Evidence from comprehensive independent validation studies for smooth pursuit dysfunction as a sensorimotor biomarker for psychosis.

Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Here, we studied quantifiable sensorimotor measures derived from smooth pursuit eye movements in a large sample of psychosis probands (N = 674) and healthy controls (N = 305) using multivariate pattern analysis. Balanced accuracies of 64% for the prediction of psychosis status are in line with recent results from other large heterogenous psychiatric samples. They are confirmed by external validation in independent large samples including probands with (1) psychosis (N = 727) versus healthy controls (N = 292), (2) psychotic (N = 49) and non-psychotic bipolar disorder (N = 36), and (3) non-psychotic affective disorders (N = 119) and psychosis (N = 51) yielding accuracies of 65%, 66% and 58%, respectively, albeit slightly different psychosis syndromes. Our findings make a significant contribution to the identification of biologically defined profiles of heterogeneous psychosis syndromes on an individual level underlining the impact of sensorimotor dysfunction in psychosis.

Limb articulation of biological motion can induce illusory motion perception during self-motion.

When one walks toward a crowd of pedestrians, dealing with their biological motion while controlling one's own self-motion is a difficult perceptual task. Limb articulation of a walker is naturally coupled to the walker's translation through the scene and allows the separation of optic flow generated by self-motion from the biological motion of other pedestrians. Recent research has shown that if limb articulation and translation mismatch, such as for walking in place, self-motion perception becomes biased. This bias may reflect an illusory motion attributed to the pedestrian crowd from the articulation of their limbs. To investigate this hypothesis, we presented observers with a simulation of forward self-motion toward a laterally moving crowd of point-light walkers and asked them to report the perceived lateral speed of the crowd. To investigate the dependence of the crowd speed percept on biological motion, we also included conditions in which the points of the walker were spatially scrambled to destroy body form and limb articulation. We observed illusory crowd speed percepts that were related to the articulation rate of the biological motion. Scrambled walkers also produced illusory motion but it was not related to articulation rate. We conclude that limb articulation induces percepts of crowd motion that can be used for interpreting self-motion toward crowds.

Modulation of reaching by spatial attention.

Attention is needed to perform goal-directed vision-guided movements. We investigated whether the direction of covert attention modulates movement outcomes and dynamics. Right-handed and left-handed volunteers attended to a spatial location while planning a reach toward the same hemifield, the opposite one, or planned a reach without constraining attention. We measured behavioral variables as outcomes of ipsilateral and contralateral reaching and the tangling of behavioral trajectories obtained through principal component analysis as a measure of the dynamics of motor control. We found that the direction of covert attention had significant effects on the dynamics of motor control, specifically during contralateral reaching. Data suggest that motor control was more feedback-driven when attention was directed leftward than when attention was directed rightward or when it was not constrained, irrespectively of handedness. These results may help to better understand the neural bases of asymmetrical neurological diseases like hemispatial neglect.

Oculomotor behavior can be adjusted on the basis of artificial feedback signals indicating externally caused errors.

Whether a saccade is accurate and has reached the target cannot be evaluated during its execution, but relies on post-saccadic feedback. If the eye has missed the target object, a secondary corrective saccade has to be made to align the fovea with the target. If a systematic post-saccadic error occurs, adaptive changes to the oculomotor behavior are made, such as shortening or lengthening the saccade amplitude. Systematic post-saccadic errors are typically attributed internally to erroneous motor commands. The corresponding adaptive changes to the motor command reduce the error and the need for secondary corrective saccades, and, in doing so, restore accuracy and efficiency. However, adaptive changes to the oculomotor behavior also occur if a change in saccade amplitude is beneficial for task performance, or if it is rewarded. Oculomotor learning thus is more complex than reducing a post-saccadic position error. In the current study, we used a novel oculomotor learning paradigm and investigated whether human participants are able to adapt their oculomotor behavior to improve task performance even when they attribute the error externally. The task was to indicate the intended target object among several objects to a simulated human-machine interface by making eye movements. The participants were informed that the system itself could make errors. The decoding process depended on a distorted landing point of the saccade, resulting in decoding errors. Two different types of visual feedback were added to the post-saccadic scene and we compared how participants used the different feedback types to adjust their oculomotor behavior to avoid errors. We found that task performance improved over time, regardless of the type of feedback. Thus, error feedback from the simulated human-machine interface was used for post-saccadic error evaluation. This indicates that 1) artificial visual feedback signals and 2) externally caused errors might drive adaptive changes to oculomotor behavior.

Eye and head movements in visual search in the extended field of view.

In natural environments, head movements are required to search for objects outside the field of view (FoV). Here we investigate the power of a salient target in an extended visual search array to facilitate faster detection once this item comes into the FoV by a head movement. We conducted two virtual reality experiments using spatially clustered sets of stimuli to observe target detection and head and eye movements during visual search. Participants completed search tasks with three conditions: (1) target in the initial FoV, (2) head movement needed to bring the target into the FoV, (3) same as condition 2 but the periphery was initially hidden and appeared after the head movement had brought the location of the target set into the FoV. We measured search time until participants found a more salient (O) or less salient (T) target among distractors (L). On average O's were found faster than T's. Gaze analysis showed that saliency facilitation occurred due to the target guiding the search only if it was within the initial FoV. When targets required a head movement to enter the FoV, participants followed the same search strategy as in trials without a visible target in the periphery. Moreover, faster search times for salient targets were only caused by the time required to find the target once the target set was reached. This suggests that the effect of stimulus saliency differs between visual search on fixed displays and when we are actively searching through an extended visual field.

Illusory percepts of curvilinear self-motion when moving through crowds.

Self-motion generates optic flow, a pattern of expanding visual motion. Heading estimation from optic flow analysis is accurate in rigid environments, but it becomes challenging when other human walkers introduce independent motion to the scene. Previous studies showed that heading perception is surprisingly accurate when moving through a crowd of walkers but revealed strong heading biases when either articulation or translation of biological motion were presented in isolation. We hypothesized that these biases resulted from misperceiving the self-motion as curvilinear. Such errors might manifest as opposite biases depending on whether the observer perceived the crowd motion as indication of his/her self-translation or self-rotation. Our study investigated the link between heading biases and illusory path perception. Participants assessed heading and path perception while observing optic flow stimuli with varying walker movements. Self-motion perception was accurate during natural locomotion (articulation and translation), but significant heading biases occurred when walkers only articulated or translated. In this case, participants often reported a curved path of travel. Heading error and curvature pointed in opposite directions. On average, participants perceived the walker motion as evidence for viewpoint rotation leading to curvilinear path percepts.

Eyeball translations affect saccadic eye movements beyond brainstem control.

Vision requires that we rotate our eyes frequently to look at informative structures in the scene. Eye movements are planned by the brain but their execution depends on the mechanical properties of the oculomotor plant, that is, the arrangement of eyeball position, muscle insertions, and pulley locations. Therefore, the biomechanics of rotations is sensitive to eyeball translation because it changes muscle levers. Eyeball translations are little researched as they are difficult to measure with conventional techniques. Here, we investigated the effects of eyeball translation on the coordination of eyeball rotation by high-speed MRI recordings of saccadic eye movements during blinks, which are known to produce strong translations. We found that saccades during blinks massively overshoot their targets and that these overshoots occur in a transient fashion such that the gaze is back on target at the time the blink ends. These dynamic overshoots were tightly coupled to the eyeball translation, both in time and in size. Saccades made without blinks were also accompanied by small amounts of transient eyeball retraction, the size of which scaled with saccade amplitude. These findings demonstrate a complex combination of rotation and translation of the eye. The mechanical consequences of eyeball translation on oculomotor control should be considered along with the neural implementation in the brainstem to understand the generation of eye movements and their disorders.NEW & NOTEWORTHY We found that saccades during blinks can massively overshoot their target when the eyeball is retracted. Our data imply that the overshoots are not part of the saccade plan prepared in the brainstem, but instead a consequence of the altered biomechanics resulting from concurrent eyeball translation and rotation. To our best knowledge, this is the first direct observation of dynamic properties of the oculomotor plant altering the execution of rotational eye movements.

A triple distinction of cerebellar function for oculomotor learning and fatigue compensation.

The cerebellum implements error-based motor learning via synaptic gain adaptation of an inverse model, i.e. the mapping of a spatial movement goal onto a motor command. Recently, we modeled the motor and perceptual changes during learning of saccadic eye movements, showing that learning is actually a threefold process. Besides motor recalibration of (1) the inverse model, learning also comprises perceptual recalibration of (2) the visuospatial target map and (3) of a forward dynamics model that estimates the saccade size from corollary discharge. Yet, the site of perceptual recalibration remains unclear. Here we dissociate cerebellar contributions to the three stages of learning by modeling the learning data of eight cerebellar patients and eight healthy controls. Results showed that cerebellar pathology restrains short-term recalibration of the inverse model while the forward dynamics model is well informed about the reduced saccade change. Adaptation of the visuospatial target map trended in learning direction only in control subjects, yet without reaching significance. Moreover, some patients showed a tendency for uncompensated oculomotor fatigue caused by insufficient upregulation of saccade duration. According to our model, this could induce long-term perceptual compensation, consistent with the overestimation of target eccentricity found in the patients' baseline data. We conclude that the cerebellum mediates short-term adaptation of the inverse model, especially by control of saccade duration, while the forward dynamics model was not affected by cerebellar pathology.

Fine-scale measurement of the blind spot borders.

The blind spot is both a necessity and a nuisance for seeing. It is the portion of the visual field projecting to where the optic nerve crosses the retina, a region devoid of photoreceptors and hence visual input. The precise way in which vision transitions into blindness at the blind spot border is to date unknown. A chief challenge to map this transition is the incessant movement of the eye, which unavoidably smears measurements across space. In this study, we used high-resolution eye-tracking and state-of-the-art retinal stabilization to finely map the blind spot borders. Participants reported the onset of tiny high-contrast probes that were briefly flashed at precise positions around the blind spot. This method has sufficient resolution to enable mapping of blood vessels from psychophysical measurements. Our data show that, even after accounting for eye movements, the transition zones at the edges of the blind spot are considerable. On the horizontal meridian, the regions with detection rates between 80% and 20% span approximately 25% of the overall width of the blind spot. These borders also vary considerably in size across different axes. These data show that the transition from full visibility to blindness at the blind spot border is not abrupt but occurs over a broad area.

Adaptive changes to saccade amplitude and target localization do not require pre-saccadic target visibility.

The accuracy of saccadic eye movements is maintained by saccadic adaptation, a learning mechanism that is proposed to rely on visual prediction error, i.e., a mismatch between the pre-saccadically predicted and post-saccadically experienced position of the saccade target. However, recent research indicates that saccadic adaptation might be driven by postdictive motor error, i.e., a retrospective estimation of the pre-saccadic target position based on the post-saccadic image. We investigated whether oculomotor behavior can be adapted based on post-saccadic target information alone. We measured eye movements and localization judgements as participants aimed saccades at an initially invisible target, which was always shown only after the saccade. Each such trial was followed by either a pre- or a post-saccadic localization trial. The target position was fixed for the first 100 trials of the experiment and, during the following 200 trials, successively shifted inward or outward. Saccade amplitude and the pre- and post-saccadic localization judgements adjusted to the changing target position. Our results suggest that post-saccadic information is sufficient to induce error-reducing adaptive changes in saccade amplitude and target localization, possibly reflecting continuous updating of the estimated pre-saccadic target location driven by postdictive motor error.

Visual perception of travel distance for self-motion through crowds.

Humans can use visual motion to estimate the distance they have traveled. In static environments, optic flow generated by self-motion provides a pattern of expanding motion that is used for the estimation of travel distance. When the environment is populated by other people, their biological motion destroys the one-to-on correspondence between optic flow and travel distance. We investigated how observers estimate travel distance in a crowded environment. In three conditions, we simulated self-motion through a crowd of standing, approaching, or leading point-light walkers. For a standing crowd, optic flow is a veridical signal for distance perception. For an approaching crowd, the visual motion is the sum of the self-motion-induced optic flow and the optic flow produced by the approaching walkers. If only optic flow were to be used, travel distance estimates would be too high because of the approaching direction of the crowd toward the observer. If, on the other hand, cues from biological motion could be used to estimate the speed of the crowd, then the excessive optic from the approaching crowd flow might be compensated. In the leading crowd condition, in which walkers of the crowd keep their distance from the observer as they walk along with the observer, no optic flow is produced. In this condition, travel distance estimation would have to rely solely on biological motion information. We found that distance estimation was quite similar across these three conditions. This suggests that biological motion information can be used (a) to compensate for excessive optic flow in the approaching crowd condition and (b) to generate distance information in the leading crowd condition.

Motivation by reward jointly improves speed and accuracy, whereas task-relevance and meaningful images do not.

Visual selection is characterized by a trade-off between speed and accuracy. Speed or accuracy of the selection process can be affected by higher level factors-for example, expecting a reward, obtaining task-relevant information, or seeing an intrinsically relevant target. Recently, motivation by reward has been shown to simultaneously increase speed and accuracy, thus going beyond the speed-accuracy-trade-off. Here, we compared the motivating abilities of monetary reward, task-relevance, and image content to simultaneously increase speed and accuracy. We used a saccadic distraction task that required suppressing a distractor and selecting a target. Across different blocks successful target selection was followed either by (i) a monetary reward, (ii) obtaining task-relevant information, or (iii) seeing the face of a famous person. Each block additionally contained the same number of irrelevant trials lacking these consequences, and participants were informed about the upcoming trial type. We found that postsaccadic vision of a face affected neither speed nor accuracy, suggesting that image content does not affect visual selection via motivational mechanisms. Task relevance increased speed but decreased selection accuracy, an observation compatible with a classical speed-accuracy trade-off. Motivation by reward, however, simultaneously increased response speed and accuracy. Saccades in all conditions deviated away from the distractor, suggesting that the distractor was suppressed, and this deviation was strongest in the reward block. Drift-diffusion modelling revealed that task-relevance affected behavior by affecting decision thresholds, whereas motivation by reward additionally increased the rate of information uptake. The present findings thus show that the three consequences differ in their motivational abilities.

Current foveal inspection and previous peripheral preview influence subsequent eye movement decisions.

Humans visually inspect the world with their fovea and select new parts of the scene using saccadic eye movements. Foveal inspection and the decision of where and when to look next proceed simultaneously, but there is mixed evidence concerning their independence. Here, we tested their interdependence using drift-diffusion modeling. Participants first made a saccade to a predetermined inspection target and subsequently decided between two selection targets. We found that the inspected target's meaningfulness and the opportunity to preview it peripherally affects fixation durations and the upcoming saccadic selection. Drift-diffusion modeling showed that meaningfulness and the absence of peripheral preview can both delay the subsequent saccadic decision process and affect the rate at which peripheral information is accumulated. Our results thus show that foveal inspection and peripheral selection are dependent on each other and that peripheral information can be maintained across the saccade to influence subsequent eye movement decisions.

Saccadic landing positions reveal that eye movements are affected by distractor-based retrieval.

Binding theories assume that stimulus and response features are integrated into short-lasting episodes and that upon repetition of any feature the whole episode is retrieved, thereby affecting performance. Such binding theories are nowadays the standard explanation for a wide range of action control tasks and aim to explain all simple actions, without making assumptions of effector specificity. Yet, it is unclear if eye movements are affected by integration and retrieval in the same way as manual responses. We asked participants to discriminate letters framed by irrelevant shapes. In Experiment 1, participants gave their responses with eye movements. Saccade landing positions showed a spatial error pattern consistent with predictions of binding theories. Saccadic latencies were not affected. In Experiment 2 with an increased interval between prime and probe, the error pattern diminished, again congruent with predictions of binding theories presuming quickly decaying retrieval effects. Experiment 3 used the same task as in Experiment 1, but participants executed their responses with manual key presses; again, we found a binding pattern in response accuracy. We conclude that eye movements and manual responses are affected by the same integration and retrieval processes, supporting the tacit assumption of binding theories to apply to any effector.

Mislocalization after inhibition of saccadic adaptation.

Saccadic eye movements are often imprecise and result in an error between expected and actual retinal target location after the saccade. Repeated experience of this error produces changes in saccade amplitude to reduce the error and concomitant changes in apparent visual location. We investigated the relationship between these two plastic processes in a series of experiments. Following a recent paradigm of inhibition of saccadic adaptation, in which participants are instructed to look at the initial target position and to continue to look at that position even if the target were to move again, our participants nevertheless perceived a visual probe presented near the saccade target to be shifted in direction of the target error. The location percept of the target gradually shifted and diverged over time from the executed saccade. Our findings indicate that changes in perceived location can be the same even when changes in saccade amplitude differ according to instruction and can develop even when the amplitude of the saccades executed during the adaptation procedure does not change. There are two possible explanations for this divergence between the adaptation states of saccade amplitude and perceived location. Either the intrasaccadic target step might trigger updating of the association between pre- and post-saccadic target positions, causing the localization shift, or the saccade motor command adjusts together with the perceived location at a common adaptation site, downstream from which voluntary control is exerted upon the executed eye movement only.

Timing and kinematics of horizontal within-blink saccades measured by EOG.

Eyeblinks are the brief closures of the lid. They are accompanied by a cocontraction of the eye muscles that temporarily pulls the whole eyeball back into its socket. When blinks occur together with execution of saccadic gaze shifts, they interfere with the saccadic premotor circuit, causing these within-blink saccades to be slower than normal and also time-locked to blinks. To analyze the trajectory of within-blink saccades, subtraction of the entangled blink-related eye movement is required. Here we propose a combination of principal component analysis (PCA) and a regression model to subtract the blink-related component of the eye movement based on the respective blink metrics. We used electrooculography (EOG) to measure eye and lid movements of 12 participants who performed saccades with and without blinks. We found that within-blink saccades are slower than without-blink saccades and are tightly coupled in time to blink onset. Surprisingly, in some participants we observed large dynamic overshoots of up to 15° for saccades of only 5° amplitude. The finding of dynamic overshoots was independently confirmed by dynamic MRI for two of the participants and challenges the current view that within-blink saccades are programmed as slow, but straight, saccades. We hypothesize that the dynamic overshoots could be attributed to inhibition of omnipause neurons during blinks, the simultaneous cocontraction of extraocular muscles, or a combination of both.NEW & NOTEWORTHY This study observed that people make large dynamic overshoots when making a saccadic eye movement within a blink but their eyes are back on target by the time the eyelids are open. We used electrooculography (EOG) to measure eye movements even when the lid is down and introduced a novel procedure to subtract blink-related EOG components. These findings challenge the current view that within-blink saccades are programmed as slow but straight saccades.

Flexible use of post-saccadic visual feedback in oculomotor learning.

Saccadic eye movements bring objects of interest onto our fovea. These gaze shifts are essential for visual perception of our environment and the interaction with the objects within it. They precede our actions and are thus modulated by current goals. It is assumed that saccadic adaptation, a recalibration process that restores saccade accuracy in case of error, is mainly based on an implicit comparison of expected and actual post-saccadic position of the target on the retina. However, there is increasing evidence that task demands modulate saccade adaptation and that errors in task performance may be sufficient to induce changes to saccade amplitude. We investigated if human participants are able to flexibly use different information sources within the post-saccadic visual feedback in task-dependent fashion. Using intra-saccadic manipulation of the visual input, participants were either presented with congruent post-saccadic information, indicating the saccade target unambiguously, or incongruent post-saccadic information, creating conflict between two possible target objects. Using different task instructions, we found that participants were able to modify their saccade behavior such that they achieved the goal of the task. They succeeded in decreasing saccade gain or maintaining it, depending on what was necessary for the task, irrespective of whether the post-saccadic feedback was congruent or incongruent. It appears that action intentions prime task-relevant feature dimensions and thereby facilitated the selection of the relevant information within the post-saccadic image. Thus, participants use post-saccadic feedback flexibly, depending on their intentions and pending actions.

Self-motion illusions from distorted optic flow in multifocal glasses.

Progressive addition lenses (PALs) are ophthalmic lenses to correct presbyopia by providing improvements of near and far vision in different areas of the lens, but distorting the periphery of the wearer's field of view. Distortion-related difficulties reported by PAL wearers include unnatural self-motion perception. Visual self-motion perception is guided by optic flow, the pattern of retinal motion produced by self-motion. We tested the influence of PAL distortions on optic flow-based heading estimation using a model of heading perception and a virtual reality-based psychophysical experiment. The model predicted changes of heading estimation along a vertical axis, depending on visual field size and gaze direction. Consistent with this prediction, participants experienced upwards deviations of self-motion when gaze through the periphery of the lens was simulated, but not for gaze through the center. We conclude that PALs may lead to illusions of self-motion which could be remedied by a careful gaze strategy.

Cerebellar signals drive motor adjustments and visual perceptual changes during forward and backward adaptation of reactive saccades.

Saccadic adaptation ($SA$) is a cerebellar-dependent learning of motor commands ($MC$), which aims at preserving saccade accuracy. Since $SA$ alters visual localization during fixation and even more so across saccades, it could also involve changes of target and/or saccade visuospatial representations, the latter ($CDv$) resulting from a motor-to-visual transformation (forward dynamics model) of the corollary discharge of the $MC$. In the present study, we investigated if, in addition to its established role in adaptive adjustment of $MC$, the cerebellum could contribute to the adaptation-associated perceptual changes. Transfer of backward and forward adaptation to spatial perceptual performance (during ocular fixation and trans-saccadically) was assessed in eight cerebellar patients and eight healthy volunteers. In healthy participants, both types of $SA$ altered $MC$ as well as internal representations of the saccade target and of the saccadic eye displacement. In patients, adaptation-related adjustments of $MC$ and adaptation transfer to localization were strongly reduced relative to healthy participants, unraveling abnormal adaptation-related changes of target and $CDv$. Importantly, the estimated changes of $CDv$ were totally abolished following forward session but mainly preserved in backward session, suggesting that an internal model ensuring trans-saccadic localization could be located in the adaptation-related cerebellar networks or in downstream networks, respectively.

Real-Time MRI Reveals Unique Insight into the Full Kinematics of Eye Movements.

Our eyes are constantly in motion and the various kinds of eye movements are closely linked to many aspects of human cognitive processing. Measuring all possible eye movements unobtrusively is not achievable with current methods. Video-based eye-trackers only measure rotational but not translational motion of the eye, require a calibration process relying on the participant's self-report of accurate fixation, and do not work if vision of the eyeball is blocked. Scleral search coils attach physical weight on the eyeball and also do not measure translation. Here, we describe a novel and fully automated method to use real-time magnetic resonance imaging (MRI) for eye tracking. We achieved a temporal resolution sufficient to measure eye rotations and translations as short as those that occur within a blink and behind a closed eyelid. To demonstrate this method, we measured the full extent of the blink-related eye movement for two individuals, suggesting that the eye approaches a holding position during lid closure and can move by as much as 35° in rotation and 2 mm in translation. We also investigated the coordination of gaze shifts with blinks. We found that the gaze shift is tightly coupled in time to the translational blink movement and that blinks can induce significant temporal shifts of the gaze trajectory between left and right eye. Our MR-based Eye Tracking (MREyeTrack) method allows measurement of eye movements in terms of both translation and rotation and enables new opportunities for studying ocular motility and its disorders.