Bidirectional brain-body interactions during natural story listening.

Narratives can synchronize neural and physiological signals between individuals, but the relationship between these signals, and the underlying mechanism, is unclear. We hypothesized a top-down effect of cognition on arousal and predicted that auditory narratives will drive not only brain signals but also peripheral physiological signals. We find that auditory narratives entrained gaze variation, saccade initiation, pupil size, and heart rate. This is consistent with a top-down effect of cognition on autonomic function. We also hypothesized a bottom-up effect, whereby autonomic physiology affects arousal. Controlled breathing affected pupil size, and heart rate was entrained by controlled saccades. Additionally, fluctuations in heart rate preceded fluctuations of pupil size and brain signals. Gaze variation, pupil size, and heart rate were all associated with anterior-central brain signals. Together, these results suggest bidirectional causal effects between peripheral autonomic function and central brain circuits involved in the control of arousal.

Common structure of saccades and microsaccades in visual perception.

We obtain large amounts of external information through our eyes, a process often considered analogous to picture mapping onto a camera lens. However, our eyes are never as still as a camera lens, with saccades occurring between fixations and microsaccades occurring within a fixation. Although saccades are agreed to be functional for information sampling in visual perception, it remains unknown if microsaccades have a similar function when eye movement is restricted. Here, we demonstrated that saccades and microsaccades share common spatiotemporal structures in viewing visual objects. Twenty-seven adults viewed faces and houses in free-viewing and fixation-controlled conditions. Both saccades and microsaccades showed distinctive spatiotemporal patterns between face and house viewing that could be discriminated by pattern classifications. The classifications based on saccades and microsaccades could also be mutually generalized. Importantly, individuals who showed more distinctive saccadic patterns between faces and houses also showed more distinctive microsaccadic patterns. Moreover, saccades and microsaccades showed a higher structure similarity for face viewing than house viewing and a common orienting preference for the eye region over the mouth region. These findings suggested a common oculomotor program that is used to optimize information sampling during visual object perception.

Peripheral vision and crowding in mental maze-solving.

Solving a maze effectively relies on both perception and cognition. Studying maze-solving behavior contributes to our knowledge about these important processes. Through psychophysical experiments and modeling simulations, we examine the role of peripheral vision, specifically visual crowding in the periphery, in mental maze-solving. Experiment 1 measured gaze patterns while varying maze complexity, revealing a direct relationship between visual complexity and maze-solving efficiency. Simulations of the maze-solving task using a peripheral vision model confirmed the observed crowding effects while making an intriguing prediction that saccades provide a conservative measure of how far ahead observers can perceive the path. Experiment 2 confirms that observers can judge whether a point lies on the path at considerably greater distances than their average saccade. Taken together, our findings demonstrate that peripheral vision plays a key role in mental maze-solving.

The effect of impaired velocity signals on goal-directed eye and hand movements.

Information about position and velocity is essential to predict where moving targets will be in the future, and to accurately move towards them. But how are the two signals combined over time to complete goal-directed movements? We show that when velocity information is impaired due to using second-order motion stimuli, saccades directed towards moving targets land at positions where targets were ~ 100 ms before saccade initiation, but hand movements are accurate. Importantly, the longer latencies of hand movements allow for additional time to process the sensory information available. When increasing the period of time one sees the moving target before making the saccade, saccades become accurate. In line with that, hand movements with short latencies show higher curvature, indicating corrections based on an update of incoming sensory information. These results suggest that movements are controlled by an independent and evolving combination of sensory information about the target's position and velocity.

Visuomotor coordination and cognitive capacity in blindsight.

Classical literature on blindsight described that some patients with lesions to the primary visual cortex could respond to visual stimuli without subjective awareness. Recent studies addressed more complex arguments on the conscious state of blindsight subjects such as existence of partial awareness, namely "feeling of something happening" in the lesion-affected visual field, termed 'type II blindsight', and high-level performance in complex cognitive tasks in blindsight model monkeys. Endeavors to clarify the visual pathways for blindsight revealed the parallel thalamic routes mediating the visual inputs from the superior colliculus to extrastriate and frontoparietal cortices, which may underlie the flexible visuomotor association and cognitive control in the blindsight subjects. Furthermore, involvement of post-lesion plasticity is suggested for these neural systems to operate.

Microsaccades as a long-term oculomotor correlate in visual perceptual learning.

Human perceptual learning, experience-induced gains in sensory discrimination, typically yields long-term performance improvements. Recent research revealed long-lasting transfer at the untrained location enabled by feature-based attention (FBA), reminiscent of its global effect (Hung & Carrasco, Scientific Reports, 11(1), 13914, (2021)). Visual Perceptual Learning (VPL) is typically studied while observers maintain fixation, but the role of fixational eye movements is unknown. Microsaccades - the largest of fixational eye movements - provide a continuous, online, physiological measure from the oculomotor system that reveals dynamic processing, which is unavailable from behavioral measures alone. We investigated whether and how microsaccades change after training in an orientation discrimination task. For human observers trained with or without FBA, microsaccade rates were significantly reduced during the response window in both trained and untrained locations and orientations. Critically, consistent with long-term training benefits, this microsaccade-rate reduction persisted over a year. Furthermore, microsaccades were biased toward the target location prior to stimulus onset and were more suppressed for incorrect than correct trials after observers' responses. These findings reveal that fixational eye movements and VPL are tightly coupled and that learning-induced microsaccade changes are long lasting. Thus, microsaccades reflect functional dynamics of the oculomotor system during information encoding, maintenance and readout, and may serve as a reliable long-term physiological correlate in VPL.

Muscles that move the retina augment compound eye vision in Drosophila.

Most animals have compound eyes, with tens to thousands of lenses attached rigidly to the exoskeleton. A natural assumption is that all of these species must resort to moving either their head or their body to actively change their visual input. However, classic anatomy has revealed that flies have muscles poised to move their retinas under the stable lenses of each compound eye1-3. Here we show that Drosophila use their retinal muscles to smoothly track visual motion, which helps to stabilize the retinal image, and also to perform small saccades when viewing a stationary scene. We show that when the retina moves, visual receptive fields shift accordingly, and that even the smallest retinal saccades activate visual neurons. Using a head-fixed behavioural paradigm, we find that Drosophila perform binocular, vergence movements of their retinas-which could enhance depth perception-when crossing gaps, and impairing the physiology of retinal motor neurons alters gap-crossing trajectories during free behaviour. That flies evolved an ability to actuate their retinas suggests that moving the eye independently of the head is broadly paramount for animals. The similarities of smooth and saccadic movements of the Drosophila retina and the vertebrate eye highlight a notable example of convergent evolution.

Distinguishing externally from saccade-induced motion in visual cortex.

Distinguishing sensory stimuli caused by changes in the environment from those caused by an animal's own actions is a hallmark of sensory processing1. Saccades are rapid eye movements that shift the image on the retina. How visual systems differentiate motion of the image induced by saccades from actual motion in the environment is not fully understood2. Here we discovered that in mouse primary visual cortex (V1) the two types of motion evoke distinct activity patterns. This is because, during saccades, V1 combines the visual input with a strong non-visual input arriving from the thalamic pulvinar nucleus. The non-visual input triggers responses that are specific to the direction of the saccade and the visual input triggers responses that are specific to the direction of the shift of the stimulus on the retina, yet the preferred directions of these two responses are uncorrelated. Thus, the pulvinar input ensures differential V1 responses to external and self-generated motion. Integration of external sensory information with information about body movement may be a general mechanism for sensory cortices to distinguish between self-generated and external stimuli.

Oculomotor Abnormalities during Reading in the Offspring of Late-Onset Alzheimer's Disease.

INTRODUCTION: Eye movement patterns during reading are well defined and documented. Each eye movement ends up in a fixation point, which allows the brain to process the incoming information and program the following saccade. In this work, we investigated whether eye movement alterations during a reading task might be already present in middle-aged, cognitively normal offspring of late-onset Alzheimer's disease (O-LOAD). METHODS: 18 O-LOAD and 18 age-matched healthy individuals with no family history of LOAD participated in the study. Participants were seated in front of a 20-inch LCD monitor, and single sentences were presented on it. Eye movements were recorded with an eye tracker with a sampling rate of 1000 Hz. RESULTS: Analysis of eye movements during reading revealed that O-LOAD displayed more fixations, shorter saccades, and shorter fixation durations than controls. CONCLUSION: The present study shows that O-LOAD experienced alterations in their eye movements during reading. O-LOAD eye movement behavior could be considered an initial sign of oculomotor impairment. Hence, the evaluation of eye movement during reading might be a useful tool for monitoring well-defined cognitive resources.

Cortical neural dynamics unveil the rhythm of natural visual behavior in marmosets.

Numerous studies have shown that the visual system consists of functionally distinct ventral and dorsal streams; however, its exact spatial-temporal dynamics during natural visual behavior remain to be investigated. Here, we report cerebral neural dynamics during active visual exploration recorded by an electrocorticographic array covering the entire lateral surface of the marmoset cortex. We found that the dorsal stream was activated before the primary visual cortex with saccades and followed by the alteration of suppression and activation signals along the ventral stream. Similarly, the signal that propagated from the dorsal to ventral visual areas was accompanied by a travelling wave of low frequency oscillations. Such signal dynamics occurred at an average of 220 ms after saccades, which corresponded to the timing when whole-brain activation returned to background levels. We also demonstrated that saccades could occur at any point of signal flow, indicating the parallel computation of motor commands. Overall, this study reveals the neural dynamics of active vision, which are efficiently linked to the natural rhythms of visual exploration.

Differential coding of goals and actions in ventral and dorsal corticostriatal circuits during goal-directed behavior.

Goal-directed behavior requires identifying objects in the environment that can satisfy internal needs and executing actions to obtain those objects. The current study examines ventral and dorsal corticostriatal circuits that support complementary aspects of goal-directed behavior. We analyze activity from the amygdala, ventral striatum, orbitofrontal cortex, and lateral prefrontal cortex (LPFC) while monkeys perform a three-armed bandit task. Information about chosen stimuli and their value is primarily encoded in the amygdala, ventral striatum, and orbitofrontal cortex, while the spatial information is primarily encoded in the LPFC. Before the options are presented, information about the to-be-chosen stimulus is represented in the amygdala, ventral striatum, and orbitofrontal cortex; at the time of choice, the information is passed to the LPFC to direct a saccade. Thus, learned value information specifying behavioral goals is maintained throughout the ventral corticostriatal circuit, and it is routed through the dorsal circuit at the time actions are selected.

Neural correlates of impaired response inhibition in the antisaccade task in Parkinson's disease.

Deficits in response inhibition are a central feature of the highly prevalent dysexecutive syndrome found in Parkinson's disease (PD). Such deficits are related to a range of common clinically relevant symptoms including cognitive impairment as well as impulsive and compulsive behaviors. In this study, we explored the cortical dynamics underlying response inhibition during the mental preparation for the antisaccade task by recording magnetoencephalography (MEG) and eye-movements in 21 non-demented patients with early to mid-stage Parkinson's disease and 21 age-matched healthy control participants (HC). During the pre-stimulus preparatory period for antisaccades we observed: Taken together, the results indicate that alterations in pre-stimulus prefrontal alpha and beta activity hinder proactive response inhibition and in turn result in higher error rates and prolonged response latencies in PD.

Oculomotor freezing indicates conscious detection free of decision bias.

The appearance of a salient stimulus rapidly and automatically inhibits saccadic eye movements. Curiously, this "oculomotor freezing" response is triggered only by stimuli that the observer reports seeing. It remains unknown, however, whether oculomotor freezing is linked to the observer's sensory experience or their decision that a stimulus was present. To dissociate between these possibilities, we manipulated decision criterion via monetary payoffs and stimulus probability in a detection task. These manipulations greatly shifted observers' decision criteria but did not affect the degree to which microsaccades were inhibited by stimulus presence. Moreover, the link between oculomotor freezing and explicit reports of stimulus presence was stronger when the criterion was conservative rather than liberal. We conclude that the sensory threshold for oculomotor freezing is independent of decision bias. Provided that conscious experience is also unaffected by such bias, oculomotor freezing is an implicit indicator of sensory awareness.NEW & NOTEWORTHY Sometimes a visual stimulus reaches awareness, and sometimes it does not. To understand why, we need objective, bias-free measures of awareness. We discovered that a reflexive freezing of small eye movements indicates when an observer detects a stimulus. Furthermore, when we biased observers' decisions to report seeing the stimulus, the oculomotor response was unaltered. This suggests that the threshold for conscious perception is independent of the decision criterion and is revealed by oculomotor freezing.

Influence of sports experience on distribution of pro-saccade reaction time under gap condition.

BACKGROUND: Previous studies indicated that substantial individual variation exists in the distribution of pro-saccade reaction times under gap condition. To investigate the influence of sports experience on the distribution, we examined distribution of the pro-saccade reaction time under overlap and gap conditions, for the basketball club, table tennis club, and non-sporting control groups. METHODS: Subjects performed pro-saccade tasks under the overlap and gap conditions, in which the intentional and reflexive disengagement of fixation are important, respectively. Under the overlap condition, the central fixation point was illuminated for a random duration of 1-3 s, then the fixation point was turned off. Just after the switch-off of the fixation point, one of the peripheral targets was illuminated for a duration of 1 s. The visual stimulus under the gap condition was almost the same as that under the overlap condition. However, only the temporal gap between the switch-off of the fixation point and the onset of the target differed between those conditions. The gap duration in the gap condition was set at 200 ms. The mean of median value of the bandwidth showing the earliest peak in the histogram was calculated for each group. Thereafter, for each subject, the bandwidth showing the earliest peak under the gap condition was defined as the criterion bandwidth (0 ms bandwidth). Based on this criterion bandwidth, the mean of the relative frequency was calculated for every 10 ms of bandwidth, for the overlap and gap conditions, in each group. RESULTS: Under the overlap condition, for all subjects, the pro-saccade reaction times showed unimodal distribution. The means of the median value of the bandwidth showing the earliest peak for the basketball and table tennis groups (approximate 170 ms) were significantly earlier than that for the control group (approximate 190 ms). Under the gap condition, the distribution was bimodal for 11 of 15 subjects in the basketball group and for 5 of 15 subjects in the control group. In the table tennis group, the distribution was not bimodal but unimodal for all 15 subjects. For the basketball group, mean of the relative frequency showed bimodal distribution with approximate 120 ms and 170 ms peaks. For the table tennis and control groups, the mean of the relative frequency showed unimodal distribution with approximate 130 ms and 140ms peak, respectively. CONCLUSIONS: The present study indicated that under the gap condition, the sports experience influenced on the distribution of the pro-saccade reaction time. The pro-saccade reaction time under the condition would show a distinct bimodal distribution for the basketball group and show a distinct and early unimodal distribution for the table tennis group. It was suggested that the physiological factor leading the group difference in the distribution was the effect of sports experience on the disengagement function of fixation.

Eye and hand movements disrupt attentional control.

Voluntary attentional control is the ability to selectively focus on a subset of visual information in the presence of other competing stimuli-a marker of cognitive control enabling flexible, goal-driven behavior. To test its robustness, we contrasted attentional control with the most common source of attentional orienting in daily life: attention shifts prior to goal-directed eye and hand movements. In a multi-tasking paradigm, human participants attended at a location while planning eye or hand movements elsewhere. Voluntary attentional control suffered with every simultaneous action plan, even under reduced task difficulty and memory load-factors known to interfere with attentional control. Furthermore, the performance cost was limited to voluntary attention: We observed simultaneous attention benefits at two movement targets without attentional competition between them. This demonstrates that the visual system allows for the concurrent representation of multiple attentional foci. Since attentional control is extremely fragile and dominated by premotor attention shifts, we propose that action-driven selection plays the superordinate role for visual selection.

Predicting and Manipulating Cone Responses to Naturalistic Inputs.

Primates explore their visual environment by making frequent saccades, discrete and ballistic eye movements that direct the fovea to specific regions of interest. Saccades produce large and rapid changes in input. The magnitude of these changes and the limited signaling range of visual neurons mean that effective encoding requires rapid adaptation. Here, we explore how macaque cone photoreceptors maintain sensitivity under these conditions. Adaptation makes cone responses to naturalistic stimuli highly nonlinear and dependent on stimulus history. Such responses cannot be explained by linear or linear-nonlinear models but are well explained by a biophysical model of phototransduction based on well-established biochemical interactions. The resulting model can predict cone responses to a broad range of stimuli and enables the design of stimuli that elicit specific (e.g., linear) cone photocurrents. These advances will provide a foundation for investigating the contributions of cone phototransduction and post-transduction processing to visual function.SIGNIFICANCE STATEMENT We know a great deal about adaptational mechanisms that adjust sensitivity to slow changes in visual inputs such as the rising or setting sun. We know much less about the rapid adaptational mechanisms that are essential for maintaining sensitivity as gaze shifts around a single visual scene. We characterize how phototransduction in cone photoreceptors adapts to rapid changes in input similar to those encountered during natural vision. We incorporate these measurements into a quantitative model that can predict cone responses across a broad range of stimuli. This model not only shows how cone phototransduction aids the encoding of natural inputs but also provides a tool to identify the role of the cone responses in shaping those of downstream visual neurons.

Brainstem Circuits Triggering Saccades and Fixation.

Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary ("fixation") but stop firing immediately before and during saccades. To locate the source of suppression, we analyzed synaptic inputs from the rostral and caudal superior colliculi (SCs) to OPNs by using intracellular recording and staining, and investigated pathways transmitting the inputs in anesthetized cats of both sexes. Electrophysiologically or morphologically identified OPNs received monosynaptic excitation from the rostral SCs with contralateral dominance, and received disynaptic inhibition from the caudal SCs with ipsilateral dominance. Cutting the tectoreticular tract transversely between the contralateral OPN and inhibitory burst neuron (IBN) regions eliminated inhibition from the caudal SCs, but not excitation from the rostral SCs in OPNs. In contrast, a midline section between IBN regions eliminated disynaptic inhibition in OPNs from the caudal SCs but did not affect the monosynaptic excitation from the rostral SCs. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in OPNs, which was facilitated by preconditioning SC stimulation. Three-dimensional reconstruction of HRP-stained cells revealed that individual OPNs have axons that terminate in the opposite IBN area, while individual IBNs have axon collaterals to the opposite OPN area. These results show that there are differences in the neural circuit from the rostral and caudal SCs to the brainstem premotor circuitry and that IBNs suppress OPNs immediately before and during saccades. Thus, the IBNs, which are activated by caudal SC saccade neurons, shut down OPN firing and help to trigger saccades and suppress ("latch") OPN activity during saccades.SIGNIFICANCE STATEMENT Saccades are the fastest eye movements to redirect gaze to an object of interest and bring its image on the fovea for fixation. Burst neurons (BNs) and omnipause neurons (OPNs) which behave reciprocally in the brainstem, are important for saccade generation and fixation. This study investigated unsolved important questions about where these neurons receive command signals and how they interact for initiating saccades from visual fixation. The results show that the rostral superior colliculi (SCs) excite OPNs monosynaptically for fixation, whereas the caudal SCs monosynaptically excite inhibitory BNs, which then directly inhibit OPNs for the initiation of saccades. This inhibition from the caudal SCs may account for the omnipause behavior of OPNs for initiation and maintenance of saccades in all directions.

Maturation of Temporal Saccade Prediction from Childhood to Adulthood: Predictive Saccades, Reduced Pupil Size, and Blink Synchronization.

When presented with a periodic stimulus, humans spontaneously adjust their movements from reacting to predicting the timing of its arrival, but little is known about how this sensorimotor adaptation changes across development. To investigate this, we analyzed saccade behavior in 114 healthy humans (ages 6-24 years) performing the visual metronome task, who were instructed to move their eyes in time with a visual target that alternated between two known locations at a fixed rate, and we compared their behavior to performance in a random task, where target onsets were randomized across five interstimulus intervals (ISIs) and thus the timing of appearance was unknown. Saccades initiated before registration of the visual target, thus in anticipation of its appearance, were labeled predictive [saccade reaction time (SRT) < 90 ms] and saccades that were made in reaction to its appearance were labeled reactive (SRT > 90 ms). Eye-tracking behavior including saccadic metrics (e.g., peak velocity, amplitude), pupil size following saccade to target, and blink behavior all varied as a function of predicting or reacting to periodic targets. Compared with reactive saccades, predictive saccades had a lower peak velocity, a hypometric amplitude, smaller pupil size, and a reduced probability of blink occurrence before target appearance. The percentage of predictive and reactive saccades changed inversely from ages 8-16, at which they reached adult-levels of behavior. Differences in predictive saccades for fast and slow target rates are interpreted by differential maturation of cerebellar-thalamic-striatal pathways.SIGNIFICANCE STATEMENT From the first moments of life, humans are exposed to rhythm (i.e., mother's heartbeat in utero), but the timeline of brain development to promote the identification and anticipation of a rhythmic stimulus, known as temporal prediction, remains unknown. Here, we used saccade reaction time (SRT) in the visual metronome task to differentiate between temporally predictive and reactive responses to a target that alternated at a fixed rate in humans aged 6-24. Periods of age-related change varied little by target rate, with matured predictive performance evident by mid-adolescence for fast and slow rates. A strong correlation among saccade, pupil, and blink responses during target prediction provides evidence of oculomotor coordination and dampened noradrenergic neuronal activity when generating rhythmic motor responses.

Psychosis Biotypes: Replication and Validation from the B-SNIP Consortium.

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called "B-SNIP1" with 711 psychosis and 274 healthy persons, and the "replication sample" with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r's from .96-.99) and temporally stable (r's from .76-.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%-89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.

App-Based Saccade Latency and Directional Error Determination Across the Adult Age Spectrum.

OBJECTIVE: We aid in neurocognitive monitoring outside the hospital environment by enabling app-based measurements of visual reaction time (saccade latency) and directional error rate in a cohort of subjects spanning the adult age spectrum. METHODS: We developed an iOS app to record subjects with the frontal camera during pro- and anti-saccade tasks. We further developed automated algorithms for measuring saccade latency and directional error rate that take into account the possibility that it might not always be possible to determine the eye movement from app-based recordings. RESULTS: To measure saccade latency on a tablet, we ensured that the absolute timing error between on-screen task presentation and the camera recording is within 5 ms. We collected over 235,000 eye movements in 80 subjects ranging in age from 20 to 92 years, with 96% of recorded eye movements either declared good or directional errors. Our error detection code achieved a sensitivity of 0.97 and a specificity of 0.97. Confirming prior reports, we observed a positive correlation between saccade latency and age while the relationship between directional error rate and age was not significant. Finally, we observed significant intra- and inter-subject variations in saccade latency and directional error rate distributions, which highlights the importance of individualized tracking of these visual digital biomarkers. CONCLUSION AND SIGNIFICANCE: Our system and algorithms allow ubiquitous tracking of saccade latency and directional error rate, which opens up the possibility of quantifying patient state on a finer timescale in a broader population than previously possible.