The Antisaccade

A Review of Basic Research and Clinical Studies

Burkhart Fischer* and Stefan Everling**

*Brain Research Unit
Institute of Biophysics
University of Freiburg

**Medical Research Council Group in Sensory-Motor Physiology
Department of Physiology
Queen's University, Kingston
Ontario K7L 3N6, Canada


Index:


Abstract

Eye movements have been studied since many years as a specific motor control system, which is capable of many different kinds of movement execution such as smooth pursuit, saccades, and nystagmus. These movements are generated and controlled automatically or they can be initiated or suppressed by the subjects conscious decision. Attentional processes are closely related to the control of gaze direction. Only recently it became clear that in addition to a saccade generating system primates have also a neural system for the control of fixation. The fact that fixation can be maintained and saccades can be directed in a meaningful way despite large numbers of irrelevant visual events in the peripheral field of view is very important for many visual functions. If a deficit occurs in the optomotor coordination a subject may be more or less severely impaired in certain optomotor functions and spatial orientation.

Lesions in different brain structures and special diseases may - in addition to other symptoms - also result in deficits in eye movement control. Therefore the analysis of eye movements has been used - mostly in neurology and psychiatry - as an extra diagnostic tool. While optokinetic and vestibular nystagmus are widely in use, saccades have been used only recently. In particular, the question came up whether saccades could be made to locations that were not defined directly by visual stimuli but rather by certain instructions, by memory, or by previous experience. Under normal viewing conditions both reflexive and voluntary saccades are directed to a visual stimulus, i. e. the direction of both eye movement components are the same. One possibility to dissociate these components is to present a visual stimulus at one side and to ask the subject to make a saccade to the opposite side. This task has been originally introduced by Hallett in 1978 and is called the antisaccade task or - more briefly - the antitask. It requires that the subject successfully suppresss the reflex (for example by effective fixation) and the ability to generate a saccade to a position with no stimulus.

When using the antitask the first observation is that normal subjects can generally follow the instruction. The second observation is, however, that they make a certain number of erratic saccades to the stimulus. The analysis of these errors shows that many of them occur after extremely short reaction times in the order of 100 ms representing the mode of express saccades. Therefore, anti and express saccades are generated under the same condition in one session by the same subject in different numbers. Third, subjects do not correct all of their reflexive saccades. Finally, a great percentage of the reflexive saccades and their corrections remain unconscious.

The antitask has been used in basic research as well as in clinical studies and in the analysis of deficits related to circumscribed brain lesions. The express saccade (Fischer, Boch, 1983); (Fischer, Ramsperger, 1984)has been used to study basic aspects of fixation and attention control on the saccade system in normal adult subjects and in dyslexic subjects as well as in psychiatric patients.

This article summarizes the results of the studies on antisaccades since 1978 and discusses the neural mechanisms (tectal, frontal, parietal) underlying the control of antisaccade generation.


Introduction

Eye movements have been studied since more than 30 years in the context of vision research and as a specific motor control system, which is capable of many different kinds of movement execution such as smooth pursuit, saccades, and nystagmus. These movements are generated and controlled automatically - without permanent conscious and voluntary control - or they can be initiated or suppressed by the subjects conscious voluntary decision. Only recently it became clear that in addition to a saccade generating system primates have also a neural system for the control of fixation, which - when activated - suppresses saccades to guarantee stable gaze direction.

The fact that fixation can be maintained and saccades can be directed in a meaningful way despite large numbers of irrelevant visual events in the near and far periphery of the field of view is very important for many visual functions in everyday life. If a deficit occurs in the coordination between visual perception and eye movement generation a subject may be more or less severely impaired in certain functions.

On the other hand, lesions in different brain structures and special diseases may - in addition to other symptoms - also result in deficits in eye movement control. Therefore the analysis of eye movements has been used - mostly in neurology and psychiatry - as an extra diagnostic tool. While optokinetic and vestibular nystagmus are widely accepted and used in relation to cerebellar and brain stem disorders, the analysis of saccades is not established.

During the last 10 years after the neurophysiology and anatomy of the visual and oculomotor system had developed quite fast the investigation of saccades became more relevant. In particular the question came up whether saccades could be made to locations that were not defined directly by visual stimuli but rather by certain instructions, by memory, or by previous experience. One most easy way of setting the conditions for such a saccade is to present a visual stimulus at one side and to ask the subject to make a quick eye movement to the opposite side. This task has been originally introduced by Peter Hallett in 1978 as a "novel task" and is now called the antisaccade task or - more briefly - the antitask (Hallett, 1978); (Hallett, Adams, 1980).

The first important observation using the antitask is that subject can follow the instruction. The second observation is that they do make a small number of erratic prosaccades to the stimulus. The analysis of these errors shows that a proportion them occurs after extremely short reaction times in the order of 100 ms representing the mode of express saccades. Longer latency errors occur also as fast regular saccades. Therefore anti and express saccades are generated under the same condition in one session by the same subject in different numbers.

The antitask has been used in basic research as well as in clinical studies and in the analysis of deficits related to circumscribed brain lesions (Guitton et al. 1982); (Guitton et al. 1985). The express saccade has been used to study the basic aspects of fixation and attention control in saccade generation in normal adult subjects and in dyslexic subjects. Recently, one has also trained monkeys to perform the antitask (Funahashi et al. 1993); (Amador et al. 1995).

This article attempts to summarize the results of the studies on antisaccades in man and monkey, provides the reader with a quick look-up on what has been gained since 1978, and outlines the neural mechanisms (tectal, frontal, parietal structures) presumably underlying the control of voluntary saccades.

The Antisaccade Task

Fig. 1 shows in part A the temporal and spatial conditions of the antisaccade task. A central fixation point is presented for some time and the subject is instructed to fixate it. The fixation point can then be either extinguished before or remains visible until a stimulus is presented. In the latter case, the condition is called the overlap task, because the stimulus and the fixation point overlap in time. In the former case, the condition is called the gap task, because there is a temporal gap (of variable length) between fixation point offset and stimulus onset. The subject is instructed to make a saccade in the direction opposite to the side where the stimulus is presented. The part B of Fig. 1 shows schematically a correct antisaccade (thin line) and indicates the definition of its reaction time (A-SRT). The heavy line shows an erratic prosaccade followed by a corrective saccade which brings the eye to the opposite side. The reaction time (E-SRT) and correction time (CRT) are defined accordingly. In any case is the reaction time measured from stimulus onset. In some studies the gap was zero, i.e., a classical condition was used which is often called the step condition.

Basic Research

Basic observations: In his very first studies Hallett reported some basic observations on the performance of the antitask (Hallett, 1978):

- the subjects were able to successfully look to the side opposite to the stimulus.

- in the beginning, however, they made quite a number of erratic saccades (30 - 80 %) toward the stimulus before they looked to the opposite side. Later they could reduce the error rate down to 5 - 7%.

- the mean reaction times of the antisaccades were prolonged as compared to prosaccades.

- antisaccade amplitude was quite variable both from subject to subject and within a subject.

- antisaccade velocity profiles were altered.

- secondary saccades followed primary antisaccades much faster than primary prosaccades.

The longer latencies of antisaccades versus prosaccades were confirmed and it was stated that there was no significant improvement with practice (Hallett, Adams, 1980). This results were later refined: when subjects were required to make antisaccades in a gap task they decreased both their error rate from an average of about 14 % to 11 % and their average latency from about 183 ms to 171 ms within 12 to 15 days of everyday practice (Fischer, Weber, 1992).

Characteristic parameters of the antisaccade: As for normal saccades the basic parameters of antisaccade are: latency, duration, velocity, size and accuracy, correction time in case of saccades undershooting or overshooting the required final position of the eye. In addition and specific for the antitask is the percent number of erratic prosaccades that are made against the subjects will inone or the other direction and the corresponding correction time. The latencies of the antisaccades depend on retinal factors like state of adaptation and rod-cone interaction. (Doma, Hallett, 1988) examined the influence of different luminance conditions on pro- and antisaccades. Photopic stimulus luminances led to longer latencies, larger angular error, less secondary saccades and more direction error in antisaccades compared with prosaccades. In scotopic stimulus luminances most differences between pro- and antisaccades disappeared. This was caused mainly by increased latencies, increased standard deviations of the angular errors and a decrease of the incidence of secondary saccades in prosaccades. Moreover, scotopic stimulus luminances increased the direction errors for prosaccades and antisaccades. For mesopic stimulus luminances, prosaccades showed a linear segment in the log latency-log luminance function which intersected at the peripheral cone threshold. In contrast, antisaccades showed a latency plateau which extended 0.7-1.0 log unit above foveal treshold. Moreover, antisaccades showed increased direction errors in this range. Additionally, antisaccadic latencies are variable for mesopic cues (Doma, Hallett, 1989). The peak velocity of antisaccades is decreased compared with prosaccades (345 deg/sec versus 512 deg/sec) and skewness of the velocity profile occurs more frequently for antisaccades than for prosaccades (Smit et al. 1987).

The role of the physical parameters on the performance of the antitask has been studied recently (Fischer and Weber, 1996 submitted). When a gap was used its duration was critical for the number of erratic prosaccades and for the latency of the correct antisaccades. For gap durations of 200-250 ms the mean error rate was maximal (15 %) and the latency minimal (175 ms) as compared with shorter and longer gap durations. The error rate increased and the latency decreased with increasing eccentricity of the stimulus from 1 deg to 12 deg. Stimulus size, on the other hand, had little or no effect.

Randomly interleaving of pro- and antitrials in a single block was of no importance when compared with blocks of only pro- or only anticommands (Hallett, Adams, 1980). These experiments were repeated using visual cues to indicate whether pro- or antisaccades were required at any given trial. It turned out that subjects made large numbers of errors eventhough the cue was given 100-200 ms ahead of time. The errors were of both kinds: erratic prosaccades on antitrials and - more surprisingly - erratic antisaccades on protrials. The analysis revealed that the subjects on many trials executed the command of the previous trial (Weber, 1995). This result clearly indicates that the generation of voluntary saccades even when they are prosaccades relies on non-visual functions, presumably of the frontal cortical system.

Failure of fixation versus failure to produce antisaccades

During the last years it became evident that monkeys as well as humans have a separate system for the control of fixation. With the fixation cells chemically deactivated at the tectal level the monkey is no longer able to maintain fixation when a peripheral stimulus is suddenly presented. Instead he makes reflex-like saccades - mostly express saccades - to the stimulus (Munoz, Wurtz, 1992). Accordingly, a subject with a unilateral lesion of the superior colliculus produced high error rates in the antisaccade task not being able to maintain fixation (Pierrot-Deseilligny et al. 1991). This behavior is rather reminiscent of that of certain human subjects who are also unableto maintain fixation (Biscaldi et al. 1996); (Cavegn, Biscaldi, 1996). These subjects have selectively lost - completely or in part - their fixation control and produce high numbers of express saccades even in the presence of a fixation point. Therefore it comes as no surprise that they are also impaired on the gap antitask, because with a weak fixation system the saccade system receives only a weak inhibition and therefore reacts more often to visual stimuli by producing a reflex-like movement. Subjects with an intact fixation system do not produce reasonable numbers of express saccades in the overlap condition and small saccades cannot be of the express type because the targets fall to close to the fovea thereby activating the fixation system (Weber et al. 1992).

When provided with valid visual cues indicating correctly the side to which the antisaccade must be made 100 ms ahead of time trial by trial normal subjects produce more errors than without the cues (Fischer, Weber, 1996). The subjects reported that they were unable to suppress the unwanted prosaccades and moreover it turned out that on average 50% of the trials with erratic prosaccades escaped their conscious recognition (Fischer and Mokler, unpublished observation). Interestingly, almost all the erratic prosaccades were corrected immediately indicating that the subjects could generate antisaccades on every trial.

By contrast, subjects (mostly children), who also produce high error rates without the cues often do not correct their errors. They have difficulties generating saccades to the side opposite to the stimulus. They are really impaired on the antisaccade task not because a lack of fixation activity but because a lack of generating voluntary saccades. An impairment to generate an antisaccade after the execution of an erractic prosaccade has also been reported for patients with frontal lesions (Guitton et al. 1985).

Therefore, when high error rates are observed in the antisaccade task, it is important to see in addition whether a subject corrects them or not. This differentiation between the components of a successful performance of the antitask has been discussed in detail in the context of the significance and interpretation of the error frequency of schizophrenics and other patients (Huerta et al. 1987);(Levy, 1996).

Little is known about the correction time of the erratic prosaccades. If, in a protask a saccade fails to reach to the target at once by over- or undershooting it a corrective saccade occur not earlier than 130 to 150 ms afetr the end of the primary saccade. Extremely short correction times are observed only when the primary saccade is made in the wrong direction thus sleaving a large retinal error. These corrective saccade can be of the express type being triggered by the onset of the target stimulus not by the end of the primary saccade (Fischer et al. 1993). The erratic prosaccade produced in the antitask also leave a large error (by definition). Yet, only small proportion of them is corrected faster than 80 ms from the end of the erratic saccade. But with a mode around 100 ms the correction times are certainly faster than those following under- or overshoots in a protask (Mokler, in preparation).

The Development of Fixation and Voluntary Saccade Generation

The dual aspect of saccade control becomes very clear when looking at its development with age. A large number of subjects between age 8 and 65 years were tested using the gap antitask and the overlap protask. Counting the numbers of errors obtained in the antitask revealed that children below age 10 are almost unable to perform the task successfully. Their error rate was in the order of 60% and decreased steeply until age 15 continuing until age 20 to a mean value of about 15%. During the same period the reaction time of the correct antisaccades decreased from a mean value of 290 ms to 220 ms. Right-left asymmetries were observed as a rule with more errors and shorter latencies to the right stimulus. The high error rate in normal children may account for the failure to find differences in the number of erratic prosaccades in children with attention deficit hyperactivity disorder (Rothlind et al. 1995).

On the other hand, the data obtained from the protask did not show much of developmental changes: the reaction times decreased from 210 to 180 ms and the percent number of express saccades decreased from about 15% to just below 10%. Comparing the data from the pro- and antitasks revealed that subjects with only a few express saccades and high error rates also failed to correct their errors on many trials indicating that they had difficulties in generating saccades to the side opposite to the stimulus (Fischer et al., submitted).

These results suggest that the fixation system preventing express saccades in the protask is pretty much developed at age 10 while the voluntary component of saccade generation develops over a much longer period. In fact, it has been reported that infants as young as 4 months can learn to inhibit automatic saccades to salient stimuli indicating the effectiveness of their fixation system (Johnson, 1995). Elderly memory-impaired people performed the antitask about as well as normal subjects of the same age exhibiting an error rate in the order of 30 - 40 % using a no-gap condition. The mean latency was almost 400 ms for both groups (Versino et al. 1993).

Attention allocation and antisaccade generation

The problem of the relationship between attention allocation and saccade generation is still a matter of discussion (Fischer, Weber, 1993). Most recently it has been suggested that the controversial views can be combined by considering two different attentional systems (Nakayama, Mackeben, 1989): a bottom-up stimulus driven fast and transient attentional component which when activated facilitates saccade generation and a top-down voluntary sustained component, which arrests saccades (Fischer, Weber, 1996);(Fischer, Weber, 1997); (Weber, Fischer, 1996).The antitask was used to test the effects of general warning, which should act in the same way for pro- and antisaccades (Reuter-Lorenz et al. 1995). They found that the gap effect was different for prosaccades with and without warning but about the same for antisaccades. When spatially valid visual precues were used to facilitate antisaccades both the error rate and the reaction times were increased indicating that the concept of automatic attention orienting cannot be applied without further changes to antisaccade generation (Fischer, Weber, 1996). The modulation of prosaccade generation due to valid and invalid cueing has been discussed in a recent study (Weber, Fischer, 1995).

Antisaccades in Dyslexia

The involvement of oculomotor deficits in dyslexia has been discussed controversely (Pavlidis, 1981); (Olson et al. 1991). Obviously, the motor part of saccade generation seems to be intact. A preponderance of express saccades in the overlap protask was also observed in the subjects with a selective impairment invloving only reading and writing, called D2-subjects (Biscaldi et al. 1994); (Biscaldi, Fischer, 1994). D1-dyslexic subjects with additional problems such as concentration difficulties or auditive discrimination or deficits in short-term memory showed scattered reaction time distributions. Using the gap antitask it was found that especially male dyslexics, D1 and D2, produce excessive numbers of errors in comparison with age-matched normally reading subjects (Biscaldi et al. 1995). D2-subjects produced their errors as express saccades, whereas D1 subjects had rather long latencies of their erratic prosaccades. A detailed analysis will have to show whether they have a weak fixation system or a weak voluntary control by looking at the corrections of the errors.

Lookup Table of Clinical Studies

Table 1 summarizes the results of the clinical studies in the order of symptoms or diseases. It serves as a look-up table and helps to find the original papers.

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