Oculomotor and Vestibular Deficits in Friedreich Ataxia - Systematic Review and Meta-Analysis of Quantitative Measurements.

Disease-specific oculomotor assessments play a crucial role in the early diagnosis of hereditary cerebellar ataxias. Whereas several studies have reported on quantitative oculomotor and vestibular measurements in Friedreich's Ataxia (FRDA), the value of specific oculomotor paradigms remains unclear. We aimed to address this knowledge gap through a systematic literature review and providing disease-specific recommendations for a tailored set of eye-movement recordings in FRDA. MEDLINE and Embase were searched for studies reporting on quantitative oculomotor and/or vestibular measurements in FRDA-patients. Data on oculomotor and vestibular parameters were extracted and correlations with a range of clinical parameters were sought. Included studies (n = 17) reported on 185 patients. Abnormalities observed included the presence of saccadic intrusions (143/161) such as square-wave jerks (SWJ, 90/109) and ocular flutter (21/43), impaired eccentric gaze-holding (40/104), abnormal pursuit (81/93) and angular vestibulo-ocular reflex (aVOR) deficits (39/48). For visually-guided saccades (VGS), we frequently observed increases in saccade latency (27/38) and dysmetric saccades (71/93), whereas saccade velocity was more often preserved (37/43). Augmented anti-saccade (AS) latency, downbeat nystagmus and frequent macro-SWJ correlated with disease duration. Increased AS-latency and VGS-latency, frequent macro-SWJ, reduced aVOR-gain and augmented aVOR peak-latency correlated with disease severity. A broad range of oculomotor and vestibular deficits are documented in the literature. Impairments in pursuit, saccades and aVOR-responses are most commonly reported, and as such, should be prioritized as disease markers. Quantitative oculomotor testing in FRDA may facilitate early diagnosis and prove valuable in monitoring disease progression and treatment response.

Progression of Clinical and Eye Movement Markers in Preataxic Carriers of Machado-Joseph Disease.

BACKGROUND: Little is known about preclinical stages of Machado-Joseph disease, a polyglutamine disorder characterized by progressive adult-onset ataxia. OBJECTIVE: We aimed to describe the longitudinal progression of clinical and oculomotor variables in the preataxic phase of disease. METHODS: Carriers and noncarriers were assessed at three visits. Preataxic carriers (Scale for Assessment and Rating of Ataxia score < 3) expected to start ataxia in ≤4 years were considered near onset (PAN). Progressions of ataxic and preataxic carriers, considering status at the end of the study, were described according to the start (or its prediction) of gait ataxia (TimeToAfterOnset) and according to the study time. RESULTS: A total of 35 ataxics, 38 preataxics, and 22 noncarriers were included. The "TimeToAfterOnset" timeline showed that Neurological Examination Scale for Spinocerebellar Ataxias (NESSCA; effect size, 0.09), Inventory of Non-Ataxia Symptoms (INAS0.07), and the vestibulo-ocular reflex gain (0.12) progressed in preataxic carriers, and that most slopes accelerate in PAN, turning similar to those of ataxics. In the study time, NESSCA (1.36) and vertical pursuit gain (1.17) significantly worsened in PAN, and 6 of 11 PANs converted to ataxia. For a clinical trial with 80% power and 2-year duration, 57 PANs are needed in each study arm to detect a 50% reduction in the conversion rate. CONCLUSIONS: NESSCA, INAS, vestibulo-ocular reflex, and vertical pursuit gains significantly worsened in the preataxic phase. The "TimeToAfterOnset" timeline unveiled that slopes of most variables are small in preataxics but increase and reach the ataxic slopes from 4 years before the onset of ataxia. For future trials in preataxic carriers, we recommend recruiting PANs and using the conversion rate as the primary outcome. © 2022 International Parkinson and Movement Disorder Society.

Three-dimensional analysis of per-rotational nystagmus.

BACKGROUND: Head rotation produces a vestibulo-ocular reflex (VOR). In horizontal rotation, not only lateral semicircular canals but also posterior semicircular canals are stimulated, because posterior canals cupulae are not horizontal in the sitting position. Therefore, theoretical nystagmus is horizontal and torsional. Convection of endolymph does not occur, because the centre of head rotation is a dens of the second cervical vertebra, not the center of lateral canal. Although per-rotational nystagmus is a result of VOR, whether it could be explained by the movement of cupula remains undetermined. To answer this question, we analysed per-rotational nystagmus using three-dimensional video-oculography. OBJECTIVE: To clarify whether per-rotational nystagmus is the same as the physical movement of cupula (theoretical nystagmus). MATERIALS AND METHODS: Five healthy human were evaluated. The participant's head was rotated (sinusoidal yaw rotation) manually (frequency, 0.33 Hz; amplitude, 60°). The experiment was performed in a dark, with the participant's eyes open. Nystagmus was recorded and converted into digital data. RESULTS: In all participants, the direction of nystagmus was rightward on rightward rotation and leftward on leftward rotation. In all participants, nystagmus was purely horizontal. CONCLUSIONS: Practical per-rotational nystagmus differs completely from the theoretical nystagmus. Therefore, VOR is strongly influenced by the central nervous system.

Analysis of 30 patients with cupulolithiasis of the posterior semicircular canal.

BACKGROUND: The diagnostic characteristics of patients with cupulolithiasis of the posterior semicircular canal are persistent torsional nystagmus in the supine position and persistent torsional nystagmus (opposite direction) in the nose-down position, which are caused by the affected canal becoming gravity sensitive. OBJECTIVE: To investigate the clinical features of posterior cupulolithiasis. MATERIALS AND METHODS: We interviewed 30 consecutive patients with cupulolithiasis of the posterior canal and categorized them by onset time into the following four groups: (1) during sleep; (2) at the time of awakening; (3) morning; and (4) afternoon. We defined disease duration as the period from onset to the day when we detected remission of positional nystagmus. RESULTS: Time of awakening was the most common onset time. The mean disease duration was 18.2 days, and 90% of patients achieved cure within 1 month. CONCLUSIONS: Physicians should take into account the duration of nystagmus, because cupulolithiasis of posterior canal exists. The etiology of posterior cupulolithiasis is closely related to sleep, because time of awakening is the most common onset time of vertigo. Most patients with posterior cupulolithiasis cure within 1 month.

Automatic Video-Oculography System for Detection of Minimal Hepatic Encephalopathy Using Machine Learning Tools.

This article presents an automatic gaze-tracker system to assist in the detection of minimal hepatic encephalopathy by analyzing eye movements with machine learning tools. To record eye movements, we used video-oculography technology and developed automatic feature-extraction software as well as a machine learning algorithm to assist clinicians in the diagnosis. In order to validate the procedure, we selected a sample (n=47) of cirrhotic patients. Approximately half of them were diagnosed with minimal hepatic encephalopathy (MHE), a common neurological impairment in patients with liver disease. By using the actual gold standard, the Psychometric Hepatic Encephalopathy Score battery, PHES, patients were classified into two groups: cirrhotic patients with MHE and those without MHE. Eye movement tests were carried out on all participants. Using classical statistical concepts, we analyzed the significance of 150 eye movement features, and the most relevant (p-values ≤ 0.05) were selected for training machine learning algorithms. To summarize, while the PHES battery is a time-consuming exploration (between 25-40 min per patient), requiring expert training and not amenable to longitudinal analysis, the automatic video oculography is a simple test that takes between 7 and 10 min per patient and has a sensitivity and a specificity of 93%.

Eye Tracking Parameters Correlate with the Level of Cerebral Oxygen Saturation in Mild Traumatic Brain Injury: A Preliminary Study.

AIM: The aim of this study was to assess the relationship between oculomotor synergies and brain oxygen status at mild traumatic brain injury (mTBI) using simultaneous comparison of eye-tracking (ET) parameters and cerebral oxygen saturation. MATERIAL AND METHODS: This non-randomised single-centre prospective study included 77 patients with mTBI (mean age was 36.3 ± 4.8 years, 48 men, 29 women, median GCS 13.7 ± 0.7). Cerebral oximetry was used to detect oxygen saturation level (SctO2) in the frontal lobe pole (FLP) region. Eye movements were measured simultaneously using the EyeTracker. Calculated parameters were: vertical and horizontal angular eyeball velocity (AV); left vertical speed (LVS); right vertical speed (RVS); left horizontal speed (LHS); and right horizontal speed (RHS). The indices of vertical and horizontal eye version (version index, Vx) were calculated as the Pearson correlation coefficient between the corresponding AV of the right and left eyes. Significance was pre-set to p < 0.05. RESULTS: SctO2 in the FLP varied from 62% to 79%. The average SctO2 values were 69.26 ± 6.96% over the left FLP and 70.25 ± 7.58% over the right FLP (p = 0.40). The total analysis of the eye-tracking data revealed the following values of gaze parameters: LVS - 0.327 ± 0.263 rad/sec; LHS - 0.201 ± 0.164 rad/sec; RVS - 0.361 ± 0.269 rad/sec; and RHS - 0.197 ± 0.124 rad/sec. The calculated vertical version index (VVx) was 0.80 ± 0.12. The calculated horizontal version index (HVx) was 0.82 ± 0.11. The VVx and HVx were correlated with SctO2 levels in the FLP (p = 0.038; r = 0.235; p = 0.048; r = 0.218, respectively p = 0.035; r = 0.241; p = 0.039; r = 0.235, respectively). CONCLUSIONS: VVx and HVx correlate with the SctO2 level in the FLP (p < 0.01) in mTBI. No significant correlation was detected between the level of the SctO2 level and vertical and horizontal AV of the eyeballs. Eye tracking can help quantify the severity of ocular conjugation impairments after mTBI, as well as explore the contribution that cerebral oxygen status disorders make to this process.

Automated alternate cover test for 'HINTS' assessment: a validation study.

OBJECTIVE: The alternate cover test (ACT) in patients with acute vestibular syndrome is part of the 'HINTS' battery test. Although quantitative, the ACT is highly dependent on the examiner's experience and could theoretically vary greatly between examiners. In this study, we sought to validate an automated video-oculography (VOG) system based on eye tracking and dedicated glasses. METHODS: We artificially induced a vertical strabismus to simulate a skew deviation on ten healthy subjects, aged from 26 to 66, using different press-on Fresnel prisms on one eye while recording eye position with VOG of the contralateral eye. We then compared the system's performance to that of a blinded trained orthoptist using conventional, semi-quantitative method of skew measurement known as the alternate prism cover test (APCT) as a gold standard. RESULTS: We found a significant correlation between the reference APCT and the Skew VOG (Pearson's R2 = 0.606, p < 0.05). There was a good agreement between the two tests (intraclass correlation coefficient 0.852, 95 CI 0.728-0.917, p < 0.001). The overall accuracy of the VOG was estimated at 80.53% with an error rate of 19.46%. There was no significant difference in VOG skew estimations compared with the gold standard except for very small skews. CONCLUSIONS: VOG offers an objective and quantitative skew measurement and proved to be accurate in measuring vertical eye misalignment compared to the ACT with prisms. Precision was moderate, which mandates a sufficient number of tests per subject.

Toward an Automatic Assessment of Cognitive Dysfunction in Relapsing-Remitting Multiple Sclerosis Patients Using Eye Movement Analysis.

Despite the importance of cognitive function in multiple sclerosis, it is poorly represented in the Expanded Disability Status Scale (EDSS), the commonly used clinical measure to assess disability, suggesting that an analysis of eye movement, which is generated by an extensive and well-coordinated functional network that is engaged in cognitive function, could have the potential to extend and complement this more conventional measure. We aimed to measure the eye movement of a case series of MS patients with relapsing−remitting MS to assess their cognitive status using a conventional gaze tracker. A total of 41 relapsing−remitting MS patients and 43 age-matched healthy controls were recruited for this study. Overall, we could not find a clear common pattern in the eye motor abnormalities. Vertical eye movement was more impaired in MS patients than horizontal movement. Increased latencies were found in the prosaccades and reflexive saccades of antisaccade tests. The smooth pursuit was impaired with more corrections (backup and catchup movements, p<0.01). No correlation was found between eye movement variables and EDSS or disease duration. Despite significant alterations in the behavior of the eye movements in MS patients, which are compatible with altered cognitive status, there is no common pattern of these alterations. We interpret this as a consequence of the patchy, heterogeneous distribution of white matter involvement in MS that provokes multiple combinations of impairment at different points in the different networks involved in eye motor control. Further studies are therefore required.

Asymmetry in Gaze-Holding Impairment in Acute Unilateral Ischemic Cerebellar Lesions Critically Depends on the Involvement of the Caudal Vermis and the Dentate Nucleus.

Stabilizing the eyes in space when looking at a target is provided by a brainstem/cerebellar gaze-holding network, including the flocculus/paraflocculus complex (non-human primate studies) and the caudal vermis, biventer, and inferior semilunar lobule (human studies). Previous research suggests that acute lateralized cerebellar lesions preferentially lead to gaze-evoked nystagmus (GEN) on ipsilesional gaze. Here, we further characterize the effect of unilateral cerebellar lesions on gaze-holding and hypothesize that the side-specific magnitude of gaze-holding impairment depends on the lesion location. Nine patients (age range = 31-62 years) with acute/subacute (≤ 10 days old) MRI-confirmed unilateral cerebellar stroke were included. Horizontal gaze holding was quantified while looking at a slowly moving (0.5°/s) flashing target (gaze angle = ±40°). Asymmetry in eye-drift velocity was calculated and compared with the different MRI patterns of cerebellar lesions. Individual peak eye-drift velocities (range = 1.7-8.8°/s) occurred at the most eccentric eye positions (gaze angle = 28-38°). We found significantly asymmetric eye-drift velocity (EDV) in eight out of nine patients. The four patients with MRI-confirmed involvement of the caudal vermis and the dentate nucleus all presented with ipsilesionally-predominant EDV, while in the five patients with lesions restricted to the cerebellar hemisphere, EDV was stronger on contralesional gaze in three out of four found with an asymmetric EDV. Involvement of the caudal vermis and the dentate nucleus is critical for determining the directional GEN asymmetry in unilateral cerebellar lesions. Thus, our findings support the occurrence of GEN without floccular/parafloccular lesions and suggest that the EDV asymmetry in relation to the side of the lesion provides information about the involvement of specific structures.

Clinical, oculographic, and vestibular test characteristics of vestibular migraine.

BACKGROUND: We characterise the history, vestibular tests, ictal and interictal nystagmus in vestibular migraine. METHOD: We present our observations on 101 adult-patients presenting to an outpatient facility with recurrent spontaneous and/or positional vertigo whose final diagnosis was vestibular migraine (n = 27) or probable vestibular migraine (n = 74). Ictal and interictal video-oculography, caloric and video head impulse tests, vestibular-evoked myogenic potentials and audiometry were performed. RESULTS: Common presenting symptoms were headache (81.2%), spinning vertigo (72.3%), Mal de Débarquement (58.4%), and motion sensitivity (30.7%). With fixation denied, ictal and interictal spontaneous nystagmus was observed in 71.3 and 14.9%, and purely positional nystagmus in 25.8 and 55.4%. Spontaneous ictal nystagmus was horizontal in 49.5%, and vertical in 21.8%. Ictal spontaneous and positional nystagmus velocities were 5.3 ± 9.0°/s (range 0.0-57.4), and 10.4 ± 5.8°/s (0.0-99.9). Interictal spontaneous and positional nystagmus velocities were <3°/s in 91.8 and 23.3%. Nystagmus velocities were significantly higher when ictal (p < 0.001/confidence interval: 2.908‒6.733, p < 0.001/confidence interval: 5.308‒10.085). Normal lateral video head impulse test gains were found in 97.8% (mean gain 0.95 ± 0.12) and symmetric caloric results in 84.2% (mean canal paresis 7.0 ± 23.3%). Air- and bone-conducted cervical-vestibular-evoked myogenic potential amplitudes were symmetric in 88.4 and 93.4% (mean corrected amplitude 1.6 ± 0.7, 1.6 ± 0.8) with mean asymmetry ratios of 13.0 and 9.0%. Air- and bone-conducted ocular-vestibular-evoked myogenic potentials were symmetric in 67.7 and 97.2% (mean amplitude 9.2 ± 6.4 and 20.3 ± 12.8 µV) with mean asymmetry ratios of 15.7 and 9.9%. Audiometry was age consistent and symmetric in 85.5%. CONCLUSION: Vestibular migraine is characterised by low velocity ictal spontaneous nystagmus, which can be horizontal, vertical, or torsional, and normal audiovestibular test results.

A cross-sectional, prospective ocular motor study in 72 patients with Niemann-Pick disease type C.

OBJECTIVE: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC). METHODS: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC). RESULTS: Some 98.2% of patients generated vertical saccades below the 95% CI of the controls' peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7-69.3]) downward versus 78.8°/s (65.9, [60.8-96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self-paced ones. Gaze-holding was normal. Ocular-motor performance depended on the age of onset and disease duration. CONCLUSIONS: This is the largest cohort of NPC patients investigated for ocular-motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis.

OpenEDS2020 Challenge on Gaze Tracking for VR: Dataset and Results.

This paper summarizes the OpenEDS 2020 Challenge dataset, the proposed baselines, and results obtained by the top three winners of each competition: (1) Gaze prediction Challenge, with the goal of predicting the gaze vector 1 to 5 frames into the future based on a sequence of previous eye images, and (2) Sparse Temporal Semantic Segmentation Challenge, with the goal of using temporal information to propagate semantic eye labels to contiguous eye image frames. Both competitions were based on the OpenEDS2020 dataset, a novel dataset of eye-image sequences captured at a frame rate of 100 Hz under controlled illumination, using a virtual-reality head-mounted display with two synchronized eye-facing cameras. The dataset, which we make publicly available for the research community, consists of 87 subjects performing several gaze-elicited tasks, and is divided into 2 subsets, one for each competition task. The proposed baselines, based on deep learning approaches, obtained an average angular error of 5.37 degrees for gaze prediction, and a mean intersection over union score (mIoU) of 84.1% for semantic segmentation. The winning solutions were able to outperform the baselines, obtaining up to 3.17 degrees for the former task and 95.2% mIoU for the latter.

Low-Noise Magnetic Coil System for Recording 3-Dimensional Eye Movements.

OBJECTIVE: Vestibular and oculomotor research often requires measurement of 3-dimensional (3D) eye orientation and movement with high spatial and temporal precision and accuracy. We describe the design, implementation, validation and use of a new magnetic coil system optimized for recording 3D eye movements using small scleral coils in animals. METHODS: Like older systems, the system design uses off-the-shelf components to drive three mutually orthogonal alternating magnetic fields at different frequencies. The scleral coil voltage induced by those fields is decomposed into 3 signals, each related to the coil's orientation relative to the axis of one field component. Unlike older systems based on analog demodulation and filtering, this system uses a field-programmable gate array (FPGA) to oversample each induced scleral coil voltage (at 25 Msamples/s), demodulate in the digital domain, and average over 25 ksamples per data point to generate 1 ksamples/s output in real time. RESULTS: Noise floor is <0.036° peak-to-peak and linearity error is < 0.1° during 345° rotations in all three dimensions. CONCLUSION AND SIGNIFICANCE: This FPGA-based design, which is both reprogrammable and freely available upon request, delivers sufficient performance to record eye movements at high spatial and temporal precision and accuracy using coils small enough for use with small animals.

Health-related quality of life and functional impairment in acute vestibular disorders.

BACKGROUND AND PURPOSE: Acute vestibular symptoms have a profound impact on patients' well-being. In this study, health-related quality of life (HRQoL) and functional impairment were investigated prospectively in patients with different peripheral and central vestibular disorders during the acute symptomatic stage to decipher the most relevant underlying factors. METHODS: In all, 175 patients with acute vestibular disorders were categorized as central vestibular (CV, n = 40), peripheral vestibular (PV, n = 68) and episodic vestibular disorders (EV, n = 67). All patients completed scores to quantify generic HRQoL (European Quality of Life Score Five Dimensions Five Levels, EQ-5D-5L) and disease-specific HRQoL (Dizziness Handicap Inventory, DHI). Vestibular-ocular motor signs were assessed by video-oculography, vestibular-spinal control by posturography and verticality perception by measurement of subjective visual vertical. RESULTS: Patients with PV had a poorer HRQoL compared to patients with CV and EV (EQ-5D-5L/DHI: PV, 0.53 ± 0.31/56.1 ± 19.7; CV, 0.66 ± 0.28/43.3 ± 24.0; EV, 0.75 ± 0.24/46.7 ± 21.4). After adjusting for age, gender, cardiovascular risk factors and non-vestibular brainstem/cerebellar dysfunction patients with PV persisted to have poorer generic and disease-specific HRQoL (EQ-5D-5L -0.17, DHI +11.2) than patients with CV. Horizontal spontaneous nystagmus was a highly relevant factor for subgroup differences in EQ-5D-5L and DHI, whilst vertical spontaneous nystagmus, subjective visual vertical and sway path were not. EQ-5D-5L decreased significantly with more intense horizontal subjective visual vertical in CV (rho = -0.57) and PV (rho = -0.5) but not EV (rho = -0.13). CONCLUSIONS: Patients with PV have the highest functional impairment of all patients with acute vestibular disorders. Vestibular-ocular motor disturbance in the yaw plane has more impact than vestibular-spinal or vestibular-perceptive asymmetry in the roll and pitch plane, suggesting that horizontal visual stability is the most critical for HRQoL.

The effects of caffeine on drowsiness in patients with narcolepsy: a double-blind randomized controlled pilot study.

PURPOSE: The effects of caffeine on drowsiness and reaction time in patients with narcolepsy are unclear. We aimed to assess the effects of caffeine as add-on therapy in narcolepsy patients. METHODS: A randomized, double-blind, placebo-control clinical pilot trial was conducted with a parallel, two-arm trial allocation ratio of 1:1. Participants attended two study visits 7 days apart. The drug was administered orally in a single opaque capsule containing 200 mg caffeine/placebo daily in the morning for 1 week. Sleepiness was assessed objectively using infrared reflectance oculography to measure the percentage of long eye closure (LEC%) and subjectively using two sleepiness scales, the Stanford Sleepiness Scale (SSS) and Karolinska Sleepiness Scale (KSS). Parameters were measured at baseline (BL) prior to taking the drug, after taking the first dose (FD), and after 1 week (WD) of daily caffeine. RESULTS: Sixteen participants with narcolepsy were included. No significant differences between groups in baseline measurements were observed. LEC% was significantly decreased after the FD and WD compared with baseline levels (BL 1.4 ± 2.1 vs. FD 0.06 ± 0.0.6 and WD 0.03 ± 0.04). Significant improvements in alertness were observed using the KSS when comparing BL with FD and WD (6.3 ± 1.6, 4.9 ± 1.7, and 4.7 ± 1.7, respectively; p = 0.01). No changes in reaction time or SSS scores were noted. CONCLUSION: Our findings suggest that a small dose of caffeine has positive effects on alertness in patients with narcolepsy. However, larger trials are required to confirm these findings. TRIAL REGISTRATION NO: ClinicalTrial.gov NCT02832336.

Mental tasking and rotary Chair-Induced vestibular nystagmus utilizing Video-Oculography.

Objective: To investigate whether the use of mental tasking, when compared to no mental task, affects measurement of nystagmus response with regard to gain, phase & symmetry, and artefact when utilising video-oculography (VOG) as the measurement technique in rotary chair testing (RCT).Design: A within-subject repeated-measures design was utilised.Study samples: Seventeen (17) healthy adults were evaluated (age 22-25 years). Each participant underwent slow harmonic acceleration (SHA) testing for 0.01, 0.02, 0.04, 0.08, and 0.16 Hz using RCT at two separate counterbalanced visits. At one visit mental tasking was utilised while the other visit did not utilise mental tasking. The following outcomes were measured for each visit: gain, phase, symmetry, and artefact.Results: No significant difference between the tasking conditions with regard to gain, phase, symmetry, or artefact. Significant frequency affects were noted, as expected, for gain, phase, and artefact. Analysis of individual subject data did, however, describe significant effects of tasking with regard to gain, phase, symmetry, and artefact.Conclusion: These results suggest that the use of mental tasking during RCT using VOG had no significant group effect on SHA gain, phase, symmetry, and artefact. However, individual subject effects were observed indicating variability in the effects of mental tasking during RCT.

Saccadic eye movements estimate prolonged time awake.

Prolonged time awake increases the need to sleep. Sleep pressure increases sleepiness, impairs human alertness and performance and increases the probability of human errors and accidents. Human performance and alertness during waking hours are influenced by homeostatic sleep drive and the circadian rhythm. Cognitive functions, especially attentional ones, are vulnerable to circadian rhythm and increasing sleep drive. A reliable, objective and practical metrics for estimating sleepiness could therefore be valuable. Our aim is to study whether saccades measured with electro-oculography (EOG) outside the laboratory could be used to estimate the overall time awake without sleep of a person. The number of executed saccades was measured in 11 participants during an 8-min saccade task. The saccades were recorded outside the laboratory (Naval Academy, Bergen) using EOG every sixth hour until 54 hr of time awake. Measurements were carried out on two occasions separated by 10 weeks. Five participants participated in both measurement weeks. The number of saccades decreased during sustained wakefulness. The data correlated with the three-process model of alertness; performance differed between participants but was stable within individual participants. A mathematically monotonous relation between performance in the saccade task and time awake was seen after removing the circadian rhythm component from measured eye movement data. The results imply that saccades measured with EOG can be used as a time-awake metric outside the laboratory.

Eye movements in idiopathic rapid eye movement sleep behaviour disorder: High antisaccade error rate reflects prefrontal cortex dysfunction.

Abnormalities of eye movements have been reported in patients with Parkinson's disease (PD). However, it is unclear if they occur in the prodromal stage of synucleinopathy represented by idiopathic rapid eye movement sleep behaviour disorder (iRBD). We thus aimed to study eye movements in subjects with iRBD and in de novo PD, to assess if their abnormalities may serve as a clinical biomarker of neurodegeneration. Fifty subjects with polysomnography-confirmed iRBD (46 male, age 40-79 years), 18 newly diagnosed, untreated PD patients (13 male, age 43-75 years) and 25 healthy controls (20 male, age 42-79 years) were prospectively enrolled. Horizontal and vertical ocular prosaccades and antisaccades were investigated with video-oculography. All patients completed the MDS-UPDRS and the Montreal Cognitive Assessment. In addition, a neuropsychological battery was performed on iRBD subjects. When compared with healthy controls, both de novo PD patients and iRBD subjects showed increased error rates in the horizontal antisaccade task (p < 0.01, p < 0.05 respectively). In the iRBD group, the error rates in horizontal and vertical antisaccades correlated with performances in the Prague Stroop Test and the Grooved Pegboard Test, as well as with motor scores of the MDS-UPDRS. De novo PD patients showed a lower gain (p < 0.01) compared with controls. In conclusion, the increased error rate in the antisaccade task of iRBD and PD patients reflects a dysfunction of the dorsolateral prefrontal cortex and is related to the impairment of executive functions and attention.

Saccadic eye movements in different dimensions of schizophrenia and in clinical high-risk state for psychosis.

BACKGROUND: Oculomotor dysfunction is one of the most replicated findings in schizophrenia. However the association between saccadic abnormalities and particular clinical syndromes remains unclear. The assessment of saccadic movements in schizophrenia patients as well as in clinical high-risk state for psychosis individuals (CHR) as a part of schizophrenia continuum may be useful in validation of saccadic movements as a possible biomarker. METHODS: The study included 156 patients who met the ICD-10 criteria for schizophrenia: 42 individuals at clinical high-risk-state for psychosis and 61 healthy controls. The schizophrenia patients had three subgroups based on the sum of the global SAPS and SANS scores: (1) patients with predominantly negative symptoms (NS, n = 62); (2) patients with predominantly positive symptoms (PS, n = 54) (3) patients with predominantly disorganization symptoms (DS, n = 40). CHR subjects were characterized by the presence of one of the groups of criteria: (1) Ultra High Risk criteria, (2) Basic Symptoms criteria or (3) negative symptoms and formal thought disorders. Horizontal eye movements were recorded by using videonystagmograph. We measured peak velocity, latency and accuracy in prosaccade, antisaccade and predictive saccade tasks as well as error rates in the antisaccade task. RESULTS: Schizophrenia patients performed worse than controls in predictive, reflexive and antisaccade tasks. Oculomotor parameters of NS were different from the other groups of patients. Latencies of predictive and reflexive saccades were significantly longer than in controls only in the NS group. The accuracy of predictive saccades was also different from controls only in the NS schizophrenia group. More prominent loss of accuracy of reflexive saccades was found in the DS group and it significantly differed from the one in other groups. Participants from DS group made more errors in antisaccade task compared to NS and PS groups. CHR subjects performed worse than controls as measured by the accuracy of reflexive saccades and antisaccades. CONCLUSIONS: The study confirms the existence of different relations between the symptom dimensions of schizophrenia and saccades tasks performances. Saccadic abnormalities were revealed in the clinical (schizophrenia) and pre-clinical (clinical high risk) populations that provide further evidence for assessing saccadic abnormalities as a possible neurobiological marker for schizophrenia.

High risk of near-crash driving events following night-shift work.

Night-shift workers are at high risk of drowsiness-related motor vehicle crashes as a result of circadian disruption and sleep restriction. However, the impact of actual night-shift work on measures of drowsiness and driving performance while operating a real motor vehicle remains unknown. Sixteen night-shift workers completed two 2-h daytime driving sessions on a closed driving track at the Liberty Mutual Research Institute for Safety: (i) a postsleep baseline driving session after an average of 7.6 ± 2.4 h sleep the previous night with no night-shift work, and (ii) a postnight-shift driving session following night-shift work. Physiological measures of drowsiness were collected, including infrared reflectance oculography, electroencephalography, and electrooculography. Driving performance measures included lane excursions, near-crash events, and drives terminated because of failure to maintain control of the vehicle. Eleven near-crashes occurred in 6 of 16 postnight-shift drives (37.5%), and 7 of 16 postnight-shift drives (43.8%) were terminated early for safety reasons, compared with zero near-crashes or early drive terminations during 16 postsleep drives (Fishers exact: P = 0.0088 and P = 0.0034, respectively). Participants had a significantly higher rate of lane excursions, average Johns Drowsiness Scale, blink duration, and number of slow eye movements during postnight-shift drives compared with postsleep drives (3.09/min vs. 1.49/min; 1.71 vs. 0.97; 125 ms vs. 100 ms; 35.8 vs. 19.1; respectively, P < 0.05 for all). Night-shift work increases driver drowsiness, degrading driving performance and increasing the risk of near-crash drive events. With more than 9.5 million Americans working overnight or rotating shifts and one-third of United States commutes exceeding 30 min, these results have implications for traffic and occupational safety.