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Biomedical subjects

R H S Carpenter

Publications and source records attributed to R H S Carpenter.

At least 19 recordsLinked to original sources

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.

Humans↗

Changes in expectation consequent on experience, modeled by a simple, forgetful neural circuit.

Our expectation of an event such as a visual stimulus clearly depends on previous experience, but how the brain computes this expectation is currently not fully understood. Because expectation influences the time to respond to a stimulus, we arranged for the probability of a visual target to suddenly change and found that the time taken to make an eye movement to it then changed continuously, eventually stabilizing at a level reflecting the new probability. The time course of this change can be modeled making a simple assumption: that the brain discounts old information about the probability of an event by a factor lambda, relative to new information. The value of lambda presumably represents a compromise between responding rapidly to genuine changes in the environment and not prematurely discarding information still of value. The model we propose may be implemented by a very simple neural circuit composed of only a few neurons.

Adult↗

A noisy transform predicts saccadic and manual reaction times to changes in contrast.

One of the most important factors affecting the time taken to respond to a visual stimulus is contrast, and studies of reaction time can provide precise, quantitative information about the underlying signal processing. In this study we measured both saccadic and manual reaction times to step increments in target contrast. Our results over a range of initial contrasts are consistent with a simple model consisting of a noisy logarithmic transducer followed by a rise-to-threshold accumulator. A systematic comparison with previous contrast-processing models also shows that the commonly used method of linear regression may not be a particularly sensitive tool in deciding between them. We found similar parameters for the contrast processor in both saccadic and manual reaction times, as might be expected if a common target detection stage precedes each type of reaction.

Adult↗

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.

Aged↗

Task switching as a two-stage decision process.

Saccades represent decisions, and the study of their latency has led to a neurally plausible model of the underlying mechanisms, LATER (Linear Approach to Threshold with Ergodic Rate), that can successfully predict reaction time behavior in simple decision tasks, with fixed instructions. However, if the instructions abruptly change, we have a more complex situation, known as task switching. Psychologists' explanations of the phenomena of task switching have so far tended to be qualitative rather than quantitative, and not intended to relate particularly clearly to existing models of decision making or to likely neural implementations. Here, we investigated task switching using a novel saccadic task: we presented the instructions by stimulus elements identical to those of the task itself, allowing us to compare decisions about instructions with decisions in the actual task. Our results support a relatively simple model consisting of two distinct LATER processes in series: the first detects the instruction, the second implements it.

Adult↗

The use of quantitative oculometry in the assessment of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterised by progressive motor, cognitive and psychiatric symptoms. Objective measurement of disease severity is of increasing importance for detecting symptomatic disease, as well as monitoring disease progression and the response to novel therapeutic interventions. Using a newly-developed infra-red scleral oculometer, we measured saccadic latencies and durations in HD patients exhibiting a broad range of symptoms (n=24) and control subjects of comparable ages (n=20) to see whether these parameters might reflect the presence or severity of HD. Latency distributions were characterised by creating reciprobit plots for each subject, whilst parametric statistics were applied to durations. Compared with the control group, we found the HD group had a significantly increased median latency, and early saccades were more prominent. In addition, HD patients exhibited an increased saccadic duration and variability of duration. Using Bayesian (likelihood) analysis, we obtained saccadic support values for the presence of clinical HD, which correlated with the motor Unified Huntington's Disease Rating Scale (UHDRS) score in these patients. A sensitivity/specificity analysis of all 44 participants showed that the use of this multivariate support measure was highly successful in predicting HD status, correctly diagnosing 75% of the HD patients, and (95%) of the controls; with a different criterion, these figures were 96 and 15%. Furthermore, we correctly predicted absence of disease in two additional subjects subsequently confirmed to be genetically unaffected. This strongly suggests that multivariate support values derived from saccadic parameters may provide an objective, quantitative biomarker of HD, especially the degree of motor impairment. However, larger longitudinal studies are required to determine whether they can reliably detect the earliest presymptomatic disease, or faithfully reflect disease progression.

Adult↗

Visual pursuit: an instructive area of cortex.

Recent experiments have revealed an area of visual cortex that provides a velocity error signal which enables the eye to learn to pursue targets when they move in a predictable way.

Animals↗

An anatomically constrained, stochastic model of eye movement control in reading.

This article presents SERIF, a new model of eye movement control in reading that integrates an established stochastic model of saccade latencies (LATER; R. H. S. Carpenter, 1981) with a fundamental anatomical constraint on reading: the vertically split fovea and the initial projection of information in either visual field to the contralateral hemisphere. The novel features of the model are its simulation of saccade latencies as a race between two stochastic rise-to-threshold LATER units and its probabilistic selection of the target for the next saccade. The model generates simulated eye movement behavior that exhibits important characteristics of actual eye movements made during reading; specifically, simulations produce realistic saccade target distributions and replicate a number of critical reading phenomena, including the effects of word frequency on fixation durations, the inverted optimal viewing position effect, the trade-off between first and second fixation durations of refixated words, and the dependence of parafoveal preview benefit on eccentricity.

Eye Movements↗

Contrast, probability, and saccadic latency; evidence for independence of detection and decision.

Many factors influence how long it takes to respond to a visual stimulus. The lowest-level factors, such as luminance and contrast, determine how easily different elements of a target can be detected. Higher-level factors are to do with whether these elements constitute a stimulus requiring a response; they include prior probability and urgency. It is natural to think of these two processes, detection and decision, as occurring in series, so that overall reaction time is essentially the sum of the contributions of each stage. Here, measurements of saccadic latency to visual targets whose contrast and prior probability are systematically manipulated demonstrate that there are indeed separable stages of detection and decision. Both can be quantitatively described by rise-to-threshold mechanisms; the average rate of rise of the first is a simple logarithmic function of target contrast, whereas the second shows the linear rise characteristic of the LATER model of neural decision making. The implication is that under normal, high-contrast conditions, in which detection is very fast, the random variability that is characteristic of all reaction times is not caused by sensory noise but is gratuitously introduced by the brain itself; paradoxically, by conferring unpredictability it may aid an organism's survival.

Contrast Sensitivity↗

Venous excess: a new approach to cardiovascular control and its teaching.

The circulatory control system is driven partly by factors relating to the arterial side and partly by factors relating to the venous side. Students are generally provided with a conceptually clear account of the arterial side, based on sound homeostatic mechanisms of negative feedback from a well-defined error signal, arterial pressure. However, on the venous side, teaching is often based on the notion of venous return, a concept that, as normally presented, is imprecise and intangible, a frequent cause of confusion that may lead to errors of clinical practice. Although one can trace these misconceptions back to some of Guyton's publications, Guyton himself was well aware of the complexities of venous resistance and capacitance but has not always been well served by subsequent misinterpretation. The fundamental problem with venous return that makes it inappropriate for controlling the circulation is that it lacks the essential requirement of being an error signal. We propose instead a new variable, venous excess, which represents the accumulation of any mismatch between the rate of blood entering the great veins and the rate of leaving, the cardiac output. As well as being directly observable without intervention (in a patient's jugular vein), it meets all of the requirements of an error signal: via the Starling mechanism it stimulates cardiac output, regulates venous compliance, and in the longer term is an important determinant of fluid intake and excretion, and these effects act to reduce the original perturbation. Based on this concept, we suggest a simple and secure basis for teaching the control of the circulation that avoids undue reliance on entities that are difficult to specify or measure and emphasizes the role of feedback and the similarities between the arterial and venous mechanisms.

Animals↗

Homeostasis: a plea for a unified approach.

Accompanying the progressive erosion of a coherent sense of physiology as an intellectual discipline, there has been a tendency to lose sight of the homeostatic principles that underpin physiological science, and to teach them in an oversimplified form. When (as is increasingly the case) these principles are rediscovered, they are often treated as something both novel and distinct from homeostasis, fragmenting what is best understood and taught as a unified whole. This article urges a more unitary approach to homeostasis, and attempts to show how such an approach can be presented.

Animals↗

Accuracy, information, and response time in a saccadic decision task.

Reaction times generally follow a simple law economically described by the LATER model, in which a decision signal rises linearly in response to information about a target to a threshold at which a response is initiated, at a rate that varies from trial to trial with a Gaussian distribution. Functionally, LATER may be regarded as an ideal decision mechanism incorporating prior probability, information, and criterion level or urgency; this can be tested quantitatively by seeing whether LATER accurately predicts the effects on latency distributions of manipulating these variables: in this case, information and urgency. We presented subjects with random-dot kinematograms while fixating a central LED. The information content of the display was varied by altering the proportion of the dots moving coherently together either left or right rather than randomly. As soon as subjects detected the direction of coherent movement, they made a saccade in the same direction to one of a pair of LEDs on each side of the fixation target. Subjects responded either carefully, taking time to ensure an accurate judgement, or more hastily and with less regard for accuracy. The distributions of latencies under the different combinations of conditions were found to conform to LATER's predictions. Providing more information or increasing urgency both reduce latency; but they alter the observed distributions in different ways, equivalent to increasing the mean rate of rise on the one hand or reducing the criterion level on the other. Making only simple assumptions about the underlying mechanisms, the observed changes can be accounted for quantitatively.

Decision Making↗

Dose-related effect of sevoflurane sedation on higher control of eye movements and decision making.

BACKGROUND: Saccadic latency may provide an objective method to assess sedative doses of anaesthetic on cortical oculomotor mechanisms and decision making. METHODS: We tested the effects of random doses of 0, 0.1, 0.2 and 0.3 MAC sevoflurane in six subjects, in a double-blind study using two measures of behavioural impairment: saccadic latency and stop signal reaction time (SSRT) in a countermanding task. RESULTS: Saccadic latency and SSRT both increased with increasing doses of sevoflurane. In both measures, reciprocal reaction time was linearly related to dose in each subject: all but two of the twelve regression coefficients were statistically significant (P<0.05). In one subject, SSRT was significantly more sensitive than simple latency (P<0.05); for the others there was no significant difference. CONCLUSION: Measurements of this kind could potentially provide estimates of cortical effects of sevoflurane sedation, and give a clinically useful measure of cognitive fitness.

Adult↗

The effect of low dose sevoflurane on saccadic eye movement latency.

We investigated the effects of a low concentration of sevoflurane on a saccadic eye movement task that reflects the performance of higher neural decision and control mechanisms. The experiments were performed double-blind in five subjects, using either 0.15% end-tidal sevoflurane in oxygen, or pure oxygen as a placebo. Saccades were recorded and analysed using a computer-based recording system that also controlled the presentation of visual targets. Administration of oxygen produced no significant change in median latency compared with breathing air; but in four of the five subjects, administration of sevoflurane in oxygen caused a significant increase in latency. These results suggest that measurement of median saccadic latency may be a useful functional measurement of impairment of performance during recovery from anaesthesia.

Adult↗

Neuropsychological and quantitative oculometric study of a case of sporadic Creutzfeldt-Jakob disease at predementia stage.

A quantitative assessment of eye movements and a detailed neuropsychological profile were conducted at predementia stage in a patient who later had histological confirmation of sporadic Creutzfeldt-Jakob disease (CJD). The patient was a middle aged man who presented with abnormal eye movements and poor balance. Neuropsychological deficits suggested orbito-mesial dysfunction, resembling progressive supranuclear palsy. Oculometry showed accurate but dramatically slowed saccades, with normal pursuit movements. Neuropsychology and quantitative oculometry may be of value in the differential diagnosis and earlier detection of dementia-akinetic-rigid syndromes; in particular, because of the highly stereotyped nature of saccades, routine quantitative oculometry can reveal significant impairment at a very early stage in some cases and could thus facilitate earlier diagnosis.

Cognition↗