Doug P. Hanes

Neural Control of Voluntary Movement Initiation

When humans respond to sensory stimulation, their reaction times tend to be long and variable relative to neural transduction and transmission times. The neural processes responsible for the duration and variability of reaction times are not understood. Single-cell recordings in a motor area of the cerebral cortex in behaving rhesus monkeys (Macaca mulatta) were used to evaluate two alternative mathematical models of the processes that underlie reaction times. Movements were initiated if and only if the neural activity reached a specific and constant threshold activation level. Stochastic variability in the rate at which neural activity grew toward that threshold resulted in the distribution of reaction times. This finding elucidates a specific link between motor behavior and activation of neurons in the cerebral cortex.

Relationship of presaccadic activity in frontal eye field and supplementary eye field to saccade initiation in macaque: Poisson spike train analysis

The purpose of this study was to investigate the temporal relationship between presaccadic neuronal discharges in the frontal eye fields (FEF) and supplementary eye fields (SEF) and the initiation of saccadic eye movements in macaque. We utilized an analytical technique that could reliably identify periods of neuronal modulation in individual spike trains. By comparing the observed activity of neurons with the random Poisson distribution generated from the mean discharge rate during the trial period, the period during which neural activity was significantly elevated with a predetermined confidence level was identified in each spike train. In certain neurons, bursts of action potentials were identified by determining the period in each spike train in which the activation deviated most from the expected Poisson distribution. Using this method, we related these defined periods of modulation to saccade initiation in specific cell types recorded in FEF and SEF. Cells were recorded in SEF while monkeys made saccades to targets presented alone. Cells were recorded in FEF while monkeys made saccades to targets presented alone or with surrounding distractors. There were no significant differences in the time-course of activity of the population of FEF presaccadic movement cells prior to saccades generated to singly presented or distractor-embedded targets. The discharge of presaccadic movement cells in FEF and SEF could be subdivided quantitatively into an early prelude followed by a high-rate burst of activity that occurred at a consistent interval before saccade initiation. The time of burst onset relative to saccade onset in SEF presaccadic movement cells was earlier and more variable than in FEF presaccadic movement cells. The termination of activity of another population of SEF neurons, known as preparatory set cells, was time-locked to saccade initiation. In addition, the cessation of SEF preparatory set cell activity coincided precisely with the beginning of the burst of SEF presaccadic movement cells. This finding raises the possibility that SEF preparatory set cells may be involved in saccade initiation by regulating the activation of SEF presaccadic movement cells. These results demonstrate the utility of the Poisson spike train analysis to relate periods of neuronal modulation to behavior.

Countermanding saccades in humans.

We used a countermanding paradigm to investigate the relationship between conflicting cues for controlling human saccades. Subjects made a saccade to a target appearing suddenly in the periphery; but on some trials, after a delay, a stop-signal was presented that instructed subjects to inhibit the saccade. As we increased this delay, subjects increasingly failed to inhibit the movement. From measurements of this relationship, and of saccadic latency in control trials, we estimated the average time needed to inhibit the saccade (the stop-signal reaction time or SSRT). SSRTs were similar across subjects, between 125 and 145 ms, and did not vary with target luminance. We then investigated a race model in which the target initiates a response preparation signal rising linearly with a rate varying randomly from trial to trial, and racing against a similarly rising signal initiated by the cue to inhibit the saccade. The first process to cross a trigger threshold determines whether the saccade is initiated or not. In Monte Carlo simulations, this model correctly predicted the probability of successful saccade inhibition as a function of the stop-signal delay, and also the statistical distributions of saccadic latency during trials in which a stop-signal was presented but the subject failed to inhibit the saccade. These findings provide a comparison to results previously described in the monkey, and show that a simple race model with a linear rise to threshold may underlie behavioural performance in tasks of this kind.

Countermanding saccades in macaque

A countermanding paradigm was utilized to investigate the regulation of saccade initiation. Two rhesus monkeys were instructed to generate a saccade to a peripheral target; however, on a fraction of trials after a delay, the monkeys were signaled to inhibit saccade initiation. With short delays between the presentation of the target and the signal to inhibit saccade generation, monkeys withheld saccades to the peripheral target. As the delay of the stop signal increased, monkeys increasingly failed to withhold the saccade. The hypothesis that the generation of the saccade is determined by a race between a go and a stop process provides three explicit means of estimating the covert latency of response to the stop signal. This latency, known as stop signal reaction time, was estimated to be on average 82 ms for both monkeys. Because the stop signal latency represents the time required to exert inhibitory control over saccade production, the countermanding paradigm will be useful for studying neural mechanisms that regulate saccade initiation.

Influence of history on saccade countermanding performance in humans and macaque monkeys

The stop-signal or countermanding task probes the ability to control action by requiring subjects to withhold a planned movement in response to an infrequent stop signal which they do with variable success depending on the delay of the stop signal. We investigated whether performance of humans and macaque monkeys in a saccade countermanding task was influenced by stimulus and performance history. In spite of idiosyncrasies across subjects several trends were evident in both humans and monkeys. Response time decreased after successive trials with no stop signal. Response time increased after successive trials with a stop signal. However, post-error slowing was not observed. Increased response time was observed mainly or only after cancelled (signal inhibit) trials and not after noncancelled (signal respond) trials. These global trends were based on rapid adjustments of response time in response to momentary fluctuations in the fraction of stop signal trials. The effects of trial sequence on the probability of responding were weaker and more idiosyncratic across subjects when stop signal fraction was fixed. However, both response time and probability of responding were influenced strongly by variations in the fraction of stop signal trials. These results indicate that the race model of countermanding performance requires extension to account for these sequential dependencies and provide a basis for physiological studies of executive control of countermanding saccade performance.

Relation of Frontal Eye Field Activity to Saccade Initiation during a Countermanding Task

The countermanding (or stop signal) task probes the control of the initiation of a movement by measuring subjects’ ability to withhold a movement in various degrees of preparation in response to an infrequent stop signal. Previous research found that saccades are initiated when the activity of movement-related neurons reaches a threshold, and saccades are withheld if the growth of activity is interrupted. To extend and evaluate this relationship of frontal eye field (FEF) activity to saccade initiation, two new analyses were performed. First, we fit a neurometric function that describes the proportion of trials with a stop signal in which neural activity exceeded a criterion discharge rate as a function of stop signal delay, to the inhibition function that describes the probability of producing a saccade as a function of stop signal delay. The activity of movement-related but not visual neurons provided the best correspondence between neurometric and inhibition functions. Second, we determined the criterion discharge rate that optimally discriminated between the distributions of discharge rates measured on trials when saccades were produced or withheld. Differential activity of movement-related but not visual neurons could distinguish whether a saccade occurred. The threshold discharge rates determined for individual neurons through these two methods agreed. To investigate how reliably movement-related activity predicted movement initiation; the analyses were carried out with samples of activity from increasing numbers of trials from the same or from different neurons. The reliability of both measures of initiation threshold improved with number of trials and neurons to an asymptote of between 10 and 20 movement-related neurons. Combining the activity of visual neurons did not improve the reliability of predicting saccade initiation. These results demonstrate how the activity of a population of movement-related but not visual neurons in the FEF contributes to the control of saccade initiation. The results also validate these analytical procedures for identifying signals that control saccade initiation in other brain structures.

Neural mechanisms of selection and control of visually guided eye movements

The selection and control of action is a critical problem for both biological and machine animated systems that must operate in complex real world situations. Visually guided eye movements provide a fruitful and important domain in which to investigate mechanisms of selection and control. Our work has focused on the neural processes that select the target for an eye movement and the neural processes that regulate the production of eye movements. We have investigated primarily an area in the frontal cortex that plays a central role in the production of purposive eye movements which is called the frontal eye field. A fundamental property of biological nervous systems is variability in the time to respond to stimuli. Thus, we have been particularly interested in examining whether the time occupied by perceptual and motor decisions explains the duration and variability of behavioral reaction times. Current evidence indicates that salient visual targets are located through a temporal evolution of retinotopically mapped visually evoked activation. The responses to non-target stimuli become suppressed, leaving the activation representing the target maximal. The selection of the target leads to growth of movement-related activity at a stochastic rate toward a fixed threshold to generate the gaze shift. For a given image, the neural concomitants of perceptual processing occupy a relatively constant interval so that stochastic variability in response preparation introduces additional variability in reaction times. Neural processes in another cortical area, the supplementary eye field, do not participate in the control of eye movements but seem to monitor performance. The signals and processes that have been observed in the cerebral cortex of behaving monkeys may provide useful examples for the engineering problems of robotics.

Effects of low-dose isoflurane on saccadic eye movement generation

The effects of 0.15% quasi‐steady‐state end‐tidal isoflurane on two saccadic eye‐movement tests were examined in five volunteers using a newly devised computer‐based recording system. The tests were saccadic latency and a countermanding task, the latter being an indicator of the highest levels of conscious performance. A moving light‐emitting diode target was displayed on a screen and in the saccadic‐latency task the latency of eye movement to the target was measured. In all five subjects the latency increased with anaesthetic by an amount which varied from 8 to 45 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In the countermanding task, the subject had to voluntarily inhibit movement to the target. Again anaesthetic increased the latency of response, which varied from 6 to 33 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In these studies it appeared that two tasks, one a simple latency test and the other, the countermanding task, requiring higher cortical processing were equally impaired at subanaesthetic concentrations of isoflurane.