133 The Effects of Chronic Sleep Restriction on Human Oculomotor Behavior

Introduction Oculomotor behavioral metrics change according to time awake and circadian phase following a distinct pattern of impairment. Acute sleep deprivation (ASD) causes large decreases in pursuit initiation and steady-state gain, and a compensatory increase in saccadic rate without any systematic change in saccadic size. It also causes large deficits in visual processing of direction and speed, and impaired saccade dynamics. Such deterioration likely reflects changes in both higher cortical and brainstem function, explaining in-part how sleep loss and circadian misalignment affect cognition. It is unclear how oculomotor behavior might change according to chronic sleep restriction (CSR). Here, we measured the same eye-movement metrics during CSR. Methods Twelve healthy participants (6 females) kept a fixed wake-time sleep-wake schedule, at home for four weeks (weeks 1 and 3 = 9h time in bed (TIB); weeks 2 and 4 randomized to 5h or 9h TIB; actigraphy confirmed). Following weeks two and four, participants completed a 13-hour laboratory visit under dim light (<15 lux), where they maintained a semi-recumbent posture and were provided with hourly isocaloric snacks. A visual tracking task was performed hourly to assess pursuit and saccadic responses and visual motion processing. Performance metrics were computed using MATLAB, including pursuit gain (eye speed/target speed), the rate and amplitude of catch-up saccades, and the accuracy and precision of direction and speed processing. Results As expected, we found a small but significant (t(11)=-2.17, p<0.03) reduction in pursuit gain (mean+/-SEM: -0.028 +/-0.013 with a large (t(11)=2.96, p<0.01) increase in saccadic rate (0.37 +/-0.13 Hz). However, surprisingly, we found a significant (t(11)=-2.52, p<0.03) decrease in the amplitude of catch-up saccades (-0.15 +/-0.06 deg). The only systematic alteration to visual motion processing was a small reduction in horizontal-vertical asymmetry, which was previously observed with ASD. Conclusion A week of CSR to 5h is associated with only mild impairment in smooth pursuit eye movements with little impact on visual motion processing. However, CSR caused a maladaptive decrease in saccade amplitude that was not observed during ASD. Eye-movement metrics reveal differential neurological effects of CSR versus ASD. Support (if any) Force Health Protection Program, ONR (SAA2402925-1), NASA Human Research Program, and agreement NNX17AE07A

Improvement of Pursuit Eye Movement Alterations after Short Visuo-Attentional Training in ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder without validated and objective diagnostic procedures. Several neurological dysfunctions in the frontal circuit, in the thalamus, and in the cerebellum have been observed in subjects with ADHD. These cortical and subcortical areas are responsible for eye movement control. Therefore, studying eye movements could be a useful tool to better understand neuronal alterations in subjects with ADHD. The aim of the present study was firstly to compare the quality of pursuit eye movements in a group of 40 children with ADHD (age 8.2 ± 1.2) and in a group of 40 sex-, IQ-, age-matched typically developing (TD) children; secondly, we aimed to examine if a short visuo-attentional training could affect pursuit performances in children with ADHD. Findings showed that children with ADHD presented a greater number of catch-up saccade and lower pursuit gain compared to TD children. Differently to TD children, in children with ADHD, the number of catch-up saccades and the pursuit gain were not significantly correlated with children’s age. Furthermore, a short visuo-attentional training period can only slightly improve pursuit performance in children with ADHD, leading to a decrease of the occurrence of catch-up saccades only, albeit the effect size was small. The absence of any improvement in pursuit performance with age could be explained by the fact that the prefrontal and fronto-cerebellar circuits responsible for pursuit triggering are still immature. Pursuit eye movements can be used as a useful tool for ADHD diagnosis. However, attentional mechanisms controlled by these cortical structures could be improved by a short visuo-attentional training period. Further studies will be necessary to explore the effects of a longer visuo-attentional training period on oculomotor tasks in order to clarify how adaptive mechanisms are able to increase the attentional capabilities in children with ADHD.

Ocular motor biomarkers in Niemann-Pick disease type C: A prospective cross-sectional multicontinental study in 72 patients

Niemann-Pick type C (NPC) is a rare lysosomal storage disorder with ocular motor involvement. In a multi-continental cross-sectional study we characterized ocular motor function in 72 patients from twelve countries by means of video-oculography. We also searched for ocular motor biomarkers interlinking with disease severity. Study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in both planes. 158 healthy controls acted as data comparison. The Modified Disability Rating Scale, Scale for Assessment and Rating of Ataxia, Spinocerebellar Ataxia Functional Index, and Montreal Cognitive Assessment were also performed. In contrast to previous publications and the common belief that the downward saccadic system degenerates to greater extent than the upward one, our measurements of vertical saccades demonstrated that the involvement in both directions was similar. Mean saccadic peak velocity to 20 deg stimulus was 63.5 deg/s (SD, 95% CIs of the mean: 59.5, [47.9-79.2]) in NPC patients and 403.1 deg/s (69.0, [392.0-414.2 deg/s]) in healthy subjects (p<0.001). Downward saccades yielded 51 deg/s (68.9, [32.7-69.3]), whilst upward 78.8 deg/s (65.9, [60.8-96.8]) (p<0.001). Vertical position smooth pursuit gain was 0.649 (0.33, [0.554-0.744]) in NPC and 0.935 (0.149 [0.91-0.959]) in HC (p<0.001). The number of patient-specific saccadic patterns, incl. slow-pursuit like, hypometric and staircase-pattern saccades suggest varying involvement of the saccadic system with fragmentation of the velocity profile as a sign of omnipause neuron dysfunction. Observed compensating strategies, such as blinks to elicit saccades, head and upper body movements to overcome the gaze palsy, should be used clinically to establish a diagnosis. Vertical reflexive saccades were more impaired and slower than self-paced ones. Ocular motor performance depended on age of onset and disease duration. We found that peak velocity and latency of horizontal saccades, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials, as they showed the strongest correlation to disease severity. By comparing saccadic with pursuit movements, we showed that 98.2% of patients generated vertical saccades (both up and down) that were below the 95% confidence intervals of the controls peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% of healthy controls. Vertical supranuclear saccade palsy and not vertical supranuclear gaze palsy is the hallmark of NPC disease. The distinction between saccadic and gaze palsy is also important in other neurodegenerative diseases and inborn errors of metabolism with ocular motor involvement, such as progressive supranuclear palsy or Gaucher disease type 3.

Eye, head, and gaze contributions to smooth pursuit in macular degeneration

This article is the first to look at eye and head movements in observers with macular degeneration. It is the first to show that in older individuals, regardless of central field defect, freedom of head movement may reduce pursuit gain. Despite oculomotor limitations due to eccentric fixation, individuals with macular degeneration do not rely on head movements more than age-matched controls, with both groups having a similarly heterogenous eye and head movement strategy for pursuit.

Normative Values of Saccades and Smooth Pursuit in Children Aged 5 to 17 Years

Background Pediatric oculomotor function can be evaluated via videonystagmography. Adult normative data for saccades and smooth pursuit tests cannot be used as a benchmark for pediatric patients because children's peripheral and central systems continue to mature throughout adolescence. Purpose The purpose of this study was to establish normative data for saccade and smooth pursuit tests that can be used clinically in the assessment of vestibular and neurological disorders in children, and to investigate the effect of age and eye movement direction (left/right) on tests parameters. Research Design The present study is prospective cross-sectional study. Study Sample A total of 120 healthy children were recruited and equally distributed according to age and gender to each of the following groups: 5-8, 9-11, 12-14, and 15-17 years old. Participants had to pass a comprehensive otological and neurological assessment prior to inclusion in the study. Each subject underwent saccade and smooth pursuit testing. Data Collection and Analysis Saccade latency, velocity and accuracy/precision, and smooth pursuit gain were analyzed across groups using a two-way repeated measure multivariate analysis of variance (MANOVA). Results Saccadic latency was longer in the youngest group aged 5-8 years old (305 ± 48 msec) in comparison to children aged 9-11 years old (276 ± 22 msec) (P = 0.017), 12-14 years old (252 ± 34 msec) (P = 0.001) adolescents 15-17 years (256 ± 33 msec) (P = 0.001). Age did not affect the results of saccadic velocity and accuracy/precision. Saccade parameters (latency, velocity, accuracy/ precision) were not affected by oculomotor direction (left vs. right). Smooth pursuit gain increased from 0.63 in children aged 5-8 years old to 0.85 in children aged 15-17 years (P = 0.0001). The percentage of gain asymmetry was significantly different in the youngest two groups. Conclusion Saccade latency decreased as age increased. Smooth pursuit gains increased with increased age. Saccade velocity and accuracy/precision did not change significantly from ages 5-8 to 15-17 years of age. These data provide normative values for pediatric oculomotor evaluation and suggest that saccade and pursuit pathways may mature at different rates.

Eye movement evaluation in Multiple Sclerosis and Parkinson’s Disease using a Standardized Oculomotor and Neuro-ophthalmic Disorder Assessment (SONDA)

Evaluating the state of the oculomotor system of a patient is one of the fundamental tests done in neuro-ophthalmology. However, up to date, very few quantitative standardized tests of eye movements quality exist, limiting this assessment to confrontational tests reliant on subjective interpretation. Furthermore, quantitative tests relying on eye movement properties such as pursuit gain and saccade dynamics are often insufficient to capture the complexity of the underlying disorders and are often (too) long and tiring. In this study, we present SONDA (Standardised Oculomotor and Neurological Disorder Assessment): this test is based on analyzing eye tracking recorded during a short and intuitive continuous tracking task. We tested patients affected by Multiple Sclerosis (MS) and Parkinson’s Disease (PD) and find that: (1) the saccadic dynamics of the main sequence alone are not sufficient to separate patients from healthy controls; (2) the combination of spatio-temporal and statistical properties of saccades and saccadic dynamics enables an identification of oculomotor abnormalities in both MS and PD patients. We conclude that SONDA constitutes a powerful screening tool that allows an in-depth evaluation of (deviant) oculomotor behavior in a few minutes of non-invasive testing.

Oculomotor Assessment in Children

Oculomotor evaluation as part of videonystagmography is an integral tool in the assessment of vestibular function providing a global assessment of the neurological pathways associated with oculomotor function. The value of an oculomotor evaluation for pediatric evaluation is well established; however, many questions can also arise with the application to the pediatric population. Oculomotor function is age dependent which can have a significant effect on the test results obtain in children. The underlying neural substrates and age effects are discussed across the literature with specific results from recent research using clinical oculomotor equipment and protocols. The evidence suggests there are several key differences in the pediatric population compared with adults. These include longer saccade latencies, reduced smooth pursuit gain, increased optokinetic asymmetry, increased variability in all responses, and increased artifact in saccade and smooth pursuit testing.

Role of motor execution in the ocular tracking of self-generated movements

When human observers track the movements of their own hand with their gaze, the eyes can start moving before the finger (i.e., anticipatory smooth pursuit). The signals driving anticipation could come from motor commands during finger motor execution or from motor intention and decision processes associated with self-initiated movements. For the present study, we built a mechanical device that could move a visual target either in the same direction as the participant's hand or in the opposite direction. Gaze pursuit of the target showed stronger anticipation if it moved in the same direction as the hand compared with the opposite direction, as evidenced by decreased pursuit latency, increased positional lead of the eye relative to target, increased pursuit gain, decreased saccade rate, and decreased delay at the movement reversal. Some degree of anticipation occurred for incongruent pursuit, indicating that there is a role for higher-level movement prediction in pursuit anticipation. The fact that anticipation was larger when target and finger moved in the same direction provides evidence for a direct coupling between finger and eye motor commands.