The Tell-Tale Tasks: A Review of Saccadic Research in Psychiatric Patient Populations

NIH Public Access
Author Manuscript
Brain Cogn. Author manuscript; available in PMC 2009 December 1.
NIH-PA Author Manuscript
Published in final edited form as:
Brain Cogn. 2008 December ; 68(3): 371-390. doi:10.1016/j.bandc.2008.08.024.
The Tell-Tale Tasks: A Review of Saccadic Research in Psychiatric
Patient Populations
Diane C. Goodingb,a and Michele A. Bassoc
b Professor of Psychology and Psychiatry, University of Wisconsin-Madison, College of Letters and
Sciences and School of Medicine and Public Health
c Associate Professor, Departments of Physiology and Ophthalmology & Visual Sciences, University
of Wisconsin-Madison School of Medicine and Public Health
Abstract
This review focuses on saccade research with adult psychiatric patients. It begins with an introduction
NIH-PA Author Manuscript
of the various types of saccades and the tasks used to evoke them. The functional significance of the
different types of eye movements is briefly discussed. Research findings regarding the saccadic
performance of different adult psychiatric patient populations are discussed in detail, with particular
emphasis on findings regarding error rates, response latencies, and any specific task parameters that
might affect those variables. Findings regarding the symptom, neurocognitive, and neural correlates
of saccadic performance and the functional significance of patients' saccadic deficits are also
discussed. We also discuss the saccadic deficits displayed by various patient groups in terms of
circuitry (e.g. cortical/basal ganglia circuits) that may be implicated in the underlying
pathophysiology of several of these disorders. Future directions for research in this growing area are
offered.
The saccadic eye movement system is responsible for rapid eye movements that bring the image
of an object onto the fovea (see glossary) (Leigh & Zee, 1983). Saccades are conjugate, ballistic
eye movements that are characterized by short reaction times, typically around 200 msec., and
brief durations, normally between approximately 20 and 120 msec. (Leigh & Zee, 1983;
Gouras, 1985; Engelken, Stevens, & Enderle, 1989). In humans, saccades can reach speeds of
up to 600 to 700 deg/sec., whereas monkeys can produce saccades that are nearly twice as fast
NIH-PA Author Manuscript
(Gouras, 1985; DeRenzi, 1988). Normal saccadic eye movements are characterized by an
invariant relationship between their peak velocity and their size; the amplitude-peak velocity
relationship is referred to as the main sequence (Bahill & Stark, 1975).
Accuracy of saccades depends on the location of a target on the retina as well as the position
of the eyes in the orbit (Gouras, 1985). There are two major classes of saccades, namely, those
that are externally triggered and automatic, and those that are internally initiated and volitional
(Lasker, Zee, Hain, Folstein, & Singer, 1987). Although saccadic eye movements are typically
elicited by the sudden appearance of a novel auditory or visual stimulus that attracts the
subject's attention (reflexive saccades), they can be produced on command, in the dark, to
remembered targets, during scanning or searching of stationary visual scenes, or with closed
aCorresponding author. Department of Psychology, 1202 West Johnson Street, Madison, WI 53706. Phone: (608) 262-3918. Fax: (608)
262-2049 email: dgooding@wisc.edu.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting
proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could
affect the content, and all legal disclaimers that apply to the journal pertain.

---

Gooding and Basso
Page 2
eyes (Leigh & Zee, 1983; Gouras, 1985; DeRenzi, 1988; Wirtschafter & Weingarden, 1988).
Saccades can be described in terms of their reaction time, namely, the time elapsing from the
NIH-PA Author Manuscript
command signal to shift one's gaze until the beginning of the saccade. Saccades are also
described in terms of their velocity and accuracy.
Diefendorf and Dodge (1908) were the first investigators to report on the functioning of the
saccadic system in schizophrenia patients. Since then, interest in the study of saccadic eye
movements in schizophrenia has risen steadily and now includes a focus on volitional saccades
as well as reflexive ones. Saccadic eye movements can be measured reliably and precisely. As
a result of basic research including single unit recordings and lesion studies as well as clinical
research and functional imaging, there is a considerable body of knowledge regarding the
neurophysiology of the saccadic eye movement subsystem. Thus, the study of saccadic eye
movements in psychiatric patient groups can provide a "window into the brain" of affected
individuals. Over the past three decades, there has also been an increase in the number of studies
of saccadic performance in other psychiatric patient groups. Much of the impetus for the focus
on saccadic eye movements in these populations comes from the fact that saccades provide a
noninvasive yet accessible means of investigating psychomotor functioning as well as higher
order cognitive processes and their underlying neural mechanisms.
In the following review, we summarize the extant literature regarding the study of saccadic
eye movements in adult psychiatric patients. In order to appreciate the growing complexity of
NIH-PA Author Manuscript
the area and the various ways in which psychiatric patient groups differ in terms of their
saccadic task performance, we introduce the major saccadic paradigms prior to summarizing
the studies for each diagnostic group. Given the disproportionately large corpus of literature
on saccadic performance in schizophrenia and schizophrenia spectrum populations, this area
will receive particular emphasis in our review. Findings regarding the symptom,
neurocognitive, and neural correlates of saccadic performance, as well as hypotheses regarding
the functional significance of patients' saccadic deficits are also discussed. In the final section
of the review, we integrate across findings, and provide a comparative analysis of saccadic
deficits in the different psychiatric disorders. This discussion is used as an opportunity for
hypothesis generation and recommendations for future directions.
Different Types of Saccade Paradigms
Because of the versatility of saccades, a number of different behavioral tasks have been
developed over the years to probe different underlying mechanisms. Below we review some
of the most commonly used saccadic eye movement tasks. The different saccade tasks include
visually-guided, memory-guided, gap, overlap, and antisaccade tasks. Each task has different
demands allowing for the assessment of the integrity of brain pathways in health and disease.
NIH-PA Author Manuscript
For example, to assess the integrity of saccade-generating circuitry subjects may perform a
visually-guided saccade task. In this task (Figure 1A), a fixation stimulus appears initially at
the center of a screen. After a timed fixation period a second stimulus (target) appears at a
peripheral location. At the same time, the fixation stimulus disappears and the subject must
initiate a saccade to the peripheral target. In this most simple version of the visually-guided
saccade task, the appearance of the peripheral target and the removal of the central fixation
occur simultaneously and as such, the task is also referred to as a reflexive visually-guided
saccade or prosaccade. In one version of the prosaccade task, known as the overlap prosaccade
task, the cue and the central fixation stimulus appear together, i.e., overlap. Imposing a delay
between the time of the appearance of the target stimulus and the disappearance of the fixation
stimulus cueing the saccade is referred to as a delayed visually-guided saccade (Figure 1B).
A commonly used type of delayed-saccade task is referred to as the oculomotor delayed-
response (ODR) or memory-guided saccade task (Figure 1C). For this subjects fixate a
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 3
centrally-illuminated stimulus. While the fixation stimulus is illuminated, the appearance of a
second peripheral stimulus occurs transiently. Following a delay-period of up to 10 seconds,
NIH-PA Author Manuscript
the central fixation stimulus disappears signaling the subject to make a saccade to the
remembered location of the previously flashed stimulus. These saccades are often referred to
as memory-guided to distinguish them from visually-guided ones (Hikosaka and Wurtz
1983). The ODR task provides a test of spatial working memory (see glossary) as well as the
ability to suppress a reflexive saccade.
In addition to prosaccade tasks, sometimes also referred to as refixation saccade tasks, there
are tasks that dissociate the location of the cue from the location of the required saccadic eye
movement. The antisaccade task (see glossary) is the most notable example. In the standard
version of the antisaccade task (Hallet, 1978; Hallet & Adams, 1980), the participant starts by
fixating on a centrally-illuminated stimulus. After a fixation interval, the stimulus disappears
and at the same time a stimulus appears at a peripheral location. The task of the subject is to
make a saccade to the location opposite the appearance of the stimulus. Thus, to perform the
task correctly the subject must inhibit a prepotent (overlearned and automatic) response, i.e.,
a reflexive saccade, and generate a volitional saccade in the opposite direction. The saccade
made in the opposite direction is called the antisaccade (Figure 1D).
There are several variants of the antisaccade task. Some include a warning sound prior to the
cue appearance and some vary the timing between the offset of the central stimulus and the
NIH-PA Author Manuscript
onset of the peripheral cue. One common variation of the antisaccade task is the gap version.
In this version the central fixation stimulus disappears shortly before the peripheral target
appears (Figure 1F). The temporal gap between the offset of the central stimulus and the onset
of the peripheral stimulus may place greater demands on the mechanisms of voluntary
inhibition (see glossary) than the standard version of the antisaccade task. A second version of
the antisaccade task increases the time in which the cue and the central fixation stimulus
appearance occur together or overlap (Sereno & Holzman, 1993). The overlap condition is an
easier version of the antisaccade task. Across all of the variants of the antisaccade task
paradigm, three processes are necessary for the successful execution of the task: first, there
must be a covert shift of exogenous attention; second, the subject must inhibit the reflexive
saccade to the cue; and third, the subject must transform the spatial position of the cue to the
spatial position of the saccade goal and then initiate a voluntary saccade in the opposite
direction to the target movement (Hallet, 1987; Harris et al, 2006).
The gap saccade paradigm is unique among the saccadic tasks in that the cue to make the
saccade is the appearance of the target. In contrast, most other saccade tasks are cued by the
removal of the fixation stimulus (Figure 1E). In the gap paradigm, the centrally located stimulus
NIH-PA Author Manuscript
appears and after a delay, disappears. During this time the subject maintains gaze at the center
of the screen despite the absence of the central fixation. The appearance of the peripheral target
is the cue for the subject to initiate a saccade to the target location (Saslow, 1967). The gap
paradigm is used to elicit express saccades, visually-guided saccades with latencies between
80 and 130 msec (Fischer & Ramsperger, 1984). The reduction in saccade latency in this task
(compared to the condition in which the fixation stimulus and the target stimulus appear with
some temporal overlap) is known as the gap effect (Saslow, 1967; Reuter-Lorenz, Hughes, &
Fendrich, 1991; Fisher & Weber, 1993).
In predictive saccade tracking tasks, subjects are required to keep their eyes on a target that
moves regularly back and forth between two known locations, i.e., left and right of center,
remaining in each position for a period of time (e.g. 500 msec). Predictive saccade tracking
tasks are used to assess participants' ability to adjust their oculomotor response to a predictably
moving visual stimulus. Typically, within a few target presentations, healthy subjects are able
to generate anticipatory saccades that are characterized by reduced latencies (Bronstein &
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 4
Kennard, 1987; Spengler et al., 2006). In contrast to prosaccade paradigms, which assess
reflexive eye movements, the antisaccade, ODR, and predictive paradigms assess intentional
NIH-PA Author Manuscript
saccadic movements. Visually guided prosaccade tasks provide an external representation of
the goal. In contrast, performance of other tasks (i.e., antisaccade, ODR, and predictive)
depends upon an internal representation of the target position. Readers are referred to the
Hutton (2008) paper, in this volume for a detailed discussion of the cognitive control of saccadic
eye movements.
Intentional or volitional saccadic eye movements can also be examined through the use of
scanpaths or visual search tasks. Repetitive sequences of saccades or scanpaths are generated
in order to examine subfeatures of a visual scene (Yarbus, 1967; Stark, 1983). In visual search
tasks, subjects are required to move their gaze as they view a complex visual scene or compare
visual stimuli. These tasks require focused visuospatial attention as well as the ability to use a
task goal to guide subsequent behavior, i.e., working memory (Kennard, 2002).
This review will focus on findings from saccade research with adult psychiatric patients. Extant
literature pertaining to saccadic performance in schizophrenia and schizophrenia-spectrum
disorders will be discussed first, followed by research on patients with mood disorders. Data
from studies that combined samples of mood disordered patients will be considered prior to
reviewing studies based on select samples of patients with major depressive disorder, bipolar
disorder, and borderline personality disorder. Findings from studies of individuals with
NIH-PA Author Manuscript
attention deficit hyperactivity disorder (ADHD), Tourette's syndrome, and obsessive
compulsive disorder (OCD) are also summarized. In this review, research findings are
organized according to the disorder discussed, rather than the type of eye movement, because
typically investigators administered more than one oculomotor task in order to assess the
functioning of the participants' saccadic system. By manipulating the demands of the tasks
requiring saccade generation, one can assay cognitive processes such as goal setting, response
generation, response inhibition, prediction, and spatial working memory. Indeed, through
comparisons of performance patterns across tasks, investigators have been able to draw
conclusions and propose models about the circuitry that may be implicated in the underlying
pathophysiology of several of these disorders.
Saccadic Performance in Schizophrenia and Schizophrenia Spectrum
Disorders
Most of the studies of saccadic performance in psychiatric samples have focused on
schizophrenia patients. Additionally, several studies have investigated performance on
saccadic tasks in schizophrenia spectrum populations such as schizotypal personality disorder
NIH-PA Author Manuscript
and/or individuals at heightened risk for the later development of schizophrenia and
schizophrenia spectrum disorders. In this review, studies focusing on schizophrenic patient
samples will be addressed first prior to discussing the findings involving individuals with
schizophrenia spectrum disorders.
1. Saccadic Refixation in Schizophrenia Patients
Saccadic performance is typically described in terms of static characteristics (e.g., accuracy,
corrective movements), saccadic reaction time, and dynamic characteristics such as velocity,
duration, and gain (Becker, 1989; Mahlberg et al., 2001). Overall, schizophrenia patients
display normal saccadic eye movements to peripherally presented visual cues that follow the
offset of a central fixation point (Barton et al, 2002; Clementz et al., 1994; Diefendorf & Dodge,
1908; Fukushima et al., 1990; Gooding, Iacono, & Grove, 1997; Gooding, Mohapatra, & Shea,
2004; Hutton et al., 1998; Iacono, Tuason, & Johnson, 1981; Klein et al., 2000; Hutton et al.,
2002; Levin et al., 1982; Mahlberg et al., 2001; Tendolkar et al., 2005; but see Boudet et al
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 5
2005, Crawford et al., 1995; Grootens et al., 2008). It is noteworthy that in the Crawford et al.
(1995) study, the schizophrenia patients were unmedicated, which may have accounted for less
NIH-PA Author Manuscript
accurate responses. Nieuwenhuis, Broerse, Nielen, and deJong (2004) observed that
schizophrenia patients displayed normal performance on the simple version of the prosaccade
task, in which saccades were explicitly required. However, when administered a more difficult
version of a prosaccade task, i.e., a cued target discrimination task in which subjects could
improve their discrimination performance by making an eye movement (prosaccade) towards
a cue, schizophrenia patients performed significantly worse than controls. Considered together,
these findings suggest that patients' basic saccadic generation circuitry is intact, but a higher
order process is impaired.
The findings regarding schizophrenia patients' ability to locate displaced targets accurately are
equivocal. Although there are some reports ( Fukushima et al., 1988; Iacono et al, 1981; Levin
et al., 1982; Gooding et al., 1997) that this ability is intact in schizophrenia, several other studies
(Cegalis et al., 1982; Clementz et al., 1994; Levin et al. 1981; Mahlberg et al., 2001; Mather
& Putchat, 1983; Moser et al., 1990; Ross et al., 1988; Schmid-Burgk, Becker, Diekmann,
Jurgens, & Kornhuber, 1982) indicate that schizophrenia patients display saccadic dysmetria.
In some samples (Clementz et al., 1994; Levin et al., 1981; Moser et al., 1990), the hypometric
(see glossary) saccades were limited to rightward visually guided saccades. Differences in
terms of eye movement recording techniques, as well as differences in target stimuli
NIH-PA Author Manuscript
displacement, predictability, and timing have been posited to account for the apparent
discrepancy in findings.
Schizophrenia patients' predictive saccades have been reportedly less accurate than controls
in some studies (e.g., Crawford et al. 1995; Hommer, Clem, Litman, & Pickar, 1991; Krebs et
al., 2001) but not in others (McDowell, Clementz, & Wixted, 1996). In their assessment of
unmedicated schizophrenia patients' performance on a predictive saccade task, Krebs' group
(2001) evaluated the subjects' non-anticipated saccades, which are externally elicited,
separately from their anticipated saccades, which are internally elicited. The patients did not
differ from controls in terms of their non-anticipated saccades' latency, peak velocity, or gain,
nor did the groups differ in terms of their final eye position. Krebs et al. (2001) interpreted the
observation that schizophrenia patients' anticipated saccades were characterized by
hypometria as indicative of an impairment in internally based motor planning. In contrast,
Sailer et al. (2007) observed that acutely ill schizophrenia inpatients did not differ from healthy
controls in terms of the accuracy (gain) of their correct and incorrect anticipatory saccades.
However, they noted that the patients generated significantly more correct anticipatory
saccades than controls; the investigators viewed this enhanced predictive saccade activity as
indicative of an impaired gating mechanism for predictive saccades. A more recent
NIH-PA Author Manuscript
investigation of medicated and unmedicated patients revealed that schizophrenia patients'
anticipated predictive saccades were characterized by lower primary and final gain, and
decreased maximum velocity relative to controls (Amado et al., 2008). Moreover, the
schizophrenia patients' nonanticipated saccades were characterized by lower primary and final
gain. The schizophrenia patients did not differ from healthy matched controls in terms of the
latencies for either the anticipated or nonanticipated saccades (Amado et al., 2008).
On simple prosaccade tasks and predictive tracking tasks, the saccadic reaction times of
schizophrenia patients are typically normal ( Fukushima et al., 1988; Levin et al., 1982; Mather
& Putchat, 1982; Tendolkar et al., 2005; Thampi et al., 2003; Grootens et al., 2008).
Schizophrenia patients may display significantly prolonged saccadic response latencies under
conditions of considerable task complexity (Done & Frith, 1984; Mackert & Flechtner, 1989;
Schmidt-Burghk et al, 1982). For example, in a complicated choice paradigm in which subjects
were required to move their eyes either left or right as directed by an imperative signal and
report upon the characteristics of a peripheral stimulus, Done and Frith (1984) observed that
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 6
schizophrenia patients had significantly longer saccadic latencies. The Mackert and Flechtner
(1989) task was similarly complex; fast-changing saccadic stimuli were presented in varying
NIH-PA Author Manuscript
positions for varying durations (800 to 1200 msec.) randomly chosen and led to prolonged
saccade latencies.
In general, investigations of average and peak saccadic velocities (Levin et al, 1981; Levin et
al, 1982; Mather & Putchat, 1983; Yee et al, 1987; Ross et al, 1988) indicate that schizophrenic
patients' velocities are within normal limits, though there has been one report (Cegalis,
Sweeney & Dellis, 1982) suggesting that they are slower. The differential findings of Cegalis
et al (1982) may be due to their use of a more difficult refixation task, in which the signal
alternately disappeared and reappeared on opposite sides of the screen. Among more recent
reports (Mahlberg et al, 2001; Ramchandran et al, 2004; Thampi et al, 2003), the findings are
mixed. While Thampi et al (2003) who included both treatment responsive and treatment
resistant schizophrenia patients, found no differences between schizophrenia patients and
controls in terms of peak saccadic velocity on the prosaccade task, the other two groups
(Mahlberg et al., 2001; Ramchandran et al. 2004) found that schizophrenia patients display
aberrant peak velocities during saccadic refixation tasks. It is noteworthy that saccadic peak
velocity is affected by sedative medications (Van Opstal & Van Gisbergen, 1987); readers are
referred to Reilly et al. (2008) for discussion of pharmacological treatment effects on eye
movement control. Mahlberg et al (2001) observed that the saccadic eye movements of the 38
NIH-PA Author Manuscript
unmedicated schizophrenic subjects were characterized by significantly increased peak
velocity on both the "prosaccade task" and the predictive saccadic task.
Ramchandran et al (2004) noted that the medicated schizophrenia patients'peak velocities
could be normal or aberrant, depending on their latency, with the velocity declining with
increasing latency. At latencies greater than 300 msec, the peak velocities were significantly
reduced relative to the healthy controls. The investigators attributed the patients' saccadic
abnormality to a failure of the continued target presence to sustain saccade-related neural
activity. While these data could be related to a larger body of literature regarding perceptual
dysfunction in schizophrenia, particularly the premature decay of sustained pattern information
(Ramchandran et al, 2004), it also suggests that schizophrenia patients' peak saccadic velocities
are quite malleable and easily affected by task parameters.
2. Antisaccade Task Performance in Schizophrenia Patients
In addition to the basic measures of saccadic task performance, namely, percent of correct
saccadic responses (and conversely, percent of directional errors), latency to initiate correct
response, and saccadic gain, antisaccade task performance can also be described in terms of
percent of corrected errors. Antisaccade errors reflect failures of response suppression and are
NIH-PA Author Manuscript
considered the most reliable measure of antisaccade performance (Ettinger et al, 2003). The
main antisaccade abnormality reported in schizophrenia is an elevated rate of reflexive saccade
error rates.
Fukushima et al. (1988) were the first investigators to administer an antisaccade task paradigm
to schizophrenia patients. The finding that schizophrenia patients display impaired antisaccade
task performance relative to healthy controls is a robust one, with over 50 replications to date.
Error rates in schizophrenia patients vary from approximately 20% to 75%, depending upon
the task parameters. Aberrant antisaccade task performance has been observed in patients with
recent onset and/or first-episode schizophrenia (Boerse, Crawford & den Boer, 2002; deWilde,
Dingemans, Boeree & Linszen, 2008; Ettinger, Kumari, Chitnis et al., 2004; Grootens et al.,
2008; Hutton et al., 2002; Hutton et al., 1998) as well as chronic schizophrenia (Boudet et al.,
2005; Curtis, Calkins, & Iacono, 2001; Fukushima et al., 1988) and remitted schizophrenia
(Curtis, Calkins, Grove, Feil, & Iacono, 2001). Increased proportions of antisaccade errors,
operationally defined as glances made in the same direction as the target, have been observed
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 7
in never-medicated schizophrenia patients (Harris et al., 2006) and unmedicated patients
(Mahlberg, Steinacher, Mackert & Flechtner, 2001) as well as in patients receiving
NIH-PA Author Manuscript
antipsychotic treatment.
Schizophrenia patients consistently produce fewer correct responses on the antisaccade tasks,
regardless of the version of the paradigm (e.g. Allen et al., 1996; Clementz et al., 1994;
Crawford et al., 1998; Curtis et al., 2001; Fukushima et al., 1988; Fukushima et al., 1990;
Gooding et al., 1997; Gooding & Tallent, 2001; Hutton et al., 2002; Klein et al., 2000;
McDowell et al., 1999; Reuter et al, 2005; Sereno & Holzman, 1995; Thaker et al., 1990). This
robust finding was recently replicated in the largest investigation of schizophrenia patients to
date, in which 141 schizophrenia patients and 193 community controls were compared (Radant
et al., 2007). The overlap between the offset of the fixation and the antisaccade cue stimulus
onset affects the magnitude of the difference between schizophrenia patients and
nonpsychiatric controls; a better separation is achieved in the overlap condition than in the
standard version of the antisaccade task (McDowell & Clementz, 1997), and a `far overlap'
version reportedly provides larger separations (i.e., 5-6 sigma) than `near overlap' versions
(McDowell, Myles-Worsley, Coon, Byerley, & Clementz, 1999). The increased effect size is
likely due to the increase in task difficulty that occurs when the cue is spatially further from
the fixation point.
The finding of increased proportions of directional errors in the antisaccade task is robust across
NIH-PA Author Manuscript
different recording techniques, including electro-oculography (EOG; Grootens et al., 2008;
Muller et al., 1999;), infrared recording (IR; Ettinger et al., 2004a,b; Gooding et al., 2004), and
the magnetic induction technique (Barton et al., 2002; Nieman et al., 2007; Ramchandran et
al., 2004). Although schizophrenic patient groups make a significantly higher percent of
directional errors in antisaccade tasks, they usually do not differ from healthy controls in terms
of their percent of corrected errors (Gooding & Tallent, 2001; Polli et al., 2008); this is
important, because it indicates that they understand the task instructions and are sufficiently
motivated to perform the task. Several models have been offered to account for the increased
frequency of antisaccade errors displayed by schizophrenia patients; these accounts will be
discussed and critiqued following review of the extant literature regarding the schizophrenic
individuals' saccadic abnormalities. This reflects our belief that the pattern of performance
across tasks may provide greater insights regarding the functional significance of schizophrenia
patients' antisaccade task deficits vis a vis the mechanisms underlying the disorder.
Some studies also measure the spatial accuracy of the correctly performed antisaccade, by
measuring the positions of the primary saccade and the final eye position and comparing them
with the target position. Schizophrenia patients have a tendency to display reduced spatial
NIH-PA Author Manuscript
accuracy, whereby the primary saccade and corrective saccade undershoot the target (Burke
& Reveley, 2002). Several studies have reported that schizophrenia patients show reduced
spatial accuracy of their correct antisaccades (Ettinger, Kumari, Chitnis et al., 2004; Ettinger,
Kumari, Crawford et al., 2004; Karoumi et al., 1998; McDowell, Myles-Worsley, Coon,
Byerley & Clementz, 1999; Ross et al., 1998). Reduced spatial accuracy of the antisaccade
response may reflect an impaired ability to generate saccades and/or a perceptual deficit thereby
limiting an accurate internal representation of the spatial layout.
Some versions of the antisaccade task paradigm do not require subjects to move their eyes as
fast as possible, so investigators do not measure response latency. However, the latencies of
correct antisaccade responses are thought to reflect the processing speed for planning and
generating voluntary action (Harris et al, 2006). Given what is required to correctly perform
the antisaccade task, the response latency may provide an index of the efficiency of visual
processing, response suppression, and/or response generation. Investigators (Barton et al.,
2002; Curtis et al., 2001; Crawford et al., 1998; deWilde et al., 2008; Fukushima et al., 1990;
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 8
Karoumi et al., 1998; Klein et al., 2000; Muller et al., 1999; Sereno & Holzman, 1995; Spengler
et al., 2006; Thaker et al., 1990) have reported that schizophrenia patients display increased
NIH-PA Author Manuscript
saccadic latency to correct antisaccade task responses (but see Clementz, McDowell & Zisook,
1994; Hutton et al., 2002; Maruff et al., 1998). It is noteworthy that Curtis et al. (2001) observed
that acutely ill schizophrenia patients, though not remitted patients, showed significantly
increased latencies on correct antisaccade trials. Although Ettinger and colleagues (2004a)
noted no difference between the first episode psychotic patients and healthy controls in terms
of response latency, it is unclear how many of these patients met diagnostic criteria for
schizophrenia.
Investigators have examined whether the saccadic latencies can be manipulated in
schizophrenia patients as they are in healthy controls, i.e., whether individuals with
schizophrenia will display the `gap effect'. The literature is consistent in indicating that
schizophrenia patients show latency reductions on visually guided saccadic tasks in which there
is a temporal delay after the fixation spot is extinguished and prior to the appearance of an
eccentric target (Clementz, 1996; Reilly, Harris, Khine, Keshavan & Sweeney, 2008; Sereno
& Holzman, 1993; Smyrnis et al., 2004). However, findings are mixed regarding whether the
gap effect is present in the antisaccade task. While in some investigations schizophrenic
individuals displayed reduced latency in the gap antisaccade condition similarly to healthy
individuals (McDowell & Clementz, 1997; Reilly et al., 2008), in another study, half of the
NIH-PA Author Manuscript
patients failed to show the gap effect (Smyrnis et al., 2004). Schizophrenia patients reportedly
do not differ from nonpsychiatric controls in terms of their latencies to error responses (Boudet
et al., 2005; Curtis et al., 2001; McDowell & Clementz, 1997), though this has been studied
considerably less often. However, as Klein (2001) demonstrated using Principal Components
Analysis, latencies to correct responses taps an aspect of performance that is distinct from
latency to error responses, and therefore should be studied separately.
Schizophrenic patients' aberrant antisaccade task performance cannot be attributed to state-
related factors. Supportive evidence for the trait-like nature of this deficit is derived from
investigations of medication effects on antisaccade performance, studies of clinical correlates
of schizophrenia patients' antisaccade task performance, and longitudinal studies of
antisaccade task performance in schizophrenia patients. Pharmacological agents exert effects
on antisaccadic performance in both healthy control subjects and schizophrenia patients.
Antisaccade performance is sensitive to various psychopharmacological manipulations in
healthy participants, including lorazepam (Green & King, 1998; Green, King, & Trimble,
2000), alcohol (Khan et al., 2003), nicotine (Rycroft et al., 2007), amphetamine (Dursun et al,
1999), and modafinil (Rycroft et al., 2007). Readers are referred to Reilly et al. (2008) for a
detailed discussion of this topic.
NIH-PA Author Manuscript
Most studies examining the relationship between psychotropic medications and antisaccade
task performance ( Fukushima et al., 1988; McDowell & Clementz, 1997; Broerse et al., 2002;
Ettinger et al., 2003; Raemakers et al., 2002; Wonodi et al., 2004; Allen et al., 1996; Karoumi
et al., 2001; Nkam et al., 2001; Maruff, Danckert, Pantelis & Currie, 1998) conclude that the
task deficits are not attributable to medication exposure. In schizophrenia patients, risperidone
has been observed to improve error rates in some schizophrenia patients (Burke & Reveley,
2002; Hutton, 2002; but see Harris et al., 2006). There have also been reports that antisaccade
performance in schizophrenia may improve with nicotine (Depatie et al., 2002; Larrison-
Faucher et al., 2004). However, to date, no pharmacological agent has been able to normalize
schizophrenic individuals' excessive number of directional errors on antisaccade compared to
nonpsychiatric controls.
Despite the fact that the group difference in directional errors is a more robust observation,
some investigators have examined the effects of pharmacologic agents on antisaccade
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 9
latencies. In their comparison of medicated and unmedicated first-episode schizophrenia
patients, Hutton et al (1998) observed increased error rates for both patient groups but
NIH-PA Author Manuscript
prolonged response latencies only in the treatment-naive group. Yet in another investigation
of treatment-naive patients (Muller et al., 1999) showed that treatment had no effect on either
antisaccade accuracy or latency.
There have been relatively few longitudinal studies of antisaccade task performance in
schizophrenia patients. Antisaccade task accuracy in schizophrenia patients shows high retest
stability (i.e., r's ranging from .75 to .90) for intervals up to one year (Thaker et al., 1990;).
Chronic schizophrenia outpatients who were tested three years after their initial assessment
displayed high test-retest reliability in terms of their antisaccade accuracy, despite changes in
their clinical status and medication regimes (Gooding, Mohapatra, & Shea, 2004). Longitudinal
findings based upon a sample of antipsychotic-naive patients were consistent with those of
Gooding and colleagues (2004). Harris et al. (2006) followed 41 healthy community-based
controls and 39 antipsychotic-naive patients who met DSM-IV criteria for either schizophrenia
or schizoaffective disorder, depressive type over a one year period. Although the patients'
antisaccade performance gradually improved over the course of the year, they showed elevated
error rates relative to the healthy controls across all time points. This finding indicates that the
patients' impaired ability to plan and initiate context-appropriate responses was stable over
time.
NIH-PA Author Manuscript
Performance on Memory-Guided (Oculomotor Delayed Response) Tasks
Schizophrenia patients' oculomotor delayed response task performance is characterized by
excessive anticipatory saccades during the delay period (Camchong et al., 2006; Everling et
al., 1996; Hommer et al., 1991; Landgraf et al., 2008; McDowell & Clementz, 1996; McDowell
et al., 2001; Park, 1997; Park & Holzman, 1992). In memory-guided saccades, schizophrenia
patients typically display increased latencies and/or decreased gain (Everling et al., 1996;
Landgraf et al, 2008; McDowell & Clementz, 1996; McDowell & Clementz, 2001; Muller et
al., 1999; Park & Holzman, 1992, 1993; Ross et al., 1998). Given that schizophrenia patients
displayed impaired performance on oculomotor delayed response tasks yet intact performance
on visually guided saccade tasks, Park and Holzman (1992, 1993) suggested that schizophrenia
patients had a selective deficit in their representational processing.
Consideration of patients' performance across tasks provides insight into the nature and extent
of their oculomotor deficits. Although schizophrenia patients display impairments in terms of
inhibiting a reflexive saccade during an antisaccade task, data from a study by Hutton et al.
(2002) suggest that the schizophrenia patients' saccadic inhibition deficit may not be global.
That is, schizophrenic patients' failure to suppress saccades may depend upon the type of
NIH-PA Author Manuscript
activity that is required at the onset of the visual stimulus. Hutton et al. (2002) observed no
deficits when schizophrenic patients were required to inhibit reflexive saccades in a fixation
with distractors task. In contrast, when the subjects were required to generate an antisaccade
rather than continue fixation, they produced significantly more reflexive saccades than the
controls. The finding that when fixation is required schizophrenia patients' inhibition is as
efficient as that of controls is consistent with prior work (e.g., Gooding, Hendershot, &
Grabowski, 2000) which indicates normal fixation in schizophrenia patients.
In a more recent investigation of schizophrenia patients' fixation stability, Barton and
colleagues (2008) observed that although a subset of schizophrenia patients had little difficulty
maintaining fixation, many of the patients displayed difficulty maintaining fixation in a simple
fixation with distractor task. The findings of Hutton et al. (2002) and Barton et al. (2008) can
be reconciled if one considers that in the former study, the different tasks (i.e., antisaccade and
fixation with distractor) were presented in blocks. In the Barton study, the antisaccade and
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---

Gooding and Basso
Page 10
fixation with distractor trials appeared pseudorandomly, possibly causing the task to be more
difficult and revealing a subset of subjects with poor fixation ability. The increased difficulty
NIH-PA Author Manuscript
unmasked a relationship between antisaccade performance and fixation ability. Indeed, Barton
and colleagues observed a higher antisaccade error rate in patients with poor fixation stability.
Schizophrenics' Performance on Scanpaths and Visual Search Tasks
When subjects were required to use visuospatial cues (arrows) to guide their sequence of
scanning, Reischies et al. (1989) observed that schizophrenia patients produced a higher
number of errors and displayed increased saccadic latency, relative to normals. When Gaebel,
Ulrich, and Frick (1987) examined the visuomotor performance of partially remitted
schizophrenia patients in a picture viewing task, they found two subgroups of patients who
displayed opposite scanning patterns, both of which differed from that of healthy controls.
Some patients engaged in minimal scanning, while other patients displayed extensive, though
relatively inefficient, visual search behavior.
Kojima's lab (Nakajima et al., 1988; Kojima, Potkin, Kharazmi, Matsushima, Herrera &
Shimazono, 1989; Kojima et al., 1990) conducted a series of investigations of schizophrenia
patients' visual search performance, all of which replicated the earlier Gaebel et al. (1987)
finding that the patients display poorer visual search performance than normal controls.
Schizophrenia patients produce fewer exploratory eye movements when presented with a
NIH-PA Author Manuscript
geometric figure to draw and then compare to two additional figures that differ slightly from
the original stimulus. Schizophrenia patients also display a more limited area of inspection
relative to normal controls and nonschizophrenic psychotic patients such as methamphetamine
psychotic patients (Kojima et al., 1990). This finding of decreased responsive visual search
behavior has been replicated in remitted schizophrenia patients as well as acutely ill patients
and remitted patients (Kojima et al., 1990). Moreover, schizophrenia patients and schizotypal
personality disordered patients do not differ in terms of their exploratory eye movements
(Tsunoda et al., 2005), suggesting that this anomaly is also observed in the schizophrenia
spectrum. In contrast, schizophrenia patients display significantly fewer exploratory eye
movements than patients outside the schizophrenia spectrum, such as depressive patients
(Kojima et al., 1992; Kojima et al., 2001; Matsushima et al., 1998). In summary, schizophrenia
patients are generally able to produce visually guided saccades, particularly when the task is
simple. Overall, their predictive saccade performance is also within normal limits, though
reaction times may be increased. The most consistent finding in the saccadic literature concerns
schizophrenia patients' antisaccade task deficits. This appears to be a nearly ubiquitous finding;
there is also compelling evidence indicating that schizophrenia patients' antisaccade task
deficits are a temporally stable trait. Schizophrenia patients also display aberrant performance
NIH-PA Author Manuscript
on memory-guided saccade tasks. Although studied less frequently, schizophrenia patients'
performance on scanning and visual search tasks reveals significant differences from healthy
controls and other patients outside the schizophrenia spectrum.
3A. Symptom Correlates of Schizophrenia Patients' saccadic abnormalities
Some investigators have explored the role of symptoms on antisaccade task performance in
schizophrenia patients. There have been a few reports of significant associations between
negative symptoms, as measured by either the SANS scale or the PANSS, and suppression
errors on antisaccade tasks (Ettinger et al., 2004a; Ettinger et al, 2006; Muller et al., 1999;
Tien et al., 1996). However, schizophrenia patient groups classified according to predominance
of negative symptoms do not differ significantly in terms of antisaccade accuracy (Nkam et
al., 2001; Rosse et al., 1993). In contrast, when patients are grouped according to the deficit
versus non-deficit distinction, differences in latency of successful antisaccades emerge (Nkam
et al., 2001; Thaker et al., 1989). In both comparisons, the deficit patients showed significantly
increased latency of antisaccades relative to the nondeficit group. Consistent with these
Brain Cogn. Author manuscript; available in PMC 2009 December 1.

---