Modelling Prosaccade Latencies across Multiple Decision-Making Tasks.

Oculomotor decision making can be investigated by a simple step task, where a person decides whether a target has jumped to the left or the right. More complex tasks include the countermanding task (look at the jumped target, except when a subsequent signal instructs you not to) and the Wheeless task (where the jumped target sometimes then quickly jumps to a new location). Different instantiations of the LATER (Linear Approach to Threshold with Ergodic Rate) model have been shown to explain the saccadic latency data arising from these tasks, despite it being almost inconceivable that completely separate decision-making mechanisms exist for each. However, these models have an identical construction with regards to predicting prosaccadic responses (all step task trials, and control trials in countermanding and Wheeless tasks, where no countermanding signal is given or when the target does not make a second jump). We measured saccadic latencies for 23 human observers each performing the three tasks, and modelled prosaccade latencies with LATER to see if model parameters were usefully preserved across tasks. We found no significant difference in reaction times and model parameters between the step and Wheeless tasks (mean 175 and 177 ms, respectively; standard deviation, SD 22 and 24 ms). In contrast, we identified prolonged latencies in the countermanding tasks (236 ms; SD 37 ms) explained by a slower rise and an elevated threshold of the decision making signal, suggesting elevated participant caution. Our findings support the idea that common machinery exists for oculomotor decision-making, which can be flexibly deployed depending upon task demands.

Not moving: the fundamental but neglected motor function.

The function of the motor system in preventing rather than initiating movement is often overlooked. Not only are its highest levels predominantly, and tonically, inhibitory, but in general behaviour it is often intermittent, characterized by relatively short periods of activity separated by longer periods of stillness: for most of the time we are not moving, but stationary. Furthermore, these periods of immobility are not a matter of inhibition and relaxation, but require us to expend almost as much energy as when we move, and they make just as many demands on the central nervous system in controlling their performance. The mechanisms that stop movement and maintain immobility have been a greatly neglected area of the study of the brain. This paper introduces the topics to be examined in this special issue of Philosophical Transactions, discussing the various types of stopping and stillness, the problems that they impose on the motor system, the kinds of neural mechanism that underlie them and how they can go wrong.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'.

LATEST: A model of saccadic decisions in space and time.

Many of our actions require visual information, and for this it is important to direct the eyes to the right place at the right time. Two or three times every second, we must decide both when and where to direct our gaze. Understanding these decisions can reveal the moment-to-moment information priorities of the visual system and the strategies for information sampling employed by the brain to serve ongoing behavior. Most theoretical frameworks and models of gaze control assume that the spatial and temporal aspects of fixation point selection depend on different mechanisms. We present a single model that can simultaneously account for both when and where we look. Underpinning this model is the theoretical assertion that each decision to move the eyes is an evaluation of the relative benefit expected from moving the eyes to a new location compared with that expected by continuing to fixate the current target. The eyes move when the evidence that favors moving to a new location outweighs that favoring staying at the present location. Our model provides not only an account of when the eyes move, but also what will be fixated. That is, an analysis of saccade timing alone enables us to predict where people look in a scene. Indeed our model accounts for fixation selection as well as (and often better than) current computational models of fixation selection in scene viewing. (PsycINFO Database Record

The random dot tachistogram: a novel task that elucidates the functional architecture of decision.

Reaction times are long and variable, almost certainly because they result from a process that accumulates noisy decision signals over time, rising to a threshold. But the origin of the variability is still disputed: is it because the incoming sensory signals are themselves noisy? Or does it arise within the brain? Here we use a stimulus - the random dot tachistogram - which demands spatial integration of information presented essentially instantaneously; with it, we demonstrate three things. First, that the latency distributions still show the variability characteristic of LATER, implying that there must be two integrators in series. Secondly, that since this variability persists despite removal of all temporal noise from the stimulus, or even trial-to-trial spatial variation, it must come from within the nervous system. Finally, that the average rate of rise of the decision signal depends linearly on how many dots move in a given direction. Taken together, this suggests a rather simple, two-stage model of the overall process. The first, detection, stage performs local temporal integration of stimuli; the local, binary, outcomes are linearly summed and integrated by LATER units in the second stage, that perform the final global decision by a process of racing competition.

Sequences show rapid motor transfer and spatial translation in the oculomotor system.

Every day we perform learnt sequences of actions that seem to happen almost without awareness. It has been argued that for learning such sequences parallel learning networks exist - one using spatial coordinates and one using motor coordinates - with sequence acquisition involving a progressive shift from the former to the latter as a sequence is rehearsed. When sequences are interrupted by an out-of-sequence target, there is a delay in the response to the target, and so here we transiently interrupt oculomotor sequences to probe the influence of oculomotor rehearsal and spatial coordinates in sequence acquisition. For our main experiments, we used a repeating sequences of eight targets in length that was first learnt either using saccadic eye movements (left/right), manual responses (left/right or up/down) or as a sequence of colour (blue/red) requiring no motor response. The sequence was immediately repeated for saccadic eye movements, during which the influence of on out-of-sequence target (an interruption) was assessed. When a sequence is learnt beforehand in an abstract way (for example, as a sequence of colours or of orthogonally mapped manual responses), interruptions are immediately disruptive to latency, suggesting neither motor rehearsal nor specific spatial coordinates are essential for encoding sequences of actions and that sequences - no matter how they are encoded - can be rapidly translated into oculomotor coordinates. The magnitude of a disruption does, however, correspond to how well a sequence is learnt: introducing an interruption to an extended sequence before it was reliably learnt reduces the magnitude of the latency disruption.

The LATER model of reaction time and decision.

How do we choose one option rather than another when faced with uncertainty about the information we receive, and the consequences of what we decide? The LATER (Linear Approach to Threshold with Ergodic Rate) model has proved to be remarkably accurate in predicting how we respond in such situations. Given its conceptual simplicity, its grounding in fundamental Bayesian principles and its very few free parameters, it is being increasingly adopted for a wider range of choice tasks, helping us to understand the underlying neural mechanisms, and in applying this to clinical disorders. Here, we provide a thorough discussion of the history behind this model, and how it can be applied to more complex decisions, including anti-saccades, Go-NoGo, countermanding and other situations where newly-arriving information means that ongoing decisions must be modified. The neuroscience of decision-making is progressing rapidly, and we anticipate that wider understanding and application of this model will help simplify the interpretation of increasingly advanced decision behaviour both in the laboratory and clinic.

Ultrafast initiation of a neural race by impending errors.

KEY POINTS: The brain makes decisions by means of races between neural units representing alternative choices. In the present study, we record the eyemovements made in the Wheeless task, when a visual stimulus is followed after a short delay by another stimulus demanding a different response. The behaviour can be very precisely described as a race between three independent decision processes: one Go process for each of the responses, and a Stop process that tries to cancel the first, now erroneous, response. To explain the high success rate for cancellation that we observe, the onset time for the Stop process must be some 10-20 ms shorter than for Go. As well as extending our understanding of the dynamics of complex decision-making, this task provides a rapid, non-invasive method for quantifying disorders of higher neural function. ABSTRACT: The brain makes decisions by means of races between neural units representing alternative choices, and such models can predict behaviour in decision tasks in a precisely quantitative way. But what is less clear is how soon after the stimulus the race actually starts. In the present study, we re-visit a complex decision experiment: the Wheeless task, in which a saccadic stimulus is followed after a short delay by a second stimulus, with the subject sometimes making a saccade to the first, now inappropriate, stimulus, and sometimes going straight to the correct one. We demonstrate that a simple model with three accumulator units, two 'Go' and one 'Stop', can then account in detail for the individual responses made, as well as their timing. This complex decision-making behaviour is predicted directly for each individual subject by their performance in a simple step saccadic task, which identifies the two free parameters that are specific for each subject. By contrast to previous assumptions, we find that it is necessary for the onset time of the Stop unit to be shorter than for Go by 10-20 ms. This suggests a specifically fast mechanism for altering responses in situations where urgent action is needed to prevent an impending error.

Saccadic foraging: reduced reaction time to informative targets.

The study of saccadic reaction times has revealed a great deal about the neural mechanisms underlying neural decision, in terms of Bayesian factors such as prior probability and information supply. In addition, recent work has shown that saccades are faster to visual targets associated with conventional monetary or food rewards. However, because the purpose of saccades is to acquire information, it could be argued that this is an unnatural situation: the most natural and fundamental reward is the amount of information supplied by a target. Here, we report the results of a study investigating the hypothesis that a saccade to a target whose colour provides information about the location of a subsequent target is faster than to one that does not. We show that the latencies of saccades to a location that provides reliable information about the location of a future target are indeed shorter, their distributions being shifted in a way that implies that the rate of rise of the underlying decision signal is increased. In a race between alternative targets, this means that expected information will be an important factor in deciding where to look, so that 'foraging' saccades are more likely to be made to useful targets.

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 (-12 hours) and after (+2 and +5 days) 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 ± 4.9 years). Following cranial surgery, saccades initiated by the cerebral hemisphere on the operated side demonstrated significant deteriorations in function after 2 days (p < 0.01) that normalised after 5 days. 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.

Basal ganglia: racing to say no.

How we choose one action over another has intrigued neuroscientists for decades. Early models of decision-making involved a race between processes representing alternative choices. To explain behaviour in complex decisions, for example, where one must cancel an impending action, a Stop unit must also join the race. Recent neuronal recordings have demonstrated just such a race between Go and Stop processes in the basal ganglia. This is a landmark advance because it neurophysiologically justifies the need for a Stop process in such tasks, and very likely in other behaviours requiring rapid cancellation of impending actions.

Target direction rather than position determines oculomotor expectation in repeating sequences.

Saccadic latencies to targets appearing to the left and right of fixation in a repeating sequence are significantly increased when a target is presented out of sequence. Is this because the target is in the wrong position, the wrong direction, or both? To find out, we arranged for targets in a horizontal plane occasionally to appear with an unexpected eccentricity, though in the correct direction. This had no significant effect on latency, unlike what is observed when targets appeared in the unexpected direction. That subjects learnt sequences of directions rather than simply positions was further confirmed in an experiment where saccade direction was a repeating sequence, but eccentricity was randomised. Latency was elevated when a target was episodically presented in an unexpected direction. Latencies were also elevated when targets appeared in the correct hemifield but at an unexpected direction (35° polar angular displacement from the horizontal, a displacement roughly equivalent in collicular spacing to our unexpected eccentricity), although this elevation was of a smaller magnitude than when targets appeared in an unexpected direction along the horizontal. Finally, we confirmed that not all changes in the stimulus cause disruption: an unexpected change in the orientation or colour of the target did not alter latency. Our results show that in a repeating sequence, the oculomotor system is primarily concerned with predicting the direction of an upcoming eye movement rather than its position. This is consistent with models of oculomotor control developed for randomly appearing targets in which the direction and amplitude of saccades are programmed separately.

Re-starting a neural race: anti-saccade correction.

In the anti-saccade task, a subject must make a saccadic eye movement in the opposite direction from a suddenly-presented visual target. This sets up a conflict between the natural tendency to make a pro-saccade towards the target and the required anti-saccade. Consequently there is a tendency to make errors, usually corrected by a second movement in the correct anti-saccade direction. In a previous paper, we showed that a very simple model, with racing LATER (Linear Approach to Threshold at Ergodic Rate) units for the pro- and anti-directions, and a stop unit that inhibits the impending error response, could account precisely for the detailed distributions of reaction times both for correct and error responses. However, the occurrence and timing of these final corrections have not been studied. We propose a novel mechanism: the decision race re-starts after an error. Here we describe measurements of all the responses in an anti-saccade task, including corrections, in a group of human volunteers, and show that the timing of the corrections themselves can be predicted by the same model with one additional assumption, that initiation of an incorrect pro-saccade also resets and initiates a corrective anti-saccade. No extra parameters are needed to predict this complex aspect of behaviour, adding weight to our proposal that we correct our mistakes by re-starting a neural decision race. The concept of re-starting a decision race is potentially exciting because it implies that neural processing of one decision can influence the next, and may be a fruitful way of understanding the complex behaviour underlying sequential decisions.

The relationship between abnormalities of saccadic and manual response times in Parkinson's disease.

BACKGROUND: Clinicians normally use subjective rating scales to estimate the impairment of patients with Parkinson's disease (PD). More objective and quantitative methods of assessment would greatly aid our understanding of the disease. One promising approach is to measure reaction time: the large amount of data recorded in a short period provides precise, reproducible evaluation of the underlying neural decision processes. Manual evoked reaction times and repetitive tapping speed are often used, but differences of experimental design and analysis tend to obscure their interpretation. Saccadic latency, in many ways a simpler and more standardised task, is also normally affected in PD, but its relation to the kind of movement impairment that affects patients' quality of life is less obvious. OBJESTIVE: The aim of this study was to evaluate these tasks in detail and also see whether their use in combination could provide a better measure than each in isolation. METHODS: We compared three reaction time tasks: saccadometry, and evoked and spontaneous tapping, using protocols as similar as possible, correlating the measurements within a group of PD patients and of age-matched controls. RESULTS: Surprisingly, manual and saccadic performance is uncorrelated in the normal population; but both are similarly affected by PD. The differences between groups are strengthened when the three measures are combined. CONCLUSIONS: Saccadic latency can be regarded as an appropriate surrogate for more general kinds of motor impairment. The combination of saccadic and manual parameters enhances their potential use in quantifying disease status and evaluating treatments.

An internationally standardised antisaccade protocol.

Detailed measurements of saccadic latency--the time taken to make an eye movement to a suddenly-presented visual target--have proved a valuable source of detailed and quantitative information in a wide range of neurological conditions, as well as shedding light on the mechanisms of decision, currently of intense interest to cognitive neuroscientists. However, there is no doubt that more complex oculomotor tasks, and in particular the antisaccade task in which a participant must make a saccade in the opposite direction to the target, are potentially more sensitive indicators of neurological dysfunction, particularly in neurodegenerative conditions. But two obstacles currently hinder their widespread adoption for this purpose. First, that much of the potential information from antisaccade experiments, notably about latency distribution and amplitude, is typically thrown away. Second, that there is no standardised protocol for carrying out antisaccade experiments, so that results from one laboratory cannot easily be compared with those from another. This paper, the outcome of a recent international meeting of oculomotor scientists and clinicians with an unusually wide experience of such measurements, sets out a proposed protocol for clinical antisaccade trials: its adoption will greatly enhance the clinical and scientific benefits of making these kinds of measurements.

Antisaccades as decisions: LATER model predicts latency distributions and error responses.

Antisaccades are widely used in the study of voluntary behavioural control: a subject told to look in the opposite direction to a stimulus must suppress the automatic response of looking towards it, leading to delays and errors that are commonly believed to be generated by competing decision processes. However, currently we lack a precise model of the details of antisaccade behaviour, or indeed detailed quantitative data in the form of full reaction time distributions by which any such model could be evaluated. We measured subjects' antisaccade latency distributions and error rates, and found that we could account precisely for both distributions and errors with a model having three competing LATER processes racing to threshold. In an even more stringent test, we manipulated subjects' expectation of the stimulus, leading to large changes in behaviour that were nevertheless still accurately predicted. The antisaccade task is widely used in the laboratory and clinic because of the relative complexity and vulnerability of the underlying decision mechanisms: our model, grounded in detailed quantitative data, is a robust way of conceptualizing these processes.

Saccadic abnormalities in frontotemporal dementia.

OBJECTIVE: To characterize saccadic eye movements, as a marker of decision-making processes, in frontotemporal dementia (FTD). METHODS: Saccadometry was performed on a cross-section of patients with FTD, using a portable saccadometer, and results compared to matched control subjects. We used the Linear Approach to Threshold with Ergodic Rate model to generate measures of decision-making speed and incidence of early saccades. Patterns of cortical atrophy were related to decision-making processes using voxel-based morphometry (VBM) analysis. RESULTS: A total of 45 subjects (22 FTD: 10 with behavioral variant FTD and 12 with primary progressive aphasia, and 23 controls) were studied. A measure of decision-making speed, µ, was reduced in FTD, resulting in prolonged saccadic latency, but the incidence of early saccades was increased compared to controls. In addition, performance on an antisaccade task was poor in FTD compared to controls. Decision-making speed and the incidence of early saccades were independently correlated with atrophy of the left frontal eye field, and decision-making speed also correlated with atrophy of the left cingulate eye field. CONCLUSION: Saccades are abnormal in FTD, reflecting reduced decision-making speed, and these abnormalities related to atrophy of the left frontal eye field. In addition, patients with FTD had an increased incidence of early saccades, which may be due to reduced inhibition of primitive responses.

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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Statistical characteristics of finger-tapping data in Huntington's disease.

Measuring the rate of finger tapping is a technique commonly used as an indicator of impairment in degenerative neurological conditions, such as Huntington's disease. The information it provides can be greatly enhanced by analysing not simply the overall tapping rate, but also the statistical characteristics of the individual times between each successive response. Recent technological improvements in the recording equipment allow the responses to be analysed extremely quickly, and permit modification of the task in the interest of greater clinical specificity. Here we illustrate its use with some pilot data from a group of manifest HD patients and age-matched controls. Even in this small cohort, differences in the responses are apparent that appear to relate to the severity of the disease as measured by conventional behavioural tests.

What Sherrington missed: the ubiquity of the neural integrator.

Despite its numerous illustrations unequivocally demonstrating the phenomenon, in Sherrington's Integrative Action of the Nervous System, he considered "integration" only in its spatial and coordinative aspects, and failed to notice time integration as an equally pervasive feature of all motor systems. First demonstrated in the oculomotor system by Robinson and others, in the vestibulo-ocular reflex, and then as a necessary component of the oculomotor "final common path" (another Sherringtonian concept), integration is manifested at two further levels: in generating optokinetic responses and in the mechanism of saccadic decision. But integration is not a purely oculomotor phenomenon: behind it lie two fundamental motor principles. First, that the brain operates in terms of change, implying differentiation in sensory systems and integration in motor ones. Second, that the molecular physiology of muscle contraction means that remaining still requires not only continual expenditure of energy but also continual computational effort--a firm and precise integrator.