Cognitive Control Under Contingencies in Anxious and
Depressed Adolescents: An Antisaccade Task
Sandra Jazbec, Erin McClure, Michael Hardin, Daniel S. Pine, and Monique Ernst
Background: Emotion-related perturbations in cognitive control characterize adult mood and anxiety disorders. Fewer data are
available to confirm such deficits in youth. Studies of cognitive control and error processing can provide an ideal template to examine
these perturbations. Antisaccade paradigms are particularly well suited for this endeavor because they provide exquisite behavioral
measures of modulation of response errors.
Methods: A new monetary reward antisaccade task was used with 28 healthy, 11 anxious, and 12 depressed adolescents.
Performance accuracy, saccade latency, and peak velocity of incorrect responses were analyzed.
Results: Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment). However,
modulation of saccade errors by incentives differed by groups. In incentive trials relative to neutral trials, inhibitory efficiency (saccade
latency) was enhanced in healthy, unaffected in depressed, and diminished in anxious adolescents. Modulation of errant actions
(saccade peak velocity) was improved in the healthy group and unchanged in both the anxious and depressed groups.
Conclusions: These findings provide grounds for testing hypotheses related to the impact of motivation deficits and emotional
interference on directed action in adolescents with mood and anxiety disorders. Furthermore, neural mechanisms can now be
examined by using this task paired with functional neuroimaging.
Key Words: Anticipation, eye movement, latency, motivation, peak
velocity, punishment, reward
A
number of current theories view mood and anxiety
disorders as conditions that result from developmental
perturbations in information processing (Gotlib et al
2004; Pine et al 1998, 2000), and in emotion regulation (Davidson
et al 2002). These theories emphasize the role of perturbed
attention allocation, particularly as a function of affective context,
in mood and anxiety disorders (Beuke et al 2003; Dalgleish et al
2003; Williams et al 1996). Furthermore, such attention– emotion
perturbations are expressed in distinct patterns of motivated
behaviors. A global lack of motivation characterizes depressive
disorders, and exacerbated avoidant behavior with enhanced
emotional interference characterizes anxiety disorders (Austin et
al 2001; Ehrenreich and Gross 2002). Although such theories are
generally well supported in studies of adults, virtually no research in adolescents employs basic neuroscience measures to
explore associations between mood or anxiety disorders and
either perturbed attention control or contingency-related information processing (Austin et al 2001). This limitation hinders
efforts to move developmental models beyond simple descriptive formulations into neuroscience-based theories.
Emotion-related attention bias in adolescent mood and anxiety disorders may manifest as perturbed control of saccadic eye
movement. Because saccades index attention allocation (Brockmole et al 2002; Godijn and Theeuwes 2003; Munoz et al 2004),
paradigms that examine motivational influences on saccadic
control might identify aberrant attention– emotion interactions.
Recent studies have begun to examine attention– emotion interactions in both adult and adolescent disorders. In adults, rela-
From the Section of Developmental and Affective Neuroscience, National
Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Address reprint requests to Monique Ernst, M.D., Ph.D., Section of Developmental and Affective Neuroscience, Mood and Anxiety Disorders Program, NIMH/NIH/HHS, 15K North Drive, Bethesda, MD 20892; E-mail:
[email protected].
Received January 4, 2005; revised March 14, 2005; accepted April 8, 2005.
0006-3223/05/$30.00
doi:10.1016/j.biopsych.2005.04.010
tively consistent attention biases are found in mood and anxiety
disorders (Gotlib et al 2004). Some forms of emotion-related
attention bias may occur in both anxiety and depressive disorders; other forms may represent disorder-specific deficits
(Dalgleish et al 2003). In adolescents, however, the few available
studies demonstrate less consistent associations than those found
in adults, possibly because of the use of attention allocation
measures that assess global dimensions of behavior (e.g., accuracy or reaction time of button press). These measures may lack
sensitivity and contribute to heterogeneity of findings (Ehrenreich and
Fischer 2002).
Saccadic eye movement tasks provide a precise assessment of
some aspects of top-down cognitive control processes that can
influence attention allocation (Munoz et al 2004; Ridderinkhof et
al 2004). Of particular interest are the measures indexing processes involved during the preparation for saccadic action and
those during the execution of action. Because incorrect responses and saccade latencies during antisaccade tasks reflect
the ability to inhibit prepotent responses (Munoz and Everling
2004), these measures may be particularly susceptible to modulation by motivationally salient stimuli, and particularly relevant
to attention– emotion related deficits in mood and anxiety disorders. The neural circuitry underlying motivational influences on
eye movement execution has been exquisitely delineated in
nonhuman primates (Ikeda and Hikosaka 2003; Kobayashi et al
2002; Takikawa et al 2002; Watanabe et al 2003a, 2003b). This
circuitry shows commonalities with the structures implicated in
cognitive control processes, including response inhibition and
error/conflict monitoring (Holroyd et al 2002; Tucker et al 2003),
depression (Drevets 2001), and anxiety (Kent and Rauch 2003).
Thus, assessments of motivational influences during saccadic
errors may index perturbed cognitive control processes observed
in adolescent mood and anxiety disorders.
The antisaccade task is one of the most frequently used
paradigms in developmental research on eye-movement control
(Luna et al 2004a, 2004b). Antisaccades are rapid voluntary eye
movements that are directed towards the mirror position of a cue
presented in the peripheral visual field (Everling and Fischer
1998; Munoz and Everling 2004). To perform a correct antisaccade, the reflexive urge to look at the target (i.e., prosaccade)
needs to be inhibited and a voluntary saccade has to be
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© 2005 Society of Biological Psychiatry
S. Jazbec et al
programmed in absence of visual input. Not surprisingly, erroneously triggered prosaccades are common in this paradigm
(Munoz et al 1998; Olincy et al 1997).
The three most common performance parameters used in this
task include accuracy, saccade latency, and saccade peak velocity (Leigh and Zee 1999; Munoz and Everling 2004). Accuracy
provides a relatively global index of quality of performance,
whereas latency and peak velocity are more precise measures of
cognitive control processes that map to specific neural function.
For example, prolonged saccade latency during antisaccades
(compared with prosaccades) reflects decreased saccade neuron
activity in the frontal eye fields and superior colliculus (Everling
et al 1998; Munoz et al 2004). Shorter latencies during incorrect
antisaccades are normal and reflect an inability to inhibit saccade
neurons (Munoz et al 2004). Less efficient cognitive control
predicts that the capacity to inhibit an erroneous response
requires more time (i.e., longer latencies). Peak velocity, on the
other hand, may assess motor regulation once execution of a
saccade is initiated. In the context of an already initiated errant
saccade, lower peak velocity may represent an effort to reduce
the error as it is being executed. In this instance, reduced peak
velocity reflects greater control exerted over the inappropriate
saccadic action.
The current work examines the degree to which incentives
modulate processes engaged during saccadic errors in adolescents with mood and anxiety disorders. Specifically, we
developed a novel monetary reward saccade task to assess
attention–reward interactions. Unlike other tasks that tap attention– emotion interaction, this task assesses relatively subtle
aspects of attention control under neutral, negative, and positivevalenced conditions: 1) failure to obtain an expected monetary
gain (“reward” errors), 2) failure to avoid monetary loss (“punishment” errors), and 3) no monetary consequences (“neutral”
errors).
The study tests three sets of hypotheses. 1) Overall, accuracy
rate of correct responses will be improved by contingencies;
however, patient groups will show less efficient facilitation of
performance by incentives, because of motivation deficits in
depression and emotional interference in anxiety. 2) Cognitive
control, assessed by saccade latency and peak velocity, will be
enhanced by incentives in healthy subjects, as evidenced by
decreased latency and decreased peak velocity of errant saccades; however, depressed and anxious adolescents will show
lesser degrees of incentive-related minimization of an errant
action. 3) Anxiety will affect performance on punishment trials
more strongly than on reward trials because of negative bias in
this disorder (Dalgleish et al 2003). Depression will influence
response to both reward and punishment trials because motivation deficits affect responses to both positive and negative
contingencies (Naranjo et al 2001).
Methods and Materials
Participants
The sample consisted of 28 healthy adolescents, 11 adolescents with anxiety disorders, and 12 adolescents with major
depressive disorder (MDD). The Institutional Review Board of
the National Institute of Mental Health approved the study.
Parents gave written informed consent, and adolescents gave
written assent prior to participation, after the study was fully
explained and all questions answered. Patients were recruited
when they sought treatment for a mood or anxiety disorder.
BIOL PSYCHIATRY 2005;58:632– 639 633
Healthy subjects were recruited through advertisements and
contacts with medical organizations.
Inclusion criteria for all subjects were age between 9 and 17
years, absence of acute or chronic medical problems, absence of
any treatment with psychotropic medications for 1 month (2
months for fluoxetine), absence of severe trauma history or
posttraumatic stress disorder (PTSD), absence of obsessive–
compulsive disorder (OCD), chronic tic disorder, mania, conduct
or oppositional defiant disorder, substance abuse, pervasive
developmental disorder, or attention-deficit/hyperactivity disorder (ADHD) of sufficient severity to require immediate treatment.
Other exclusion criteria comprised mental retardation (IQ ⬍ 70),
use of any medication, and pregnancy. All participants were
tested for IQ prior to entering the study with the Wechsler
Abbreviated Scale of Intelligence (WASI; Wechsler 1999).
Patients in the MDD group met DSM-IV criteria for current
MDD and were required to exhibit elevated symptoms on the
Child Depression Rating Scale (CDRS ⱖ 39). Patients in the
anxiety disorder group met criteria for lifetime generalized
anxiety disorder (GAD) and were required to show elevated
symptoms on the Pediatric Anxiety Rating Scale (PARS ⬎ 10).
Immediately following assessment and testing (including eye
movement tracking), patients were provided treatment.
Healthy adolescents met criteria for no current or past psychiatric disorders. All participants were evaluated through semistructured psychiatric interviews using the Kiddie Schedule for
Affective Disorders and Schizophrenia for School-Age Children
(K-SADS-PL). These evaluations were performed by experienced
clinicians who each had demonstrated acceptable inter-rater
reliability (␬ ⬎ .75) for all relevant diagnoses (Kaufman et al
1997).
Procedures
Recordings were obtained in a room lit by standard overhead
fluorescent lights. Following initial calibration of eye position,
eye movements were measured with high-resolution infrared
oculography (Applied Science Laboratories [ASL] Model 504;
Bedford, Massachusetts). Calibration was repeated between runs
as needed. Before performing the task, subjects were thoroughly
trained to prevent any learning effect. They also were debriefed
after the completion of the task.
Task
The task measured rapid reflexive and voluntary eye movements in three contingency contexts: monetary gain (reward
condition), monetary loss (punishment condition), and no incentive (neutral condition). It comprised three phases: 1) the initial
cue phase (1250 –170 msec), which informed the subject about
the type of trial (prosaccade or antisaccade; reward, punishment,
or neutral); 2) the target phase or saccade phase (1850 msec); 3)
and the feedback phase (1000 msec; Figure 1).
Each trial started with one of six cues displayed at the center
of a black computer screen, and subtending approximately .5°
visual angle. The cues included a plus sign (⫹), a minus sign (–),
or a small circle (䡩), presented in either white or gray. White cues
signaled a prosaccade (i.e., an eye movement towards the
target), and gray cues signaled an antisaccade (i.e., an eye
movement to the mirror position of the target). The shape of the
cue indicated the valence of the trial: a plus sign meant a $1
monetary gain for a correct eye movement or no gain for an
incorrect eye movement (reward condition); a minus sign meant
a $1 monetary loss for an incorrect eye movement, or no loss for
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634 BIOL PSYCHIATRY 2005;58:632– 639
S. Jazbec et al
Eye Movement Recording
Eye movements were measured with an ASL Model 504 eye
tracker with remote pan and tilt optics, autofocusing lens, and
with magnetic head tracker. The spatial accuracy of the eye
tracker is .25° visual angle. Sampling rate is 60 Hz.
Use of a magnetic head tracking and an autofocusing lens
minimized the possibility of artifacts due to head movements.
Participants were instructed to remain still, and a chinrest was
employed when necessary. Differences in eye-screen distance
across subjects were corrected for in the offline analysis of the
raw data. The distance from the eye to the screen was on average
26.35 ⫾ 1.96 inches for healthy subjects and 25.72 ⫾ 1.91 for
patients.
Figure 1. Paradigm of the Reward Saccade Task: A cue (1250 to 1750 msec
duration) is presented at the onset of each trial. The cue indicates the type of
trial (gray for antisaccade and white for prosaccade) and the incentive
condition of the trial (‘o’ for neutral, ‘⫹’ for gain, and ‘⫺‘ for loss). As the cue
disappears, a target appears on the right or left side of the screen (1850 msec
duration), until the feedback appears for 1000 msec. As the feedback disappears, the next trial starts with appearance of the central fixation cue. The
number of the trials for each condition is presented below.
Antisaccade
⫹
⫺
o
Total
Prosaccade
Right
Left
Right
Left
Total
12
12
12
36
12
12
12
36
12
12
12
36
12
12
12
36
48
48
48
144
.
a correct eye movement (punishment condition); and a circle
meant the absence of monetary incentive (neutral condition).
After a variable period of 1250 –1750 msec, the cue was
replaced by a white target stimulus that appeared laterally on the
screen. The target, an asterisk subtending .5° visual angle,
appeared at approximately 6.15° eccentricity on the horizontal
meridian either to the left or the right of the centrally located cue
position. The target duration was 1850 msec. To succeed on a
trial, subjects had to fixate for at least 100 ms an area of 60 pixels
radius around the correct location. Fixation also had to occur
within 500 msec after target appearance. Subjects were asked to
maintain fixation until they received feedback.
Feedback (1000 msec) was presented 1850 msec after target
onset and subtended approximately 1.8° visual angle. Feedback
consisted of dollar amounts (⫹$1, ⫺$1, $0). The feedback
appeared at the location where the subject was supposed to have
gazed, replacing the target in the prosaccade trials, or appearing
in the mirror location of the target in the antisaccade trials.
Subjects were asked to keep their eyes on the appropriate site
until they saw the feedback cue. The feedback cue was green
when the gaze was correct and red when the gaze was incorrect.
The task consisted of three runs of 4 min duration each. Each
run comprised 48 trials, with four trials per side (right, left) and
condition (antisaccade-reward, antisaccade-punishment, antisaccade-neutral, prosaccade-reward, prosaccade-punishment, and
prosaccade-neutral). The task included a total of 144 trials (24
trials per condition).
Subjects started with $0 and could win up to $48 per run.
Control adolescents won on average $25.8 ⫾ $10.9, anxious
patients $23.5 ⫾ $13.5, and depressed patients $26.3 ⫾ $12.2.
Participants were told that they would receive the dollar amount
they won and were sent a check at the completion of the study.
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Eye Movement Analysis
The raw data were analyzed offline with software provided by
ASL (EYENAL). This program calculates fixations (gazes) based
on an algorithm that takes into account the distance of the eye to
the screen for each subject. According to this fixation algorithm,
a fixation starts when the standard deviation of the x and y
coordinates of six consecutive samples (corresponding to 100
msec duration) is below .5° visual angle. A saccade was defined
as an eye movement between two fixations.
The saccadic measures used in this study were latency and
peak velocity. The latency is defined as the time period elapsed
between the onset of the target and the onset of the first
subsequent saccade. The peak velocity was calculated as the
saccade amplitude in degrees visual angle divided by half the
saccade duration in sec (Carpenter 1988).
Participants can make three kinds of saccades: anticipatory
(latency ⬍ 80 msec), direct response (80 msec ⬍ latency ⬍ 700
msec), and delayed response (latency ⬎ 700 msec; Fischer and
Weber 1992; Klein et al 2003). Because more than 90% of the
saccades were direct saccades, only direct saccades were examined in this study. A correct response was defined as a saccade
that occurred within 80 msec and 700 msec after target onset and
ended up with the pupil projecting on a point within a circle of
a 60 pixels radius around the correct point (mirror location of the
target on a horizontal line in antisaccades).
Because this study focused on behavior during errors, the
analysis sampled parameters of direction errors of antisaccades,
that is, unwanted reflexive prosaccades. In addition to accuracy
(number of incorrect antisaccades), two independent parameters
were analyzed: latency and peak velocity. We did not include
saccade amplitude and duration because these variables are
highly correlated with peak velocity, given the stereotyped
pattern of saccades (Fischer et al 1992).
Repeated-measures analyses of variance used saccade performance variables as dependent measures with diagnostic group
(control vs. anxious vs. MDD) as the between-subjects factor,
and accuracy (correct vs. error) and contingency (punishment vs.
reward vs. neutral) as the within-subjects factors.
We treated subjects with MDD alone or MDD comorbid with
anxiety as a single group for two reasons. First, prior studies of
attentional dysfunction in adolescent MDD find that individuals
diagnosed with MDD alone or MDD with anxiety perform
similarly, but that they differ from adolescents with anxiety
disorders alone (Taghavi et al 1999). Second, longitudinal and
family-based studies suggest that adolescents frequently present
with anxiety in the absence of MDD but that adolescent MDD
virtually always presents with anxiety either concurrently or at
some other point during development (Costello et al 2002).
Finally, because groups were comparable in age, IQ, and gender,
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S. Jazbec et al
Table 1. Diagnoses in the Patient Groups
Group (Subject No.)
Anxious (1)
Anxious (2)
Anxious (3)
Anxious (4)
Anxious (5)
Anxious (6)
Anxious (7)
Anxious (8)
Anxious (9)
Anxious (10)
Anxious (11)
Depressed (1)
Depressed (2)
Depressed (3)
GAD
y
y
y
y
y
y
y
y
ya
y
y
SepAD
y
y
y
y
y
y
y
SocPh
SpecPh
y
y
y
y
y
y
y
Only three depressed children are included in this table because no
comorbid diagnoses were present in the other nine depressed patients.
GAD, generalized anxiety disorder; SepAD, separation anxiety disorder;
SocPh, social phobia; SpecPh, specific phobias.
ya Lifetime history of GAD but not currently meeting severity criteria for
GAD.
these variables were not included in the analysis. Significant
main effects or interactions were decomposed using post hoc
analyses. All conclusions are based on two-tailed tests with an a
priori ␣ ⫽ .05.
For completeness, correlations between performance scores
and ratings of severity of symptoms (CDRS and PARS) were
conducted in the combined patient sample and in each patient
group separately. No significant correlations were found.
Finally, a debriefing questionnaire was completed by all
participants after the eye tracking study. We collected data on
how difficult the task seemed to subjects and how well
subjects could distinguish between the gray and white cue
(4-point rating scales: 1 not at all, 4 extremely). Subjects rated
the question “How difficult was the task?” between “a little and
somewhat difficult” with a mean rating of 1.8 ⫾ .7 for the
healthy group, 2.0 ⫾ .7 for the anxious group, and 1.8 ⫾ .6 for
the depressed group. This subjective rating of difficulty was
not correlated with age (r ⫽ –.12, n ⫽ 46, p ⫽ .4). In response
to the question “How well could you make the difference
between the gray and white cue?” the three groups scored in
the “very well” range: 3.4 ⫾ .7 for the healthy group, 3.2 ⫾ .7
for the anxious group, and 2.9 ⫾ .9 for the depressed group.
This subjective rating was not correlated with age (r ⫽ –.17
p ⫽ .3). Therefore, effects of difficulty did not differ among
groups and could not account for the group differences in task
performance.
Results
Sample
The sample included 28 healthy adolescents (13 boys, 15
girls; mean ⫾ SD: age 13.0 ⫾ 2.5; IQ 107.3 ⫾ 13.3), 12
depressed adolescents (4 boys, 8 girls; mean ⫾ SD: age 13.9 ⫾
2.5; IQ 109.3 ⫾ 18.3), and 11 anxious adolescents (8 boys, 3
girls; mean ⫾ SD: age 12.2 ⫾ 1.6; IQ 112.7 ⫾ 10.9). As noted
above, groups did not differ significantly on gender distribution, IQ, or age.
All anxiety patients met lifetime DSM-IV criteria for GAD, and
10 of 11 met criteria for ongoing GAD (one did not meet criteria
for ongoing GAD but continued to meet criteria for separation
anxiety disorder and social phobia). In addition, comorbid
anxiety disorders in the anxiety group were common (see Table
1). Among participants with MDD, three had a comorbid anxiety
disorder (see Table 1).
Three anxious patients also met criteria for ADHD. However,
the symptoms of ADHD were less severe than their anxiety
symptoms.
Performance on Antisaccade Trials: Incorrect Responses
All means and standard errors are presented in Table 2. For
completeness, data on correct responses are also included in
this table, although analyses examine between-group differences only during saccadic errors. Performance scores during
the neutral condition did not differ among groups, reflecting
similar baseline performance in healthy, anxious, and MDD
adolescents.
Accuracy. The total number of recorded antisaccade responses per condition ranged between 21.7 and 22.8 for all
groups. Thus, an average of two antisaccade responses were
not detected by the eye-tracker in each group (total number of
trials per condition ⫽ 24). This loss of data was due to blinking
or to the eye camera losing the pupillary signal.
The mean number of incorrect responses per condition
ranged between 5.9 and 9.4 across the whole sample (Figure
2). For all three groups, as hypothesized, the number of
incorrect responses was lower in the reward and punishment
trials than in the neutral trials [Contingency: F (2,88) ⫽ 6.54;
p ⫽ .002], reflecting better performance under reinforcement
conditions (reward or punishment). However, no main group
effect or group-by-contingency interaction emerged. Thus,
incentive-related changes in accuracy did not differ significantly among groups.
Table 2. Mean (SE) of Number of Incorrect and Correct Antisaccades,
Latency to Saccades, and Peak Velocity by Group and Condition
Healthy (n ⫽ 28)
Punishment
Reward
Neutral
Punishment
Reward
Neutral
Punishment
Reward
Neutral
Punishment
Reward
Neutral
Punishment
Reward
Neutral
Punishment
Reward
Neutral
Anxious (n ⫽ 11)
Depressed (n ⫽ 12)
Number of Incorrect Antisaccades
5.88 (.78)
7.73 (1.56)
5.89 (.71)
7.64 (1.63)
8.89 (.94)
9.36 (1.64)
Number Correct Antisaccades
15.54 (.96)
13.55 (1.26)
15.04 (.90)
13.36 (1.22)
11.82 (1.11)
11.82 (1.57)
Latency to Incorrect Antisaccades
184.11 (11.44)
223.72 (14.66)
185.60 (10.58)
213.73 (11.65)
208.21 (9.52)
191.41 (7.94)
Latency to Correct Antisaccades
322.14 (11.24)
336.88 (15.10)
316.66 (8.68)
317.91 (14.73)
318.02 (9.95)
326.34 (12.48)
Peak Velocity of Incorrect Antisaccades
280.61 (14.91)
323.39 (7.31)
273.73 (15.06)
325.31 (8.04)
313.51 (9.79)
326.76 (6.75)
Peak Velocity of Correct Antisaccades
355.32 (8.21)
370.78 (15.40)
358.97 (10.02)
372.89 (9.89)
347.24 (10.16)
369.77 (17.11)
7.42 (.97)
8.00 (.78)
8.50 (1.60)
15.73 (1.21)
14.83 (1.49)
13.83 (1.49)
184.24 (17.05)
198.63 (12.45)
191.71 (16.61)
305.77 (16.83)
291.09 (17.64)
304.68 (20.06)
316.21 (20.82)
342.98 (10.13)
314.75 (16.79)
384.71 (10.85)
359.61 (19.08)
353.65 (21.60)
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Figure 2. Mean (SE) number of incorrect antisaccades (unwanted reflexive prosaccades) in healthy,
anxious, and depressed groups, by incentive
condition
Latency. In the case of errant saccades, longer latencies
reflect the inability to perform correctly despite longer periods of
preparation (Figure 3). As hypothesized, contingencies had
distinct effects across groups for the latency of incorrect responses [group-by-contingency F (4,84) ⫽ 3.18; p ⫽ .017].
This interaction was decomposed by examining the effects
of contingencies on latency separately in each of the three
groups. For the healthy adolescents, contingencies were associated with expected reductions in latency [F (2,22) ⫽ 3.41;
p ⫽ .05]. Similar effects emerged for both rewards and
punishments relative to neutral contingencies, with no difference between the two incentive conditions; however, this
effect did not emerge in adolescents with MDD, in whom
there was no effect of either contingency on latency [F (2,9) ⫽
.72; p ⫽ .52]. For the anxious group, in contrast, incentives
were associated with an increase in latency, particularly for
punished trials [F (2,24) ⫽ 5.6; p ⫽ .027]. Thus, in each of the
three groups, latency on incorrect trials exhibited a distinct
Figure 3. Mean (SE) latency of incorrect antisaccades (unwanted reflexive prosaccades) in healthy,
anxious, and depressed groups, by incentive
condition
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pattern of modulation related to the anticipation of positive or
negative contingencies (see Figure 3).
Peak Velocity. Peak velocity during the execution of a
saccade error quantifies the engagement of compensatory mechanisms. The lower the velocity, the more inhibited the saccade.
Thus, reduced velocity reflects the greater engagement of compensatory influences during the execution of an incorrect action.
As with the latency variable, contingencies exerted distinct
effects across patient groups for peak velocity on incorrect trials
[group-by-contingency F (4,84) ⫽ 3.27; p ⫽ .015].
In healthy subjects, peak velocity was reduced by both
reward and punishment incentives relative to neutral trials
[F (2,46) ⫽ 4.96; p ⫽ .011]. This reflects the expected greater
regulation in trials associated with potential monetary gain or
loss. Anxious patients failed to show any alteration in peak
velocity in the presence of incentives [F (2,20) ⫽ .11; p ⫽ .84].
Similarly to the anxious group, the MDD group failed to show
any incentive-related alteration in peak velocity [F (2,20) ⫽ .89;
S. Jazbec et al
p ⫽ .19], although the MDD group tended to exhibit an increase
in peak velocity on reward trials. No differences emerged
between the GAD and MDD groups.
Discussion
This study presents results from a novel saccadic control
task. Overall, the results demonstrate that attention-related
processes engaged during errant execution of a saccade are
sensitive to experimentally manipulated reward contingencies. Moreover, results point to perturbations in the degree to
which these contingencies affect cognitive control processes
in adolescents with anxiety or MDD, relative to healthy
adolescents.
The three hypotheses tested in this study were partly supported by the findings. 1) Overall, accuracy was improved by
contingencies: fewer errors occurred during reward and punishment trials than during no-incentive trials. Accuracy did not differ
among healthy, anxious, and MDD adolescents, however (Figure 2). 2) Cognitive control, indexed by saccade latency and
peak velocity of errant antisaccades, was facilitated by contingencies in healthy adolescents: shorter latency and lower peak
velocity occur in reward and punishment trials relative to noincentive trials. Anxious and depressed adolescents showed
either no improvement or worsening of these parameters with
contingencies. 3) The distinct effects of contingencies on performance as a function of positive, negative, and neutral conditions
was different in anxious and depressed adolescents: anxious
adolescents were most deviant in the negative condition,
whereas depressed adolescents were abnormal in both positive
and negative conditions. Depression was associated with a
similar pattern of deficient influence of incentives on both
saccade preparation and control of saccade execution, that is,
absence of improved performance under both positive and
negative incentives. In contrast, anxiety was associated with a
different pattern of perturbed influence of incentives on saccade
preparation and saccade execution, that is, worsening of efficiency of inhibition (saccade preparation) under positive and
negative incentives, particularly negative incentives, and absence
of improvement in minimizing error execution (saccade execution).
BIOL PSYCHIATRY 2005;58:632– 639 637
sence of group
difference in accuracy suggests that this
variable provides a global measure of performance, relatively
insensitive to mood and anxiety disorders; however, this negative finding, as with all negative findings in this study, should be
interpreted with caution given the small number of patients.
Thus, a global performance deficit on this task related to mood
and anxiety disorders cannot be ruled out. The measures of
saccade latency and peak velocity during error execution probe
specific processes that occur either before or during the engagement of an errant saccadic behavior.
Latency is the period of time elapsed between the appearance
of a lateral target and the initiation of a motor response toward
this target (prosaccade) or away from this target (antisaccade).
The antisaccade latency represents the period of time necessary
to inhibit a reflexive saccade toward a suddenly appearing target
and to initiate a saccade away from this target (Leigh and Zee
1999). Therefore, longer latencies indicate that subjects have
more time to inhibit an errant target. Longer latencies of incorrect
saccades are associated with a weaker capacity to inhibit a
reflexive saccade: subjects still fail to inhibit unwanted reflexive
saccades despite longer latencies.
Peak velocity, a measure of the magnitude of a saccade,
indexes control of motor execution. After an errant saccade is
released, the reduction of the magnitude of this saccade reflects
the capacity to reduce error after the movement is initiated (Leigh
and Zee 1999): reduced peak velocity of incorrect saccades
implies greater capacity to minimize error.
Thus, these measures of capacity for inhibiting (latency) or
minimizing (peak velocity) incorrect actions permit probing of
the efficiency of cognitive control. Findings from the present
study suggest that processes controlling both the preparation and
execution of eye movements are modulated by incentives differently in youth with MDD and with GAD, relative to healthy
adolescents.
Latency: Efficiency of Inhibitory Preparatory Control
Healthy adolescents showed enhanced performance (shorter
latencies) under both positive and negative incentive conditions
relative to nonincentive condition. This finding corroborates
facilitation of behavior under contingencies (Wasserman et al
1997).
Figure 4. Mean (SE) peak velocity of incorrect antisaccades (unwanted reflexive prosaccades) in
healthy, anxious, and depressed groups, by incentive condition
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638 BIOL PSYCHIATRY 2005;58:632– 639
In contrast, anxious adolescents responded with increased
latency to the presence of incentives compared with the neutral
condition in errant saccades. In other words, longer preparatory
periods were not sufficient to inhibit errors. The punishment
condition (potential monetary loss) was the most affected condition (longest latencies) in anxious adolescents (see Figure 3).
This suggests that, whereas both positive and negative contingencies diminished efficiency of inhibiting a reflexive prosaccade
in anxious adolescents, negative contingencies were more disruptive. This finding is consistent with the negative attention bias
reported in this population (Ehrenreich and Gross 2002). We
propose that the presence of contingencies, positive or negative,
creates an interference effect. The possibility of reward (or failure
to obtain reward) or of punishment may induce a state in which
attentional resources are partly diverted away from cognitive
control processes towards emotion based processes. This attention diversion would result in a reduction of the attentional
resources allocated to inhibit a prepotent action (prosaccade).
Deficits in cognitive control could reflect dysfunction of the
anterior cingulate (Brown and Braver 2005; Carter et al 1998;
Holroyd et al 2004) and hyperactivity in other limbic and
paralimbic areas (Cannistraro and Rauch 2003). Such interpretation could be tested using functional neuroimaging paired with
the reward saccade task. When contrasting brain activity during
errant saccades in a reward or punishment condition with that
during a nonincentive condition, we would expect reduced
activation in the anterior cingulate, a key structure in cognitive
control (Brown and Braver 2005; Carter et al 1998; Holroyd et al
2004) and enhanced activation in paralimbic and limbic structures such as ventral prefrontal cortex and amygdala in anxious
adolescents compared to healthy adolescents (Cannistraro et al
2003).
Finally, depressed adolescents were characterized by the
failure of contingencies to influence latency and, by inference,
cognitive control. This finding is consistent with the presence of
motivation deficits, which neutralize the power of incentives to
enhance behavior, such as attention engagement during errant
prosaccades.
Peak Velocity: Efficiency of Motor Execution Control
Peak velocity indexes regulatory influences on already
initiated actions, as opposed to latency, which indexes regulatory influences that occur before initiation of an action. Here
again, contingencies improved the control of errors in healthy
adolescents, with lower peak velocities during reward and
punishment conditions relative to nonincentive condition
(Figure 4). In contrast, contingencies showed no modulatory
influence on peak velocity in anxious and depressed adolescents. This deficit in modulating the execution of an action
under different incentive conditions might also reflect difficulty in mobilizing resources to correct an error. Whereas this
control mechanism is tested here in the context of motor
execution, it is conceivable that similar controls are exerted
toward inhibiting unwanted thoughts or emotions.
These results need to be considered in light of some
limitations. First, the sample size was relatively small, particularly with respect to patients. Nonetheless, it was sufficiently
large to detect differences among groups. Negative findings
must be interpreted with particular caution. For example, a
larger sample may provide sufficient power to detect hypothesized group differences on accuracy. In addition, the sample
size did not permit examination of age and gender effects on
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S. Jazbec et al
the performance scores. These effects will be examined in
future larger studies of healthy individuals as a first step.
Second, we combined adolescents with MDD and comorbid
anxiety disorders and adolescents with only MDD. Although
the primary diagnosis in these adolescents was MDD, the
inclusion of subjects with comorbid anxiety may have diminished potential differences between the anxiety and MDD
groups. Of note, analyses not shown here, performed after
excluding the three subjects with comorbid diagnoses, generated identical conclusions. Nevertheless, future studies of
specificity might exclude subjects with comorbid MDD and
anxiety. Third, three anxious patients also met criteria for mild
ADHD. Although their performance did not differ significantly
from that of the remaining patients with anxiety, it is not
possible to evaluate the potential impact of such comorbidity
on the performance of this task with only three subjects with
comorbid ADHD. This is particularly salient given findings of
impaired antisaccade performance in children with ADHD
(Klein et al 2003). Fourth, although all anxiety patients had a
history of GAD, they were heterogeneous with respect to
other anxiety disorders. As a first study, we opted to include
adolescents with more than one anxiety disorders because
these conditions typically occur together (Pine et al 1998). The
next step will be to examine these disorders separately. Fifth,
it is possible that motivation to do well on the task was
different in patients compared with healthy subjects because
of their seeking treatment. It was made clear to these participants, however, that they did not have to complete this task
to be in the treatment study. In addition, seeking treatment
was initiated by the parents rather than by the adolescents.
These circumstances mitigate the possibility of different
sources of motivation to do the task between patients and
healthy volunteers.
Despite these limitations, we found that depressed and anxious adolescents demonstrated distinct patterns of incentiverelated modulation of the execution of unwanted reflexive
movements. Anxious adolescents showed some modulation of
response errors, particularly during the punishment condition,
whereas depressed adolescents had difficulty modulating these
responses during either reward or punishment conditions. These
findings suggest different mechanisms underlying the incentiverelated modulation of actions as a function of diagnosis. The
reward antisaccade task permits the parsing out of different
processes that contribute to cognitive control in motor preparation and execution. Functional neuroimaging studies using this
task will be able to refine our understanding of the mechanisms
underlying these controls of action and their alterations in mood
and anxiety disorders. Another important question is whether
these deficits precede the manifestation of symptoms and thus
constitute vulnerability factors, or contribute to symptom expressions, and respond to pharmacologic treatment. In the same vein,
a developmental study of these deficits from childhood through
adulthood could help to clarify the etiologic and functional
significance of these alterations.
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