Ocular Motor Abnormalities in Anti-IgLON5 Disease

ObjectiveAnti-IgLON5 disease forms an interface between neuroinflammation and neurodegeneration and includes clinical phenotypes that are often similar to those of neurodegenerative diseases. An early diagnosis of patients with anti-IgLON5 disease and differentiation from neurodegenerative diseases is necessary and may have therapeutic implications.MethodsIn our small sample size study we investigated oculomotor function as a differentiating factor between anti-IgLON5 disease and neurodegenerative disorders. We examined ocular motor and vestibular function in four patients suffering from anti-IgLON5 disease using video-oculography (VOG) and a computer-controlled rotational chair system (sampling rate 60 Hz) and compared the data with those from ten age-matched patients suffering from progressive supranuclear palsy (PSP) and healthy controls (CON).ResultsPatients suffering from anti-IgLON5 disease differed from PSP most strikingly in terms of saccade velocity and accuracy, the presence of square wave jerks (SWJ) (anti-IgLON5 0/4 vs. PSP 9/10) and the clinical finding of supranuclear gaze palsy (anti-IgLON5 1/4). The presence of nystagmus, analysis of smooth pursuit eye movements, VOR and VOR suppression was reliable to differentiate between the two disease entities. Clear differences in all parameters, although not always significant, were found between all patients and CON.DiscussionWe conclude that the use of VOG as a tool for clinical neurophysiological assessment can be helpful in differentiating between patients with PSP and patients with anti-IgLON5 disease. VOG could have particular value in patients with suspected PSP and lack of typical Parkinson’s characteristics. future trials are indispensable to assess the potential of oculomotor function as a biomarker in anti-IgLON5 disease.

Eye Movement Abnormalities in Major Depressive Disorder

Background: Despite their high lifetime prevalence, major depressive disorder (MDD) is often difficult to diagnose, and there is a need for useful biomarkers for the diagnosis of MDD. Eye movements are considered a non-invasive potential biomarker for the diagnosis of psychiatric disorders such as schizophrenia. However, eye movement deficits in MDD remain unclear. Thus, we evaluated detailed eye movement measurements to validate its usefulness as a biomarker in MDD.Methods: Eye movements were recorded from 37 patients with MDD and 400 healthy controls (HCs) using the same system at five University hospitals. We administered free-viewing, fixation stability, and smooth pursuit tests, and obtained 35 eye movement measurements. We performed analyses of covariance with group as an independent variable and age as a covariate. In 4 out of 35 measurements with significant group-by-age interactions, we evaluated aging effects. Discriminant analysis and receiver operating characteristic (ROC) analysis were conducted.Results: In the free-viewing test, scanpath length was significantly shorter in MDD (p = 4.2 × 10−3). In the smooth pursuit test, duration of saccades was significantly shorter and peak saccade velocity was significantly lower in MDD (p = 3.7 × 10−3, p = 3.9 × 10−3, respectively). In the fixation stability test, there were no significant group differences. There were significant group differences in the older cohort, but not in the younger cohort, for the number of fixations, duration of fixation, number of saccades, and fixation density in the free-viewing test. A discriminant analysis using scanpath length in the free-viewing test and peak saccade velocity in the smooth pursuit showed MDD could be distinguished from HCs with 72.1% accuracy. In the ROC analysis, the area under the curve was 0.76 (standard error = 0.05, p = 1.2 × 10−7, 95% confidence interval = 0.67–0.85).Conclusion: These results suggest that detailed eye movement tests can assist in differentiating MDD from HCs, especially in older subjects.

Bilateral control of interceptive saccades: evidence from the ipsipulsion of vertical saccades after caudal fastigial inactivation

The caudal fastigial nuclei (cFN) are the output nuclei by which the medio-posterior cerebellum influences the production of saccades toward a visual target. On the basis of the organization of their efferences to the premotor burst neurons and the bilateral control of saccades, the hypothesis was proposed that the same unbalanced activity accounts for the dysmetria of all saccades during cFN unilateral inactivation, regardless of whether the saccade is horizontal, oblique, or vertical. We further tested this hypothesis by studying, in two head-restrained macaques, the effects of unilaterally inactivating the caudal fastigial nucleus on saccades toward a target moving vertically with a constant, increasing or decreasing speed. After local muscimol injection, vertical saccades were deviated horizontally toward the injected side with a magnitude that increased with saccade size. The ipsipulsion indeed depended upon the tested target speed, but not its instantaneous value because it did not increase (decrease) when the target accelerated (decelerated). By subtracting the effect on contralesional horizontal saccades from the effect on ipsilesional ones, we found that the net bilateral effect on horizontal saccades was strongly correlated with the effect on vertical saccades. We explain how this correlation corroborates the bilateral hypothesis and provide arguments against the suggestion that instantaneous saccade velocity would somehow be "encoded" by the discharge of Purkinje cells in the oculomotor vermis.

Diagnostic value of video-oculography in progressive supranuclear palsy: a controlled study in 100 patients

Background The eponymous feature of progressive supranuclear palsy (PSP) is oculomotor impairment which is one of the relevant domains in the Movement Disorder Society diagnostic criteria. Objective We aimed to investigate the value of specific video-oculographic parameters for the use as diagnostic markers in PSP. Methods An analysis of video-oculography recordings of 100 PSP patients and 49 age-matched healthy control subjects was performed. Gain of smooth pursuit eye movement and latency, gain, peak eye velocity, asymmetry of downward and upward velocities of saccades as well as rate of saccadic intrusions were analyzed. Results Vertical saccade velocity and saccadic intrusions allowed for the classification of about 70% and 56% of the patients, respectively. By combining both parameters, almost 80% of the PSP patients were covered, while vertical velocity asymmetry was observed in approximately 34%. All parameters had a specificity of above 95%. The sensitivities were lower with around 50–60% for the velocity and saccadic intrusions and only 27% for vertical asymmetry. Conclusions In accordance with oculomotor features in the current PSP diagnostic criteria, video-oculographic assessment of vertical saccade velocity and saccadic intrusions resulted in very high specificity. Asymmetry of vertical saccade velocities, in the opposite, did not prove to be useful for diagnostic purposes.

A velocity plan with internal feedback control best explains modulation of saccade kinematics during eye-hand coordination

ABSTRACTFast movements like saccadic eye movements that occur in the absence of sensory feedback are often thought to be under internal feedback control. In this framework, a desired input in the form of desired displacement signal is widely believed to be encoded in a spatial map of the superior colliculus (SC). This is then converted into a dynamic velocity signal that drives the oculomotor neurons. However, recent evidence has shown the presence of a dynamic signal within SC neurons, which correlates with saccade velocity. Hence, we used models based on optimal control theory to test whether saccadic execution could be achieved by a velocity based internal feedback controller. We compared the ability of a trajectory control model based on velocity to that of an endpoint control model based on final displacement to capture saccade behavior of modulation of peak saccade velocity by the hand movement, independent of the saccade amplitude. The trajectory control model tracking the desired velocity in optimal feedback control framework predicted this saccade velocity modulation better than an endpoint control model. These results suggest that the saccadic system has the flexibility to incorporate a velocity plan based internal feedback control that is imposed by task context.NEW & NOTEWORTHYWe show that the saccade generation system may use an explicit velocity tracking controller when demand arises. Modulation of peak saccade velocity due to modulation of the velocity of the accompanying hand movement was better captured using a velocity tracking stochastic optimal control model compared to an endpoint model of saccade control. This is the first evidence of trajectory planning and control for the saccadic system based on optimal control theory.

EEG signals index a global signature of arousal embedded in neuronal population recordings

Electroencephalography (EEG) has long been used to index brain states, from early studies describing activity during visual stimulation to modern work employing complex perceptual tasks. These studies shed light on brain-wide signals but lacked explanatory power at the single neuron level. Similarly, single neuron studies can suffer from inability to measure brain-wide signals. Here, we combined these techniques while monkeys performed a change detection task and discovered a link between EEG and a signal embedded in spiking responses. This ‘slow drift’ was associated with arousal: decreases in pre-stimulus α power/increases in P1 amplitude were accompanied by :1) increases in pupil size, false alarm rate and saccade velocity; and 2) decreases in microsaccade rate and reaction time. These results show that brain-wide EEG signals can be used to index modes of activity acquired from direct neural recordings, that in turn reflect global changes in brain state that influence perception and behavior.

Exploring the Cognitive Load of Expert and Novice Map Users Using EEG and Eye Tracking

The main objective of this research is to explore the cognitive processes of expert and novice map users during the retrieval of map-related information, within varying difficulty levels (i.e., easy, moderate, hard), by using eye tracking and electroencephalogram (EEG). In this context, we present a spatial memory experiment consisting of a large number of stimuli to study the effect of task difficulty on map users’ behavior through cognitive load measurements. Next to the reaction time and success rate, we used fixation and saccade related eye tracking metrics (i.e., average fixation duration, the number of fixations per second, saccade amplitude and saccade velocity), and EEG power spectrum (i.e., event-related changes in alpha and theta frequency bands) to identify the cognitive load. While fixation metrics indicated no statistically significant difference between experts and novices, saccade metrics proved the otherwise. EEG power spectral density analysis, on the other side, suggested an increase in theta (i.e., event-related synchronization) and a decrease in alpha (except moderate tasks) (i.e., event-related desynchronization) at all difficulty levels of the task for both experts and novices, which is an indicator of cognitive load. Although no significant difference emerged between two groups, we found a significant difference in their overall performances when the participants were classified as good and relatively bad learners. Triangulating EEG results with the recorded eye tracking data and the qualitative analysis of focus maps indeed provided a detailed insight on the differences of the individuals’ cognitive processes during this spatial memory task.

Does ‘Action Viewing’ Really Exist? Perceived Dynamism and Viewing Behaviour

Throughout the 20th century, there have been many different forms of abstract painting. While works by some artists, e.g., Piet Mondrian, are usually described as static, others are described as dynamic, such as Jackson Pollock’s ‘action paintings’. Art historians have assumed that beholders not only conceptualise such differences in depicted dynamics but also mirror these in their viewing behaviour. In an interdisciplinary eye-tracking study, we tested this concept through investigating both the localisation of fixations (polyfocal viewing) and the average duration of fixations as well as saccade velocity, duration and path curvature. We showed 30 different abstract paintings to 40 participants — 20 laypeople and 20 experts (art students) — and used self-reporting to investigate the perceived dynamism of each painting and its relationship with (a) the average number and duration of fixations, (b) the average number, duration and velocity of saccades as well as the amplitude and curvature area of saccade paths, and (c) pleasantness and familiarity ratings. We found that the average number of fixations and saccades, saccade velocity, and pleasantness ratings increase with an increase in perceived dynamism ratings. Meanwhile the saccade duration decreased with an increase in perceived dynamism. Additionally, the analysis showed that experts gave higher dynamic ratings compared to laypeople and were more familiar with the artworks. These results indicate that there is a correlation between perceived dynamism in abstract painting and viewing behaviour — something that has long been assumed by art historians but had never been empirically supported.

A dynamic, imperturbable link between midbrain activity and saccade velocity

We make a saccadic eye movement once every few hundred milliseconds; however, the neural control of saccade execution is not fully understood. Dynamic, moment-by-moment variations in saccade velocity are typically thought to be controlled by neurons in the lower, but not the upper regions of the brainstem. In a recent report, Smalianchuk et al. (Smalianchuk I, Jagadisan UK, Gandhi NJ. J Neurosci 38: 10156–10167, 2018) provided strong evidence for a role of the superior colliculus, a midbrain structure, in the instantaneous control of saccade velocity, suggesting the revision of long-standing models of oculomotor control.