Antisaccade Trials Research Articles

Schizophrenic subjects show deficient inhibition but intact task switching on saccadic tasks

Background: Schizophrenic patients have executive function deficits, presumably on the basis of prefrontal cortex dysfunction. Although they consistently show impaired inhibition, the evidence of a task switching deficit is less consistent and is often based on performance of neuropsychological tests that require several cognitive processes (e.g., the Wisconsin Card Sort Test [WCST]). We investigated inhibition and task switching using saccadic tasks to determine whether schizophrenic patients have selective impairments of these executive functions. Methods: Sixteen normal and 21 schizophrenic subjects performed blocks of randomly mixed prosaccade and antisaccade trials. This gave rise to four trial types: prosaccades and antisaccades that were either repeated or switched. Response accuracy and latency were measured. Schizophrenic subjects also performed the WCST. Results: Schizophrenic subjects showed abnormal antisaccade and WCST performance. In contrast, task switching was normal and unrelated to either antisaccade or WCST performance. Conclusions: The finding of intact task switching performance that is unrelated to other measures of executive function demonstrates selective rather than general impairments of executive functions in schizophrenia. The findings also suggest that abnormal WCST performance is unlikely to be a consequence of deficient task switching. We hypothesize that inhibition and task switching are mediated by distinct neural networks, only one of which is dysfunctional in schizophrenia.

Influence of stimulus eccentricity and direction on characteristics of pro- and antisaccades in non-human primates.

The ability to inhibit reflexes in favor of goal-oriented behaviors is critical for optimal exploration and interaction with our environment. The antisaccade task can be used to investigate the ability of subjects to suppress a reflexive saccade (prosaccade) to a suddenly appearing visual stimulus and instead generate a voluntary saccade (antisaccade) to its mirror location. To understand the neural mechanisms required to perform this task, our lab has developed a non-human primate model. Two monkeys were trained on a task with randomly interleaved pro- and antisaccade trials, with the color of the central fixation point (FP) instructing the monkey to either make a prosaccade (red FP) or an antisaccade (green FP). In half of the trials, the FP disappeared 200 ms before stimulus presentation (gap condition) and in the remaining trials, the FP remained visible (overlap condition) during stimulus presentation. The effect of stimulus eccentricity and direction was examined by presenting the stimulus at one of eight different radial directions (0-360 degrees ) and five eccentricities (2, 4, 8, 10, and 16 degrees ). Antisaccades had longer saccadic reaction times (SRTs), more dysmetria, and lower peak velocities than prosaccades. Direction errors in the antisaccade task were more prevalent in the gap condition. The difference in mean SRT between correct pro- and antisaccades, the anti-effect, was greater in the overlap condition. The difference in mean SRT between the overlap and the gap condition, the gap effect, was larger for antisaccades than for prosaccades. The manipulation of stimulus eccentricity and direction influenced SRT and the proportion of direction errors. These results are comparable to human studies, supporting the use of this animal model for investigating the neural mechanisms subserving the generation of antisaccades.

Neuronal Correlates for Preparatory Set Associated with Pro-Saccades and Anti-Saccades in the Primate Frontal Eye Field

Diversity in behavioral responses to sensory stimuli has been attributed to variations in preparatory set. Variability in oculomotor responses toward identical visual stimuli has been well documented, but the neuronal processes underlying this variability are poorly understood. Here, we report evidence for set-related activity for saccadic eye movements in single neurons in the frontal eye field (FEF) in monkeys trained on a task in which they either had to look toward a visual stimulus (pro-saccade) or away from the stimulus (anti-saccade) depending on a previous instruction. A portion of FEF neurons were identified as neurons projecting directly to the superior colliculus (SC) with antidromic activation techniques. Saccade-related neurons in the FEF had lower prestimulus and stimulus-related activity on anti-saccade trials compared with pro-saccade trials. The level of prestimulus activity correlated with saccadic reaction times, express saccade occurrence, and errors in the anti-saccade task. In addition, saccade-related activity in the FEF was higher for pro-saccades than for anti-saccades. These results demonstrate that the direct descending pathway from the FEF to the SC carries preparatory set-related activity for pro-saccades and anti-saccades. The results also provide insights into the neuronal basis of variations in saccadic reaction times and in the control of the prepotent response to glance to a flashed stimulus.

Role of Primate Superior Colliculus in Preparation and Execution of Anti-Saccades and Pro-Saccades

We investigated how the brain switches between the preparation of a movement where a stimulus is the target of the movement, and a movement where a stimulus serves as a landmark for an instructed movement elsewhere. Monkeys were trained on a pro-/anti-saccade paradigm in which they either had to generate a pro-saccade toward a visual stimulus or an anti-saccade away from the stimulus to its mirror position, depending on the color of an initial fixation point. Neural activity was recorded in the superior colliculus (SC), a structure that is known to be involved in the generation of fast saccades, to determine whether it was also involved in the generation of anti-saccades. On anti-saccade trials, fixation during the instruction period was associated with an increased activity of collicular fixation-related neurons and a decreased activity of saccade-related neurons. Stimulus-related and saccade-related activity was reduced on anti-saccade trials. Our results demonstrate that the anti-saccade task involves (and may require) the attenuation of preparatory and stimulus-related activity in the SC to avoid unwanted pro-saccades. Because the attenuated pre-saccade activity that we found in the SC may be insufficient by itself to elicit correct anti-saccades, additional movement signals from other brain areas are presumably required.

Antisaccade performance predicted by neuronal activity in the supplementary eye field.

The voluntary control of gaze implies the ability to make saccadic eye movements specified by abstract instructions, as well as the ability to repress unwanted orientating to sudden stimuli. Both of these abilities are challenged in the antisaccade task, because it requires subjects to look at an unmarked location opposite to a flashed stimulus, without glancing at it. Performance on this task depends on the frontal/prefrontal cortex and related structures, but the neuronal operations underlying antisaccades are not understood. It is not known, for example, how excited visual neurons that normally trigger a saccade to a target (a prosaccade) can activate oculomotor neurons directing gaze in the opposite direction. Visual neurons might, perhaps, alter their receptive fields depending on whether they receive a pro- or antisaccade instruction. If the receptive field is not altered, the antisaccade goal must be computed and imposed from the top down to the appropriate oculomotor neurons. Here we show, using recordings from the supplementary eye field (a frontal cortex oculomotor centre) in monkeys, that visual and movement neurons retain the same spatial selectivity across randomly mixed pro- and antisaccade trials. However, these neurons consistently fire more before antisaccades than prosaccades with the same trajectories, suggesting a mechanism through which voluntary antisaccade commands can override reflexive glances.

Regional profiles of cortical gray matter volume deficits in schizophrenia and alcoholism

The antisaccade task is a prominent tool to investigate the response inhibition component of cognitive control. Recent theoretical accounts explain performance in terms of parallel programming of exogenous and endogenous saccades, linked to the horse race metaphor. Previous studies have tested the hypothesis of competing saccade signals at the behavioral level by selectively slowing the programming of endogenous or exogenous processes e.g. by manipulating the probability of antisaccades in an experimental block. To gain a better understanding of inhibitory control processes in parallel saccade programming, we analyzed task-related eye movements and blood oxygenation level dependent (BOLD) responses obtained using functional magnetic resonance imaging (fMRI) at 3T from 16 healthy participants in a mixed antisaccade and prosaccade task. The frequency of antisaccade trials was manipulated across blocks of high (75%) and low (25%) antisaccade frequency. In blocks with high antisaccade frequency, antisaccade latencies were shorter and error rates lower whilst prosaccade latencies were longer and error rates were higher. At the level of BOLD, activations in the task-related saccade network (left inferior parietal lobe, right inferior parietal sulcus, left precentral gyrus reaching into left middle frontal gyrus and inferior frontal junction) and deactivations in components of the default mode network (bilateral temporal cortex, ventromedial prefrontal cortex) compensated increased cognitive control demands. These findings illustrate context dependent mechanisms underlying the coordination of competing decision signals in volitional gaze control.

Ocular motor abnormalities in human immunodeficiency virus infection

We studied ocular motor performance in 47 subjects with human immunodeficiency virus (HIV) infection and 25 normal control subjects. Saccade accuracy was the most sensitive measure, being significantly poorer for all four HIV-positive groups (asymptomatic, acquired immunodeficiency syndrome [AIDS] without dementia, and AIDS with dementia, and AIDS-related complex) than for control subjects. While saccade duration and peak velocity were not significantly different across groups, the scatter of saccade duration was increased in all HIV-positive groups. Saccade latency was not significantly affected. In both simple and complex antisaccade tasks, the asymptomatic, AIDS, and AIDS dementia groups made significantly fewer correct-way antisaccades than did control subjects. Latencies of correct-way antisaccades were increased for AIDS and AIDS dementia groups in the simple antisaccade trials, and for all HIV-positive groups in the complex trials. Fixation stability was significantly worse in the AIDS dementia group than in control subjects. Smooth pursuit gain was decreased in the asymptomatic, AIDS, and AIDS dementia groups for the least demanding trial. One or more ocular motor abnormalities were present in 15 (88%) asymptomatic subjects, 11 (69%) with AIDS-related complex, and 14 (100%) AIDS patients without or with dementia.