Cerebral Cortex, 2020;00: 1–11

doi: 10.1093/cercor/bhz277
Advance Access Publication Date:
Original Article

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ORIGINAL ARTICLE

Impaired Fixation-Related Theta Modulation Predicts

Reduced Visual Span and Guided Search Deficits in
Schizophrenia
Elisa C. Dias1,2,*, Abraham C. Van Voorhis1 , Filipe Braga1,† , Julianne Todd1 ,
Javier Lopez-Calderon1,‡ , Antigona Martinez1,3 and Daniel C Javitt1,3,*
1 Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10920 USA,
2 Department of Psychiatry, New York University School of Medicine, New York, NY 10016 USA, and
3 Department of Experimental Therapeutics, College of Physicians and Surgeons, Columbia University, New

York, NY, 10032 USA

Address correspondence to Elisa C. Dias and Daniel C. Javitt, Nathan Kline Institute, 140 Old Orangeburg Rd., Bldg 35, Orangeburg, NY 10962 USA. Email:
dias@nki.rfmh.org; javitt@nki.rfmh.org.
† Current address: Laboratório de Psicobiologia, Universidade Federal do Rio de Janeiro, Macaé, RJ, Brazil
‡ Current address: Facultad de Ingeniería, Universidad Autónoma de Chile, Talca, Chile

Abstract
During normal visual behavior, individuals scan the environment through a series of saccades and fixations. At each
fixation, the phase of ongoing rhythmic neural oscillations is reset, thereby increasing efficiency of subsequent visual
processing. This phase-reset is ref lected in the generation of a fixation-related potential (FRP). Here, we evaluate the
integrity of theta phase-reset/FRP generation and Guided Visual Search task in schizophrenia. Subjects performed serial
and parallel versions of the task. An initial study (15 healthy controls (HC)/15 schizophrenia patients (SCZ)) investigated
behavioral performance parametrically across stimulus features and set-sizes. A subsequent study (25-HC/25-SCZ)
evaluated integrity of search-related FRP generation relative to search performance and evaluated visual span size as an
index of parafoveal processing. Search times were significantly increased for patients versus controls across all conditions.
Furthermore, significantly, deficits were observed for fixation-related theta phase-reset across conditions, that fully
predicted impaired reduced visual span and search performance and correlated with impaired visual components of
neurocognitive processing. By contrast, overall search strategy was similar between groups. Deficits in theta phase-reset
mechanisms are increasingly documented across sensory modalities in schizophrenia. Here, we demonstrate that deficits
in fixation-related theta phase-reset during naturalistic visual processing underlie impaired efficiency of early visual
function in schizophrenia.

Key words: eye movements, fixation-related potential (FRP), intertrial coherence, visual search

Introduction
Schizophrenia is associated with deficits in early sensory
processing that contribute to higher-order disabilities (reviewed
in Javitt (2015) and Javitt and Freedman (2015)). In the visual
system, patients show consistent deficits in magnocellular
function as demonstrated using behavioral, functional mag-
netic resonance imaging, and neurophysiological approaches
(Martinez et al. 2012; Bedwell et al. 2013; Gracitelli et al. 2013;
Leonard et al. 2014; Kim et al. 2015; Martinez et al. 2015). These
deficits, moreover, interrelate with impairments in higher-order

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 2 Cerebral Cortex, 2020, Vol. 00, No. 00
visual functions including perceptual closure, visual working
memory, and face emotion recognition (Doniger et al. 2002;
Butler et al. 2009; Dias et al. 2011).
To date, the vast majority of physiological studies of visual
processing in schizophrenia have utilized stimuli presented
while subjects fixate on a single spot (“central fixation”). By
contrast, in natural vision, individuals continually move their
eyes to seek out relevant information through a series of
saccades and fixations, a process termed “active sensing” (Konig
and Luksch 1998; Schroeder et al. 2010; Ito et al. 2013; Hessels et
al. 2018; Concha-Miranda et al. 2019). Integrity of these processes
has been studied in schizophrenia to only a limited degree.
Here, we utilize eye-tracking combined with neurophysiological
assessment to evaluate both causes and consequences of active
sensing deficits in schizophrenia during a visual Guided-Search
task.
In Guided Search, subjects view successive search-fields con-
taining arrays of multiple background stimuli (“distractors”) as
well as a single predesignated “target” stimulus (Treisman 1982;
Nuechterlein et al. 2009). To find the target, subjects must sam-
ple the search-field through a series of saccades and fixations.
The time required to complete a search-field depends primarily
upon the number of eye movements needed. At each fixation,
individuals process visual information with high spatial reso-
lution only within the “foveal” region, that is, approximately
the central ∼1◦ of visual space. By contrast, the surrounding
“parafoveal” (∼1–5◦ ) and “perifoveal” (∼5–10◦ of visual space) are
sensitive primarily to low spatial frequency information, with a
fall-off of sensitivity with increasing eccentricity (Poletti et al.
2017).
When targets differ from distractors in only a single phys-
ical feature (“feature-search”), target stimuli “pop out” from
the visual field, permitting “efficient”, or “parallel-search” of
the field (Treisman 1982; Nuechterlein et al. 2009). By contrast,
when targets differ by a conjunction of features (“conjunction-
search”), subjects must use top–down attentional allocation to
serially “shine a spotlight” on subsets of stimuli for further
detailed evaluation (Treisman 1982). In this case, the search time
increases linearly with the number of stimuli (set-size) within
the stimulus array even as the size of the search-field remains
constant.
The slope of the increase in reaction time (RT) with set-size
indicates the degree to which subjects successfully limit their
search only to a subset of stimuli, and thus may serve as an index
of integrity of top–down attentional control (Nuechterlein et al.
2009). It has been shown that distinct networks of cortical areas
are activated for the different types of search due to the different
strategies required in each. (Nobre et al. 2003).
When subjects fixate, they generate an occipital fixation-
related potential (FRP)—also termed the λ potential (Fourment
et al. 1976; Kazai and Yagi 2003). As opposed to more traditional
visual event-related potentials (ERP) that are time-locked to the
presentation of a stimulus, FRPs are time-locked to fixation
onset as detected using an external eye tracker (Kamienkowski
et al. 2012). Although FRPs are sensitive to stimulus properties
in the to-be-fixated region, they occur even in the dark, or
while subjects are viewing a blank screen, and are thought to
reflect “priming” of visual cortex to process the to-be-fixated
information rather than response to the stimulus itself (Rajkai
et al. 2008; Ito et al. 2013).
In nonhuman primates, the FRP consists primarily of a
phase-concentration in the theta- (4–8 Hz) frequency range
(Rajkai et al. 2008). Visual search tasks are especially well suited
to study FRPs in active sensing as the subject is required to fixate
on a series of similar stimuli while they search for the target,
thus providing many fixations per trial.
Here, we used distractor stimuli that differed in either
orientation-alone (feature-search) or a conjunction of both
contrast and orientation (conjunction-search) (Fig. 1A). In the
feature (parallel) search condition, all stimuli were low-contrast,
and target stimuli differed only in orientation (vertical vs.
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horizontal). In the conjunction (serial) search condition, the
target was a single vertically oriented, low-contrast stimulus,
among more frequent high-contrast vertical and low-contrast
horizontal stimuli. Based upon the stimulus configurations, we
hypothesized that search times in the feature-search condition
would be independent of set-size within the array, whereas in
the conjunction-search condition the RT would increase linearly
with increases in the number of stimuli.
Eye-tracking data were collected along with target detection
time to permit with analyses across groups as well as calculation
of the FRPs. In an initial behavior pilot study (PS), we evaluated
behavioral performance across a range of stimulus contrasts
and array densities. In a subsequent neurophysiological study,
we chose a single contrast variation and set-size and collected
FRPs along with behavioral measures. We hypothesized that
FRP generation would be significantly reduced in schizophrenia,
and that deficits would correlate with impaired search-related
neurocognitive impairments.
Materials and Methods
Subjects
Subjects (Table 1) were recruited from the Nathan Kline Institute
and affiliated clinics, and signed informed consent following
full description of study procedures. The study was approved by
the Institutional Review Board associated with the NYS Office of
Mental Health.
All subjects had corrected 20/32 vision or better on the
Logarithmic Visual Acuity Chart (Precision Vision, LaSalle, IL).
Symptoms were assessed using Positive and Negative Syndrome
Scale (PANSS) (Kay et al. 1987). Neurocognitive function was
assessed using the MATRICS consensus cognitive battery (MCCB)
(Nuechterlein et al. 2008).
Stimuli
Stimuli were 21◦ square search-fields with 5.5 cycles/◦ Gabor-
patches, ∼1◦ diameter, displayed against a solid gray back-
ground, and randomly distributed within a virtual 8 × 8 grid
(e.g., in Fig. 1A). Search-field images were created in Matlab (The
Mathworks, Natick, Massachusetts).
In the Behavioral Pilot conjunction-search condition, the target
consisted of a low-contrast, vertically oriented Gabor-patch, pre-
sented amidst high-contrast (100%), vertical, and low-contrast
(3, 5, 7, 10, 20, 40, and 75% of the high contrast) horizontal
distractors. Set-sizes varied from 6 to 64 stimuli per search field
(6, 12, 24, 48, and 64).
Search fields with all contrasts and set-sizes were presented
in pseudorandom order in 8 blocks for a total of 296 trials. Dis-
tractor ratio effects were assessed by varying only the number of
low-contrast (10% contrast) stimuli; set-sizes (high/low contrast)
were as follows: 48 (24/24), 36 (24/12), and 30 (24/6) (Shen et al.
2000). For feature search (parallel), only high-contrast stimuli
were used, for 64 trials, presented in two separate blocks.
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Figure 1. (A) Example search paths from a representative control and patient with performance similar to the group mean. Circles represent random-search fixations,
with diameter representing fixation duration. Gray squares represent prefinal fixation. Thick black circles show final fixation on target. Dashed circle indicates location
of the target stimulus. (B) Pilot Behavior Study results. Mean (SEM) search time per search-field as a function of set-size during serial search (note log RT scale). In
rmANOVA across conditions by subject, a significant effect of group (P = 0.001) and a significant linear effect of density (P < 0.0001) were observed the group X density
effect was nonsignificant (P = 0.7) ∗∗P < 0.01 across densities.

Table 1 Demographic, neurocognitive and visual search parameters

Pilot Study Neurophysiology Study

Controls (HC) Patients (SzP) Controls (HC) Patients (SzP)

(N = 15) (N = 15) (N = 25) (N = 24)

Demographics
Age 35.9 (10.0) 34.5 (9.0) 35.6 (9.3) 36.6 (9.6)
Parental SESa 39.9 (13.1) 36.1 (13.5) 42.0 (14.6) 38.4 (12.3)
Individual SESb 40.7 (11.8) 23.0 (10.4)∗∗ 43.9 (11.9) 24.9 (7.7)∗∗
Years educationc 14.4 (3.0) 11.4 (1.6)∗∗ 15.3 (2.1) 12.0 (2.4)∗∗
Quick IQb 103.7 (11.5) 94.4 (13.6) 105.6 (8.7) 97.3 (8.5)∗∗
MCCBd
Processing speede 49.5 (9.5) 29.0 (10.5)∗∗ 51.5 (10.3) 33.3 (11.8)∗∗
Attention/vigilancef 51.1 (5.9) 32.4 (12.7)∗∗ 52.1 (10.8) 36.2 (11.7)∗∗
Working memorye 47.5 (11.3) 34.7 (11.2)∗ 50.9 (9.5) 38.0 (10.1)∗∗
Verbal learninge 44.0 (6.5) 36.7 (8.2) 47.4 (8.6) 36.2 (6.9)∗∗
Visual learninge 45.7 (10.1) 36.0 (19.6) 46.3 (12.1) 32.7 (13.8)∗∗
Reasoning/problem Solvinge 48.3 (9.7) 28.7 (7.7)∗∗ 49.5 (11.6) 40.5 (10.0)∗∗
Serial search behavioral data
Accuracy 97.6 (8.9) 93.3 (10.9) 100 (0.2) 99 (2.6)
PANSS scoresg
Positive symptoms – 19.3 (5.4) – 19.7 (5.4)
Negative symptoms – 16.5 (3.7) – 19.5 (4.2)
Global psychopathology – 32.3 (5.6) – 39.4 (8.2)
symptoms

∗P < 0.05; ∗∗P < 0.01. Missing data from: a 5 patients from PS, 7 patients from NS; b 1 patient NS; c 1 patient PS, 1 patient and 1 control NS; d 1 control NS; e 4 controls and
8 patients PS; f 3 controls and 1 patient PS; g 5 patients NS; and one control in PS for all.

In the Neurophysiology study (NS) conjunction search, 192
search-fields were presented in blocks of 48 each, with a 5-min
rest between blocks. A set-size of 48 stimuli with half at low-
(40%) contrast (Shen et al. 2000) was used across search-fields.
For feature search, 288 search-fields were presented as the task
was faster.
Eye Movements
Search fields were presented on a monitor distant 57 cm from
the subject’s eyes (Iiyama Vision Master Pro 512 cathode ray tube
(CRT) monitor, refresh rate of 85 Hz, and a screen resolution set
to 1024 × 768 pixels). Stimuli presentation was programmed and
controlled by Experiment Builder, and the experiment ran either
an Eyelink 1000 system, with tower configuration (SR Research
Ltd, Canada), or a remote eye-tracking system using monopolar
pupil-tracking at 1000 Hz (500 Hz for the NS). Head movement
was minimized by use of a chinrest.
Before each block of trials, an instruction screen prompted
the participant to look for the lower contrast vertical stimulus.
Subjects responded by pressing a button on a Sidewinder Plug
& Play Gamepad (Microsoft Corporation). A 9-point calibration
procedure and validation procedure was performed at the begin-
ning of the task and was repeated following any breaks.
 4 Cerebral Cortex, 2020, Vol. 00, No. 00
A drift correction was applied while the subjects fixated on
a dot in the center of the screen, followed by a reminder screen
indicating the contrast of the upcoming target. The trial ended
when the subject fixated on the target and pressed a button on
the controller, or timed out after 30 s. To lessen random guessing,
the system would only accept a response as correct if a fixation
had been made within a 3◦ window around the target, within 2 s
of the button press.
Fixation and saccade measures were obtained offline using
DataViewer (SR Research Ltd, Canada). Saccades were defined
using a velocity threshold of 30◦ /s, an acceleration threshold
of 8000◦ /s2 , and a minimum motion-threshold of 0.5◦ . Fixation
onset was indexed by saccade end. In the Neurophysiology (but
not Behavioral Pilot) study, eye-fixations were also analyzed
relative to stimulus locations to determine the characteristic
of the stimulus closest to each fixation, as well as the quanti-
tative distance between prefinal and final fixations and target
location.
Neurophysiology
Subjects were tested in an electrically shielded, darkened room.
Electroencephalography (EEG) data were recorded continuously
using an ANT/“Duke” layout Waveguard electrode cap with 64
equidistant scalp electrodes, which increases sampling of occip-
ital regions (Supplementary Fig. S1) and the ANT recording sys-
tem (ANT Neuro, Einschede, Netherlands) with a sampling rate
of 1024 Hz. Impedances were maintained below 10 kΩ. Data were
processed offline in MATLAB (Mathworks) using the EEGlab and
ERPLAB Toolboxes (Delorme and Makeig 2004; Lopez-Calderon
and Luck 2014).
Processing steps included bandpass filtering (0.1–80 Hz),
nearest-neighbor bad channel interpolation, and independent
component analysis (ICA)-based eye-movement correction.
In general, the number of sweeps surviving artifact rejection
was higher for patients than controls, reflecting the increased
number of fixations needed per search-field for target detection
(Supplementary Table S1).
To minimize remaining eye-movement contributions to FRP
analyses, data were re-referenced to linked mastoids. Epochs
(−200–600 ms) were indexed by fixation onset, and data in any
electrode channel (excluding Electrooculography (EOG)) with a
change in amplitude greater than 120 µV during a 200 ms time
window were excluded from averaging.
Epochs were categorized into “random-search” (i.e., all fix-
ations preceding the prefinal), “prefinal”, and “final” fixations
for each search-field, and averaged. Time frequency (TF) mea-
sures included evoked amplitude, intertrial coherence (ITC), and
single-trial amplitude, and were calculated using 3-cycle and
6-cycle Morlet wavelet convolution for frequencies below and
above 25 Hz, respectively.
Before statistical analysis, data were baseline corrected rela-
tive to a −150 to −50 ms prefixation interval. An occipitoparietal
ROI was defined based upon cross-group topographic maps
(Supplementary Fig. S1), and included electrodes POz, Pz, CPz,
PO3, PO4, P1, and P2. Predetermined theta (4–8 Hz), delta (0.5–
3.5 Hz) and gamma (25–60 Hz) frequency bands were used in the
analyses. FRP-related P1 (P1f ) and P300 (P300f ) amplitudes were
measured from 85 to 135 ms and 150 to 300 ms postfixation,
respectively. Corresponding TF Integration windows were −50–
150 ms (theta) and 150–300 ms (delta). For gamma, separate win-
dows of −50–0 ms (prefixation gamma) and 0–150 (postfixation
gamma) were used.
Statistical Analysis
Data were analyzed with SPSS (v24, IBM). RT data were log-
transformed. Behavioral data were analyzed by mixed model
regression (MMRM) with factors of group and task, and with con-
trast and density as covariates. Follow-up rmANOVA were per-
formed by task to assess linear effects FRP data were analyzed
by rmMANOVA across fixation types (random, prefinal, final).
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For across-group correlations, an initial analysis of covari-
ance (ANCOVA) assessed similarity of slopes between the
two groups. Across-group partial correlations (rp ) or multiple
regressions covaried for group were conducted only if the
group X covariate ratio in the ANCOVA was nonsignificant.
Within group correlations were conducted using Pearson (r)
correlations. Gaussian distribution analyses were performed
using nonlinear curve fitting in PRISM 5.0 (Graphpad.com).
Scan patterns were compared across groups using intraclass
correlations for absolute agreement. All statistics are two-tailed
with preset α-level for significance of P < 0.05.
Results
Behavioral Pilot Study
An omnibus test across both tasks and all contrasts/set-sizes
showed a highly significant main effect of group (F1,36.9 = 16.2,
P = 0.0003, d = 1.33). As expected, there were highly signifi-
cant main effects of contrast (F1,12 300 = 82.2, P < 0.0001) and
set-size (F1,12 300 = 135.5, P < 0.0001), as well as significant
task X contrast (F1,12 000 = 103.9, P < 0.0001), task X set-size
(F1,12 300 = 77.3, P < 0.0001) and task X contrast X set-size
(F1,12 000 = 43.9, P < 0.0001) interactions. However, the group X
contrast (F1,12 300 = 0.37, P = 0.54), group X set-size (F1,12 300 = 2.67,
P = 0.10) and group X contrast X set-size (F1,12 300 = 1.15, P = 0.28)
interactions were all nonsignificant.
The group X task interaction was also significant (F1,12 300 = 7.16,
P = 0.007), although higher-order interactions involving group
were not (all P > 0.2). Separate analyses were, therefore,
performed for serial and parallel tasks independently. The main
effect of group was independently significant for both the serial
(F1,37.9 = 6.72, P = 0.013) and parallel (F1,38.5 = 16.7, P = 0.0002).
Group X contrast effects were not significant for either task
alone (both P > 0.1). The group X set-size effect was not signifi-
cant in the serial search condition (F1,8126 = 0.13, P = 0.7) (Fig. 1B),
but was significant in the orientation-alone parallel-search
condition (F1,4146 = 4.25, P = 0.039). Similar effects were observed
in the contrast-alone condition (Supplementary Fig. S2A).
In follow-up analyses, a significant between group difference
was observed for fixation number (F1,47 = 4.08, P = 0.049) but
not for fixation duration (F1,32.4 = 0.05, P = 0.83) across tasks.
These effects were further confirmed in an rmANOVA incor-
porating mean subject data from the serial search task alone
(Supplementary Fig. S2B,C).
Distractor ratio: Across groups, decreasing the ratio of high-
to low-contrast distractors from 50 to 20% significantly reduced
search time (F2,27 = 52.2, P < 0.0001), with no significant main
effect of group (F1,28 = 1.82, P = 0.19) or group X ratio interaction
(F1,28 = 0.13, P = 0.88) (Supplementary Fig. S3).
Neurophysiology Study
Serial Search
As in the behavioral PS, patients required a significantly greater
amount of time per search-field to detect the targets (F1,47 = 7.39,
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Figure 2. Behavioral performance during serial search in the NS. (A) Mean (SEM) time per search-field in controls (Ctl) and patients (Pat). (B) Mean number of fixations
per search-field. (C) Mean fixation duration. (D) Mean distance between prefinal and final fixation locations and center of the target. The horizontal reference line
indicates the border between foveal and parafoveal processing. (E) Scatter plot showing the relationship between Prefinal distance and Search time across groups. The
correlation was significant both across groups covaried for group (shown) and in patients alone (P < 0.001). In a separate ANCOVA, the group X covariate interaction
was nonsignificant (F1,45 = 2.67, P = 0.11) indicating similar slope across groups. ∗∗P < 0.01 patient versus control.

P = 0.009, d = 0.80) (Fig. 2A), again reflecting a significant increase
in the number of fixations per search-field (F1,47 = 7.62, P = 0.008,
d = 0.81) (Fig. 2B) with no significant difference in fixation dura-
tion (F1,47 = 0.95, P = 0.34) (Fig. 2C).
As predicted, prefinal fixation distance—defined as the dis-
tance between the last fixation before target detection and
the center of the target—was significantly smaller in patients
versus controls (F1,47 = 7.84, P = 0.008, d = 0.80) (Fig. 2D), reflecting
a smaller visual span. In turn, the increase in prefinal dis-
tance strongly predicted mean time per search-field both across
groups (Fig. 2E) and in patients alone (r = −.75, P < 0.001). Fol-
lowing covariation for prefinal distance, neither the mean time
per search-field (F1,46 = 1.71, P = 0.2) nor the number of fixations
(F1,46 = 1.34, P = 0.25) remained significant across groups.
FRP Analyses
FRPs to all fixation types included an initial biphasic wave
that preceded fixation onset, followed by a biphasic N1f /P1f
component response between 0 and 150 ms. An additional P3f
component occurred between 150 and 300 ms for prefinal and
final fixations only (Fig. 3A). As opposed to standard visual
ERP (Martinez et al. 2018), FRPs both occur earlier and involve
phase-reset to a greater degree, suggesting different underlying
processes (Supplementary Fig. S4).
In TF analyses (Fig. 3B–D), the prefixation activity corre-
sponded primarily to an increase in gamma activity immedi-
ately preceding fixation. By contrast, the N1f /P1f corresponded
primarily to an increase in theta activity and the P3f component
primarily to an increase in delta (1–4 Hz) activity. An omnibus
test across all 3 components and all fixation types showed
both a highly significant main effect of group (F1,47 = 11.2,
P = 0.002, d = 0.98) and a significant component X group
interaction (F2,46 = 4.72, P = 0.014, d = 0.63). Follow-up analyses
were, therefore, conducted for each component individually to
resolve the interaction.
Prefixation activity/gamma: The amplitude of the
prefixation gamma was not significantly different between
groups (F1,47 = 0.01, P = 0.92). Both the main effect of fix-
ation type (F2,46 = 2.07, P = 0.14) and the fixation X group
interaction (F2,46 = 0.26, P = 0.77) were also nonsignificant
(Supplementary Table S2).
P1f /theta: Across all fixation types, both P1 amplitude
(F1,47 = 6.67, P = 0.013, d = 0.75) (Supplementary Table S2) and
underlying theta activity (F1,47 = 13.3, P = 0.001, d = 1.08) were
significantly reduced in patients versus controls across fixation
types. The main effect of fixation type (F2,46 = 0.95, P = 0.39) and
the fixation-type X group interaction (F2,46 = 0.27, P = 0.77) were
nonsignificant (Fig. 4A). For correlational analyses, therefore,
theta amplitudes were combined across the three fixation types.
In single-trial TF analyses, the between-group difference
in theta ITC was highly significant (F1,47 = 20.1, P < 0.0001,
d = 1.32) (Fig. 4B). Across groups, the main effect of fixation type
was significant with somewhat lower ITC to prefinal or final
versus random-search fixations (F1,47 = 6.19, P = 0.016). However,
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Figure 3. Mean occipitoparietal activity to fixation onset for Random-search (top row), prefinal (middle row) and Final (bottom row) fixations. Electrodes used for
average: CPz, Pz, POz, P1/P2, and PO3/4. (A) Time–domain potentials showing fixation P1f and P3f potentials, scalp distribution (“headmaps”) and corresponding
integration windows. Headmaps for Prefinal fixations were highly similar to those of Random and were omitted. (B–D) TF analyses showing mean evoked amplitude
(B), ITC (C) and single-trial analysis amplitude (D) for controls and patients. The black horizontal line indicates transition from 3- to 6-cycle Morlet waveform used in
analysis. The red box indicates the integration window for P1f -related theta analyses. The black box indicates the fixation window for P3f -related delta analyses.

Figure 4. Mean (SEM) FRP-related values from the serial search task as a function of fixation type across groups. (A) Evoked Theta amplitude (corresponding to P1f ).
(B) Theta ITC. (C) Single-trial theta amplitude. (D) Evoked delta-amplitude (corresponding to P3f ). (E) Correlation between evoked theta amplitude and search time in
patients. (F) Correlation between evoked theta amplitude and prefinal fixation distance in patients.

the fixation type X group interaction was nonsignificant although to a lesser degree. As with ITC, there was a signif-
(F2,46 = 0.92, P = 0.4). icant main effect of fixation type (F2,46 = 4.06, P = 0.02), with
The between-group difference in single-trial theta amplitude lower single-trial amplitude to random-search fixations than
was also significant (F1,47 = 4.32, P = 0.04, d = 0.61) (Fig. 4C), prefinal/final (F1,47 = 8.30, P = 0.006). Between-group differences
 Fixation-Related Potentials and Visual Search in Schizophrenia Dias et al.
in theta ITC remained strongly significant even following
covariation for amplitude changes (all P < 0.001).
P3f /delta: For both P3f- and evoked delta-amplitude, there was
a significant stepwise increase from random-search to prefinal
to final fixation. Although the P3f did not significantly discrimi-
nate between groups (F1,47 = 1.47, P = 0.23), delta evoked ampli-
tude was significantly reduced in patients vs. controls across
all fixation types (F1,47 = 4.73, P = 0.035) (Fig. 4D). The fixation
type X group was nonsignificant (F2,46 = 2.21, P = 0.12), suggesting
equivalent reductions across the fixation types.
In single-trial analyses, delta ITC also differed significantly
across groups across all fixation types (F1,47 = 4.62, P = 0.037)
(Supplementary Table S2). Across groups, ITC was not signifi-
cantly different between random-search and prefinal fixations
(F1,47 = 2.40, P = 0.13), but increased significantly from prefinal to
final fixation (F1,47 = 94.3, P < 0.0001). The fixation type X group
interaction was nonsignificant (F2,46 = 1.31, P = 0.28), reflecting
the parallel increases between groups.
By contrast, delta single-trial amplitude did not differ sig-
nificantly between groups (F1,47 = 2.47, P = 0.12). Across groups,
a progressive increase was observed from random-search to
prefinal (F1,47 = 36.6, df = 1,47, P < 0.0001) and prefinal to final
(F1,47 = 60.8, P < 0.0001) fixation. The fixation type X group inter-
action (F2,46 = 0.28, P = 0.75) was nonsignificant.
Correlation between measures: Across groups (covaried for
group membership), evoked theta amplitude correlated sig-
nificantly with both total search time (rp = −.34, P = 0.018)
and prefinal fixation distance (rp = 0.39, P = 0.008). Significant
correlations were also observed with the schizophrenia group
alone for both total search time (Fig. 4E) and prefinal fixation
distance (Fig. 4F). By contrast, no significant correlations were
observed with the healthy controls (HC) group alone (both
P > 0.1).
Theta ITC also correlated significantly with both total search
time (rp = −.31, P = 0.033) and prefinal fixation distance (rp = 0.38,
P = 0.007), while correlations with single-trial amplitude were
nonsignificant. The correlation between ITC and prefinal fix-
ation distance was also highly significant within the patient
group alone (r = 0.53, P = 0.008).
Across groups, reductions in evoked delta-amplitude
correlated strongly with reductions in evoked theta (rp = 0.50,
P = 0.004). Correlations were significant within the patient
(r = 0.46, P = 0.023) and control (r = 0.52, P = 0.007) groups,
respectively. Following covariation for theta, deficits in delta
were no longer significant between groups (F1,46 = 0.12, P = 0.73)
(Supplementary Fig. S5).
NS, Parallel Search
As in the serial search task, patients showed a significant
increased mean search time (F1,47 = 5.60, P = 0.022) as well
as number of fixations (F1,47 = 5.38, P = 0.025). Mean fixation
duration was not significantly different (F1,47 = 3.15, P = 0.083)
(Supplementary Table S4).
Also, as in the serial search task, the distance from prefinal
fixation to the target was significantly smaller in patients vs.
controls (F1,47 = 7.67, P = 0.008), and between-group differences
in search time (F1,47 = 1.02, P = 0.32) and number of fixations per
search-field (F1,47 = 0.89, =0.35) between groups were no longer
significant following covariation for prefinal fixation distance.
In a rmANOVA across the serial and parallel tasks, the main
effect of group for prefinal fixation distance was highly sig-
nificant (F1,47 = 8.35, P = 0.006) as was the main effect of task
7
(F1,47 = 238.9, P < 0.0001). By contrast, the group X task interaction
was nonsignificant (F1,47 = 2.43, P = 0.13).
FRP: In the parallel-search task, because of the limited
number of saccades/fixations per search-field, FRPs were only
resolved to prefinal and target fixations (Supplementary Fig. S6).
As in the serial search task, a prominent P1f component
was observed, and was reduced in schizophrenia (F1,47 = 4.03,
P = 0.05). In TF analyses, reductions were observed in both
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evoked theta amplitude (F1,47 = 4.15, P = 0.047) and ITC (F1,47 = 5.72,
P = 0.021). (Supplementary Table S4). P1f amplitudes correlated
significantly with search time (rp = −.55, P < 0.0001), number of
fixations (rp = −0.37, P = 0.01) and penultimate fixation distance
(rp = 0.54, P < 0.0001) across groups (covaried for group), as well
as in patients individually.
Across-Task Comparisons
A final analysis evaluated the statistical distribution of pre-
final fixation distances for serial versus parallel-search tasks
across groups. For all subjects and both tasks, mean prefinal
fixation distances fell within the parafoveal/perifoveal span (1–
8◦ ). All distributions were accounted for well by a single Gaussian
distribution (all R2 > 0.6) (Fig. 5A,B). Mean values were signifi-
cantly larger for parallel than serial across both groups. For both
serial (F1,18 = 40.0, P < 0.0001) and parallel (F1,18 = 9.59, P = 0.006)
tasks the mean distance was shifted significantly to the left in
patients, suggesting reduced visual span.
In a 2-way analysis of variance across tasks, the main effects
of group (F1,47 = 9.01, P = 0.004) and task (F1,47 = 272.8, P < 0.0001)
were strongly significant, whereas the interaction effect was
not (F1,47 = 0.27, P = 0.61). Moreover, strong correlations were
observed across subjects for the two measures (Fig. 5C).
In both the serial and parallel-search tasks, patients showed
similar scanning patterns to those of controls across search-
fields with highly significant correlations between groups
(Fig. 5D, Supplementary Fig. S7). Furthermore, both controls and
patients equivalently “oversampled” the low-contrast stimuli
during serial search, as shown by a significantly increased
number of fixations near low- versus high-contrast stimuli
across groups (F1,47 = 22.7, P < 0.0001) (Fig. 5E). Although the total
number of fixations per search-field was significantly higher in
patients than controls (F1,47 = 7.50, P = 0.009), the stimulus-type
X group interaction was nonsignificant (F1,47 = 1.30, P = 0.26).
When calculated as percentages, both groups showed a similar
preferential sampling of the low-contrast stimuli, with no
significant difference (t = −.06, P = 0.95) between-groups (Fig. 5F),
suggesting similar search strategies.
Clinical Correlations
As expected, patients showed a highly significant reduction
in neurocognitive function as assessed using the MCCB
(F1,46 = 39.7, P < 0.0001, d = 1.8) (Table 1). Within patients,
evoked theta response correlated with attention-vigilance
(r = 0.56, P = 0.005) and speed of processing (SoP, r = 0.50,
P = 0.014) (Supplementary Fig. S8). By contrast, correlations with
nonvisual components of the MCCB, such as auditory working
memory or reasoning/problem solving, were nonsignificant
(P > 0.4). The correlation with attention-vigilance, but not
SoP, remained significant even following control for multiple
comparisons (n = 6, critical P = 0.008).
Delta-amplitude correlated significantly with negative
symptoms (P < 0.028). However, the correlation did not remain
 8 Cerebral Cortex, 2020, Vol. 00, No. 00
Figure 5. Fixation analyses. (A,B) Distributions of prefinal fixation distances to the target for the serial and parallel-search tasks for controls (A) and patients (B). (C)
Correlation between prefinal distances on the serial and parallel-search tasks, across groups. (D) Correlation between patients vs. controls fixation time as a function
of grid location. (E) Relative number of fixations to low- and high-contrast distractors in patients and controls. ∗∗∗P < 0.000. (F) Percentage of fixations on low-contrast
stimuli for both groups, showing no significant difference between groups.
significant following control for multiple comparisons. All other
correlations to either symptoms or medication dosage were
nonsignificant.
Discussion
Deficits in auditory and visual sensory processing in schizophre-
nia have become increasingly appreciated over recent years
(Javitt 2009; Javitt and Freedman 2015). Nevertheless, the degree
to which these affect naturalistic functions remains to be
determined. Here, we used a visual Guided-Search task com-
bined with eye-tracking and EEG to investigate contributions
of visual active sensing to behavioral disturbance. Although
visual Guided Search has been endorsed as an informative
paradigm for investigating neural mechanisms underlying
attentional allocation and sensory processing impairments
in schizophrenia (Nuechterlein et al. 2009), to our knowledge,
this is the first study to utilize combined eye-tracking and
neurophysiological measures to investigate underlying neural
mechanisms.
As expected, patients showed substantially increased search
times compared to controls in both the serial- and parallel-
search versions of the task (VanMeerten et al. 2016). In both
cases, the increased search time was associated with an increase
in the number—but not duration—of fixations per search-field,
which in turn was associated with a markedly (P = 0.008) reduced
distance, over which targets could be detected in peripheral
(parafoveal) vision relative to the point of fixation (Elahipanah
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et al. 2011). Once the decrease in size of the visual “spotlight”
(visual span) during search was considered, increased search
times on this task were no longer significant.
At the neurophysiological level, the reduced visual span was
associated with reduced FRP generation over posterior visual
cortex (Fig. 3). Consistent with primate studies, the human FRP
response corresponded specifically to a phase-reset of ongo-
ing theta-rhythms with little alteration in single-trial power
(Rajkai et al. 2008). Overall, these findings are consistent with
a model in which impaired visual active sensing—as reflected
in reduced FRP—leads to narrowing of the visual span which,
in turn, drives behavioral impairment (Fig. 4E,F). These findings
also converge with a growing body of literature suggesting theta
response abnormalities in schizophrenia across both auditory
(Lee et al. 2017; Javitt et al. 2018) and visual (Martinez et al.
2015) sensory systems, and support prior studies demonstrating
reduced stimulus-related processing during visual search versus
nonsearch tasks in schizophrenia (Davenport et al. 2006; Van-
Meerten et al. 2016).
By contrast to the deficits in FRP and visual span, the
slope of the RT increase as a function of set-size did not
differ significantly between groups (Fig. 1B). Furthermore,
patients and controls fixated on similar areas of search-
fields (Supplementary Fig. S7), and both groups equivalently
“oversampled” the low- versus high-contrast distractors (Fig. 5E).
In addition, both groups showed similar effects of distractor
ratio manipulation (Supplementary Fig. S3), consistent with a
prior report (Elahipanah et al. 2008).
 Fixation-Related Potentials and Visual Search in Schizophrenia Dias et al.
Prior studies of visual search in schizophrenia have yielded
mixed results in the “target present” condition such as used here
(Mori et al. 1996; Fuller et al. 2006; Gold et al. 2007; Tanaka et al.
2007), potentially related to methodological issues. For example,
in prior studies between-group differences may also have been
driven in part by use of raw, rather than log-transformed RT data,
which are inherently right-skewed. Also, different stimuli were
used across studies. Here, stimulus contrast was detectable from
each Gabor-patch as a whole, encouraging its use to preselect
stimuli for further evaluation, whereas orientation could only
be resolved by more detailed examination.
However, it remains to be determined whether the use of
other stimulus features to guide processing (e.g., color, shape)
may have resulted in changes in slope as well as impairments
related primarily to visual-level processing, reflecting additional
“top–down” impairments. The absence of physiological data in
prior studies also limits comparability across studies.
Unexpectedly, in secondary analyses of the parallel-search
data from the behavioral pilot we observed a significant interac-
tion between group and set-size, suggesting potential different
strategies for performing the task. The finding should be treated
cautiously as the group X set-size interaction was not significant
in the primary analyses or in either group independently. The
finding may nevertheless deserve further investigation.
FRP: The P1f (λ potential) has been the focus of increasing
investigation in a range of contexts including Guided-Search
tasks and naturalistic reading in normal volunteers (Kaunitz et
al. 2014). However, to our knowledge, this is the first study of
FRP generation in schizophrenia and also the first study to use
TF analyses of the FRP in humans to analyze underlying mech-
anisms. The P1f potential shows a similar scalp distribution
to that of the stimulus-driven P1 potential, which we (Doniger
et al. 2002; Friedman et al. 2012; Javitt 2015) and others (Luck
et al. 2006) have also found to be reduced in schizophrenia.
Both components also map similarly into the theta-frequency
range. However, the intracortical mechanisms by which they are
generated differ significantly (Rajkai et al. 2008).
Specifically, although both the P1 and P1f originate from
visual sensory cortex, the laminar profile of activity differs such
that the stimulus-evoked P1 is driven primarily by thalamo-
cortical input into layer 4, whereas the P1f is driven dispropor-
tionately by nonthalamic inputs that bypass layer 4 (Rajkai et
al. 2008). At present, the source of these inputs is unknown,
and could include top–down projections from frontoparietal
cortex, or bottom–up projections from subcortical (e.g., lat-
eral–pulvinar, intranuclear–thalamic) or brainstem regions
(Rajkai et al. 2008).
In both intracranial recordings (Rajkai et al. 2008) and our
study, the P1f consists primarily of fixation-driven phase-reset
of the ongoing theta-rhythms in visual cortex, in contrast to
the stimulus-evoked P1, which shows proportionate theta-band
increases in both ITC and power (e.g., Rajkai et al. 2008; Martinez
et al. 2018; Supplementary Fig. S4). Nevertheless, future studies
investigating the relationship between impaired P1 and P1f gen-
eration in schizophrenia are needed.
In addition to the reduction in P1f , deficits were observed
in the P3f , which occurs only to prefinal, and, especially, to
final fixations and is thus likely related to target detection.
During search, amplitudes of both P1f and P3f can be enhanced
by increasing attentional demands, for example by introduc-
ing a competing auditory task (Ries et al. 2016). In such con-
ditions, however, the amplitudes of the P1f and P3f compo-
nents increase in parallel, along with P3f latency. Here, P1f
9
was diminished disproportionately to P3f with no significant
between group difference in accuracy and no prolongation of P3f
latency.
Present findings converge with recent suggestions that
theta-phase significantly modulates local gain within sensory
regions (Fiebelkorn and Kastner 2019) and contributes to
integration versus segregation of visual information (Wutz
et al. 2016), as well as with recent findings of impaired
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auditory “active sensing” in schizophrenia (Lakatos et al. 2013).
As opposed to gamma rhythms that interrelate primarily
with parvalbumin-type gamma-aminobutyric acid interneu-
rons in cortex, theta-rhythms interrelate additionally with
somatostatin-type interneurons. Optogenetic silencing of
somatostatin-, but not parvalbumin-, interneurons in rodent
visual cortex reproduce patterns of visual ERP deficits observed
in schizophrenia (Hamm and Yuste 2016).
Limitations
Sample sizes for the present study are relatively limited.
Although significant between-group effects were observed
both in the behavioral pilot (n = 15/group) and in the neu-
rophysiological study (n = 25/group), the degree to which
results will replicate within larger samples remains to be
determined. Also, all subjects were on medication at the
time of testing. Although no correlations were observed
between our experimental measures and antipsychotic dose
measured in chlorpromazine (CPZ) equivalents, an effect
of medication cannot be excluded. Finally, although we
postulate that deficits in FRP generation in Sz reflect impaired
subcortical input into primary visual cortex, future neu-
roimaging studies are required to interrogate underlying
circuits.
Overall, the present study provides the first demonstration
of impaired visual active sensing in schizophrenia, echoing
recent findings in the auditory system (Lakatos et al. 2013).
Impaired sensory processing represents a critical, yet under-
studied, contributor to impaired neurocognitive dysfunction in
schizophrenia. Correlations between reduced FRP amplitude
and visually dependent cognitive domains, such as SoP
and attention-vigilance highlight the importance of visual
active sensing deficits to overall patterns of neurocognitive
impairments in schizophrenia.
Supplementary Material
Supplementary material is available at Cerebral Cortex online.
Funding
The National Institutes of Health (MH049334 to D.C.J.); National
Research Council of Brazil (CNPq and CAPES to Dr F.B.).
Notes
We thank Gail Silipo, Walter Machado-Pinheiro, and José Magal-
hães de Oliveira for their assistance.
References
Bedwell JS, Chan CC, Cohen O, Karbi Y, Shamir E, Rassovsky Y.
2013. The magnocellular visual pathway and facial emotion
 10 Cerebral Cortex, 2020, Vol. 00, No. 00
misattribution errors in schizophrenia. Prog Neuropsychophar-
macol Biol Psychiatry. 44:88–93.
Butler PD, Abeles IY, Weiskopf NG, Tambini A, Jalbrzikowski M,
Legatt ME, Zemon V, Loughead J, Gur RC, Javitt DC. 2009.
Sensory contributions to impaired emotion processing in
schizophrenia. Schizophr Bull. 35:1095–1107.
Concha-Miranda M, Rios J, Bou J, Valdes JL, Maldonado PE. 2019.
Timing is of the essence: improvement in perception during
active sensing. Front Behav Neurosci. 13:96.
Davenport ND, Sponheim SR, Stanwyck JJ. 2006. Neural anoma-
lies during visual search in schizophrenia patients and
unaffected siblings of schizophrenia patients. Schizophr Res.
82:15–26.
Delorme A, Makeig S. 2004. EEGLAB: an open source tool-
box for analysis of single-trial EEG dynamics including
independent component analysis. J Neurosci Methods. 134:
9–21.
Dias EC, Butler PD, Hoptman MJ, Javitt DC. 2011. Early sensory
contributions to contextual encoding deficits in schizophre-
nia. Arch Gen Psychiatry. 68:654–664.
Doniger GM, Foxe JJ, Murray MM, Higgins BA, Javitt DC.
2002. Impaired visual object recognition and dorsal/ventral
stream interaction in schizophrenia. Arch Gen Psychiatry.
59:1011–1020.
Elahipanah A, Christensen BK, Reingold EM. 2008.
Visual selective attention among persons with
schizophrenia: the distractor ratio effect. Schizophr Res. 105:
61–67.
Elahipanah A, Christensen BK, Reingold EM. 2011. Controlling
the spotlight of attention: visual span size and flexibility in
schizophrenia. Neuropsychologia. 49:3370–3376.
Fiebelkorn IC, Kastner S. 2019. A rhythmic theory of attention.
Trends Cog Sci. 23:87–101.
Fourment A, Calvet J, Bancaud J. 1976. Electrocorticography
of waves associated with eye movements in man dur-
ing wakefulness. Electroencephalogr Clin Neurophysiol. 40:
457–469.
Friedman T, Sehatpour P, Dias E, Perrin M, Javitt DC. 2012. Dif-
ferential relationships of mismatch negativity and visual p1
deficits to premorbid characteristics and functional outcome
in schizophrenia. Biol Psychiatry. 71:521–529.
Fuller RL, Luck SJ, Braun EL, Robinson BM, McMahon RP, Gold JM.
2006. Impaired control of visual attention in schizophrenia. J
Abnorm Psychol. 115:266–275.
Gold JM, Fuller RL, Robinson BM, Braun EL, Luck SJ. 2007. Impaired
top-down control of visual search in schizophrenia. Schizophr
Res. 94:148–155.
Gracitelli CP, Vaz de Lima FB, Bressan RA, Paranhos JA. 2013.
Visual field loss in schizophrenia: evaluation of magnocellu-
lar pathway dysfunction in schizophrenic patients and their
parents. Clin Ophthalmol. 7:1015–1021.
Hamm JP, Yuste R. 2016. Somatostatin interneurons control a key
component of mismatch negativity in mouse visual cortex.
Cell Rep. 16:597–604.
Hessels RS, Niehorster DC, Nystrom M, Andersson R, Hooge ITC.
2018. Is the eye-movement field confused about fixations and
saccades? A survey among 124 researchers. R Soc Open Sci.
5:180502.
Ito J, Maldonado P, Grun S. 2013. Cross-frequency interaction of
the eye-movement related LFP signals in V1 of freely viewing
monkeys. Front Sys Neurosci. 7:1.
Javitt DC. 2009. When doors of perception close: bottom-up
models of disrupted cognition in schizophrenia. Annu Rev Clin
Psychol. 5:249–275.
Javitt DC. 2015. Neurophysiological models for new treatment
development in schizophrenia: early sensory approaches.
Ann N Y Acad Sci. 1344:92–104.
Javitt DC, Freedman R. 2015. Sensory processing dysfunction
in the personal experience and neuronal machinery of
schizophrenia. Am J Psychiatry. 172:17–31.
Javitt DC, Lee M, Kantrowitz JT, Martinez A. 2018. Mismatch neg-
ativity as a biomarker of theta band oscillatory dysfunction
Downloaded from https://academic.oup.com/cercor/advance-article-abstract/doi/10.1093/cercor/bhz277/5728649 by guest on 09 February 2020
in schizophrenia. Schizophr Res. 191:51–60.
Kamienkowski JE, Ison MJ, Quiroga RQ, Sigman M. 2012. Fixation-
related potentials in visual search: a combined EEG and eye
tracking study. J Vis. 12:4.
Kaunitz LN, Kamienkowski JE, Varatharajah A, Sigman M,
Quiroga RQ, Ison MJ. 2014. Looking for a face in the crowd:
fixation-related potentials in an eye-movement visual search
task. Neuroimage. 89:297–305.
Kay SR, Fiszbein A, Opler LA. 1987. The positive and negative
syndrome scale (PANSS) for schizophrenia. Schizophr Bull.
13:261–76.
Kazai K, Yagi A. 2003. Comparison between the lambda response
of eye-fixation-related potentials and the P100 component of
pattern-reversal visual evoked potentials. Cogn Affect Behav
Neurosci. 3:46–56.
Kim DW, Shim M, Song MJ, Im CH, Lee SH. 2015. Early visual pro-
cessing deficits in patients with schizophrenia during spatial
frequency-dependent facial affect processing. Schizophr Res.
161:314–321.
Konig P, Luksch H. 1998. Active sensing–closing multiple loops.
Z Naturforsch C. 53:542–549.
Lakatos P, Schroeder CE, Leitman DI, Javitt DC. 2013. Predic-
tive suppression of cortical excitability and its deficit in
schizophrenia. J Neurosci. 33:11692–11702.
Lee M, Sehatpour P, Hoptman MJ, Lakatos P, Dias EC, Kantrowitz
JT, Martinez AM, Javitt DC. 2017. Neural mechanisms of mis-
match negativity dysfunction in schizophrenia. Mol Psychia-
try. 22:1585–1593.
Leonard CJ, Robinson BM, Hahn B, Gold JM, Luck SJ. 2014.
Enhanced distraction by magnocellular salience signals in
schizophrenia. Neuropsychologia. 56:359–366.
Lopez-Calderon J, Luck SJ. 2014. ERPLAB: an open-source toolbox
for the analysis of event-related potentials. Front Hum Neu-
rosci. 8:213.
Luck S, Fuller R, Braun E, Robinson B, Summerfelt A, Gold J. 2006.
The speed of visual attention in schizophrenia: electrophys-
iological and behavioral evidence. Schizophr Res. 85:174–195.
Martinez A, Gaspar PA, Hillyard SA, Andersen SK, Lopez-
Calderon J, Corcoran CM, Javitt DC. 2018. Impaired motion
processing in schizophrenia and the attenuated psychosis
syndrome: etiological and clinical implications. Am J Psychia-
try. 175:1243–1254.
Martinez A, Gaspar PA, Hillyard SA, Bickel S, Lakatos P, Dias EC,
Javitt DC. 2015. Neural oscillatory deficits in schizophrenia
predict behavioral and neurocognitive impairments. Front
Hum Neurosci. 9:371.
Martinez A, Hillyard SA, Bickel S, Dias EC, Butler PD, Javitt DC.
2012. Consequences of magnocellular dysfunction on pro-
cessing attended information in schizophrenia. Cereb Cortex.
22:1282–1293.
Mori S, Tanaka G, Ayaka Y, Michitsuji S, Niwa H, Uemura M,
Ohta Y. 1996. Preattentive and focal attentional processes in
schizophrenia: a visual search study. Schizophr Res. 22:69–76.
Nobre AC, Coull JT, Walsh V, Frith CD. 2003. Brain activations dur-
ing visual search: contributions of search efficiency versus
feature binding. Neuroimage. 18:91–103.
 Fixation-Related Potentials and Visual Search in Schizophrenia Dias et al.
Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen
JD, Essock S, Fenton WS, Frese FJ 3rd, Gold JM et al. 2008. The
MATRICS consensus cognitive battery, part 1: test selection,
reliability, and validity. Am J Psychiatry. 165:203–213.
Nuechterlein KH, Luck SJ, Lustig C, Sarter M. 2009. CNTRICS
final task selection: control of attention. Schizophr Bull. 35:
182–196.
Poletti M, Rucci M, Carrasco M. 2017. Selective attention within
the foveola. Nat Neurosci. 20:1413–1417.
Rajkai C, Lakatos P, Chen CM, Pincze Z, Karmos G, Schroeder
CE. 2008. Transient cortical excitation at the onset of visual
fixation. Cereb Cortex. 18:200–209.
Ries AJ, Touryan J, Ahrens B, Connolly P. 2016. The impact of task
demands on fixation-related brain potentials during guided
search. PLoS One. 11:e0157260.
Schroeder CE, Wilson DA, Radman T, Scharfman H, Lakatos P.
2010. Dynamics of active sensing and perceptual selection.
Curr Opin Neurobiol. 20:172–176.
11
Shen J, Reingold EM, Pomplun M. 2000. Distractor ratio influ-
ences patterns of eye movements during visual search.
Perception. 29:241–250.
Tanaka G, Mori S, Inadomi H, Hamada Y, Ohta Y, Ozawa H. 2007.
Clear distinction between preattentive and attentive process
in schizophrenia by visual search performance. Psychiatry Res.
149:25–31.
Treisman A. 1982. Perceptual grouping and attention in visual
Downloaded from https://academic.oup.com/cercor/advance-article-abstract/doi/10.1093/cercor/bhz277/5728649 by guest on 09 February 2020
search for features and for objects. J Exp Psychol Hum Percept
Perform. 8:194–214.
VanMeerten NJ, Dubke RE, Stanwyck JJ, Kang SS, Sponheim SR.
2016. Abnormal early brain responses during visual search
are evident in schizophrenia but not bipolar affective disor-
der. Schizophr Res. 170:102–108.
Wutz A, Muschter E, van Koningsbruggen MG, Weisz N, Melcher
D. 2016. Temporal integration windows in neural processing
and perception aligned to saccadic eye movements. Curr Biol:
CB. 26:1659–1668.