Istradefylline Improves Impaired Smooth Pursuit Eye Movements in Parkinson's Disease.

INTRODUCTION: Patients with Parkinson's disease (PD) exhibit alterations in eye movement control, primarily diverse oculomotor deficits which include hypometric saccade and impaired smooth pursuit with reduced pursuit-gain necessitating catch-up saccades. The effects of dopaminergic treatment of PD on eye movements are controversial. Previous studies suggest that smooth pursuit eye movements (SPEMs) are not directly influenced by the dopaminergic system. The nondopaminergic drug istradefylline, a selective adenosine A2A receptor antagonist, reduces the OFF time and improves somatomotor function in levodopa-treated PD. Here, we investigated whether istradefylline improves SPEMs in PD, and determined whether oculomotor performance is associated with somatomotor performance. METHODS: Using an infrared video eye tracking system, we quantified horizontal SPEMs in six patients with PD before and 4-8 weeks after initiation of istradefylline administration. A further five patients with PD were tested before and after a 4-week interval without istradefylline to control for practice effects. We evaluated smooth pursuit gain (eye velocity/target velocity), accuracy of smooth pursuit velocity, and saccade rate during pursuit before and after istradefylline administration during the ON state. RESULTS: Patients received istradefylline by single daily oral administration at 20 to 40 mg. Eye tracking data were obtained 4-8 weeks after initiation of istradefylline administration. Istradefylline increased smooth pursuit gain and the accuracy of smooth pursuit velocity, and tended to decrease saccade rates during pursuit. CONCLUSIONS: Istradefylline ameliorated the oculomotor deficit in SPEM of patients with PD, although differences in somatomotor performance before and after istradefylline treatment were not significant during ON periods. The discrepancy observed between the oculomotor and somatomotor responses to istradefylline supports previous findings that SPEM is at least partially under nondopaminergic control.

The Effects of Different Kinds of Smooth Pursuit Exercises on Center of Pressure and Muscle Activities during One Leg Standing.

This study examined the effects of gaze fixation and different kinds of smooth-pursuit eye movements on the trunk and lower extremity muscle activities and center of pressure. METHODS: Twenty-four subjects were selected for the study. The activity of trunk and lower limb muscles (tibialis anterior, lateral gastrocnemius, medial gastrocnemius, vastus midialis obliques, vastus lateralis, biceps femoris, rectus abdominis, and erector spinae) and the COP (center of pressure) (surface area ellipse, length, and average speed) were measured to observe the effects of gaze fixation and different kinds of smooth-pursuit eye movements on the center of pressure and muscle activities during one leg standing. Before the experiment, a Gaze point GP3 HD Eye Tracker (Gazept, Vancouver, BC, Canada) was used to train eye movement so that the subjects would be familiar with smooth eye movement. Repeated each exercise 3 times at random. In order to avoid the sequence deviation caused by fatigue, the movement sequence is randomly selected. RESULT: The center of pressure and muscle activities were increased significantly when the smooth-pursuit eye movement with one leg standing compared with gaze fixation with one leg standing. In smooth-pursuit eye movements, the changes in the center of pressure and muscle activities were increased significantly with eye and head movement. When the head and eyes moved in opposite directions, the center of pressure and muscle activities were increased more than with any other exercises. CONCLUSION: Smooth-pursuit eye movement with one leg movement affects balance. In particular, in the smooth-pursuit eye movement with one leg standing, there were higher requirements for balance when the eyes and head move in the opposite direction. Therefore, this movement can be recommended to people who need to enhance their balance ability.

Bedside video-oculographic evaluation of eye movements in acute supratentorial stroke patients: A potential biomarker for hemispatial neglect.

BACKGROUND AND PURPOSE: The presence of hemispatial neglect adversely affects functional outcomes in stroke patients; consequently, it warrants early targeted rehabilitative intervention. Nevertheless, hemispatial neglect in the acute phase of stroke has often been underdiagnosed. In this study, we aimed to detect hemispatial neglect at the bedside in acute stroke patients by measuring eye movements using video-oculography (VOG). METHODS: Forty-seven patients with acute unilateral supratentorial stroke were enrolled. We quantitatively measured horizontal saccade (latency, velocity, and amplitude) and smooth pursuit (gain) at the bedside using VOG and compared these variables with scores on the Behavioral Inattention Test (BIT), a screening battery to assess hemispatial neglect. RESULTS: Contralesional saccade latency, velocity, and amplitude, and ipsilesional smooth pursuit gain were suppressed compared with those in the opposite directions (p = 0.08, 0.02, 0.04, and 0.02, respectively). These directional ocular hypokinesia values correlated with the total BIT score (correlation coefficients -0.53, 0.48, 0.51, and 0.39, respectively). The association was significant even after adjusting for age and stroke severity. CONCLUSIONS: Eye movement measurements performed using VOG significantly correlated with the tendency for hemispatial neglect in acute supratentorial stroke patients. Bedside VOG measurement may be a simple biomarker for detecting hemispatial neglect even in patients in the supine position during the acute phase of stroke.

A passive BCI for monitoring the intentionality of the gaze-based moving object selection.

Objective.The use of an electroencephalogram (EEG) anticipation-related component, the expectancy wave (E-wave), in brain-machine interaction was proposed more than 50 years ago. This possibility was not explored for decades, but recently it was shown that voluntary attempts to select items using eye fixations, but not spontaneous eye fixations, are accompanied by the E-wave. Thus, the use of the E-wave detection was proposed for the enhancement of gaze interaction technology, which has a strong need for a mean to decide if a gaze behavior is voluntary or not. Here, we attempted at estimating whether this approach can be used in the context of moving object selection through smooth pursuit eye movements.Approach.Eighteen participants selected, one by one, items which moved on a computer screen, by gazing at them. In separate runs, the participants performed tasks not related to voluntary selection but also provoking smooth pursuit. A low-cost consumer-grade eye tracker was used for item selection.Main results.A component resembling the E-wave was found in the averaged EEG segments time-locked to voluntary selection events of every participant. Linear discriminant analysis with shrinkage regularization classified the intentional and spontaneous smooth pursuit eye movements, using single-trial 300 ms long EEG segments, significantly above chance in eight participants. When the classifier output was averaged over ten subsequent data segments, median group ROC AUC of 0.75 was achieved.Significance.The results suggest the possible usefulness of the E-wave detection in the gaze-based selection of moving items, e.g. in video games. This technique might be more effective when trial data can be averaged, thus it could be considered for use in passive interfaces, for example, in estimating the degree of the user's involvement during gaze-based interaction.

Properties of smooth pursuit adaptation induced by theta motion.

Current study attempted to determine whether repeated smooth pursuit trials using theta motion, in which the directions of retinal image-motion and object-motion are opposed, yield pursuit adaptation. Adaptation trials consisted of 350 step-ramp trials using theta motion, and pre- and post-trials using first-order motion were conducted. As a result, initial acceleration in post-adaptation increased significantly than pre-adaptation trials. This was the case even though there was no adaptive change throughout adaptation (350 trials) using theta motion. Our results suggest that smooth pursuit could adapt to theta motion even with challenges associated with opposite retinal slip.

Following Forrest Gump: Smooth pursuit related brain activation during free movie viewing.

Most fMRI studies investigating smooth pursuit (SP) related brain activity have used simple synthetic stimuli such as a sinusoidally moving dot. However, real-life situations are much more complex and SP does not occur in isolation but within sequences of saccades and fixations. This raises the question whether the same brain networks for SP that have been identified under laboratory conditions are activated when following moving objects in a movie. Here, we used the publicly available studyforrest data set that provides eye movement recordings along with 3 â€‹T fMRI recordings from 15 subjects while watching the Hollywood movie "Forrest Gump". All three major eye movement events, namely fixations, saccades, and smooth pursuit, were detected with a state-of-the-art algorithm. In our analysis, smooth pursuit (SP) was the eye movement of interest, while saccades were acting as the steady state of viewing behaviour due to their lower variability. For the fMRI analysis we used an event-related design modelling saccades and SP as regressors initially. Because of the interdependency of SP and content motion, we then added a new low-level content motion regressor to separate brain activations from these two sources. We identified higher BOLD-responses during SP than saccades bilaterally in MT+/V5, in middle cingulate extending to precuneus, and in the right temporoparietal junction. When the motion regressor was added, SP showed higher BOLD-response relative to saccades bilaterally in the cortex lining the superior temporal sulcus, precuneus, and supplementary eye field, presumably due to a confounding effect of background motion. Only parts of V2 showed higher activation during saccades in comparison to SP. Taken together, our approach should be regarded as proof of principle for deciphering brain activity related to SP, which is one of the most prominent eye movements besides saccades, in complex dynamic naturalistic situations.

Quantitative comparison of a mobile and a stationary video-based eye-tracker.

Vision represents the most important sense of primates. To understand visual processing, various different methods are employed-for example, electrophysiology, psychophysics, or eye-tracking. For the latter method, researchers have recently begun to step outside the artificial environments of laboratory setups toward the more natural conditions we usually face in the real world. To get a better understanding of the advantages and limitations of modern mobile eye-trackers, we quantitatively compared one of the most advanced mobile eye-trackers available, the EyeSeeCam, with a commonly used laboratory eye-tracker, the EyeLink II, serving as a gold standard. We aimed to investigate whether or not fully mobile eye-trackers are capable of providing data that would be adequate for direct comparisons with data recorded by stationary eye-trackers. Therefore, we recorded three different, commonly used eye movements-fixations, saccades, and smooth-pursuit eye movements-with both eye-trackers, in successive standardized paradigms in a laboratory setting with eight human subjects. Despite major technical differences between the devices, most eye movement parameters were not statistically different between the two systems. Differences could only be found in overall gaze accuracy and for time-critical parameters such as saccade duration, for which a higher sample frequency is especially useful. Although the stationary EyeLink II system proved to be superior, especially on a single-subject or even a single-trial basis, the ESC showed similar performance for the averaged parameters across both trials and subjects. We concluded that modern mobile eye-trackers are well-suited to providing reliable oculomotor data at the required spatial and temporal resolutions.

Motion direction representation in multivariate electroencephalography activity for smooth pursuit eye movements.

Visually-guided smooth pursuit eye movements are composed of initial open-loop and later steady-state periods. Feedforward sensory information dominates the motor behavior during the open-loop pursuit, and a more complex feedback loop regulates the steady-state pursuit. To understand the neural representations of motion direction during open-loop and steady-state smooth pursuits, we recorded electroencephalography (EEG) responses from human observers while they tracked random-dot kinematograms as pursuit targets. We estimated population direction tuning curves from multivariate EEG activity using an inverted encoding model. We found significant direction tuning curves as early as about 60 ms from stimulus onset. Direction tuning responses were generalized to later times during the open-loop smooth pursuit, but they became more dynamic during the later steady-state pursuit. The encoding quality of retinal motion direction information estimated from the early direction tuning curves was predictive of trial-by-trial variation in initial pursuit directions. These results suggest that the movement directions of open-loop smooth pursuit are guided by the representation of the retinal motion present in the multivariate EEG activity.

Motion integration is anisotropic during smooth pursuit eye movements.

Smooth pursuit eye movements (pursuit) are used to minimize the retinal motion of moving objects. During pursuit, the pattern of motion on the retina carries not only information about the object movement but also reafferent information about the eye movement itself. The latter arises from the retinal flow of the stationary world in the direction opposite to the eye movement. To extract the global direction of motion of the tracked object and stationary world, the visual system needs to integrate ambiguous local motion measurements (i.e., the aperture problem). Unlike the tracked object, the stationary world's global motion is entirely determined by the eye movement and thus can be approximately derived from motor commands sent to the eye (i.e., from an efference copy). Because retinal motion opposite to the eye movement is dominant during pursuit, different motion integration mechanisms might be used for retinal motion in the same direction and opposite to pursuit. To investigate motion integration during pursuit, we tested direction discrimination of a brief change in global object motion. The global motion stimulus was a circular array of small static apertures within which one-dimensional gratings moved. We found increased coherence thresholds and a qualitatively different reflexive ocular tracking for global motion opposite to pursuit. Both effects suggest reduced sampling of motion opposite to pursuit, which results in an impaired ability to extract coherence in motion signals in the reafferent direction. We suggest that anisotropic motion integration is an adaptation to asymmetric retinal motion patterns experienced during pursuit eye movements. NEW & NOTEWORTHY This study provides a new understanding of how the visual system achieves coherent perception of an object's motion while the eyes themselves are moving. The visual system integrates local motion measurements to create a coherent percept of object motion. An analysis of perceptual judgments and reflexive eye movements to a brief change in an object's global motion confirms that the visual and oculomotor systems pick fewer samples to extract global motion opposite to the eye movement.

Modulation of Complex-Spike Duration and Probability during Cerebellar Motor Learning in Visually Guided Smooth-Pursuit Eye Movements of Monkeys.

Activation of an inferior olivary neuron powerfully excites Purkinje cells via its climbing fiber input and triggers a characteristic high-frequency burst, known as the complex spike (CS). The theory of cerebellar learning postulates that the CS induces long-lasting depression of the strength of synapses from active parallel fibers onto Purkinje cells, and that synaptic depression leads to changes in behavior. Prior reports showed that a CS on one learning trial is linked to a properly timed depression of simple spikes on the subsequent trial, as well as a learned change in pursuit eye movement. Further, the duration of a CS is a graded instruction for single-trial plasticity and behavioral learning. We now show across multiple learning paradigms that both the probability and duration of CS responses are correlated with the magnitudes of neural and behavioral learning in awake behaving monkeys. When the direction of the instruction for learning repeatedly was in the same direction or alternated directions, the duration and probability of CS responses decreased over a learning block along with the magnitude of trial-over-trial neural learning. When the direction of the instruction was randomized, CS duration, CS probability, and neural and behavioral learning remained stable across time. In contrast to depression, potentiation of simple-spike firing rate for ON-direction learning instructions follows a longer time course and plays a larger role as depression wanes. Computational analysis provides a model that accounts fully for the detailed statistics of a complex set of data.

The Roles of Non-retinotopic Motions in Visual Search.

In visual search, a moving target among stationary distracters is detected more rapidly and more efficiently than a static target among moving distracters. Here we examined how this search asymmetry depends on motion signals from three distinct coordinate systems-retinal, relative, and spatiotopic (head/body-centered). Our search display consisted of a target element, distracters elements, and a fixation point tracked by observers. Each element was composed of a spatial carrier grating windowed by a Gaussian envelope, and the motions of carriers, windows, and fixation were manipulated independently and used in various combinations to decouple the respective effects of motion coordinate systems on visual search asymmetry. We found that retinal motion hardly contributes to reaction times and search slopes but that relative and spatiotopic motions contribute to them substantially. Results highlight the important roles of non-retinotopic motions for guiding observer attention in visual search.

Bedside evaluation of smooth pursuit eye movements in acute sensory stroke patients.

BACKGROUND AND PURPOSE: Unilateral saccadic pursuit is reported to be suggestive of a pontine lesion in sensory stroke patients. We attempted to verify this eye sign in just-hospitalized pontine sensory stroke patients. METHODS: Horizontal smooth pursuit eye movements were evaluated upon hospital arrival in 4 pontine sensory stroke patients and were compared with those in 6 thalamic sensory stroke patients. Eye movements were evaluated with the patient lying down on the emergency room or stroke care unit bed by means of a newly developed video-oculography-based eye movement recording system equipped to project a moving laser pointer onto the ceiling. RESULTS: Laterality of horizontal smooth pursuit gain in pontine sensory stroke patients was evident upon arrival; in thalamic sensory stroke patients, horizontal smooth pursuit gain was equal in both directions. These characteristics were easily detected at bedside. CONCLUSION: Unilateral saccadic pursuit in pontine sensory stroke patients may be a practical diagnostic sign that can be detected even in the emergency room. The video-oculography-based recording system equipped to project a moving laser pointer onto the ceiling may be useful for detecting this eye sign.

Role of plasticity at different sites across the time course of cerebellar motor learning.

Learning comprises multiple components that probably involve cellular and synaptic plasticity at multiple sites. Different neural sites may play their largest roles at different times during behavioral learning. We have used motor learning in smooth pursuit eye movements of monkeys to determine how and when different components of learning occur in a known cerebellar circuit. The earliest learning occurs when one climbing-fiber response to a learning instruction causes simple-spike firing rate of Purkinje cells in the floccular complex of the cerebellum to be depressed transiently at the time of the instruction on the next trial. Trial-over-trial depression and the associated learning in eye movement are forgotten in <6 s, but facilitate long-term behavioral learning over a time scale of ∼5 min. During 100 repetitions of a learning instruction, simple-spike firing rate becomes progressively depressed in Purkinje cells that receive climbing-fiber inputs from the instruction. In Purkinje cells that prefer the opposite direction of pursuit and therefore do not receive climbing-fiber inputs related to the instruction, simple-spike responses undergo potentiation, but more weakly and more slowly. Analysis of the relationship between the learned changes in simple-spike firing and learning in eye velocity suggests an orderly progression of plasticity: first on Purkinje cells with complex-spike (CS) responses to the instruction, later on Purkinje cells with CS responses to the opposite direction of instruction, and last in sites outside the cerebellar cortex. Climbing-fiber inputs appear to play a fast and primary, but nonexclusive, role in pursuit learning.

Smooth pursuit eye movement, prepulse inhibition, and auditory paired stimuli processing endophenotypes across the schizophrenia-bipolar disorder psychosis dimension.

BACKGROUND: This study examined smooth pursuit eye movement (SPEM), prepulse inhibition (PPI), and auditory event-related potentials (ERP) to paired stimuli as putative endophenotypes of psychosis across the schizophrenia-bipolar disorder dimension. METHODS: Sixty-four schizophrenia probands (SZP), 40 psychotic bipolar I disorder probands (BDP), 31 relatives of SZP (SZR), 26 relatives of BDP (BDR), and 53 healthy controls (HC) were tested. Standard clinical characterization, SPEM, PPI, and ERP measures were administered. RESULTS: There were no differences between either SZP and BDP or SZR and BDR on any of the SPEM, PPI, or ERP measure. Compared with HC, SZP and BDP had lower SPEM maintenance and predictive pursuit gain and ERP theta/alpha and beta magnitudes to the initial stimulus. PPI did not differ between the psychosis probands and HC. Compared with HC, SZR and BDR had lower predictive pursuit gain and ERP theta/alpha and beta magnitudes to the first stimulus with differences ranging from a significant to a trend level. Neither active symptoms severity nor concomitant medications were associated with neurophysiological outcomes. SPEM, PPI, and ERP scores had low intercorrelations. CONCLUSION: These findings support SPEM predictive pursuit and lower frequency auditory ERP activity in a paired stimuli paradigm as putative endophenotypes of psychosis common to SZ and BD probands and relatives. PPI did not differ between the psychosis probands and HC. Future studies in larger scale psychosis family samples targeting putative psychosis endophenotypes and underlying molecular and genetic mediators may aid in the development of biology-based diagnostic definitions.

Illusory position shift induced by motion within a moving envelope during smooth-pursuit eye movements.

The static envelope of a Gabor patch with a moving carrier appears to shift in the direction of the carrier motion; this phenomenon is known as the motion-induced position shift (De Valois & De Valois, 1991; Ramachandran & Anstis, 1990). This conventional stimulus configuration contains at least three covarying factors: the retinal carrier velocity, the environmental carrier velocity, and the carrier velocity relative to the envelope velocity, which happens to be zero. We manipulated these velocities independently to identify which is critical, and we measured the perceived position of the moving Gabor patch relative to a reference stimulus moving in the same direction at the same speed. In the first experiment, the position of the moving envelope observed with fixation appeared to shift in the direction of the carrier velocity relative to the envelope velocity. Furthermore, the illusion was more pronounced when the carrier moved in a direction opposite to that of the envelope. In the second and third experiments, we measured the illusion during smooth-pursuit eye movement in which the envelope was either static or moving, thereby dissociating retinal and environmental velocities. Under all conditions, the illusion occurred according to the envelope-relative velocity of the carrier. Additionally, the illusion was more pronounced when the carrier and envelope moved in opposite directions. We conclude that the carrier's envelope-relative velocity is the primary determinant of the motion-induced position shift.