptin receptor-deficient (db/db) mice exhibit reduced hypothalamic SST neurons, particularly in the periventricular nucleus. We model this finding, using adeno-associated virus delivery of diphtheria toxin subunit A (DTA) driven by an SST-cre system to deplete these neurons in Sstcre/gfp mice (SST-DTA). SST-DTA mice exhibit enhanced hypothalamic c-Fos expression and brain inflammation as demonstrated by microglial and astrocytic activation. Bone marrow from SST-DTA mice undergoes skewed haematopoiesis, generating excess granulocyte-monocyte progenitors and increased proinflammatory (C-C chemokine receptor type 2; CCR2hi) monocytes. SST-DTA mice exhibited a 'diabetic retinopathy-like' phenotype: reduced visual function by optokinetic response (0.4 vs 0.25 cycles/degree; SST-DTA vs control mice); delayed electroretinogram oscillatory potentials; and increased percentages of retinal monocytes. Finally, mesenteric visceral adipose tissue from SST-DTA mice was resistant to catecholamine-induced lipolysis, displaying 50% reduction in isoprenaline (isoproterenol)-induced lipolysis compared with control littermates. Importantly, hyperglycaemia was not observed in SST-DTA mice. The isolated reduction in hypothalamic SST neurons was able to recapitulate several hallmark features of type 2 diabetes in disease-relevant tissues.

Affordable and effective optokinetic response methods to assess visual acuity and contrast sensitivity in larval to juvenile zebrafish

The optokinetic response (OKR) is an effective behavioural assay to investigate functional vision in zebrafish. The rapid and widespread use of gene editing, drug screening and environmental modulation technologies has resulted in a broader need for visual neuroscience researchers to access affordable and more sensitive OKR, contrast sensitivity (CS) and visual acuity (VA) assays. Here, we demonstrate how 2D- and 3D-printed, striped patterns or drums coupled with a motorised base and microscope provide a simple, cost-effective but efficient means to assay OKR, CS and VA in larval-juvenile zebrafish. In wild-type, five days post-fertilisation (dpf) zebrafish, the 2D or 3D drums printed with the standard OKR stimulus of 0.02 cycles per degree (cpd), 100% black-white contrast evoked equivalent responses of 24.2 or 21.8 saccades per minute, respectively. Furthermore, although the OKR number was significantly reduced compared to the 0.02 cpd drum (p<0.0001), the 2D and 3D drums evoked equivalent responses with the 0.06 and 0.2 cpd drums. Notably, standard OKRs varied with time of day; peak responses of 29.8 saccades per minute occurred in the early afternoon with significantly reduced responses occurring in the early morning or late afternoon (18.5 and 18.4 saccades per minute, respectively). A customised series of 2D printed drums enabled analysis of VA and CS in 5-21 dpf zebrafish. The saccadic frequency in VA and CS assays was inversely proportional to age, spatial frequency and contrast of the stimulus. OKR, VA and CS of zebrafish larvae can be efficiently measured using 2D- or 3D-printed striped drums. For data consistency the luminance of the OKR light source, the time of day when the analysis is performed, and the order of presentation of VA and CS drums must be considered. These simple methods allow effective and more sensitive analysis of functional vision in zebrafish.

Effects of Covid-19 on the audio-vestibular system

PurposeIt was aimed to investigate the effects of COVID-19 infection on hearing and the vestibular system. MethodsTwenty-six patients whose treatment had been completed and who had no previous hearing or balance complaints were included in the study. Patients diagnosed with the disease by PCR were included in the study. Patients with at least one month of illness were included in the study. The hearing of patients was evaluated with transient evoked otoacoustic emissions (TEOAE) and pure-tone audiometry. Bedside tests, the European Evaluation of Vertigo scale (EEV), Video Head Impulse Test (vHIT), Ocular Vestibular Myogenic Evoked Potential (oVEMP), Cervical Vestibular Myogenic Evoked Potential (cVEMP) and Videonystagmography (VNG) tests were applied to evaluate the vestibular system. ResultsA statistically significant difference was found between the COVID-19 positive and control groups according to the mean values of the 4000 Hz and 8000 Hz in both the right and left ears (p < 0.05). No statistically significant difference was found in the other frequencies and TEOAE. No statistically significant difference was found between the COVID-19 positive and control groups in terms of their normal or pathological VNG saccade, optokinetic and spontaneous nystagmus values (p > 0.05). The normal and pathological VNG head shake values were found to be significantly different between the COVID-19 positive and control groups (p < 0.05). ConclusıonThe high frequencies in audiometry in the COVID-19 positive group were worse than those in the control group. In the vestibular system, especially in oVEMP and cVEMP, asymmetric findings were obtained in comparison to the control group, and a low gain in vHIT was shown. This study shows that the audiovestibular system of people with COVID-19 infection may be affected.

Estimation of the degree of autism spectrum disorder by the slow phase of optokinetic nystagmus in typical adults

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.

Behavioural red-light sensitivity in fish according to the optomotor response.

Various procedures have been adopted to investigate spectral sensitivity of animals, e.g. absorption spectra of visual pigments, electroretinography, optokinetic response, optomotor response (OMR) and phototaxis. The use of these techniques has led to various conclusions about animal vision. However, visual sensitivity should be evaluated consistently for a reliable comparison. In this study, we retrieved behavioural data of several fish species using a single OMR procedure and compared their sensitivities to near-infrared light. Besides cavefish that lack eyes, some species were not appropriate for the OMR test because they either stayed still or changed swimming direction frequently. Eight of 13 fish species tested were OMR positive. Detailed analyses using medaka, goldfish, zebrafish, guppy, stickleback and cichlid revealed that all the fish were sensitive to light at a wavelength greater than or equal to 750 nm, where the threshold wavelengths varied from 750 to 880 nm. Fish opsin repertoire affected the perception of red light. By contrast, the copy number of long-wavelength-sensitive (LWS) genes did not necessarily improve red-light sensitivity. While the duplication of LWS and other cone opsin genes that has occurred extensively during fish evolution might not aid increasing spectral sensitivity, it may provide some other advantageous ophthalmic function, such as enhanced spectral discrimination.

Mechanisms of punctuated vision in fly flight

To guide locomotion, animals control gaze via movements of their eyes, head, and/or body, but how the nervous system controls gaze during complex motor tasks remains elusive. In many animals, shifts in gaze consist of periods of smooth movement punctuated by rapid eye saccades. Notably, eye movements are constrained by anatomical limits, which requires resetting eye position. By studying tethered, flying fruit flies (Drosophila), we show that flies perform stereotyped head saccades to reset gaze, analogous to optokinetic nystagmus in primates. Head-reset saccades interrupted head smooth movement for as little as 50ms-representing less than 5% of the total flight time-thereby enabling punctuated gaze stabilization. By revealing the passive mechanics of the neck joint, we show that head-reset saccades leverage the neck's natural elastic recoil, enabling mechanically assisted redirection of gaze. The consistent head orientation at saccade initiation, the influence of the head's angular position on saccade rate, the decrease in wing saccade frequency in head-fixed flies, and the decrease in head-reset saccade rate in flies with their head range of motion restricted together implicate proprioception as the primary trigger of head-reset saccades. Wing-reset saccades were influenced by head orientation, establishing a causal link between neck sensory signals and the execution of body saccades. Head-reset saccades were abolished when flies switched to a landing state, demonstrating that head movements are gated by behavioral state. We propose a control architecture for active vision systems with limits in sensor range of motion. VIDEO ABSTRACT.

Circuit Organization Underlying Optic Flow Processing in Zebrafish

Animals’ self-motion generates a drifting movement of the visual scene in the entire field of view called optic flow. Animals use the sensation of optic flow to estimate their own movements and accordingly adjust their body posture and position and stabilize the direction of gaze. In zebrafish and other vertebrates, optic flow typically drives the optokinetic response (OKR) and optomotor response (OMR). Recent functional imaging studies in larval zebrafish have identified the pretectum as a primary center for optic flow processing. In contrast to the view that the pretectum acts as a relay station of direction-selective retinal inputs, pretectal neurons respond to much more complex visual features relevant to behavior, such as spatially and temporally integrated optic flow information. Furthermore, optic flow signals, as well as motor signals, are represented in the cerebellum in a region-specific manner. Here we review recent findings on the circuit organization that underlies the optic flow processing driving OKR and OMR.

Affordable and Effective Optokinetic Response Methods to Assess Visual Acuity and Contrast Sensitivity in Larval to Juvenile Zebrafish

Affordable and Effective Optokinetic Response Methods to Assess Visual Acuity and Contrast Sensitivity in Larval to Juvenile Zebrafish

Affordable and Effective Optokinetic Response Methods to Assess Visual Acuity and Contrast Sensitivity in Larval to Juvenile Zebrafish

Affordable and Effective Optokinetic Response Methods to Assess Visual Acuity and Contrast Sensitivity in Larval to Juvenile Zebrafish

Anatomy and function of retinorecipient arborization fields in zebrafish.

In 1994, Burrill and Easter described the retinal projections in embryonic and larval zebrafish, introducing the term "arborization fields" (AFs) for the retinorecipient areas. AFs were numbered from 1 to 10 according to their positions along the optic tract. With the exception of AF10 (neuropil of the optic tectum), annotations of AFs remained tentative. Here we offer an update on the likely identities and functions of zebrafish AFs after successfully matching classical neuroanatomy to the digital Max Planck Zebrafish Brain Atlas. In our system, individual AFs are neuropil areas associated with the following nuclei: AF1 with the suprachiasmatic nucleus; AF2 with the posterior parvocellular preoptic nucleus; AF3 and AF4 with the ventrolateral thalamic nucleus; AF4 with the anterior and intermediate thalamic nuclei; AF5 with the dorsal accessory optic nucleus; AF7 with the parvocellular superficial pretectal nucleus; AF8 with the central pretectal nucleus; and AF9d and AF9v with the dorsal and ventral periventricular pretectal nuclei. AF6 is probably part of the accessory optic system. Imaging, ablation, and activation experiments showed contributions of AF5 and potentially AF6 to optokinetic and optomotor reflexes, AF4 to phototaxis, and AF7 to prey detection. AF6, AF8 and AF9v respond to dimming, and AF4 and AF9d to brightening. While few annotations remain tentative, it is apparent that the larval zebrafish visual system is anatomically and functionally continuous with its adult successor and fits the general cyprinid pattern. This study illustrates the synergy created by merging classical neuroanatomy with a cellular-resolution digital brain atlas resource and functional imaging in larval zebrafish.

Long-Term Decrease of Intraocular Pressure in Rats by Viral Delivery of miR-146a.

PurposeTo evaluate the effects of miR-146a in trabecular meshwork (TM) cells and on intraocular pressure (IOP) in vivo via viral delivery of miR-146a to the anterior chamber of rat eyes.MethodsHuman TM cells were transfected with miR-146 mimic or inhibitor. Some cells from each group were then subjected to cyclic mechanical stress (CMS). Other cells from each group had no force applied. Gene expression was then analyzed by quantitative polymerase chain reaction (qPCR). Replication-deficient adenovirus and lentivirus expressing miR-146a were inoculated into the anterior segment of Brown Norway rat eyes. IOP was monitored by rebound tonometry, visual acuity was evaluated by optokinetic tracking (OKT), and inflammation markers in the anterior segment were examined by slit-lamp, qPCR, and semi-thin sections.ResultsmiR-146 affected the expression of genes potentially involved in outflow homeostasis at basal levels and under CMS. Both lentiviral and adenoviral vectors expressing miR-146a resulted in sustained decreases in IOP ranging from 2.6 to 4.4 mmHg. Long term follow-up of rats injected with lentiviral vectors showed a sustained effect on IOP of 4.4 ± 2.9 mmHg that lasted until rats were sacrificed more than 8 months later. Eyes showed no signs of inflammation, loss of visual acuity, or other visible abnormalities.ConclusionsIntracameral delivery of miR-146a can provide a long-term decrease of IOP in rats without signs of inflammation or other visible adverse effects.Transitional RelevanceThe IOP-lowering effects of miR-146 observed in rats provides a necessary step toward the development of an effective gene therapy for glaucoma in humans.

Kdm3b haploinsufficiency impairs the consolidation of cerebellum-dependent motor memory in mice

Histone modifications are a key mechanism underlying the epigenetic regulation of gene expression, which is critically involved in the consolidation of multiple forms of memory. However, the roles of histone modifications in cerebellum-dependent motor learning and memory are not well understood. To test whether changes in histone methylation are involved in cerebellar learning, we used heterozygous Kdm3b knockout (Kdm3b+/−) mice, which show reduced lysine 9 on histone 3 (H3K9) demethylase activity. H3K9 di-methylation is significantly increased selectively in the granule cell layer of the cerebellum of Kdm3b+/− mice. In the cerebellum-dependent optokinetic response (OKR) learning, Kdm3b+/− mice show deficits in memory consolidation, whereas they are normal in basal oculomotor performance and OKR acquisition. In addition, RNA-seq analyses revealed that the expression levels of several plasticity-related genes were altered in the mutant cerebellum. Our study suggests that active regulation of histone methylation is critical for the consolidation of cerebellar motor memory.

Optokinetic Stimulation as a Treatment for Parkinson’s Disease

Background: Parkinson’s disease (PD) is a neurological movement disorder, typically affecting older adults. It affects both motor and non-motor brain functions, impairing activities of daily living (ADLs). Additionally, as falling increases with age, PD patients are at a higher risk with an impaired vestibular system. Optokinetic stimulation, which works by observing moving visual targets to encourage optical scanning, provides a treatment option to restore balance. Previous studies on optokinetic stimulation have been effective and successful in stroke patients, reducing sway and normalizing optokinetic nystagmus. The goal is to translate this idea to PD patients as well.

The Rac-GAP alpha2-Chimaerin Signals via CRMP2 and Stathmins in the Development of the Ocular Motor System.

A precise sequence of axon guidance events is required for the development of the ocular motor system. Three cranial nerves grow toward, and connect with, six extraocular muscles in a stereotyped pattern, to control eye movements. The signaling protein alpha2-chimaerin (α2-CHN) plays a pivotal role in the formation of the ocular motor system; mutations in CHN1, encoding α2-CHN, cause the human eye movement disorder Duane Retraction Syndrome (DRS). Our research has demonstrated that the manipulation of α2-chn signaling in the zebrafish embryo leads to ocular motor axon wiring defects, although the signaling cascades regulated by α2-chn remain poorly understood. Here, we demonstrate that several cytoskeletal regulatory proteins-collapsin response mediator protein 2 (CRMP2; encoded by the gene dpysl2), stathmin1, and stathmin 2-bind to α2-CHN. dpysl2, stathmin1, and especially stathmin2 are expressed by ocular motor neurons. We find that the manipulation of dpysl2 and of stathmins in zebrafish larvae leads to defects in both the axon wiring of the ocular motor system and the optokinetic reflex, impairing horizontal eye movements. Knockdowns of these molecules in zebrafish larvae of either sex caused axon guidance phenotypes that included defasciculation and ectopic branching; in some cases, these phenotypes were reminiscent of DRS. chn1 knock-down phenotypes were rescued by the overexpression of CRMP2 and STMN1, suggesting that these proteins act in the same signaling pathway. These findings suggest that CRMP2 and stathmins signal downstream of α2-CHN to orchestrate ocular motor axon guidance and to control eye movements.SIGNIFICANCE STATEMENT The precise control of eye movements is crucial for the life of vertebrate animals, including humans. In humans, this control depends on the arrangement of nerve wiring of the ocular motor system, composed of three nerves and six muscles, a system that is conserved across vertebrate phyla. Mutations in the protein alpha2-chimaerin have previously been shown to cause eye movement disorders (squint) and axon wiring defects in humans. Our recent work has unraveled how alpha2-chimaerin coordinates axon guidance of the ocular motor system in animal models. In this article, we demonstrate key roles for the proteins CRMP2 and stathmin 1/2 in the signaling pathway orchestrated by alpha2-chimaerin, potentially giving insight into the etiology of eye movement disorders in humans.

A distributed saccade-associated network encodes high velocity conjugate and monocular eye movements in the zebrafish hindbrain

Saccades are rapid eye movements that redirect gaze. Their magnitudes and directions are tightly controlled by the oculomotor system, which is capable of generating conjugate, monocular, convergent and divergent saccades. Recent studies suggest a mainly monocular control of saccades in mammals, although the development of binocular control and the interaction of different functional populations is less well understood. For zebrafish, a well-established model in sensorimotor research, the nature of binocular control in this key oculomotor behavior is unknown. Here, we use the optokinetic response and calcium imaging to characterize how the developing zebrafish oculomotor system encodes the diverse repertoire of saccades. We find that neurons with phasic saccade-associated activity (putative burst neurons) are most frequent in dorsal regions of the hindbrain and show elements of both monocular and binocular encoding, revealing a mix of the response types originally hypothesized by Helmholtz and Hering. Additionally, we observed a certain degree of behavior-specific recruitment in individual neurons. Surprisingly, calcium activity is only weakly tuned to saccade size. Instead, saccade size is apparently controlled by a push–pull mechanism of opposing burst neuron populations. Our study reveals the basic layout of a developing vertebrate saccade system and provides a perspective into the evolution of the oculomotor system.

Spherical arena reveals optokinetic response tuning to stimulus location, size, and frequency across entire visual field of larval zebrafish.

Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs. We measured the optokinetic response gain of immobilised zebrafish larvae to stimuli of different steradian size and visual field locations. We find that the two eyes are less yoked than previously thought and that spatial frequency tuning is similar across visual field positions. However, zebrafish react most strongly to lateral, nearly equatorial stimuli, consistent with previously reported spatial densities of red, green, and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.

Correcting QUEST Magnetic Resonance Imaging-Sensitive Free Radical Production in the Outer Retina In Vivo Does Not Correct Reduced Visual Performance in 24-Month-Old C57BL/6J Mice.

PurposeTo test the hypothesis that acutely correcting a sustained presence of outer retina free radicals measured in vivo in 24-month-old mice corrects their reduced visual performance.MethodsMale C57BL/6J mice two and 24 months old were noninvasively evaluated for unremitted production of paramagnetic free radicals based on whether 1/T1 in retinal laminae are reduced after acute antioxidant administration (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]). Superoxide production was measured in freshly excised retina (lucigenin assay). Combining acute antioxidant administration with optical coherence tomography (i.e., QUEST OCT) tested for excessive free radical–induced shrinkage of the subretinal space volume. Combining antioxidant administration with optokinetic tracking tested for a contribution of uncontrolled free radical production to cone-based visual performance declines.ResultsAt two months, antioxidants had no effect on 1/T1 in vivo in any retinal layer. At 24 months, antioxidants reduced 1/T1 only in superior outer retina. No age-related change in retinal superoxide production was measured ex vivo, suggesting that free radical species other than superoxide contributed to the positive QUEST MRI signal at 24 months. Also, subretinal space volume did not show evidence for age-related shrinkage and was unresponsive to antioxidants. Finally, visual performance declined with age and was not restored by antioxidants that were effective per QUEST MRI.ConclusionsAn ongoing uncontrolled production of outer retina free radicals as measured in vivo in 24 mo C57BL/6J mice appears to be insufficient to explain reductions in visual performance.

Prevalence of Vestibular Disorders in Independent People Over 50 That Experience Dizziness.

People aged over 50 are the most likely to present to a physician for dizziness. It is important to identify the main cause of dizziness in order to develop the best treatment approach. Our goal was to determine the prevalence of benign paroxysmal positional vertigo (BPPV), and peripheral and central vestibular function in people that had experienced dizziness within the past year aged over 50. One hundred and ninety three community-dwelling participants aged 51–92 (68 ± 8.7 years; 117 females) were tested using the clinical and video head impulse test (cHIT and vHIT) to test high-frequency vestibular organ function; the head thrust dynamic visual acuity (htDVA) test to test high-frequency visual-stability; the dizziness handicap inventory (DHI) to measure the impact of dizziness; as well as sinusoidal and unidirectional rotational chair testing to test low- to mid-frequency peripheral and central vestibular function. From these assessments we computed the following measures: HIT gain; htDVA score; DHI score; sinusoidal (whole-body; 0.1–2 Hz with 30°/s peak-velocity) vestibulo-ocular reflex (VOR) gain and phase; transient (whole-body, 150°/s2 acceleration to 50°/s constant velocity) VOR gain and time constant; optokinetic nystagmus (OKN) gain and time constant (whole-body, 50°/s constant velocity rotation). Our study showed that BPPV, and peripheral or central vestibular hypofunction were present in 34% of participants, suggesting a vestibular cause to their dizziness. Over half (57%) of these with a likely vestibular cause had BPPV, which is more than twice the percentage reported in other dizzy clinic studies. Our findings suggest that the physical DHI score and VOR time constant were best at detecting those with non-BPPV vestibular loss, but should always be used in conjunction with cHIT or vHIT, and that the htDVA score and vHIT gain were best at detecting differences between ipsilesional and contralesional sides.

Risk factors related balance disorder for patients with dizziness/vertigo

BackgroundWhen dizziness/vertigo patients presented with balance disorder, it will bring severe morbidity. There is currently lack of research to explore risk factor related balance disorder in dizziness patients, especially in those who walk independently.AimTo investigate risk factors related balance disorder in dizziness/vertigo patients who walk independently.MethodsMedical data of 1002 dizziness/vertigo patients registered in vertigo/balance disorder registration database were reviewed. The demographic data, medical history, and risk factors for atherosclerosis (AS) were collected. Enrolled dizziness/vertigo patients could walk independently, completed Romberg test, videonystagmography (VNG), and limits of stability (LOS). The subjective imbalance was patient complained of postural symptom when performing Romberg test. Multivariable logistic regression analyzed risk factors related balance disorder. The receiver operating characteristic (ROC) curve evaluated the utility of regression model.ResultsFive hundred fifty-three dizziness/vertigo patients who walk independently were included in the final analysis. According to LOS, patients were divided into 334 (60%) normal balance and 219 (40%) balance disorder. Compared with normal balance, patients with balance disorder were older (P = 0.045) and had more risk factors for AS (P<0.0001). The regression showed that risk factors for AS (OR 1.494, 95% CI 1.198–1.863), subjective imbalance (OR 4.835, 95% CI 3.047–7.673), and abnormality of optokinetic nystagmus (OR 8.308, 95% CI 1.576–43.789) were related to balance disorder. The sensitivity and specificity of model were 71 and 63% (P<0.0001). The area under the curve (AUC) was 0.721.ConclusionsRisk factors for AS, subjective imbalance, and abnormality of optokinetic nystagmus were predictors for balance disorder in patients with dizziness/vertigo who walk independently.

Increasing Altitude and the Optokinetic Cervical Reflex.

INTRODUCTION: When an aircraft banks pilots will reflexively tilt their heads in the opposite direction, known as the optokinetic cervical reflex (OKCR). This is elicited by the appearance of the horizon and is an attempt to keep the moving horizon stable on the pilots retina to help maintain spatial orientation. The appearance of the horizon and the visual environment changes at higher altitudes and there is little research studying the effects of this. Our hypothesis was that increasing altitude would alter the visual cues present and decrease the OKCR.METHODS: There were 16 subjects who flew two flights in a flight simulator while their head tilt, aircraft altitude, and angle of aircraft bank were recorded. The flights were at an altitude of under 1500 ft above ground and above 15,000 ft above ground.RESULTS: Aircraft bank caused head tilt in the opposite direction at both altitudes. A two-way ANOVA with Bonferroni post hoc tests showed that 86% of aircraft bank angles from 0 to 90 in either direction had a head tilt that was statistically significantly smaller at high altitude.DISCUSSION: This study shows that there appears to be a difference between the OKCR at low and high altitude. Pilots at higher altitude seem to exhibit a smaller head tilt for the same aircraft bank angle. More research is required to fully understand why there is a decrease in the OKCR at high altitude, as well as the actual consequences of the decreased reflex on pilot orientation.Stewart MA, Pingali S, Newman DG. Increasing altitude and the optokinetic cervical reflex. Aerosp Med Hum Perform. 2021; 92(5):319325.