Oculomotor Abnormalities in a Sheep (Ovis aries) Model of Huntington's Disease: Towards a Biomarker for Assessing Therapeutic Efficacy.

BACKGROUND: Huntington's disease (HD) is characterized by a loss of control of motor function that causes the presence of abnormal eye movements at early stages. OBJECTIVE: To determine if, compared to normal sheep, HD sheep have abnormal eye movements. METHODS: We measured eye movements in a transgenic sheep (Ovis aries) model of HD using a purpose-built, head-mounted sheep oculometer. This allows us to measure saccades without the need for either behavioral training or head fixation. At the age of testing (6 years old), the HD sheep were pre-manifest. We used 21 sheep (11 HD, 10 normal). RESULTS: We found small but significant differences in eye movements between normal (control) and HD sheep during vestibular ocular reflex (VOR)- and vestibular post-rotational nystagmus (PRN)-based tests. CONCLUSIONS: Two measures were identified that could distinguish normal from HD sheep; the number of PRN oscillations when tested in the dark and the gain (eye movement to head movement ratio) during the VOR when tested in the light. To our knowledge, this is the first study in which eye movements have been quantified in sheep. It demonstrates the feasibility of measuring and quantifying human-relevant eye movements in this species. The HD-relevant deficits show that even in 'premanifest' sheep there are measurable signs of neurological dysfunction that are characterized by loss of control of eye movements.

Vergence eye movements impairments in schizophrenia and bipolar disorder.

One of the most evaluated eye tracking tasks in schizophrenia (SZ) and bipolar disorder (BD) are smooth pursuit eye movements. They rely on the maintenance of slowly moving object on the fovea. While most of the studies evaluated tracking of a target that moves in the fronto-parallel plane, only two assessed vergence eye movements (VEM), which relies on the pursuit of object that moves in depth. The aim of our study was to compare VEM performance in SZ and BD. We evaluated 28 SZ patients, 32 BD patients and 25 healthy controls (HC). Participants underwent thorough optometric examination before eye tracking task. VEM were measured with the use of infrared eye tracker and dedicated vergence stimuli generator. SZ patients showed higher mean break and recovery points of fusion and shorter correct tracking time than HC. BD individuals revealed tracking accuracy deficits and higher number of saccades than HC. Compared to BD, SZ patients showed decrease of maximal convergence and divergence. Moreover, they presented tracking accuracy deficits of non-dominant eye: altered eyes positioning error during convergence and divergence gain. Exploratory analysis revealed significant gender differences between groups in terms of binocular VEM parameters. In this study we have recognized pattern of eye movement disturbances differentiating abovementioned groups. SZ patients showed decreased vergence tracking range with shorter tracking time and impaired accuracy of non-dominant eye, while BD patients showed higher number of saccades with decreased tracking accuracy. Neuroimaging studies are necessary to identify neuronal underpinnings of VEM impairments in SZ and BD.

Vergence eye movements in bipolar disorder. / Ruchy wergencyjne w chorobie afektywnej dwubiegunowej.

OBJECTIVES: With respect to bipolar disorder (BD), previous research have demonstrated saccadic eye movements abnormalities, manifested mainly as an increase in reaction time (latency) in both prosaccadic and antisaccadic task. So far, there were no studies related to vergence eye movements in subjects with BD. Our primary aim was to evaluate vergence tracking performance in this clinical group. METHODS: 30 patients with BD in remission and 23 healthy controls were enrolled. Subjects underwent optometric examination where near point of convergence was measured by the use of Wolff Wand. Instrumented convergence measurements were performed using infrared eye tracker and dedicated vergence stimuli generator. RESULTS: BD patients presented significantly higher average error between eyes' convergence and convergence required to fixate the target and higher number of saccadic intrusions compared with healthy controls group. Principal component analysis performed on oculometric parameters revealed differences between BD patients and healthy controls. Significant correlations between the vergence disturbances and saccadic intrusions were found. CONCLUSIONS: BD patients showed the alterations of the vergence eye movements similar to the disturbances of eye movements in the fronto-parallel plane. While the abnormalities of vergence eye movements in some mental disorders have been reported, we have for the first time objectively measured this phenomenon in BD.

Gap effect and express saccades generation in amblyopia.

Amblyopia is a neurodevelopmental vision disorder that is associated with abnormal visual stimulation during early childhood. Although our knowledge regarding spatial vision deficits in amblyopic subjects is well established, the neural control of eye movements in amblyopia is yet to be explored. In the present study we have evaluated the gap effect, and for the first time (to our best knowledge), express saccades generation in amblyopic (strabismic as well as anisometropic) and age-matched control subjects. We have compared the saccadic latency under different gap conditions ("no gap," 50 ms gap, and 200 ms gap), between the amblyopic and control groups. Our results have shown that saccadic latency was reduced during the gap paradigms both for amblyopic and control groups for all viewing conditions. Furthermore, the size of the gap effect was comparable for all groups and viewing conditions (both for short and long gap durations). In addition, consistent with previous results, the amblyopic eye has manifested an increased saccadic latency as compared to the nondominant eye in the control group. Regarding the occurrence of express saccades, the 200 ms gap condition was associated with an increased number of express saccades as compared to 50 ms gap and "no gap" conditions, both for amblyopic and control subjects. We did not observe any significant difference in terms of express saccades production between the control and amblyopic subjects. Our findings may suggest that amblyopia does not alter physiological mechanisms related to the efficiency of visual attention/fixation disengagement as supported by the observation that the gap effect and express saccades production was comparable between the normal and amblyopic subjects.

Not only amblyopic but also dominant eye in subjects with strabismus show increased saccadic latency.

Amblyopia is a developmental disorder of vision usually associated with the presence of strabismus and/or anisometropia during early childhood. Subject literature has shown that both the amblyopic and fellow eyes (especially in strabismic subjects) may manifest a variety of perceptual and oculomotor deficits. Previous studies using simple saccadic responses (pro-saccades) showed an increased saccadic latency only for the amblyopic eye viewing conditions. So far, there have appeared no saccadic latency studies in strabismic amblyopia for more complex volitional saccades. In order to maximize the contribution of the central retina in the process of saccade initiation, we decided to use delayed saccadic responses in order to test the hypothesis about saccadic latency increase in both eyes in strabismic amblyopes. The results from our study have shown that saccadic latency is increased both in the dominant and amblyopic eyes. In addition, the amblyopic eye in the strabismic group showed greater increase in saccadic latency compared to an amblyopic eye in the anisometropic group from our previous study. The observed increase in saccadic reaction time for the dominant eye is novel and provides further evidence that the visual pathway associated with the dominant eye might be also impaired in strabismic amblyopia. Since an abnormal binocular input during visual system development may affect gaze stability in both eyes, we speculate that unsteady fixation accompanied with subtle perceptual deficits contribute to an increase in saccadic latency that is observed in the dominant eye. Moreover, it appears that the cortical processes related to saccade decisions are delayed both for amblyopic and fellow eyes in strabismic subjects.

Eye movement abnormalities in essential tremor.

Essential tremor (ET) is the most prevalent movement disorder, characterized mainly by an action tremor of the arms. Only a few studies published as yet have assessed oculomotor abnormalities in ET and their results are unequivocal. The aim of this study was to assess the oculomotor abnormalities in ET patients compared with the control group and to find the relationship between oculomotor abnormalities and clinical features of ET patients. We studied 50 ET patients and 42 matched by age and gender healthy controls. Saccadometer Advanced (Ober Consulting, Poland) was used to investigate reflexive, pace-induced and cued saccades and conventional electrooculography for evaluation of smooth pursuit and fixation. The severity of the tremor was assessed by the Clinical Rating Scale for Tremor. Significant differences between ET patients and controls were found for the incidence of reflexive saccades dysmetria and deficit of smooth pursuit. Reflexive saccades dysmetria was more frequent in patients in the second and third phase of ET compared to the first phase. The reflexive saccades latency increase was correlated with severity of the tremor. In conclusion, oculomotor abnormalities were significantly more common in ET patients than in healthy subjects. The most common oculomotor disturbances in ET were reflexive saccades dysmetria and slowing of smooth pursuit. The frequency of reflexive saccades dysmetria increased with progression of ET. The reflexive saccades latency increase was related to the severity of tremor.

The amblyopic eye in subjects with anisometropia show increased saccadic latency in the delayed saccade task.

The term amblyopia is used to describe reduced visual function in one eye (or both eyes, though not so often) which cannot be fully improved by refractive correction and explained by the organic cause observed during regular eye examination. Amblyopia is associated with abnormal visual experience (e.g., anisometropia) during infancy or early childhood. Several studies have shown prolongation of saccadic latency time in amblyopic eye. In our opinion, study of saccadic latency in the context of central vision deficits assessment, should be based on central retina stimulation. For this reason, we proposed saccade delayed task. It requires inhibitory processing for maintaining fixation on the central target until it disappears-what constitutes the GO signal for saccade. The experiment consisted of 100 trials for each eye and was performed under two viewing conditions: monocular amblyopic/non-dominant eye and monocular dominant eye. We examined saccadic latency in 16 subjects (mean age 30 ± 11 years) with anisometropic amblyopia (two subjects had also microtropia) and in 17 control subjects (mean age 28 ± 8 years). Participants were instructed to look at central (fixation) target and when it disappears, to make the saccade toward the periphery (10°) as fast as possible, either left or the right target. The study results have proved the significant difference in saccadic latency between the amblyopic (mean 262 ± 48 ms) and dominant (mean 237 ± 45 ms) eye, in anisometropic group. In the control group, the saccadic latency for dominant (mean 226 ± 32 ms) and non-dominant (mean 230 ± 29 ms) eye was not significantly different. By the use of LATER (Linear Approach to the Threshold with Ergodic Rate) decision model we interpret our findings as a decrease in accumulation of visual information acquired by means of central retina in subjects with anisometropic amblyopia.

Statistical characteristics of finger-tapping data in Huntington's disease.

Measuring the rate of finger tapping is a technique commonly used as an indicator of impairment in degenerative neurological conditions, such as Huntington's disease. The information it provides can be greatly enhanced by analysing not simply the overall tapping rate, but also the statistical characteristics of the individual times between each successive response. Recent technological improvements in the recording equipment allow the responses to be analysed extremely quickly, and permit modification of the task in the interest of greater clinical specificity. Here we illustrate its use with some pilot data from a group of manifest HD patients and age-matched controls. Even in this small cohort, differences in the responses are apparent that appear to relate to the severity of the disease as measured by conventional behavioural tests.

Objective assessment of the hemisphere-specific neurological outcome of carotid endarterectomy: a quantitative saccadometric analysis.

BACKGROUND: Carotid endarterectomy (CEA) improves the cerebrovascular prognosis of patients with carotid stenosis but carries a risk of causing postoperative neurological deterioration. OBJECTIVE: We assessed hemisphere-specific changes in saccadic eye movements to determine the utility of saccadometry as a quantitative neurosurgical outcome measure. METHODS: Visually evoked saccades were recorded at the bedside before and 2 days after surgery from 30 patients undergoing CEA for symptomatic carotid stenosis. Hemisphere-specific latency distributions were compared using Kolmogorov-Smirnov statistics. Latency distributions were fitted using the Linear Approach to Threshold with Ergodic Rate model and compared with binomial logistic regression. RESULTS: There were 21 males and mean age at surgery was 71±7 years. Following CEA, the distribution of saccades initiated by the cerebral hemisphere distal to the operated artery significantly changed in 25 patients. By contrast, there were 14 significant contralateral-hemisphere saccadic changes (P<.001). Significant contralateral saccadic changes always co-occurred with significant ipsilateral changes and 10 of 14 patients with contralateral saccadic change had contralateral carotid stenosis. There was a significantly greater postoperative reduction in early saccades generated by the ipsilateral hemisphere than by the contralateral hemisphere (P<.02) CONCLUSION: CEA leads to significant hemisphere-specific subclinical changes in saccadic performance and, in particular, differentially affects the proportion of early saccades, a measure of the ability of the frontal cortex to successfully inhibit lower centers, generated by the 2 hemispheres. Saccadometry, a bedside test, provides data that can be statistically compared for individual and groups of patients. It could allow the neurological outcome of carotid surgery to be objectively quantified.

Eye motion parameters correlate with level of experience in video-assisted surgery: objective testing of three tasks.

BACKGROUND: Laparoscopic skills vary with experience and training; however, objective measures to ascertain the level of training have not yet been established. New technology allows noninterfering measurement of eye motion parameters that correlate with attention and distraction during visually oriented tasks. Our objective was to apply this new technology in the setting of video-assisted surgery to evaluate eye motion parameters among surgeons of varying experience. MATERIALS AND METHODS: Subjects with various levels of laparoscopic experience (novice, intermediate, and expert) were fitted with a noninvasive, Food and Drug Administration approved, eye motion monitoring device. The device was used to measure and record parameters of eye motion, including saccadic rate (SR), standardized peak velocity (PV), standardized saccadic amplitude (SA), and the duration of gaze fixation (FD), during the performance of 3 basic laparoscopic tasks on a laparoscopic training station. RESULTS: A total of 24 subjects (3 groups of 8 each) participated in this study. Experience level was found to have a main significant effect on SR (P = 0.047) and PV (P = 0.028). Two-way ANOVA demonstrated that experience level approached significance for SA (P = 0.058) and FD (P = 0.055). CONCLUSION: The advancement of laparoscopic techniques and instrumentation relies, in part, on expanding the current understanding of operator/instrument interactions. This places an increasing demand on objective methods of monitoring such interactions during laparoscopy. Our study demonstrates a significant difference in eye motion parameters in surgeons with differing levels of experience. Further testing is needed in actual clinical settings to determine the importance of eye motion during surgery.