Saccade Parameters Research Articles

Reader response: Teaching Video NeuroImages: Vestibulo-ocular reflex defect in cerebellar stroke.

We read with interest the Teaching Video NeuroImage article by Witsch et al.1 The authors stated that abnormal vestibulo-ocular reflex, which cannot be measured by the naked eye, is indirectly implied by way of observing a corrective catch-up saccade. Our group demonstrated with quantitative head impulse test that catch-up saccade can be generated in acute cerebellar stroke, even when the gain of the vestibulo-ocular reflex is not abnormal.2 We suggest, with the widespread availability of portable video head impulse test,3 that abnormal clinical head impulse test should be rapidly confirmed at point of care by measuring both the vestibulo-ocular reflex gain and catch-up saccade parameters.

Modulation of local field potentials and neuronal activity in primate hippocampus during saccades.

Primates use saccades to gather information about objects and their relative spatial arrangement, a process essential for visual perception and memory. It has been proposed that signals linked to saccades reset the phase of local field potential (LFP) oscillations in the hippocampus, providing a temporal window for visual signals to activate neurons in this region and influence memory formation. We investigated this issue by measuring hippocampal LFPs and spikes in two macaques performing different tasks with unconstrained eye movements. We found that LFP phase clustering (PC) in the alpha/beta (8-16 Hz) frequencies followed foveation onsets, while PC in frequencies lower than 8 Hz followed spontaneous saccades, even on a homogeneous background. Saccades to a solid grey background were not followed by increases in local neuronal firing, whereas saccades toward appearing visual stimuli were. Finally, saccade parameters correlated with LFPs phase and amplitude: saccade direction correlated with delta (≤4 Hz) phase, and saccade amplitude with theta (4-8 Hz) power. Our results suggest that signals linked to saccades reach the hippocampus, producing synchronization of delta/theta LFPs without a general activation of local neurons. Moreover, some visual inputs co-occurring with saccades produce LFP synchronization in the alpha/beta bands and elevated neuronal firing. Our findings support the hypothesis that saccade-related signals enact sensory input-dependent plasticity and therefore memory formation in the primate hippocampus.

Saccadic fatigability in the oculomotor system

BackgroundFatigue is one of the most common and disabling symptoms in multiple sclerosis (MS), but challenging to quantify. This prospective study investigated if repeated saccadic eye movements enable measurement of oculomotor fatigability and can reflect on perceived fatigue in MS. MethodsA standardized infrared oculography protocol (DEMoNS) was used for quantifying saccades in MS patients and healthy controls which included a first and a repeated pro-saccadic task (FPT and RPT). Saccadic peak velocity, latency, gain, area under the curve (AUC) and peak velocity divided by amplitude (Pv/Am) were calculated in both tasks. Perception based fatigue was assessed using the Checklist Individual Strength and the Neurological Fatigue Index (NFI). Linear regression models were used for assessing the relation between saccadic parameters and perceived fatigue. ResultsThis study included 181 MS patients and 58 healthy controls subjects. From FPT to RPT, there were significant changes in saccadic parameters. Latency of both tasks was significantly related to NFI summary score (FPT: β = 0.022, p = .049, RPT: β 0.023, p = .021). These relationships were weakened after adjustment for Expanded Disability Status score (p > .05). There was however no significant group difference in changes in saccadic parameters. ConclusionsThis study presents an objective and reproducible method for measuring saccadic fatigability. Saccadic fatigability was found to be of limited use in MS, and should be tested in conditions affecting ocular muscles or the neuromuscular junction.

Measuring attention bias in observers of strabismus subjects

Despite the known negative psychosocial impact and the importance of facial aesthetics for individuals with strabismus, the gaze pattern of the presumed attention bias has not been documented previously. Thirty images (15 digitally reconstructed color photographs to show strabismus and 15 photographs of volunteers without strabismus) were viewed in random order by 25 naïve participants (age range, 23-63years; 15 females). Visual scan paths of participants were recorded using an infrared corneal image eye movement recorder, and the individual parameters of saccades, fixations, and dwell time were assessed using DataViewer software. Viewers primarily tended to fixate on the eyes, the nose was the next most prominent point of focus (both P<0.001). Time to first fixation and the presence of strabismus in the images presented were significantly associated (P<0.001). When the eyes were viewed, there was more time spent looking at the strabismic eye (P<0.001), although the number of fixations toward the eyes did not differ significantly between normal and strabismic faces (P=0.2). Our results confirm that the presence of strabismus in the features of the human face draws longer attention from the average viewer to the eye region, and particularly to the strabismic eye.

Adduction-Abduction Asymmetry in Saccades During Video-Oculographic Monocular Recording: A Word of Caution

ABSTRACTIn eye movement examination, video-oculographic monocular recording has become more popular than electro-oculographic binocular recording. The aim of this study was to examine the characteristics of monocular movements recorded using video-oculography. In 66 healthy subjects, the horizontal saccades and smooth pursuit eye movements of the right eye within a range of 30º were evaluated using a video-oculographic eye movement recording system. Saccade latency, velocity, accuracy, and smooth pursuit gain were measured and analysed by age and direction. Saccade parameters (latency, velocity, and amplitude) and smooth pursuit gain deteriorated with age in healthy subjects. Saccade velocity and accuracy were significantly larger during adduction than during abduction. The smooth pursuit gain did not differ between adduction and abduction. In conclusion, unlike smooth pursuit eye movements, saccadic eye movements have adduction-abduction asymmetry. In video-oculographic monocular recording of saccades, it is necessary to recognise the possibility of the existence of adduction-abduction asymmetry.

Recovery Pattern of High-Frequency Acceleration Vestibulo-Ocular Reflex in Unilateral Vestibular Neuritis: A Preliminary Study.

Objective: To explore the recovery pattern of the high-frequency acceleration vestibulo-ocular reflex (VOR) function in unilateral vestibular neuritis (UVN).Methods: Forty-seven consecutive patients with UVN were recruited within 10 days of symptom onset for this study. The high-frequency acceleration horizontal VOR function was assessed using the video head impulse test (vHIT). Patients returned for follow-up evaluation at ~6 months after the onset of symptoms. According to the dizziness handicap inventory questionnaire (DHI), the patients were classified into the normal to mild dizziness group (DHI score ≤30) and moderate to severe dizziness group (DHI score >30) at the follow-up. All the obtained horizontal vHIT gains and corrective saccades parameters were analyzed.Results: vHIT results showed a significantly horizontal VOR gain recovery in UVN patients at the follow-up on the lesion side (p < 0.01). A significantly reduction in the occurrence of corrective saccades (overt and covert) and velocity of corrective saccades (overt and covert) were observed at the follow-up (p < 0.05). At the follow-up, the normal to mild dizziness group (DHI score ≤30) had a significantly higher normal rate of VOR gain, the mean vHIT gains and occurrence of isolated covert saccades (P < 0.05). Furthermore, the occurrence of mixed saccades and the mean velocity of covert saccades were significantly lower in normal to mild dizziness group (P < 0.05).Conclusion: Apart from the recovery of the VOR gain, recovery pattern of corrective saccades can play a key role in vestibular compensate.

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

Background: Pediatric oculomotor function can be evaluated via videonystagmography. Adult normativedata for saccades and smooth pursuit tests cannot be used as a benchmark for pediatric patientsbecause children’s peripheral and central systems continue to mature throughout adolescence.&lt;br /&gt;Purpose: The purpose of this study was to establish normative data for saccade and smooth pursuit teststhat can be used clinically in the assessment of vestibular and neurological disorders in children, and toinvestigate the effect of age and eye movement direction (left/right) on tests parameters.&lt;br /&gt;Research Design: The present study is prospective cross-sectional study.&lt;br /&gt;Study Sample: A total of 120 healthy children were recruited and equally distributed according to ageand gender to each of the following groups: 5–8, 9–11, 12–14, and 15–17 years old. Participants had topass a comprehensive otological and neurological assessment prior to inclusion in the study. Each subjectunderwent saccade and smooth pursuit testing.&lt;br /&gt;Data Collection and Analysis: Saccade latency, velocity and accuracy/precision, and smooth pursuitgain were analyzed across groups using a two-way repeated measure multivariate analysis of variance(MANOVA).&lt;br /&gt;Results: Saccadic latency was longer in the youngest group aged 5–8 years old (305 ± 48 msec) incomparison 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 theresults 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 from0.63 in children aged 5–8 years old to 0.85 in children aged 15–17 years (P = 0.0001). The percentage ofgain asymmetry was significantly different in the youngest two groups.&lt;br /&gt;Conclusion: Saccade latency decreased as age increased. Smooth pursuit gains increased with increasedage. Saccade velocity and accuracy/precision did not change significantly from ages 5–8 to15–17 years of age. These data provide normative values for pediatric oculomotor evaluation and suggestthat saccade and pursuit pathways may mature at different rates.&lt;br /&gt;

Assessment of Vestibulo-ocular Reflex Gain and Catch-up Saccades During Vestibular Rehabilitation.

To assess, in patients referred to vestibular rehabilitation (VR) for persistence of disability after acute unilateral vestibulopathy (AUV), whether the video head impulse test (vHIT) can be a useful technique to define the efficacy of the treatment. Prospective clinical study. Tertiary academic referral hospitals. Thirty patients with residual symptoms after AUV were included. Patients underwent a 10-week VR program. Evaluation of dizziness handicap inventory score, high-velocity vestibulo-ocular reflex gain, asymmetry index, and catch-up saccade parameters before and after VR. All patients reported a clear clinical improvement after VR, also demonstrated by better dizziness handicap inventory scores (p < 0.001). A consistent increased gain and decreased asymmetry index were also observed (p < 0.001 for both). Patients did not show any change in covert catch-up saccades, while a statistically significant reduction of the number and amplitude of the overt catch-up saccades was interestingly detected (p = 0.009 and p = 0.030, respectively). VR is a valid approach for patients with residual disability after AUV. A reduction in number and amplitude of overt catch-up saccades seems useful to evaluate the efficacy of VR and to be related to clinical improvement.

Using artificial neural networks to identify patients with concussion and postconcussion syndrome based on antisaccades.

Artificial neural networks (ANNs) have shown considerable promise as decision support tools in medicine, including neurosurgery. However, their use in concussion and postconcussion syndrome (PCS) has been limited. The authors explore the value of using an ANN to identify patients with concussion/PCS based on their antisaccade performance. Study participants were prospectively recruited from the emergency department and head injury clinic of a large teaching hospital in Toronto. Acquaintances of study participants were used as controls. Saccades were measured using an automated, portable, head-mounted device preprogrammed with an antisaccade task. Each participant underwent 100 trials of the task and 11 saccade parameters were recorded for each trial. ANN analysis was performed using the MATLAB Neural Network Toolbox, and individual saccade parameters were further explored with receiver operating characteristic (ROC) curves and a logistic regression analysis. Control (n = 15), concussion (n = 32), and PCS (n = 25) groups were matched by age and level of education. The authors examined 11 saccade parameters and found that the prosaccade error rate (p = 0.04) and median antisaccade latency (p = 0.02) were significantly different between control and concussion/PCS groups. When used to distinguish concussion and PCS participants from controls, the neural networks achieved accuracies of 67% and 72%, respectively. This method was unable to distinguish study patients with concussion from those with PCS, suggesting persistence of eye movement abnormalities in patients with PCS. The authors' observations also suggest the potential for improved results with a larger training sample. This study explored the utility of ANNs in the diagnosis of concussion/PCS based on antisaccades. With the use of an ANN, modest accuracy was achieved in a small cohort. In addition, the authors explored the pearls and pitfalls of this novel approach and identified important future directions for this research.

Prodromal Alzheimer's Disease Demonstrates Increased Errors at a Simple and Automated Anti-Saccade Task.

Saccade alterations are potential early signs of Alzheimer's disease. However, uncertainty persists in how early and reliably automated saccade recording systems detect impairments. This multicenter pathophysiological case-control transversal study explored saccade execution in carefully diagnosed amnestic mild cognitive impairment patients fulfilling research criteria for prodromal Alzheimer's disease (n = 29), as compared to both aged-matched mild Alzheimer's disease patients (n = 23) and controls (n = 27). Auto-coded saccades from horizontal (gap) vertical (step) stimulus elicited pro-saccades, and anti-saccade (gap) tasks were compared across the 3 groups. Mild cognitive impairment patients committed significantly more anti-saccade errors compared to controls (46.9 versus 24.3%, p < 0.001). Conventional analyses of the auto-coded stimulus elicited saccades parameters did not distinguish the amnestic mild cognitive impairment from controls or the mild Alzheimer's disease group. However, an offline analysis of manually coded saccade latencies, using resampling statistics did reveal subtle differences among the groups. Analysis of the manually coded data revealed that the mild Alzheimer's disease group had a reliably larger self-corrected error-rate than in amnestic mild cognitive impairment and controls (p = 0.003). Analysis of the manually coded saccade latencies, using more sensitive lognormal bootstrap analysis revealed a continuum, from amnestic mild cognitive impairment to mild Alzheimer's disease, of an increased severity of impaired inhibition of stimulus elicited saccades and correct voluntary saccade initiation. Anti-saccade error rates and psychometric measures of executive and several other cognitive functions were moderately and negatively correlated. Overall, inhibitory impairments in stimulus elicited saccades, characteristic of Alzheimer's disease, may be detected early in presumed prodromal patients using a simple, automated anti-saccade task.

Difference between vertical and horizontal saccades across the human lifespan

The purpose of the study was to analyze vertical saccade parameters (latency, peak velocity, amplitude gain), and compare them to those of horizontal saccades in a cross-sectional study across the ages of the human lifespan. One hundred and thirty one participants (62 males) between the ages of 3 and 86 years made vertical prosaccades of 2–44° in response to a dot stimulus projected on a screen. A subset of participants also made horizontal prosaccades of 2–60° under the same conditions. The El-Mar (Downsview, Ontario, Canada) eye tracker was used to record binocular eye movements. Measures of saccadic latency, peak velocity and amplitude gain were calculated for each participant. Differences between saccade parameters for upward & downward saccades were calculated. Vertical saccade parameters were evaluated as a function of age and age related differences between vertical and horizontal saccade parameters were determined. There was no significant difference between upward and downward saccades and no effect of age for either latency or peak velocity. Downward saccades had significantly higher gains than upward saccades (p = 0.0001) and this difference increased significantly with age (p = 0.001). Vertical saccadic latency initially decreased from about 400 ms at 4 years of age, remained stable for a period of time and then increases again in later life. The lowest peak velocities were found in participants under 20 and over 70 years of age, while the highest peak velocities were seen in participants between 20 and 60 years of age. The majority of vertical saccades were hypometric. Saccadic amplitude gains varied depending on both the stimulus size (p = 0.0001) and age (p = 0.0001) of participants. Vertical saccades are most accurate for small amplitudes and for participants between 20 and 30 years of age. Vertical saccades had significantly longer latencies than horizontal saccades (p = 0.0001) but there was no significant effect of age. Vertical saccades had lower peak velocities than horizontal saccades in very young children but this difference decreased with age (p = 0.0015). Large vertical saccades were more hypometric than their horizontal counterparts across all ages. The observed differences in saccadic parameters could be related to the different areas in the brain used for saccadic generation, different periods and/or mechanisms of development and senescence within the visual system and brain and/or the effects of differential use.

Effect of subthalamic nucleus deep brain stimulation on visual scanning

ObjectiveDeep brain stimulation (DBS) can provide insights into the workings of the basal ganglia (BG) by interfering with their function. In patients with Parkinson's disease (PD) treated with DBS of the subthalamic nucleus, we studied the effect of DBS on scanning eye movements. MethodsIn the visual memory task, subjects viewed images of various complexities for later recall. In visual search tasks, subjects looked for and fixated one odd target ring, embedded among 48 Landolt rings, which either stood out or not from the distractors. We compared the parameters of scanning saccades when DBS was on and off. ResultsIn the visual memory task, DBS increased the amplitude of saccades scanning simple but not complex drawings. In the visual search tasks, DBS showed no effect on saccade amplitude or frequency. ConclusionsSaccades when viewing simple images were affected by DBS since they are internally guided saccades, for which the involvement of BG is large. In contrast, saccades when viewing complex images or during visual search, made with the help of visual cues in the images (externally guided saccades) and less dependent on BG, were resistant to the effect of DBS. SignificanceDBS affects saccades differentially depending on the task.

Changes of video head impulse test results in lateral semicircular canal plane by different peak head velocities in patients with vestibular neuritis

Background: The peak head velocity influences on the video head impulse test (vHIT) results, but it has been not known how much the difference is.Aims: To evaluate the clinical evidence for the superiority of high-velocity compared to low-velocity vHIT.Material and methods: vHIT was performed in 30 patients with vestibular neuritis using two peak head velocities (mean 80 vs. 240°/s). vHIT gains and parameters of corrective saccades (CSs) were compared. A vHIT gain of ≤0.8 or a peak CS velocity of ≥100°/s was considered pathologic.Results: The vHIT gains were significantly lower (mean 0.5 vs. 0.6), and GA was larger (35 vs. 25%) at high-velocity vHIT, compared to low-velocity vHIT. CSs were significantly more frequent (100 vs. 80%) and peak CS velocities were larger (252 vs. 112°/s) at high-velocity vHIT. The abnormal rates based on vHIT gains were higher (90% vs. 73%) and CSs occurred more frequently (100% vs. 80%) at high-velocity vHIT. The abnormal rates based on the peak CS velocity were significantly higher at high-velocity vHIT (100% vs. 57%).Conclusion: High-velocity vHIT is superior to low-velocity vHIT with a difference of 17–20% based on pathologic vHIT gains and presence of CSs.

Neuronal Correlates of Serial Decision-Making in the Supplementary Eye Field.

Human behavior is influenced by serial decision-making: past decisions affect choices that set the context for selecting future options. A primate brain region that may be involved in linking decisions across time is the supplementary eye field (SEF), which, in addition to its well known visual responses and saccade-related activity, also signals the rules that govern flexible decisions and the outcomes of those decisions. Our hypotheses were that SEF neurons encode events during serial decision-making and link the sequential decisions with sustained activity. We recorded from neurons in the SEF of two rhesus monkeys (Macaca mulatta, one male, one female) that performed a serial decision-making task. The monkeys used saccades to select a rule that had to be applied later in the same trial to discriminate between visual stimuli. We found, first, that SEF neurons encoded the spatial parameters of saccades during rule selection but not during visual discrimination, suggesting a malleability to their movement-related tuning. Second, SEF activity linked the sequential decisions of rule selection and visual discrimination, but not continuously. Instead, rule-encoding activity appeared in a "just-in-time" manner before the visual discrimination. Third, SEF neurons encoded trial outcomes both prospectively, before decisions within a trial, and retrospectively, across multiple trials. The results thus identify neuronal correlates of rule selection and application in the SEF, including transient signals that link these sequential decisions. Its activity patterns suggest that the SEF participates in serial decision-making in a contextually dependent manner as part of a broader network.SIGNIFICANCE STATEMENT Much research has gone into studying the neurobiological basis of single, isolated decisions. An important next step is to understand how the brain links multiple decisions to generate a coherent stream of thought and behavior. We studied neural activity related to serial decision-making in an area of frontal cortex known as the supplementary eye field (SEF). Neural recordings were conducted in monkeys that performed a serial decision-making task in which they selected and applied rules. We found that SEF neurons convey signals for serial decision-making, including transient encoding of one decision at the time it is needed for the next one and longer-term representations of trial outcomes, suggesting that the region plays a role in continuity of cognition and behavior.

Estimation of Neural Inputs and Detection of Saccades and Smooth Pursuit Eye Movements by Sparse Bayesian Learning.

Eye movements reveal a great wealth of information about the visual system and the brain. Therefore, eye movements can serve as diagnostic markers for various neurological disorders. For an objective analysis, it is crucial to have an automatic and robust procedure to extract relevant eye movement parameters. An essential step towards this goal is to detect and separate different types of eye movements such as fixations, saccades and smooth pursuit. We have developed a model-based approach to perform signal detection and separation on eye movement recordings, using source separation techniques from sparse Bayesian learning. The key idea is to model the oculomotor system with a state space model and to perform signal separation in the neural domain by estimating sparse inputs which trigger saccades. The algorithm was evaluated on synthetic data, neural recordings from rhesus monkeys and on manually annotated human eye movement recordings with different smooth pursuit paradigms. The developed approach shows a high noise-robustness, provides saccade and smooth pursuit parameters, as well as estimates of the position, velocity and acceleration profiles. In addition, by estimating the input to the oculomotor system, we obtain an estimate of the neural inputs to the oculomotor muscles.

Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits.

Saccadic eye movements are controlled by a network of parietal, frontal, striatal, cerebellar and brainstem regions. The saccadic peak velocity is an established biomarker of benzodiazepine effects, with benzodiazepines reliably reducing the peak velocity. In this study, we aimed to replicate the effects of benzodiazepines on peak velocity and we investigated effects on previously less studied measures of saccades. We also explored the roles of sex, task characteristics and the baseline variables age, intelligence and trait anxiety in these effects. Healthy adults ( N = 34) performed a horizontal step prosaccade task under 1 mg lorazepam, 2 mg lorazepam and placebo in a double-blind, within-subjects design. We replicated the dose-dependent reduction in peak velocity with lorazepam and showed that this effect is stronger for saccades to targets at smaller eccentricities. We also demonstrated that this effect is independent of sex and other baseline variables. Lorazepam effects were widespread, however, occurring on mean and variability measures of most saccadic variables. Additionally, there were sex-dependent lorazepam effects on spatial consistency of saccades, indicating more adverse effects in females. We conclude that saccadic peak velocity is a sensitive and robust biomarker of benzodiazepine effects. However, lorazepam has pronounced effects also on other parameters of horizontal saccades. Sex-dependent drug effects on spatial consistency may reflect cerebellar mechanisms, given the role of the cerebellum in saccadic spatial accuracy.

Binocular advantages for parafoveal processing in reading

During reading, binocular visual input results in superior performance and is particularly important in the pre-processing of parafoveal text prior to direct fixation. It is not yet clear whether binocular vision in the parafovea is necessary for accurate saccadic targeting, or for efficient pre-processing of upcoming text, prior to direct fixation. In the present sentence reading experiment, we used a dichoptic gaze-contingent moving window paradigm in order to establish 1) how much parafoveal binocular input is necessary for fluent reading and 2) which aspect of parafoveal processing is more reliant on binocular vision. Eye movement measures revealed that reading was disrupted unless word N + 1 was entirely binocular in the parafovea, though no additional benefit was observed when word N + 2 was also binocular. Additionally, while fixation durations and reading times were clearly affected by the manipulation, similarly pronounced changes in binocular saccadic parameters such as accuracy, speed, amplitude and velocity were not observed. We concluded that the disruption to reading caused by presenting monocular text to the right of fixation cannot be attributed to difficulties in targeting binocular saccacdes, but instead results from a decreased efficiency in the pre-processing of parafoveal text. These results provide further demonstration for the importance of binocular vision during written text processing.

Personality and individual differences: the potential of using preferences for visual stimuli to predict the Big Five traits

Although personality dimensions figure prominently in what people prefer or like about a display, little is known about precisely how personality dimensions can be predicted through our visual preferences. We investigated the feasibility for predicting continuous dimensions of personality traits (Big Five dimensions) from preferences captured by users’ eye movements while scanning the preferred regions in a visual presentation. The eye-movement behavior of 96 participants was examined to identify their preferences in five visual design presentations. A multi-target learning method was used to build the prediction model of continuous dimensions of personality based on fixation and saccadic eye parameters. The results showed that participants’ preferences for certain visual elements tended to explain their personality profile. Our findings offer new insights for personality assessment, human–computer interaction, personalization, and rational choice theories. It also addresses new trends related to the regulation of eye movements toward regions of interest based on the proportion of personality dimensions.

Heritability of saccadic eye movements in spinocerebellar ataxia type 2: insights into an endophenotype marker

BackgroundSaccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2), nevertheless the heritability of this trait has not been properly demonstrated. Thus the present paper was aimed to assess the heritability of different saccadic parameters in SCA2.MethodsForty-eight SCA2 patients, 25 preclinical carriers and 24 non-SCA2 mutation carriers underwent electronystagmographical assessments of saccadic eye movements as well as neurological examination and ataxia scoring. Estimates of heritability based on the intraclass correlation coefficients were calculated for saccade velocity, accuracy and latency as well as for age at disease onset from 36, 17 and 15 sibling pairs of SCA2 patients, preclinical carriers and controls, respectively.ResultsSaccade velocity was significantly reduced in SCA2 patients and preclinical carriers, whereas decreased saccade accuracy and increased saccade latency were only observed in the patients cohort. Intraclass correlation coefficient for saccade velocity was highly significant in SCA2 patients, estimating a heritability around 94%, whereas for the age at ataxia onset this estimate was around 68%.ConclusionsElectronystagmographical measure of saccade velocity showed higher familial aggregation between SCA2 patients leading the suitability of this disease feature as endophenotype marker, with potential usefulness for the search of modifier genes and neurobiological underpinnings of the disease and as outcome measure in future neuroprotective clinical trials.

Characteristic Eye Movements in Ataxia-Telangiectasia-Like Disorder: An Explanatory Hypothesis.

To investigate cerebellar dysfunctions and quantitatively characterize specific oculomotor changes in ataxia-telangiectasia-like disorder (ATLD), a rare autosomal recessive disease caused by mutations in the MRE11 gene. Additionally, to further elucidate the pathophysiology of cerebellar damage in the ataxia-telangiectasia (AT) spectrum disorders. Saccade dynamics, metrics, and visual fixation deficits were investigated in two Italian adult siblings with genetically confirmed ATLD. Visually guided saccades were compared with those of 40 healthy subjects. Steady fixation was tested in primary and eccentric positions. Quantitative characterization of saccade parameters, saccadic intrusions (SI), and nystagmus was performed. Patients showed abnormally hypermetric and fast horizontal saccades to the left and greater inaccuracy than healthy subjects in all saccadic eye movements. Eye movement abnormalities included slow eye movements that preceded the initial saccade. Horizontal and vertical spontaneous jerk nystagmus, gaze-evoked, and rebound nystagmus were evident. Fixation was interrupted by large square-wave jerk SI and macrosaccadic oscillations. Slow eye movements accompanying saccades, SI, and cerebellar nystagmus are frequently seen in AT patients, additionally our ATLD patients showed the presence of fast and hypermetric saccades suggesting damage of granule cell-parallel fiber-Purkinje cell synapses of the cerebellar vermis. A dual pathogenetic mechanism involving neurodevelopmental and neurodegenerative changes is hypothesized to explain the peculiar phenotype of this disease.