Distinctive features of saccadic intrusions and microsaccades in progressive supranuclear palsy.
ABSTRACT: The eyes do not stay perfectly still during attempted fixation; fixational eye movements and saccadic intrusions (SIs) continuously change the position of gaze. The most common type of SI, square-wave jerks (SWJs), consists of saccade pairs that appear purely horizontal on clinical inspection: the first saccade moves the eye away from the fixation target, and after a short interval, the second saccade brings it back toward the target. SWJs are prevalent in certain neurological disorders, including progressive supranuclear palsy (PSP). Here, we developed an objective method to identify SWJs. We found that SWJs are more frequent, larger, and more markedly horizontal in PSP patients than in healthy human subjects. Furthermore, the loss of a vertical component in fixational saccades and SWJs was the eye movement feature that best distinguished PSP patients from controls. We moreover determined that, in PSP patients and controls, the larger the saccade the more likely it was part of a SWJ. Furthermore, saccades produced by PSP patients had equivalent properties whether they were part of a SWJ or not, suggesting that normal fixational saccades (microsaccades) are rare in PSP. We propose that fixational saccades and SIs are generated by the same neural circuit and that, both in PSP patients and in controls, SWJs result from a coupling mechanism that generates a second corrective saccade shortly after a large fixation saccade. Because of brainstem and/or cerebellum impairment, fixational saccades in PSP are abnormally large and thus more likely to trigger a corrective saccade, giving rise to SWJs.
Project description:Saccadic intrusions (SIs), predominantly horizontal saccades that interrupt accurate fixation, include square-wave jerks (SWJs; the most common type of SI), which consist of an initial saccade away from the fixation target followed, after a short delay, by a return saccade that brings the eye back onto target. SWJs are present in most human subjects, but are prominent by their increased frequency and size in certain parkinsonian disorders and in recessive, hereditary spinocerebellar ataxias. SWJs have been also documented in monkeys with tectal and cerebellar etiologies, but no studies to date have investigated the occurrence of SWJs in healthy nonhuman primates. Here we set out to determine the characteristics of SWJs in healthy rhesus macaques (Macaca mulatta) during attempted fixation of a small visual target. Our results indicate that SWJs are common in healthy nonhuman primates. We moreover found primate SWJs to share many characteristics with human SWJs, including the relationship between the size of a saccade and its likelihood to be part of a SWJ. One main discrepancy between monkey and human SWJs was that monkey SWJs tended to be more vertical than horizontal, whereas human SWJs have a strong horizontal preference. Yet, our combined data indicate that primate and human SWJs play a similar role in fixation correction, suggesting that they share a comparable coupling mechanism at the oculomotor generation level. These findings constrain the potential brain areas and mechanisms underlying the generation of fixational saccades in human and nonhuman primates.
Project description:<h4>Purpose</h4>Fixational saccades shift the foveal image to counteract visual fading related to neural adaptation. Drifts are slow eye movements between two adjacent fixational saccades. We quantified fixational saccades and asked whether their changes could be attributed to pathologic drifts seen in amblyopia, one of the most common causes of blindness in childhood.<h4>Methods</h4>Thirty-six pediatric subjects with varying severity of amblyopia and eleven healthy age-matched controls held their gaze on a visual target. Eye movements were measured with high-resolution video-oculography during fellow eye-viewing and amblyopic eye-viewing conditions. Fixational saccades and drifts were analyzed in the amblyopic and fellow eye and compared with controls.<h4>Results</h4>We found an increase in the amplitude with decreased frequency of fixational saccades in children with amblyopia. These alterations in fixational eye movements correlated with the severity of their amblyopia. There was also an increase in eye position variance during drifts in amblyopes. There was no correlation between the eye position variance or the eye velocity during ocular drifts and the amplitude of subsequent fixational saccade. Our findings suggest that abnormalities in fixational saccades in amblyopia are independent of the ocular drift.<h4>Discussion</h4>This investigation of amblyopia in pediatric age group quantitatively characterizes the fixation instability. Impaired properties of fixational saccades could be the consequence of abnormal processing and reorganization of the visual system in amblyopia. Paucity in the visual feedback during amblyopic eye-viewing condition can attribute to the increased eye position variance and drift velocity.
Project description:Reduced eye velocity and overt or covert compensatory saccades during horizontal head impulse testing are the signs of reduced vestibular function. However, here we report the unusual case of a patient who had enhanced eye velocity during horizontal head impulses followed by a corrective saccade. We term this saccade a "backup saccade" because it acts to compensate for the gaze position error caused by the enhanced velocity (and enhanced VOR gain) and acts to return gaze directly to the fixation target as shown by eye position records. We distinguish backup saccades from overt or covert compensatory saccades or the anticompensatory quick eye movement (ACQEM) of Heuberger et al. (1) ACQEMs are anticompensatory in that they are in the same direction as head velocity and so, act to take gaze off the target and thus require later compensatory (overt) saccades to return gaze to the target. Neither of these responses were found in this patient. The patient here was diagnosed with unilateral definite Meniere's disease (MD) on the right and had enhanced VOR (gain of 1.17) for rightward head impulses followed by backup saccades. For leftwards head impulses eye velocity and VOR gain were in the normal range (VOR gain of 0.89). As further confirmation, testing with 1.84 Hz horizontal sinusoidal head movements in the visual-vestibular (VVOR) paradigm also showed these backup saccades for rightwards head turns but normal slow phase eye velocity responses without backup saccades for leftwards had turns. This evidence shows that backup saccades can be observed in some MD patients who show enhanced eye velocity responses during vHIT and that these backup saccades act to correct for gaze position error caused by the enhanced eye velocity during the head impulse and so have a compensatory effect on gaze stabilization.
Project description:Small saccades occur frequently during fixation, and are coupled to changes in visual stimulation and cognitive state. Neurophysiologically, fixational saccades reflect neural activity near the foveal region of a continuous visuomotor map. It is well known that competitive interactions between neurons within visuomotor maps contribute to target selection for large saccades. Here we asked how such interactions in visuomotor maps shape the rate and direction of small fixational saccades. We measured fixational saccades during periods of prolonged fixation while presenting pairs of visual stimuli (parafoveal: 0.8° eccentricity; peripheral: 5° eccentricity) of various contrasts. Fixational saccade direction was biased toward locations of parafoveal stimuli but not peripheral stimuli, ?100-250ms following stimulus onset. The rate of fixational saccades toward parafoveal stimuli (congruent saccades) increased systematically with parafoveal stimulus contrast, and was suppressed by the simultaneous presentation of a peripheral stimulus. The suppression was best characterized as a combination of two processes: a subtractive suppression of the overall fixational saccade rate and a divisive suppression of the direction bias. These results reveal the nature of suppressive interactions within visuomotor maps and constrain models of the population code for fixational saccades.
Project description:Background and objectives:Slowed and curved rapid eye movements, saccades, are the well-known features of progressive supranuclear palsy (PSP). We hypothesized that the saccades in PSP are not only slow and curved, but they are also irregular and have timing deficits. Methods:We tested this hypothesis in 12 patients with PSP by measuring vertical and horizontal visually guided saccades using a limbus tracker. Results:Both, horizontal and vertical saccades were slow and had irregular trajectory and velocity profiles, but deficits were much more robust in vertical saccades. The irregularity in the saccade velocity was due to premature interruptions that either completely stopped the eyes, or moved the eyes at much slower velocity along or in the opposite direction of the ongoing saccade. The direction of the eyes' trajectory was often changed after the interruption. We simulated a conductance based single-compartment model of the burst neurons embedded in local feedback circuit for saccade generation. This model mimicked anatomical and physiological realism, while allowing the liberty to selectively change the activation of individual burst neurons or the pause neurons. The PSP saccades were comparable to the simulations during reduced activity of the inhibitory and excitatory burst neurons. Conclusion:PSP saccades are due to the paucity in burst generation at the excitatory and imprecise timing signal from the inhibitory burst neurons. Premature discharge of the inhibitory burst neuron further leads to breaks in the saccade trajectory, and maladaptive superior colliculus activity leading to aberrant saccades changing the intended trajectory of the ongoing saccade.
Project description:During steady fixation, observers make small fixational saccades at a rate of around 1-2 per second. Presentation of a visual stimulus triggers a biphasic modulation in fixational saccade rate-an initial inhibition followed by a period of elevated rate and a subsequent return to baseline. Here we show that, during passive viewing, this rate signature is highly sensitive to small changes in stimulus contrast. By training a linear support vector machine to classify trials in which a stimulus is either present or absent, we directly compared the contrast sensitivity of fixational eye movements with individuals' psychophysical judgements. Classification accuracy closely matched psychophysical performance, and predicted individuals' threshold estimates with less bias and overall error than those obtained using specific features of the signature. Performance of the classifier was robust to changes in the training set (novel subjects and/or contrasts) and good prediction accuracy was obtained with a practicable number of trials. Our results indicate a tight coupling between the sensitivity of visual perceptual judgements and fixational eye control mechanisms. This raises the possibility that fixational saccades could provide a novel and objective means of estimating visual contrast sensitivity without the need for observers to make any explicit judgement.
Project description:Even when the body is stationary, the whole retinal image is always in motion by fixational eye movements and saccades that move the eye between fixation points. Accumulating evidence indicates that the brain is equipped with specific mechanisms for compensating for the global motion induced by these eye movements. However, it is not yet fully understood how the retina processes global motion images during eye movements. Here we show that global motion images evoke novel coordinated firing in retinal ganglion cells (GCs). We simultaneously recorded the firing of GCs in the goldfish isolated retina using a multi-electrode array, and classified each GC based on the temporal profile of its receptive field (RF). A moving target that accompanied the global motion (simulating a saccade following a period of fixational eye movements) modulated the RF properties and evoked synchronized and correlated firing among local clusters of the specific GCs. Our findings provide a novel concept for retinal information processing during eye movements.
Project description:An internal model for predictive saccades in frontal cortex was investigated by recording neurons in monkey frontal eye field (FEF) during an inferred motion task. Monkeys were trained to make saccades to the extrapolated position of a small moving target that was rendered temporarily invisible and whose trajectory was altered. On approximately two-thirds of the trials, monkeys made multiple saccades while the target was invisible. Primary saccades were correlated with extrapolated target position. Secondary saccades significantly reduced residual errors resulting from imperfect accuracy of the first saccade. These observations suggest that the second saccade was corrective. Because there was no visual feedback, corrective saccades could only be driven by an internally generated error signal. Neuronal activity in the frontal eye field was directionally tuned before both primary and secondary saccades. Separate subpopulations of cells encoded either saccade direction or direction error before the second saccade. These results suggest that FEF neurons encode the error after the first saccade, as well as the direction of the second saccade. Hence, FEF appears to contribute to detecting and correcting movement errors based on internally generated signals.
Project description:Due to the foveal organization of our visual system we have to constantly move our eyes to gain precise information about our environment. Doing so massively alters the retinal input. This is problematic for the perception of moving objects, because physical motion and retinal motion become decoupled and the brain has to discount the eye movements to recover the speed of moving objects. Two different types of eye movements, pursuit and saccades, are combined for tracking. We investigated how the way we track moving targets can affect the perceived target speed. We found that the execution of corrective saccades during pursuit initiation modifies how fast the target is perceived compared with pure pursuit. When participants executed a forward (catch-up) saccade they perceived the target to be moving faster. When they executed a backward saccade they perceived the target to be moving more slowly. Variations in pursuit velocity without corrective saccades did not affect perceptual judgments. We present a model for these effects, assuming that the eye velocity signal for small corrective saccades gets integrated with the retinal velocity signal during pursuit. In our model, the execution of corrective saccades modulates the integration of these two signals by giving less weight to the retinal information around the time of corrective saccades.
Project description:<b>Background:</b> Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that, especially in the early stages of the disease, is clinically difficult to distinguish from Parkinson's disease (PD). <b>Objective:</b> This study aimed at assessing the use of eye-tracking in head-mounted displays (HMDs) for differentiating PSP and PD. <b>Methods:</b> Saccadic eye movements of 13 patients with PSP, 15 patients with PD, and a group of 16 healthy controls (HCs) were measured. To improve applicability in an inpatient setting and standardize the diagnosis, all the tests were conducted in a HMD. In addition, patients underwent atlas-based volumetric analysis of various brain regions based on high-resolution MRI. <b>Results:</b> Patients with PSP displayed unique abnormalities in vertical saccade velocity and saccade gain, while horizontal saccades were less affected. A novel diagnostic index was derived, multiplying the ratios of vertical to horizontal gain and velocity, allowing segregation of PSP from PD with high sensitivity (10/13, 77%) and specificity (14/15, 93%). As expected, patients with PSP as compared with patients with PD showed regional atrophy in midbrain volume, the midbrain plane, and the midbrain tegmentum plane. In addition, we found for the first time that oculomotor measures (vertical gain, velocity, and the diagnostic index) were correlated significantly to midbrain volume in the PSP group. <b>Conclusions:</b> Assessing eye movements in a HMD provides an easy to apply and highly standardized tool to differentiate PSP of patients from PD and HCs, which will aid in the diagnosis of PSP.