Saccade Latency Distributions Research Articles

The eyes prefer targets nearby fixation: Quantifying eccentricity-dependent attentional biases in oculomotor selection

An important function of peripheral vision is to provide the target of the next eye movement. Here we investigate the extent to which the eyes are biased to select a target closer to fixation over one further away. Participants were presented with displays containing two identical singleton targets and were asked to move their eyes to either one of them. The targets could be presented at three different eccentricities relative to central fixation. In one condition both singletons were presented at the same eccentricity, providing an estimate of the speed of selection at each of the eccentricities. The saccadic latency distributions from this same-eccentricity condition were then used to predict the selection bias when both targets were presented at different eccentricities. The results show that when targets are presented at different eccentricities, participants are biased to select the item closest to fixation. This eccentricity-based bias was considerably stronger than predicted on the basis of saccadic latency distributions in the same-eccentricity condition. This rules out speed of processing per se as a sole explanation for such a bias. Instead, the results are consistent with attentional competition being weighted in favour of items close to fixation.

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

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. 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. 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. 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.

Measuring Saccade Latency Using Smartphone Cameras.

Accurate quantification of neurodegenerative disease progression is an ongoing challenge that complicates efforts to understand and treat these conditions. Clinical studies have shown that eye movement features may serve as objective biomarkers to support diagnosis and tracking of disease progression. Here, we demonstrate that saccade latency-an eye movement measure of reaction time-can be measured robustly outside of the clinical environment with a smartphone camera. To enable tracking of saccade latency in large cohorts of patients and control subjects, we combined a deep convolutional neural network for gaze estimation with a model-based approach for saccade onset determination that provides automated signal-quality quantification and artifact rejection. Simultaneous recordings with a smartphone and a high-speed camera resulted in negligible differences in saccade latency distributions. Furthermore, we demonstrated that the constraint of chinrest support can be removed when recording healthy subjects. Repeat smartphone-based measurements of saccade latency in 11 self-reported healthy subjects resulted in an intraclass correlation coefficient of 0.76, showing our approach has good to excellent test-retest reliability. Additionally, we conducted more than 19 000 saccade latency measurements in 29 self-reported healthy subjects and observed significant intra- and inter-subject variability, which highlights the importance of individualized tracking. Lastly, we showed that with around 65 measurements we can estimate mean saccade latency to within less-than-10-ms precision, which takes within 4 min with our setup. By enabling repeat measurements of saccade latency and its distribution in individual subjects, our framework opens the possibility of quantifying patient state on a finer timescale in a broader population than previously possible.

Oculomotor effects of medical and surgical treatments of Parkinson's disease.

Oculomotor abnormalities are fast becoming a proxy for disease diagnosis and progression. Saccades-ballistic eye movements-are known to be affected by dopaminergic cell loss in the basal ganglia, caused by Parkinson's disease. Pharmaceutical and neurosurgical interventions such as deep brain stimulation and functional neurosurgery have both been noted to have an effect on saccades. Comparing and contrasting these effects may yield insights into Parkinson's disease pathophysiology, and the mechanisms of pharmacological and neurosurgical treatments. Computational models of saccadic control, such as the LATER model, can help to interpret the distribution of saccadic latencies, providing a framework for objectively comparing the effects of pharmaceutical interventions and deep brain stimulation.

Determination of Saccade Latency Distributions using Video Recordings from Consumer-grade Devices.

Quantitative and accurate tracking of neurocognitive decline remains an ongoing challenge. We seek to address this need by focusing on robust and unobtrusive measurement of saccade latency - the time between the presentation of a visual stimulus and the initiation of an eye movement towards the stimulus - which has been shown to be altered in patients with neurocognitive decline or neurodegenerative diseases. Here, we present a novel, deep convolutional-neuralnetwork-based method to measure saccade latency outside of the clinical environment using a smartphone camera without the need for supplemental or special-purpose illumination. We also describe a model-based approach to estimate saccade latency that is less sensitive to noise compared to conventional methods. With this flexible and robust system, we collected over 11,000 saccade-latency measurements from 21 healthy individuals and found distinctive saccade-latency distributions across subjects. When analyzing intra-subject variability across time, we observed noticeable variations in the mean saccade latency and associated standard deviation. We also observed a potential learning effect that should be further characterized and potentially accounted for when interpreting saccade latency measurements.

Disrupted Saccade Control in Chronic Cerebral Injury: Upper Motor Neuron-Like Disinhibition in the Ocular Motor System.

Saccades rapidly direct the line of sight to targets of interest to make use of the high acuity foveal region of the retina. These fast eye movements are instrumental for scanning visual scenes, foveating targets, and, ultimately, serve to guide manual motor control, including eye–hand coordination. Cerebral injury has long been known to impair ocular motor control. Recently, it has been suggested that alterations in control may be useful as a marker for recovery. We measured eye movement control in a saccade task in subjects with chronic middle cerebral artery stroke with both cortical and substantial basal ganglia involvement and in healthy controls. Saccade latency distributions were bimodal, with an early peak at 60 ms (anticipatory saccades) and a later peak at 250 ms (regular saccades). Although the latencies corresponding to these peaks were the same in the two groups, there were clear differences in the size of the peaks. Classifying saccade latencies relative to the saccade “go signal” into anticipatory (latencies up to 80 ms), “early” (latencies between 80 and 160 ms), and “regular” types (latencies longer than 160 ms), stroke subjects displayed a disproportionate number of anticipatory saccades, whereas control subjects produced the majority of their saccades in the regular range. We suggest that this increase in the number of anticipatory saccade events may result from a disinhibition phenomenon that manifests as an impairment in the endogenous control of ocular motor events (saccades) and interleaved fixations. These preliminary findings may help shed light on the ocular motor deficits of neurodegenerative conditions, results that may be subclinical to an examiner, but clinically significant secondary to their functional implications.

Using saccades to diagnose covert hepatic encephalopathy.

Covert Hepatic Encephalopathy (CHE), previously known as Minimal Hepatic Encephalopathy, is a subtle cognitive defect found in 30-70% of cirrhosis patients. It has been linked to poor quality of life, impaired fitness to drive, and increased mortality: treatment is possible. Despite its clinical significance, diagnosis relies on psychometric tests that have proved unsuitable for use in a clinical setting. We investigated whether measurement of saccadic latency distributions might be a viable alternative. We collected data on 35 cirrhosis patients at Addenbrooke's Hospital, Cambridge, with no evidence of clinically overt encephalopathy, and 36 age-matched healthy controls. Performance on standard psychometric tests was evaluated to determine those patients with CHE as defined by the World Congress of Gastroenterology. We then compared visually-evoked saccades between those with CHE and those without, as well as reviewing blood test results and correlating saccadic latencies with biochemical parameters and prognostic scores. Cirrhosis patients have significantly longer median saccadic latencies than healthy controls. Those with CHE had significantly prolonged saccadic latencies when compared with those without CHE. Analysis of a cirrhosis patient's saccades can diagnose CHE with a sensitivity of 75% and a specificity of 75%. We concluded that analysis of a cirrhosis patient's saccadic latency distributions is a fast and objective measure that can be used as a diagnostic tool for CHE. This improved early diagnosis could direct avoidance of high-risk activities such as driving, and better inform treatment strategies.

Bedside saccadometry as an objective and quantitative measure of hemisphere-specific neurological function in patients undergoing cranial surgery

Cranial surgery continues to carry a significant risk of neurological complications. New bedside tools that can objectively and quantitatively evaluate cerebral function may allow for earlier detection of such complications, more rapid initiation of therapy, and improved patient outcomes. We assessed the potential of saccadic eye movements as a measure of cerebral function in patients undergoing cranial surgery peri-operatively. Visually evoked saccades were measured in 20 patients before (−12hours) and after (+2 and +5days) undergoing cranial surgery. Hemisphere specific saccadic latencies were measured using a simple step-task and saccadic latency distributions were compared using the Kolmogorov–Smirnov test. Saccadic latency values were incorporated into an empirically validated mathematical model (Linear Approach to Threshold with Ergodic Rate [LATER] model) for further analysis (using Wilcoxon signed rank test). Thirteen males and seven females took part in our study (mean age 55±4.9years). Following cranial surgery, saccades initiated by the cerebral hemisphere on the operated side demonstrated significant deteriorations in function after 2days (p<0.01) that normalised after 5days. Analysis using the LATER model confirmed these findings, highlighting decreased cerebral information processing as a potential mechanism for noted changes (p<0.05). No patients suffered clinical complications after surgery. To conclude, bedside saccadometry can demonstrate hemisphere-specific changes after surgery in the absence of clinical symptoms. The LATER model confirms these findings and offers a mechanistic explanation for this change. Further work will be necessary to assess the practical validity of these changes in relation to clinical complications after surgery.

Implicit and explicit timing in oculomotor control.

The passage of time can be estimated either explicitly, e.g. before leaving home in the morning, or implicitly, e.g. when catching a flying ball. In the present study, the latency of saccadic eye movements was used to evaluate differences between implicit and explicit timing. Humans were required to make a saccade between a central and a peripheral position on a computer screen. The delay between the extinction of a central target and the appearance of an eccentric target was the independent variable that could take one out of four different values (400, 900, 1400 or 1900 ms). In target trials, the delay period lasted for one of the four durations randomly. At the end of the delay, a saccade was initiated by the appearance of an eccentric target. Cue&target trials were similar to target trials but the duration of the delay was visually cued. In probe trials, the duration of the upcoming delay was cued, but there was no eccentric target and subjects had to internally generate a saccade at the estimated end of the delay. In target and cue&target trials, the mean and variance of latency distributions decreased as delay duration increased. In cue&target trials latencies were shorter. In probe trials, the variance increased with increasing delay duration and scalar variability was observed. The major differences in saccadic latency distributions were observed between visually-guided (target and cue&target trials) and internally-generated saccades (probe trials). In target and cue&target trials the timing of the response was implicit. In probe trials, the timing of the response was internally-generated and explicitly based on the duration of the visual cue. Scalar timing was observed only during probe trials. This study supports the hypothesis that there is no ubiquitous timing system in the brain but independent timing processes active depending on task demands.

I06 Can the ageing brain serve as the test field for identifying methods allowing to detect functional deterioration of pre-manifest HD?

To study ageing of the central nervous system in our laboratory we usually use two prosaccade tasks—the standard one, and another designed by us, the rapid-target-walk (RTW) paradigm. In RTW task, target moves to the left or right by 10 or 20 degree and it doesn9t returns back to the central position after each trial, as it is taking place in standard paradigm. Target9s movements appear for the subject to be random, but in fact they form the predefined sequences counter-balancing potential effects of stimuli history. RTW task allows to shorten the duration of saccadic latency examination and is experienced by the subjects as being less boring than standard, providing also sustaining of attention on the task. Our previous experiences have shown that the increase of prosaccadic latency can be an effective marker of slowdowns that accompany nervous system ageing, however in detection of these changes an important role may play the capturing and effective holding of subjects attention on the task. We decided to examine sensitivity of Standard prosaccade task and rapid-target walk paradigm on subtle changes that appear in ageing nervous system within 1 year. We examined a group of 21 older adults aged 58–91 years two times after 1 year. Reaction times collected using RTW task were shorter as compared to latencies measured using Standard paradigm, what probably was the result of increased urgency or higher level of capturing subjects9 attention on RTW paradigm. Statistical analysis for dependent variables revealed that mean and median of saccadic latency significantly differ after 1 year (in case of both: Standard and RTW task). Analysis of saccadic latency distributions for each subjects individually, revealed significant differences for five subjects (in case of both standard and RTW task).

Altered interictal saccadic reaction time in migraine: a cross-sectional study

The underlying mechanisms of migraine remain poorly understood, partly because we lack objective methods for quantitative analysis of neurological function. To address this issue, we measured interictal saccadic latency in migraineurs and controls. In a cross-sectional study, we compared interictal saccadic latency distributions of 12,800 saccades in 32 migraineurs with 32 age- and sex-matched controls. The variability of migraineurs' reaction time distributions was significantly smaller (σ = 1.01 vs. 1.13; p < 0.05) compared with controls. In addition, a smaller proportion of migraineurs generated 'early' saccades (31% vs. 56%: p < 0.05). Sensitivity/specificity analysis demonstrated the potential benefit of this technique to diagnostic discrimination. The migraineur's brain behaves significantly differently from that of a control during the interictal period. By analysing whole distributions, rather than just means, data can be related directly to current neurophysiological models: specifically, the observed decrease in variability suggests a functional deficit in the noradrenergic systems influencing the cerebral cortex. From a clinical perspective, this novel method of characterising neurological function in migraine is more rapid, practicable, inexpensive, objective and quantitative than previous methods such as evoked potentials and transcranial magnetic stimulation, and has the potential both to improve current diagnostic discrimination and to help guide future research into the underlying neural mechanisms.

Differing proportions of ‘express saccade makers’ in different human populations

Debate continues about cultural influences on processes such as perception and memory. One underlying assumption is that high level, top-down influences that differ between populations (culture) act on identical brain structures and functions to produce different behaviours. More specifically, it has been reported that in various types of complex visual task, eye movement patterns differ systematically between Chinese and non-Chinese subjects. We investigated a relatively simple behaviour (reflexive eye saccades), comparing the saccade latency distributions of Chinese and Caucasian subjects. In a task in which the fixation target remained illuminated when the saccade target appeared (overlap task), 10 out of 34 (29%) Chinese subjects exhibited a high proportion (>30%) of low latency 'express' saccades. This pattern of response had been reported to be very uncommon in healthy, naïve subjects. We therefore subsequently confirmed that only 1 out of 38 Caucasian subjects exhibited it. The results suggest important population differences with regard to the expression of distinct oculomotor behaviours.

Express saccades: the conditions under which they are realized and the brain structures involved

Repeated eye movements made to visual targets can yield a bimodal distribution of saccadic latencies the first mode of which was termed express saccades by Fischer and Boch. We have carried out a series of experiments in monkeys to identify the conditions necessary for express saccade generation, the rules involved, and the brain structures responsible. Express saccades are produced to singly appearing targets but not when several stimuli appear at the same time. Learning plays a central role in express saccade generation. What is learned is the vector of the saccade to be produced, not the location of the target is space or the orbital position of the eye. The frequency with which express saccades are made depends on expectation; express saccades seldom arise when targets appear at unexpected locations. Increasing the gap time between fixation spot termination and target onset and decreasing the number of expected target locations increases the frequency of express saccade generation. Express saccades are made with high frequency to the second of two successive targets as long as the vector is one that has been learned. Pre-cuing can increase the frequency of express saccades only within a limited range. Free viewing of natural scenes commonly yields saccades in the express range but the distribution is not bimodal. Lesions of the frontal eye fields, of the medial eye fields, and of areas V4 and MT do not interfere with the generation of express saccades. Neither does the disruption of either the magnocellular or parvocellular systems. But superior colliculus lesions eliminate express saccades; no recovery is evident It appears therefore that the cortical areas involved in express saccade generation send their signals to the brainstem through the superior colliculus.

Modelling contralesional movement slowing after unilateral brain damage

Effective interaction with the world requires the brain to signal behaviourally relevant events and organise an appropriate and timely motor response to such events. Unilateral brain lesion typically results in a reduction and slowing of motor behaviour directed to contralesional space. Accumulator models of choice and reaction time can distinguish between two possible functional causes of this deficit: slowed extraction of evidence in favour of a motor response or an increase in the required amount of evidence for response generation. Three patients with unilateral damage to the right hemisphere were tested on a visually guided saccade task. All three patients showed a dramatic increase in the latency of their responses to targets in the contralesional visual field. We fit their saccade latency distributions with a number of competing accumulator models that embody the alternative functional causes of this deficit. The latency difference between the two hemifields was best accounted for as an increase in the amount of evidence required for a contralesional response.

Conditions that alter saccadic eye movement latencies and affect target choice to visual stimuli and to electrical stimulation of area V1 in the monkey

In this study, we examined procedures that alter saccadic latencies and target selection to visual stimuli and electrical stimulation of area V1 in the monkey. It has been shown that saccadic eye movement latencies to singly presented visual targets form a bimodal distribution when the fixation spot is turned off a number of milliseconds prior to the appearance of the target (the gap period); the first mode has been termed express saccades and the second regular saccades. When the termination of the fixation spot is coincident with the appearance of the target (0 ms gap), express saccades are rarely generated. We show here that a bimodal distribution of saccadic latencies can also be obtained when an array of visual stimuli is presented prior to the appearance of the visual target, provided the elements of the array overlap spatially with the visual target. The overall latency of the saccadic eye movements elicited by electrical stimulation of area V1 is significantly shortened both when a gap is introduced between the termination of the fixation spot and the stimulation and when an array is presented. However, under these conditions, the distribution of saccadic latencies is unimodal. When two visual targets are presented after the fixation spot, introducing a gap has no effect on which target is chosen. By contrast, when electrical stimulation is paired with a visual target, introducing a gap greatly increases the frequency with which the electrical stimulation site is chosen.

The spatial scale of attention strongly modulates saccade latencies.

We have previously shown that when a stimulus consisting of two concentric rings moves, saccade latencies are much longer (by 150 ms) when attention is directed to the larger ring than to the smaller ring. Here, we investigated whether this effect can be explained by a deferral of the "cost" of making a saccade while the target remains inside the attentional field, or by purely visual factors (eccentricity or contrast). We found 1) latencies were shorter when attention was directed to small features irrespective of retinal eccentricity; 2) saccade latency distributions were systematically determined by the ratio between the amplitude of the stimulus step and the diameter of the attended ring: stimulus steps that were larger than the attended ring resulted in short latencies, whereas steps smaller than the attended ring resulted in proportionally longer and more variable latencies; 3) this effect was not seen in manual reaction times to the same target movement; and 4) suprathreshold changes in the contrast of targets, mimicking possible attentional effects on perceived contrast and saliency, had little effect on latency. We argue that the spatial scale of attention determines the urgency of saccade motor preparation processes by changing the rate and rate variability of the underlying decision signal, to defer the cost of saccades that result in little visual benefit.

Capture of the eyes by relevant and irrelevant onsets

During early visual processing the eyes can be captured by salient visual information in the environment. Whether a salient stimulus captures the eyes in a purely automatic, bottom-up fashion or whether capture is contingent on task demands is still under debate. In the first experiment, we manipulated the relevance of a salient onset distractor. The onset distractor could either be similar or dissimilar to the target. Error saccade latency distributions showed that early in time, oculomotor capture was driven purely bottom-up irrespective of distractor similarity. Later in time, top-down information became available resulting in contingent capture. In the second experiment, we manipulated the saliency information at the target location. A salient onset stimulus could be presented either at the target or at a non-target location. The latency distributions of error and correct saccades had a similar time-course as those observed in the first experiment. Initially, the distributions overlapped but later in time task-relevant information decelerated the oculomotor system. The present findings reveal the interaction between bottom-up and top-down processes in oculomotor behavior. We conclude that the task relevance of a salient event is not crucial for capture of the eyes to occur. Moreover, task-relevant information may integrate with saliency information to initiate saccades, but only later in time.

Diagnostic Potential of Saccadometry in Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP), an atypical parkinsonian syndrome characterized by extrapyramidal features, imbalance, supranuclear gaze paresis and dementia, can be difficult to diagnose, especially in the early stages. From the clinician's point of view, the main difficulty with this disorder is the inability to provide an accurate diagnosis, at least for the initial stages of the disease, where symptoms are often confused with other parkinsonian disorders. This inability complicates the recruitment of patients with early-stage parkinsonism to trials of disease-modifying therapy. To determine whether quantitative, objective examination of saccadic latency distributions can help to distinguish PSP patients from other groups of parkinsonian patients. We used a newly developed portable saccadometer to compare saccadic latency distributions of a group of PSP patients with two other groups in whom the initial differential diagnosis included PSP: one of these groups had Parkinson's disease and the other had developed a range of parkinsonian conditions (multiple system atrophy, dementia with Lewy bodies and corticobasal degeneration). The use of a combination of saccadic parameters provided a greater discriminative power than the use of only one parameter, such as median latency. Statistical analysis and parameterization of the distributions robustly distinguished the three groups. This approach appears to have considerable diagnostic potential in allowing a more accurate diagnosis of PSP, and may help particularly to eliminate misdiagnosis with other parkinsonian conditions.

LATER predicts saccade latency distributions in reading

When saccades are evoked by suddenly presented visual stimuli, the stochastic distribution of their reaction times is typically recinormal, in conformity with the LATER model of decision-making, sometimes with an additional sub-population of early responses. In the real world, saccades are more often spontaneous responses to static features of the visual world; nevertheless, the time between the end of one saccade and the start of the next may be regarded as a reaction time to the new image that is presented to the retina. The distribution of these times is qualitatively similar to that of evoked saccades, but typically with a longer median and more of the early responses. Here, we analyse the statistical distributions of fixation times from a large database of spontaneous saccades made while reading and show that the distributions are altered in characteristic ways by particular features of the current fixation: likely familiarity of the currently fixated word, and its proximity to the preceding fixation. These alterations are of the kind predicted by LATER: familiarity appears to influence the mean rate at which the decision signal approaches completion, whereas proximity to the previous fixation, presumably because it provides partial prior information about the upcoming word, appears to increase prior probability. We conclude that spontaneous saccades may be successfully described by the same decision-making model that can be used for evoked ones.

Saccadic latency distributions in Parkinson’s disease and the effects of l-dopa

Parkinson's disease (PD) is associated with a loss of central dopaminergic pathways in the brain leading to an abnormality of movement, including saccades. In PD, analysis of saccadic latency distributions, rather than mean latencies, can provide much more information about how the neural decision process that precedes movement is affected by disease or medication. Subject to the constraints of intersubject variation and reproducibility, latency distribution may represent an attractive potential biomarker of PD. Here we report two studies that provide information about these parameters, and demonstrate a novel effect of dopamine on saccadic latency, implying that it influences the neural decision process itself. We performed a detailed cross-sectional study of saccadic latency distributions during a simple step task in 22 medicated patients and 27 age-matched controls. This revealed high intersubject variability and an overlap of PD and control distributions. A second study was undertaken on a different population specifically to investigate the effects of dopamine on saccadic latency distributions in 15 PD patients. L-dopa was found to prolong latency, although the magnitude of the effect varied between subjects. The implications of these observations for the use of saccadic latency distributions as a potential biomarker of PD are discussed, as are the effects of L-dopa on neural decision making, where it is postulated to increase the criterion level of evidence required before the decision to move is made.