Early Expression of a Pathophysiological Feature of Schizophrenia: Saccadic Intrusions
into Smooth Pursuit Eye Movements in School-Age Children Vulnerable to
Schizophrenia
Randal G Ross MD
SUPPLEMENTAL INFORMATION
A more detailed account of the recording and analysis of the smooth pursuit eye
movement (SPEM) task follows:
Subjects were seated 43 cm in front of a video monitor on which a small target was
displayed against a black background in an otherwise dark room. The subject's head was
stabilized with a bite bar and head rest. Horizontal eye movements were recorded using
an infra-red photoelectric limbus detection eye tracking device, which is accurate to
within 0.25 of visual angle and has a time constant of 4 ms. The analog output of the
device was sampled at 500 Hz using a 12-bit analog-to-digital converter. Disconjugate
gaze is likely absent in most subjects; thus, left eye and right eye recordings are highly
correlated (Lencer et al., 2000). Our experience suggests that minimizing calibration
time decreases the time subjects must maintain head position and improves the quality of
the recording. Therefore, data were collected only from the eye for which the most rapid
and accurate calibration could be obtained.
For the smooth pursuit eye movement task, the target moved horizontally back and
forth over 30 degrees with a constant velocity of 16.7 per second and a 1.4-second
fixation period between ramps, a "trapezoidal pattern." A trapezoidal pattern is employed
as it allows each ramp to be independently calibrated during the fixation period. Subjects
were told to "keep your eyes on the target wherever it goes." Representative tracings are
presented in Figure 1 in the published article.
All eye movement data were analyzed with a computerized pattern recognition
program, with computer analyzed results confirmed with visual inspection by an
experienced eye movement evaluator (RGR). Subject identity was blinded prior to visual
review. Software generated dependent measures have excellent test-retest reliability
(Roy-Byrne et al., 1995). This analysis system has been described elsewhere (Radant and
Hommer, 1992; Ross et al., 2000) and will be briefly described here. Raw data consist of
eye position and target position for each 2 ms of recorded tracking. Eye movements were
divided into discrete segments, and then each segment was classified as saccade, smooth
pursuit, or artifact. Saccades were identified on the basis of peak velocity (greater than
35/s), initial acceleration (greater than 2000/s2), and duration (> 9 ms). Segments not
meeting velocity and acceleration criteria were considered smooth pursuit or fixation.
Artifactual segments caused by eye blinks and head movements show distinct
morphology and were removed from the analysis by the pattern recognition software.
Terming this task “smooth pursuit eye movements” is something of a misnomer, as
accurate performance requires the integrated activity of a number of neural systems,
including smooth pursuit and saccadic systems. In order to avoid confusion, we have
taken the convention of referring to the task by its acronym, SPEM, and reserve the
spelled out term “smooth pursuit” to refer to the neural system responsible for smooth
pursuit. Over the last 15 years, there has been increasing effort to focus on types of errors
that can be made during a SPEM task (Abel and Ziegler, 1988), with hopes that more
specific measures may increase sensitivity and specificity for genetic vulnerability.
Although SPEM abnormalities have been associated with schizophrenia for almost 100
years (Diefendorf and Dodge, 1908), the optimal SPEM measure for genetic studies
remains incompletely identified. Part of the problem is due to different laboratories
utilizing the same term with different operational definitions. Over the last decade, we
have undertaken a number of studies, across the lifespan, to develop an empirically
derived nosology (Olincy et al., 2002; Ross et al., 2002; Ross et al., 1996; Ross et al.,
1997; Ross et al., 1998; Ross et al., 1999b; Ross et al., 1999a; Ross et al., 2000; Ross et
al., 2001). Figure 2, in the published article, summarizes those results. The global SPEM
dysfunction associated with genetic vulnerability to schizophrenia appears to primarily be
due to an increase in the frequency of leading saccades.
Gain for a given interval of smooth pursuit is defined as mean eye velocity divided
by target velocity. Global smooth pursuit gain is defined as the mean gain, weighted for
time, of all intervals of true smooth pursuit (Abel et al., 1991). Intervals defined as
saccades are not included in computing smooth pursuit gain. During trapezoidal tasks,
eye movements during fixation or within 250 ms of a change in target motion were
discarded from the analysis, as these movements may not represent normal pursuit
(Lisberger and Pavelko, 1989). Many authors exclude periods of slowed pursuit after
task-inappropriate intrusive saccades to focus this measure as reflective of smooth pursuit
system performance (Clementz and Sweeney, 1990), while other authors include all
segments of smooth pursuit and present gain as a measure of global function (Radant and
Hommer, 1992). The difference in gain scores across definitions varies by less than 2%
with a greater than 0.95 correlation (Ross et al., 1997). For this report, we include all
segments of smooth pursuit and present gain as a measure of global functioning.
As can be seen in Figure 1 in the published article, lowered smooth pursuit gain can
occur secondary to either impairment in the smooth pursuit system or as a compensatory
mechanism to task-inappropriate saccades that intrude upon otherwise normal pursuit
(Abel and Ziegler, 1988; Clementz and Sweeney, 1990). Catch-up saccades are used as
the dependent measure of smooth pursuit system performance. Catch-up saccades
function to significantly reduce error between foveal gaze and target location and
compensate for poor smooth pursuit system performance (eye velocity below that of
target velocity). Saccades, which are in the same direction as target motion and begin
and end behind the target, are defined as catch-up saccades. In addition, saccades which
are in the same direction as target motion but which begin behind target location and end
ahead of target location are also classified as catch-up saccades if post-saccadic position
error is < 50% of pre-saccadic position error; ie. the saccade functions to dramatically
decrease the mismatch between visual gaze and target location.
One type of task-inappropriate saccade, which intrudes upon otherwise normal
smooth pursuit, is the anticipatory saccade. Anticipatory saccades must (a) be in the
direction of target motion, (b) either begin and end ahead of target location or increase
position error by 100%, and (c) be followed by a 50 ms interval of eye velocity less than
50% of target velocity. This definition of anticipatory saccades is based on analyses of
parameters that maximize schizophrenic-normal differences (Ross et al., 1999b; Ross et
al., 2001). Many authors also include a minimum amplitude criterion when defining
anticipatory saccades, generally greater than 4-5 (Abel and Ziegler, 1988; Clementz and
Sweeney, 1990). Strik et al. (, 1992) has suggested that larger and smaller saccades may
not reflect the same physiological process, a suggestion supported by differences between
these two types of saccades in the effects of age (Ross et al., 1999a), specificity to
schizophrenia (Ross et al., 2000), and response to nicotine exposure (Olincy et al., 1998).
Thus, we subdivide anticipatory saccades into large anticipatory saccades (with
amplitudes greater than 4) and leading saccades (with amplitudes of 1-4 degrees: see
Ross et al., 1999b for details).
Smooth pursuit, catch-up saccades, and anticipatory saccades account for more than
90% of eye movements during smooth pursuit tracking (Litman et al., 1994; Radant and
Hommer, 1992). Other components (e.g. square wave jerks, backup saccades, etc.)
constitute only a small portion of smooth pursuit tracking and generally do not differ
between schizophrenic subjects and controls (Litman et al., 1994; Radant and Hommer,
1992). Some saccades begin behind the target, end in front of the target, and do not
dramatically increase or decrease position error. These saccades do not meet the
definition for either catch-up or anticipatory saccades, are defined as indeterminate
saccades, and are not considered here. All saccades are reported as frequency (number
per minute of artifact free tracking) measures.
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