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A growing body of evidence supports the link between eye movement anomalies and brain health. Indeed, the oculomotor system is composed of a diverse network of cortical and subcortical structures and circuits that are susceptible to a variety of degenerative processes. Here we show preliminary findings from the baseline measurements of an ongoing longitudinal cohort study in MS participants, designed to determine if disease and cognitive status can be estimated and tracked with high accuracy based on eye movement parameters alone. Using a novel gaze-tracking technology that can reliably and accurately track eye movements with good precision without the need for infrared cameras, using only an iPad Pro embedded camera, we show in this cross-sectional study that several eye movement parameters significantly correlated with clinical outcome measures of interest. Eye movement parameters were extracted from fixation, pro-saccade, anti-saccade, and smooth pursuit visual tasks, whereas the clinical outcome measures were the scores of several disease assessment tools and standard cognitive tests such as the Expanded Disability Status Scale (EDSS), Brief International Cognitive Assessment for MS (BICAMS), the Multiple Sclerosis Functional Composite (MSFC) and the Symbol Digit Modalities Test (SDMT). Furthermore, partial least squares regression analyses show that a small set of oculomotor parameters can explain up to 84% of the variance of the clinical outcome measures. Taken together, these findings not only replicate previously known associations between eye movement parameters and clinical scores, this time using a novel mobile-based technology, but also the notion that interrogating the oculomotor system with a novel eye-tracking technology can inform us of disease severity, as well as the cognitive status of MS participants. [ABSTRACT FROM AUTHOR]

The idea that eye movements can reflect certain aspects of brain function and inform on the presence of neurodegeneration is not a new one. Indeed, a growing body of research has shown that several neurodegenerative disorders, such as Alzheimer's and Parkinson's Disease, present characteristic eye movement anomalies and that specific gaze and eye movement parameters correlate with disease severity. The use of detailed eye movement recordings in research and clinical settings, however, has been limited due to the expensive nature and limited scalability of the required equipment. Here we test a novel technology that can track and measure eye movement parameters using the embedded camera of a mobile tablet. We show that using this technology can replicate several wellknown findings regarding oculomotor anomalies in Parkinson's disease (PD), and furthermore show that several parameters significantly correlate with disease severity as assessed with the MDS-UPDRS motor subscale. A logistic regression classifier was able to accurately distinguish PD patients from healthy controls on the basis of six eye movement parameters with a sensitivity of 0.93 and specificity of 0.86. This tablet-based tool has the potential to accelerate eye movement research via affordable and scalable eye-tracking and aid with the identification of disease status and monitoring of disease progression in clinical settings. [ABSTRACT FROM AUTHOR]

About 25 years ago, the discovery of receptive field (RF) remapping in the parietal cortex of nonhuman primates revealed that visual RFs, widely assumed to have a fixed retinotopic organization, can change position before every saccade. Measuring such changes can be deceptively difficult. As a result, studies that followed have generated a fascinating but somewhat confusing picture of the phenomenon. In this review, we describe how observations of RF remapping depend on the spatial and temporal sampling of visual RFs and saccade directions. Further, we summarize some of the theories of how remapping might occur in neural circuitry. Finally, based on neurophysiological and psychophysical observations, we discuss the ways in which remapping information might facilitate computations in downstream brain areas. [ABSTRACT FROM AUTHOR]

During gaze shifts, the eyes and head collaborate to rapidly capture a target (saccade) and fixate it. Accordingly, models of gaze shift control should embed both saccadic and fixation modes and a mechanism for switching between them. We demonstrate a model in which the eye and head platforms are driven by a shared gaze error signal. To limit the number of free parameters, we implement a model reduction approach in which steady-state cerebellar effects at each of their projection sites are lumped with the parameter of that site. The model topology is consistent with anatomy and neurophysiology, and can replicate eye-head responses observed in multiple experimental contexts: 1) observed gaze characteristics across species and subjects can emerge from this structure with minor parametric changes; 2) gaze can move to a goal while in the fixation mode; 3) ocular compensation for head perturbations during saccades could rely on vestibular-only cells in the vestibular nuclei with postulated projections to burst neurons; 4) two nonlinearities suffice, i.e., the experimentally-determined mapping of tectoreticular cells onto brain stem targets and the increased recruitment of the head for larger target eccentricities; 5) the effects of initial conditions on eye/head trajectories are due to neural circuit dynamics, not planning; and 6) "compensatory" ocular slow phases exist even after semicircular canal plugging, because of interconnections linking eye-head circuits. Our model structure also simulates classical vestibulo-ocular reflex and pursuit nystagmus, and provides novel neural circuit and behavioral predictions, notably that both eye-head coordination and segmental limb coordination are possible without trajectory planning. [ABSTRACT FROM AUTHOR]

Psychophysical studies have shown that subjects are often unaware of visual stimuli presented around the time of an eye movement. This saccadic suppression is thought to be a mechanism for maintaining perceptual stability. The brain might accomplish saccadic suppression by reducing the gain of visual responses to specific stimuli or by simply suppressing firing uniformly for all stimuli. Moreover, the suppression might be identical across the visual field or concentrated at specific points. To evaluate these possibilities, we recorded from individual neurons in cortical area V4 of nonhuman primates trained to execute saccadic eye movements. We found that both modes of suppression were evident in the visual responses of these neurons and that the two modes showed different spatial and temporal profiles: while gain changes started earlier and were more widely distributed across visual space, nonspecific suppression was found more often in the peripheral visual field, after the completion of the saccade. Peripheral suppression was also associated with increased noise correlations and stronger local field potential oscillations in the α frequency band. This pattern of results suggests that saccadic suppression shares some of the circuitry responsible for allocating voluntary attention. [ABSTRACT FROM AUTHOR]

Saccades are useful for directing the high-acuity fovea to visual targets that are of behavioral relevance. The selection of visual targets for eye movements involves the superior colliculus (SC), where many neurons respond to visual stimuli. Many of these neurons are also activated before and during saccades of specific directions and amplitudes. Although the role of the SC in controlling eye movements has been thoroughly examined, far less is known about the nature of the visual responses in this area. We have, therefore, recorded from neurons in the intermediate layers of the macaque SC, while using a sparse-noise mapping procedure to obtain a detailed characterization of the spatiotemporal structure of visual receptive fields. We find that SC responses to flashed visual stimuli start roughly 50 ms after the onset of the stimulus and last for on average ∼70 ms. About 50% of these neurons are strongly suppressed by visual stimuli flashed at certain locations flanking the excitatory center, and the spatiotemporal pattern of suppression exerts a predictable influence on the timing of saccades. This suppression may, therefore, contribute to the filtering of distractor stimuli during target selection. We also find that saccades affect the processing of visual stimuli by SC neurons in a manner that is quite similar to the saccadic suppression and postsaccadic enhancement that has been observed in the cortex and in perception. However, in contrast to what has been observed in the cortex, decreased visual sensitivity was generally associated with increased firing rates, while increased sensitivity was associated with decreased firing rates. Overall, these results suggest that the processing of visual stimuli by SC receptive fields can influence oculomotor behavior and that oculomotor signals originating in the SC can shape perisaccadic visual perception. [ABSTRACT FROM AUTHOR]

Humans routinely use coordinated eye-head gaze saccades to rapidly and accurately redirect the line of sight (Land MF. Vis Neurosci 26: 51-62, 2009). With a fixed body, the gaze control system combines visual, vestibular, and neck proprioceptive sensory information and coordinates two moving platforms, the eyes and head. Classic engineering tools have investigated the structure of motor systems by testing their ability to compensate for perturbations. When a reaching movement of the hand is subjected to an unexpected force field of random direction and strength, the trajectory is deviated and its final position is inaccurate. Here, we found that the gaze control system behaves differently. We perturbed horizontal gaze shifts with long-duration torques applied to the head that unpredictably either assisted or opposed head motion and very significantly altered the intended head trajectory. We found, as others have with brief head perturbations, that gaze accuracy was preserved. Unexpectedly, we found also that the eye compensated well--with saccadic and rollback movements--for long-duration head perturbations such that resulting gaze trajectories remained close to that when the head was not perturbed. However, the ocular compensation was best when torques assisted, compared with opposed, head motion. If the vestibuloocular reflex (VOR) is suppressed during gaze shifts, as currently thought, what caused invariant gaze trajectories and accuracy, early eye-direction reversals, and asymmetric compensations? We propose three mechanisms: a gaze feedback loop that generates a gaze-position error signal; a vestibular-to-oculomotor signal that dissociates self-generated from passively imposed head motion; and a saturation element that limits orbital eye excursion. [ABSTRACT FROM AUTHOR]

Our ability to explore our surroundings requires a combination of high-resolution vision and frequent rotations of the visual axis toward objects of interest. Such gaze shifts are themselves a source of powerful retinal stimulation, and so the visual system appears to have evolved mechanisms to maintain perceptual stability during movements of the eyes in space. The mechanisms underlying this perceptual stability can be probed in the laboratory by briefly presenting a stimulus around the time of a saccadic eye movement and asking subjects to report its position. Under such conditions, there is a systematic misperception of the probes toward the saccade end point. This perisaccadic compression of visual space has been the subject of much research, but few studies have attempted to relate it to specific brain mechanisms. Here, we show that the magnitude of perceptual compression for a wide variety of probe stimuli and saccade amplitudes is quantitatively predicted by a simple heuristic model based on the geometry of retinotopic representations in the primate brain. Specifically, we propose that perisaccadic compression is determined by the distance between the probe and saccade end point on a map that has a logarithmic representation of visual space, similar to those found in numerous cortical and subcortical visual structures. Under this assumption, the psychophysical data on perisaccadic compression can be appreciated intuitively by imagining that, around the time of a saccade, the brain confounds nearby oculomotor and sensory signals while attempting to localize the position of objects in visual space. [ABSTRACT FROM AUTHOR]

The superior colliculus (SC) encodes a saccade via the spatial position of an ensemble of active neurons on its motor map. Downstream circuits control muscles with the temporal code of firing frequency and duration. The moving hill hypothesis resolves the SC-tobrainstem spatiotemporal transformation (STT) enigma by proposing feedback to the SC which "pushes" a hill of activity (height = frequency) caudorostrally such that its instantaneous position encodes the angular error [gaze-position error (GPE)] between gaze and target. This mechanism, proposed for cat but controversial in primate, has not been tested in the head-unrestrained monkey. We do this here. During large~60° control gaze shifts in the dark, a hill of activity began in the caudal SC and moved rostrally, but too sluggishly to encode veridical GPE. At gaze end the peak had not reached the rostral pole and only arrived there ~80 ms later. No moving hill accompanied ~20° gaze shifts, in agreement with previous studies of head-fixed monkeys. To investigate feedback to the SC, we perturbed large gaze shifts producing initial and corrective gaze saccades separated by 50-800 ms of gaze immobility, the gaze plateau. Map activity was dramatically remodeled: the sluggishly moving hill stopped during the plateau, at the site encoding the corrective gaze saccade, thereby providing a tonic stationary spatially encoded memory signal of plateau GPE. A burst occurred before the corrective saccade. Conclusion: Feedback to map moves activity which encodes a low-pass filtered GPE signal, a process too slow to implement the STT but adequate for corrective gaze saccades. [ABSTRACT FROM AUTHOR]

Summary: A prominent hypothesis in motor control is that endpoint errors are minimized because motor commands are updated in real time via internal feedback loops. We investigated in monkey whether orienting saccadic gaze shifts made in the dark with coordinated eye-head movements are controlled by feedback. We recorded from superior colliculus fixation neurons (SCFNs) that fired tonically during fixation and were silent during gaze shifts. When we briefly (≤700 ms) interrupted gaze shifts by transiently braking head movements, SCFNs fired steadily during brake-induced gaze immobility, and their mean frequency was inversely related to the remaining distance between current gaze position and the target. After head release, a corrective gaze saccade brought gaze on the unseen goal, and SCFN firing frequency peaked. The results support gaze feedback control and show that the SC is part of a network that encodes, during orientation, the distance between eye and target, irrespective of gaze trajectory characteristics. [Copyright &y& Elsevier]

Rapid coordinated eye- head movements, called saccadic gaze shifts, displace the line of sight from one location to another. A critical structure in the gaze control circuitry is the superior colliculus (SC) of the midbrain, which drives gaze saccades by relaying cortical commands to brainstem eye and head motor circuits. We proposed that the SC lies within a gaze feedback loop and generates an error signal specifying gaze position error (GPE), the distance between target and current gaze positions. We investigated this feedback hypothesis in cats by briefly stopping head motion during large (&asym;50°) gaze saccades made in the dark. This maneuver interrupted intended gaze saccades and briefly immobilized gaze (a plateau). After brake release, a corrective gaze saccade brought the gaze on goal. In the caudal SC, the firing frequency of a cell gradually increased to a maximum that just preceded the optimal gaze saccade encoded by the position of the cell and then declined back to zero near gaze saccade end. In brake trials, the activity level just preceding a brake-induced plateau continued steadily during the plateau and waned to zero only near the end of the corrective saccade. The duration of neural activity was stretched to reflect the increased time to target acquisition, and firing frequency during a plateau was proportional to the GPE of the plateau. In comparison, in the rostral SC, the duration of saccade-related pauses in fixation cell activity increased as plateau duration increased. The data show that the cat's SC lies in a gaze feedback loop and that it encodes GPE. [ABSTRACT FROM AUTHOR]

The superior colliculus (SC) is important for generating coordinated eye-head gaze saccades. Its deeper layers contain a retinotopically organized motor map in which each site is thought to encode a specific gaze saccade vector. Here we show that this fundamental assumption in current models of collicular function does not hold true during horizontal multi-step gaze shifts in darkness that are directed to a goal and composed of a sequence of gaze saccades separated by periods of steady fixation. At the start of a multi-step gaze shift in cats, neural activity on the SC's map was located caudally to encode the overall amplitude of the gaze displacement, not the first saccade in the sequence. As the gaze shift progressed, the locus of activity moved to encode the error between the goal and the current gaze position. Contrary to common belief, the locus of activity never encoded gaze saccade amplitude, except for the last saccade in the sequence. [ABSTRACT FROM AUTHOR]

A visual scene is scrutinized during sequential periods of steady fixation, connected by saccades that shift the visual axis (gaze) to new positions. During such exploratory scan paths, gaze frequently strays from and then returns to salient features. How the brain keeps track of major end-goals and intermediate subgoals is not understood. We studied the discharge of fixation neurons of the brainstem's superior colliculus during multiple-step gaze shifts composed of a sequence of saccades made in the dark and separated by short periods of steady fixation. Cells were initially silent. As sequential gaze saccades approached the goal, firing began; its frequency increased progressively and peaked when gaze was on the remembered target location. We conclude that these fixation neurons encode the error between desired and actual gaze positions, irrespective of trajectory characteristics. [ABSTRACT FROM AUTHOR]

A hallmark of visual expertise is the acquired ability to extract at a glance information that novices can only obtain after careful scrutiny [e.g., Rheingold & Sheridan, 2011]. This expertise has been associated with what psychologists call "chunking": experts perceive larger patterns in a visual stimulus while novices inspect smaller elements individually. The mechanisms by which observers learn this integration is unknown but data suggest an important role for saccadic eye movements. Many neurons in visual cortex are able to integrate information across discrete retinal locations during saccades; a physiological mechanism called remapping because it manifests as a presaccadic shift of a receptive field across visual space [Duhamel et al. 1992]. There is strong psychophysical evidence that human subjects can use remapping to combine information across specific retinal locations, as would be required for the "chunking" of patterns in the image [e.g., Szinte et al. 2016, 2018]. These considerations led us to hypothesize that remapping facilitates the acquisition of visual expertise. To test this idea, we used a paradigm in which observers made saccades while evaluating a motion stimulus at a fixed location in retinal space. Consistent with previous reports on remapping, our observers integrated visual information across saccades. More importantly, through extensive training, observers acquired the ability to integrate such visual information without making saccades; i.e., during fixation. Because these effects are specific to the retinal locations that are involved in remapping, we suggest that remapping could serve as a mechanism for linking together distinct chunks of visual scenes. [ABSTRACT FROM AUTHOR]

Summary A fundamental concept in neuroscience is the receptive field, the area of space over which a neuron gathers information. Until about 25 years ago, visual receptive fields were thought to be determined entirely by the pattern of retinal inputs, so it was quite surprising to find neurons in primate cortex with receptive fields that changed position every time a saccade was executed [1] . Although this discovery has figured prominently into theories of visual perception, there is still much debate about the nature of the phenomenon: Some studies report forward remapping [1–3] , in which receptive fields shift to their postsaccadic locations, and others report convergent remapping , in which receptive fields shift toward the saccade target [4] . These two possibilities can be difficult to distinguish, particularly when the two types of remapping lead to receptive field shifts in similar directions [5] , as was the case in virtually all previous experiments. Here we report new data from neurons in primate cortical area V4, where both types of remapping have previously been reported [3,6] . Using an experimental configuration in which forward and convergent remapping would lead to receptive field shifts in opposite directions, we show that forward remapping is the dominant type of receptive field shift in V4. [ABSTRACT FROM AUTHOR]