Schizophrenia Bulletin vol. 46 no. 4 pp.

955–963, 2020
doi:10.1093/schbul/sbaa010
Advance Access publication 13 February 2020

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Localization of Early-Stage Visual Processing Deficits at Schizophrenia Spectrum
Illness Onset Using Magnetoencephalography

Alfredo L. Sklar1,2, , Brian A. Coffman1,2, and Dean F. Salisbury*,1,2

Clinical Neurophysiology Research Laboratory, UPMC Western Psychiatric Hospital, Department of Psychiatry, University of
1

Pittsburgh School of Medicine, Pittsburgh, PA; 2UPMC Western Psychiatric Hospital, Department of Psychiatry, University of
Pittsburgh School of Medicine, Pittsburgh, PA
*To whom correspondence should be addressed; Clinical Neurophysiology Research Laboratory, UPMC Western Psychiatric Hospital,
Department of Psychiatry, University of Pittsburgh School of Medicine, 3501 Forbes Avenue, Suite 420 Oxford Building, Pittsburgh,
PA 15213, USA; tel: +1-412-246-5123, fax: 412-246-6636, e-mail: salisburyd@upmc.edu

Impairments in early-stage visual processing are observed Introduction

in chronic psychosis. However, their presence, localization
Visual processing deficits have been well documented in
within the brain, and contribution to cognitive symptoms
schizophrenia using both behavioral paradigms such as
remain less well established early in disease course. The
backwards masking1,2 and neurophysiological techniques.
present study utilized magnetoencephalography (MEG)
In the latter case, deficits in visual evoked potentials
to examine sensory responses within primary visual cortex
(VEPs) recorded using electroencephalography (EEG)
(V1). MEG was recorded from 38 individuals diagnosed
including the P13–6 and, to a lesser extent, C17,8 have been
with a schizophrenia spectrum illness at first psychotic epi-
observed. Both VEPs are considered early-latency cor-
sode (FESz) and 38 matched healthy controls (HC) during
tical components of the brain’s response to visual stimuli
visual search tasks. The inverse solution for cortical activity
reflective of initial sensory-perceptual processes.9 In ad-
contributing to the M100 visual evoked field was derived.
dition, there has been a growing appreciation for the con-
Task performance and V1 activation were compared be-
tribution of these early-stage visual impairments to the
tween groups. FESz exhibited a reduced V1 response rela-
more well-established deficits in selective attention and
tive to HC. This group deficit, however, was selective for the
working memory.10,11 These findings emphasize the im-
left hemisphere (LH). A  similar interaction was observed
portance of dysfunctional sensory processes in psychosis
for response time with FESz exhibiting slower responses to
and their role as potential mediators of its associated cog-
right visual field targets, a difference not observed among
nitive deficits, symptoms highly predictive of long-term
HC. Among FESz, larger LH V1 activity was associated
functional outcomes.12–14 As a result, significant work has
with larger hallucination subscale scores on the Scale for
been dedicated to determining their utility as potential
the Assessment of Positive Symptoms. Early-stage visual
biomarkers of disease15,16 as well as targets for therapeutic
processing deficits localized to V1 are present at disease
interventions.17,18
onset in the schizophrenia spectrum. This impairment ap-
Despite the association between impaired early-stage
pears to be restricted to the LH, consistent with previous
visual processing deficits and community functioning19,20
reports detailing a predominantly LH disease process in
as well as the established impact of early interventions
early psychosis, and activity within this region was associ-
on these outcome measures,21,22 visual processing deficits
ated with an increased experience of hallucinations. These
early in disease course remain relatively understudied.
findings detail the cortical responses contributing to visual
Although most of the research in this area has focused
processing impairments and their relationship with symp-
on individuals in chronic stages of their illness, there has
toms at disease onset, advancing our understanding of
been one study that identified P1 deficits in adolescent
their developmental trajectory over the course of psychotic
cases of schizophrenia23 and another reporting a similar
illness.
impairment at first psychotic break.24 In the study of ad-
olescent onset psychosis, reductions in P1 were associated
Key words: schizophrenia spectrum/first-break/sensory with deficits in working memory encoding, a similar rela-
impairment/lateralization tionship to that observed in chronic stages of the illness.10

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955
A. L. Sklar et al
Further investigation into the development of these
sensory-perceptual visual processing deficits and their
contribution to cognitive dysfunctions during early stages
of a schizophrenia spectrum illness may provide novel in-
formation about primary disease processes and new tar-
gets for sensory remediation as therapeutic interventions.
Characterization of the neural mechanisms underlying
these sensory deficits is equally critical to identifying po-
tential treatment targets. Studies of visual processing con-
ducted among chronic disease populations have applied
inverse modeling to VEP deficits recorded at scalp EEG
electrodes, localizing these impairments to early visual
cortices as well as various regions along the dorsal visual
stream.4,6 In an attempt to obtain a more refined localiza-
tion of cortical deficits, studies have also combined EEG
with fMRI. Using this approach, reductions in BOLD
signals, a correlate of neural activity, have been observed
within primary (V1) and secondary (V2) visual cortices.25
However, in contrast to EEG that suffers from tissue
boundary- and scalp-induced distortions of electrical
fields and the delayed hemodynamic response used to
generate fMRI BOLD signals, magnetoencephalography
(MEG) affords high spatial and temporal resolution
combined in a single modality unaffected by different
tissue conductivities.26 This precision becomes particu-
larly important when interrogating sensory and percep-
tual processes operating on a millisecond time scale under
the control of a complex network of cortical structures.
Within the MEG visual processing literature, the M100
visual evoked field (VEF) is considered analogous to the
P1 VEP. Leveraging the enhanced precision of this im-
aging modality, cortical source localization of the M100
VEF has identified V1 as its primary generator.27,28
The present investigation was designed to determine
whether early-stage visual processing deficits were present
among individuals with a schizophrenia spectrum illness
following their first psychotic episode (FESz). To interro-
gate disruptions in the initial stages of visual processing,
MEG was used to identify a reliable marker of early
sensory-perceptual processing (ie, the M100) and distrib-
uted source modeling was applied to localize the cortical
activity contributing to it within V1. Data were recorded
during 2 visual search tasks that differentially empha-
sized either stimulus-driven, parallel search strategies (ie,
a pop-out) or a controlled serial search of stimuli (ie, a
serial search). We predicted impaired processing of target
stimuli within V1 and associations between this deficit
and performance on the visual search task. An effect of
the attentional manipulation in the visual search task was
not expected at this early stage of stimulus processing.
Methods
Participants
Participants included FESz and healthy controls (HC).
Eighty-four participants (38 HC; 46 FESz) completed
956
the study. Two FESz were excluded due to poor-quality
MEG data. To ensure groups were matched on age,
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gender, Wechsler Abbreviated Scale of Intelligence IQ,
and parental socioeconomic status (PSES), 6 additional
FESz were excluded from analysis resulting in a final
sample of 38 HC and 38 FESz. These 6 FESz individ-
uals were excluded due to low PSES scores. Data from
a subset of these participants (32 HC; 32 FESz) were in-
cluded in a separate manuscript exploring neurophysio-
logical markers of selective attention during visual search
(Sklar et al, under review).
FESz were recruited from UPMC Western Psychiatric
Hospital inpatient and outpatient services. The Structured
Clinical Interview for DSM-IV (SCID-P) was used to es-
tablish diagnoses. Twenty-three FESz were diagnosed
with schizophrenia, 6 with schizoaffective disorder (4 de-
pressive and 2 bipolar types), and 9 with psychotic dis-
order not otherwise specified. FESz participated within
2 months of their first clinical contact and had less than
2  months of lifetime treatment with an antipsychotic
medication. Thirteen (34%) were unmedicated at the time
of testing. All patients were clinically stable at the time
of testing.
All participants were screened for colorblindness
using pseudoisochromatic plates and had at least 9 years
of schooling. None had a history of head injury with
sequelae, alcohol or drug addiction, or neurological co-
morbidity. All participants completed the MATRICS
Cognitive Consensus Battery and FESz were assessed
using the Scale for the Assessment of Negative Symptoms
(SANS) and Scale for the Assessment of Positive
Symptoms (SAPS).
All procedures were approved by the University of
Pittsburgh IRB and participants provided informed con-
sent and were paid for participation.
Stimuli and Procedures
During the testing session, participants completed 2
visual search tasks depicted in figure 1. Trials from each
task began with a centrally presented fixation cross
(1°, 500  ms) followed by a central cue (0.65°, 500  ms)
depicting the color of the to-be-presented target.
A stimulus array (500 ms) comprised of 6 eccentrically
arranged annuli, each subtending 0.65° and positioned
2° from fixation, was then presented. One annulus, pre-
sented in either the right (RVF) or left (LVF) visual
field, was identified as the target based on its color.
Finally, a small gap then appeared on either the right or
left side of each annulus in the array. Participants were
required to indicate the side of the gap on the target an-
nulus via button-press within a 2000-ms time window.
If the participant responded correctly on 0 or 1 of the
previous 3 trials, the gap was 0.65°, 0.33° if 2 of 3 cor-
rect responses and 0.22° if the previous 3 responses
were correct.

Pop-out
+ + + data, and an adaptive mixture independent component
Serial Search
+ + + with a multi-echo 3D MPRAGE sequence (TR/TE/
Fixaon Color Cue Aenon Response
(500 ms) (500 ms) Selecon Selecon
(500 ms) (2000 ms)
Fig. 1.  Pop-out and serial search tasks. Participants were
instructed to identify the target annulus based on the color cue
and then indicate via button-press the side on which the gap
appears on the target.
During the pop-out (PO) task, all distractor annuli had
a uniform color in contrast to the serial search (SS) task
in which all colors of distractor annuli were unique. PO
and SS tasks were run as separate blocks and their order
was counterbalanced across participants in each group.
Each block consisted of 144 trials, 72 with RVF targets
and 72 with LVF targets.
MEG Recordings and Pre-processing
MEG data were recorded in a magnetically shielded
room using a 306-channel whole-head system (Elekta
Neuromag). Channels were arranged in 128 triplets,
each comprising 1 magnetometer and 2 planar gradiom-
eters. Data were recorded using a sampling rate of 1000
Hz (online bandpass filter = 0.1–330 Hz). Bipolar leads
placed above and below the left eye (VEOG) and lat-
eral to the outer canthi of both eyes (HEOG) recorded
blinks and eye movements and bipolar ECG leads re-
corded cardiac activity. A  3D-digitizer (ISOTRAK;
Polhemus, Inc., Colchester, VT) was used to record
the location of 4 head position indicator coils placed
on the scalp of each participant relative to their nasion
and preauricular points. Head position was monitored
continuously throughout the experiment. Neuromag
MaxFilter software (http://imaging.mrc-cbu.cam.ac.uk/
meg/Maxfilter_V2.2) was used to correct for head mo-
tion during the scan.
Electromagnetic noise originating from outside the
MEG helmet was separated from brain signal using
the temporal extension of the Signal Space Separation
method.29 The MATLAB-based EEGLAB Toolbox30 was
used to remove channels (interpolated following comple-
tion of pre-processing) and segments of data corrupted
by excessive noise. There was no difference between HC
Visual Processing Deficits in First Psychosis
(M = 2.2; SD = 1.9) and FESz (M = 2.9; SD = 2.2) in the
number of channels interpolated (t74  =  −1.5; P = .14).
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A high-pass filter (0.5 Hz; 12 dB/oct) was applied to the
analysis was performed to remove eye-blink and ECG
components.
Structural MRI scans, necessary for accurate cor-
tical localization of MEG activity, were obtained for
each participant. T1-weighted sagittal images were
obtained using a Siemens TIM Trio 3 Tesla MRI system
TI = 2530/1.74, 3.6, 5.46, 7.32/1260  ms, flip angle = 7°,
field of view = 220 × 220 mm, 1-mm isotropic voxel size,
176 slices, GRAPPA acceleration factor = 2).
MEG Sensor Processing
Offline processing VEFs was conducted using BrainVision
Analyzer2 (Brain Products GMBH). A  low-pass (100
Hz; 24 dB/oct) filter was applied, followed by segmenta-
tion of the data into 600-ms epochs, including a 100-ms
baseline window, constructed around the presentation of
the stimulus array during each trial. Segments with data
exceeding ± 5pT were excluded, and the remaining trial
segments were averaged.
MEG Source Analysis
MRIlab (Elekta-Neuromag Oy, Helsinki, Finland) was
used to register MEG sensor data to each participant’s
structural MRI. Possible dipole sources were constrained
to the gray/white matter boundary which was segmented
from MRI data using Freesurfer (http://www.surfer.nmr.
mgh.harvard.edu) and tessellated into an icosohedron
with 5-mm spacing between vertices. Cortical activity
contributing to the sensor-level data was estimated from
the 204 gradiometers using MNE, a distributed inverse
source solution. The forward solution, modeled as a
single sphere, and the noise covariance matrix calculated
from the baseline window were used to create a linear in-
verse operator using an orientation constraint of 0.4 with
depth weighting applied.31,32 The dSPM statistic, an esti-
mate of the signal-to-noise value, was calculated for each
vertex normalizing the current estimate to prestimulus
baseline variance.
Given potential hemispheric difference in responses
to the lateralized targets in the stimulus array, separate
segments for LVF and RVF targets were derived. V1, de-
fined using Brodmann Area Maps and Hinds V1 atlas
available in Freesurfer, was selected as our a priori region
of interest (ROI) given its role as the primary generator
of the M100.26,27 Activity within this ROI in each hemi-
sphere was measured over the 75- to 125-ms post-target
time window corresponding to the M100 VEF, which is
the earliest, clearly observable component depicted in the
waveforms of figure 2.
957
A. L. Sklar et al

Data Analysis to ensure that our 3 groups (ie, Schizophrenia,

Demographic variables (table  1) were compared be- Schizoaffective Disorder, and Psychosis NOS) within

tween groups using chi-square and t-tests. Task accu-
racy (ACC) and response time (RT) were subjected to a
2 (task: PO/SS) × 2 (group: HC/FESz) × 2 (visual field:
LVF/RVF targets) analysis of variance (ANOVA).
Given violations of normality, ACC and RT data were
subject to log transformation prior to analysis. MEG
sensor-level data were not subjected to statistical ana-
lyses, but rather used to visualize VEFs and establish
a time window for comparison of their associated cor-
tical source activity. A 2 (task: PO/SS) × 2 (group: HC/
FESz) × 2 (hemisphere: LH/RH) ANOVA was applied
to V1 cortical activity. Independent t-tests were used
to follow-up significant effects between groups, and
dependent t-tests were used to follow-up significant
effects involving task condition and target location
observed across groups. An analysis exploring poten-
tial effects of diagnostic classification was conducted
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the schizophrenia spectrum did not differ regarding
outcome measures of interest. There was no main ef-
fect of diagnostic group or interaction involving diag-
nosis for measures of ACC (p’s > .1), RT (p’s > .1), or
V1 activity (p’s > .2).
Results
Task Performance
ACC and RT data are reported in table 2. Overall, FESz re-
sponded less accurately than HC during the visual search
task (t7 4 = 2.64, P = .01, d = 0.61). ACC was also lower
during SS compared with PO across groups (t75 = 3.24,
P < .01, d = 0.37). Neither a main effect of visual field
(P = .06) nor the interaction between group and target lo-
cation (P = .08) reached statistical significance. No inter-
actions involving task were observed (P’s > .2).

30 30
HC FESz
20 20
Amplitude (fT)

10 10

0 0

-10 -10

-20 -20

-30 -30
-100 0 100 200 300 400 500 -100 0 100 200 300 400 500
Time (ms) Time (ms)
Fig. 2.  Butterfly plots of visual evoked field (VEFs) in response to stimulus array collapsed across tasks. The gray box indicates the 75- to
100-ms time window of interest. Plots depict data recorded from one set of gradiometers.

Table 1.  Demographics and Clinical Assessment Data (Mean ± SD) by Group

HC (n = 38) FESz (n = 38) t/χ 2 P

Age 22.8 ± 5.0 21.8 ± 4.4 0.91 .37

Female/male 13/25 14/24 0.06 1.0
Education (y) 14.1 ± 3.2 12.4 ± 2.4 2.58 .01
WASI 108.2 ± 10.6 107.3 ± 14.2 0.31 .76
MATRICS-Total 48.2 ± 7.6 38.2 ± 14.3 3.79 .00
SES 34.2 ± 14.6 29.4 ± 13.2 1.46 .15
PSES 53.0 ± 13.7 47.6 ± 15.0 1.62 .11
SANS — 31.2 ± 8.0
SAPS — 19.2 ± 11.6
Unmedicated/medicated — 13/25
Medication (CPZ mg/d) — 193.3 ± 165.5

Note: HC, healthy controls and FESz, first psychotic episode; CPZ, chlorpromazine equivalent dose; PSES, parental socioeconomic
status; SANS, Scale for the Assessment of Negative Symptoms; SAPS, Scale for the Assessment of Positive Symptoms; SES, socioeco-
nomic status; WASI, Wechsler Abbreviated Scale of Intelligence. Bolded values represent significant differences between groups.

958
 Visual Processing Deficits in First Psychosis

In addition to responding less accurately, FESz re- reported in table 2. Overall, FESz exhibited significantly
sponded more slowly than HC (t74  =  2.66, P = .01, reduced V1 activity compared with HC (t74  =  −2.06,

d = 0.61). There was also a main effect of visual field with
slower responses to trials with RVF compared with LVF
targets across groups (t75 = 3.23, P < .01, d = 0.37). An in-
teraction was present between group and target location
(F1,74 = 6.01, P = .02). Although the observed group differ-
ence was present for targets presented in both visual fields
(LVF: t74  =  −2.32, P = .02, d = 0.53; RVF: t74  =  −2.69,
P < .01, d = 0.62), FESz exhibited slower responses to RVF
compared with LVF targets (t37 = 3.03, P < .01, d = 0.49)
whereas HC did not (P = .13). There was no effect of task
or any interactions involving it on RT (P’s > .05).
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P = .04, d = 0.47) over the 75- to 125-ms time window.
The observed group effect, however, differed based on
hemisphere (F1,74 = 7.03, P = .01). FESz showed reduced
LH (t74 = 2.78, P < .01, d = 0.64), but not RH (P = .27)
V1 activity compared with HC. In addition, HC exhib-
ited larger V1 activity in the LH compared with RH
(t37  =  2.09, P = .04, d = 0.34), whereas no hemispheric
effect was present among FESz (P = .11). As expected,
there were no main effects of task (P = .26) and no inter-
actions involving task (P’s > .1). No main effect of hemi-
sphere was present (P = .52).

Sensor-Level Data Correlations Between Neurophysiology, Performance,

Butterfly plots of averaged waveforms recorded from one
set of gradiometers for HC and FESz during both visual
search tasks are depicted in figure 2. Although not sub-
jected to statistical analysis, this data were used to iden-
tify the 75- to 125-ms time window of the M100 VEF, a
homologue of the P1 recorded using EEG.
V1 Cortical Activity
Cortical activity and its quantification averaged across the
V1 ROI are depicted in figure 3, and means and SD are
and Clinical Measures
Among healthy controls, larger LH V1 activity was as-
sociated with more rapid responses to RVF targets
(r = −.45, P < .01) and larger RH V1 activity was associ-
ated with more rapid responses to LVF targets (r = −.38,
P = .02). There were no significant correlations between
any measure of ACC and cortical activity (P’s > .1). In
FESz, a similar inverse correlation between LH V1 ac-
tivity and RVF target RT (r = −.34, P = .04), but not
between RH V1 activity and LVF RT (P = .23), was

Table 2.  Results From the Visual Search Tasks (Mean ± SD) by Group and Target Location

HC FESz

LVF Targets RVF Targets LVF Targets RVF Targets

ACC (%) pop-out 98.0 ± 3.1 98.3 ± 2.9 96.7 ± 5.4 95.2 ± 6.7

ACC (%) serial search 97.2 ± 2.4 96.9 ± 3.2 94.7 ± 5.0 94.0 ± 6.7
RT (ms) pop-out 532.9 ± 105 534.1 ± 116 599.3 ± 147 626.0 ± 159
RT (ms) serial search 530.3 ± 83 538.8 ± 85 591.0 ± 130 609.9 ± 134
Contralateral V1 activity (dSPM) pop-out 3.87 ± 1.5 4.27 ± 1.9 3.59 ± 1.5 3.40 ± 1.5
Contralateral V1 activity (dSPM) serial search 4.14 ± 2.0 4.51 ± 2.1 3.61 ± 1.6 3.33 ± 1.1

Note: FESz, first psychotic episode and HC, healthy controls; LVF, left visual field and RVF, right visual field; ACC, accuracy and RT, re-
sponse time.

A 5
HC
FESz
4
V1 Activity (dSPM)

B 2

0
LH RH

Fig. 3.  Cortical activity averaged over 75- to 125-ms post-stimulus array collapsed across tasks for HC (A) and first psychotic episode
(FESz) (B). Bar graph depicts activity averaged across the V1 ROI. Of note, the scale has been set differently for healthy controls (HC)
and FESz to allow for proper visualization of cortical activity. Error bars represent SEM.
959
A. L. Sklar et al
present. There were no significant correlations between
ACC measures and V1 activity in FESz (P’s > .2).
Among FESz, activity within LH V1 was positively
correlated with total SAPS scores (r = .38; P = .02). This
relationship was not present for the RH (P = .1). The as-
sociation between a larger LH V1 response and higher
SAPS scores was present for global ratings on the hal-
lucination subscale (r = .37; P = .03), but not the delu-
sions, bizarre behaviors, or thought disorder subscales
(P’s > .1). Among the hallucinatory phenomena, LH V1
activity was associated with auditory (r = .38; P = .02),
but not visual (r = .13; P = .43) hallucinations. No signif-
icant correlations were observed between V1 activity in
either hemisphere and SANS or MATRICS overall and
subscale scores (P’s > .05).
Medication Effects
There was no effect of medication status or interactions
involving it on V1 activity (P’s > .1) or behavioral
(P’s > .1) measure.
Discussion
Although deficits in visual processing have been exten-
sively reported within the schizophrenia spectrum, their
presence and the dysfunctional neural mechanisms
contributing to them remain understudied at disease
onset. The present study extends the existing literature
documenting early-stage visual processing impairment in
psychosis, identifying its presence at first break and cou-
pling it to dysfunction within the left hemisphere (LH)
primary visual cortex at this stage of the illness. In ad-
dition, activation within this region in response to visual
stimuli, while reduced compared with HC, was associ-
ated with reports of increased hallucinatory phenomena.
These findings detail impairments in sensory-perceptual
processing and their relationship to symptoms afflicting
individuals at disease onset, informing potential develop-
mental trajectories of visual processing deficits in schizo-
phrenia spectrum disorders.
The diminished response within V1 to stimuli during
visual search may reflect histological changes within V1
in individuals diagnosed with schizophrenia including a
reduction in neuronal population and overall volume of
this region.33 This impairment is also consistent with ana-
tomical changes such as cortical thinning34 and disrupted
white matter integrity35,36 in medial occipital lobe detected
using structural imaging techniques. In addition to these
cortical abnormalities, impairments in lower-level struc-
tures involved in the relay of visual information to the
cortex37 might have also contributed to the observed V1
deficit. Unfortunately, these investigations were mostly
conducted in individuals during chronic stages of their
illness and cannot speak directly to the impaired re-
sponse observed in our sample. A  preliminary analysis
960
examining structural brain difference using the MRIs
obtained in the current study revealed no significant dif-
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ferences in gray matter volume between FESz and HC
within V1 (unpublished data). However, although struc-
tural MRI data were acquired to perform cortical source
reconstruction of MEG sensor data, high-resolution T1
and T2 scans necessary for precise volumetric analyses
were not obtained. Future studies utilizing scans better
optimized for this purpose may reveal group differences
not observed in the present data set.
Beyond a simple group effect, the relative impairment
among FESz in V1 processing differed by hemisphere. This
statistical interaction was in part due to a more robust LH
response within HC, a finding previously observed among
healthy individuals38 and possibly related to morphologic
asymmetries in V1 including increased neuronal size39 and
overall cellular density40 of the LH. The absence of a sim-
ilar lateralization among FESz and their blunted LH V1
response compared with HC suggests an LH lateralized
pathology in this patient population. This conclusion is
supported by findings of a similar hemispheric interaction
in task performance where FESz responds more slowly to
targets located in the RVF, a pattern previously reported
in patients during chronic stages of psychotic illness.41,42
The lateralized V1 dysfunction is also consistent with the
broader schizophrenia spectrum literature identifying
both structural43–45 and functional46,47 pathological pro-
cesses preferentially affecting the LH. However, caution
is warranted when drawing conclusions regarding the lat-
eralization of the observed V1 deficit as the proximity of
midline cortical structures begins to approach the limit at
which MEG can isolate distinct regions of activity with a
high degree of confidence.
The biological mechanisms underlying the asymmetry
in V1 pathology remain uncertain, though it may reflect
dysfunction within the magnocellular visual pathway
present in individuals with schizophrenia.48 For example,
stimuli presented with high temporal frequency, a char-
acteristic biasing processing toward the magnocellular
pathway, are detected more rapidly and with a higher de-
gree of accuracy when presented in the right visual field
in healthy individuals.49 However, to date, there has been
no study documenting anatomical asymmetry within the
magnocellular pathway that would suggest a LH dom-
inance. Another possibility for the lateralization of V1
deficits in FESz relates to asymmetric top-down mod-
ulation of this cortical region. Although the V1 deficit
observed 75–125  ms following stimulus presentations is
suggestive of a purely sensory deficit, this response may
represent a relatively late stage of information proc-
essing, a point at which cognitive control networks have
been shown to exert influence over activity within visual
cortices.50,51 In fact, even the earliest cortical responses to
visual stimuli recorded within V1 (~50 ms) are susceptible
to modulation by top-down processes.52,53 Given the pres-
ence of LH lateralized deficits within higher-order frontal

and temporal networks in individuals diagnosed with a
schizophrenia spectrum illness, it is possible that their
modulation of activity within V1 is asymmetric as well.
Although the impaired V1 response among FESz was
not associated with MATRICS scores, it was correlated
with poorer performance during the visual search task
indicating a relationship between deficits in early-stage
visual processing and attention. Furthermore, despite
reduced LH V1 activity relative to HC, larger stimulus-
evoked activity within this region was associated with
reports of more significant hallucinatory experiences
among FESz. This finding is consistent with previously
observed relationships between reports of hallucinations
and stimulus-evoked gamma-band oscillations within
sensory cortices.54–56 Based on these findings, it has been
postulated that baseline hyperexcitability within these
sensory regions contributes to both hallucinatory ex-
periences and an impaired stimulus-evoked response.
However, in contrast to these previous studies, the cur-
rent sample exhibited predominantly cross-modal asso-
ciations between V1 activity and auditory hallucinations.
The absence of an intramodal correlation in the current
sample is likely the result of the relative lack of visual hal-
lucinations reported (mean SAPS item score of 0.9 with
14 nonhallucinators). Regarding the cross-modal associ-
ation, the existence of structural connections between au-
ditory and visual cortices57 and the presence of functional
connectivity between sensory cortices in individuals with
specific sensory impairments58,59 provide plausible ex-
planations a link between pathology in the visual cortex
and auditory symptoms. However, the mechanisms un-
derlying this association remain largely speculative at this
point and merit further consideration.
Conclusions
The present investigation used MEG recordings to ex-
amine early cortical responses evoked by target stimuli
during a visual search task and their relationship to
down-stream selective attention processes in individuals
following their first psychotic episode. Localization of the
cortical activity associated with the M100 VEF inculpates
dysfunction within the primary visual cortex in sensory-
level visual processing deficits at this early stage of the
illness. Furthermore, the impaired V1 cortical response
appears to be lateralized to the LH, adding to the con-
ceptualization of an asymmetric disease process with pa-
thology spanning across sensory modalities and cognitive
domains in the LH. The contribution of higher-order, cog-
nitive control processes to the observed V1 dysfunction at
disease onset warrants further examination, as does poten-
tial lateralization of previously reported deficits in lower-
level structures involved in the relay of visual information
to the cortex. Connectivity analyses, both structural (eg,
white-matter tractography) and functional (eg, frequency
band synchronization and coupling), would also provide
Visual Processing Deficits in First Psychosis
a more comprehensive understanding of the complex net-
works guiding our processing of the visual world and how
Downloaded from https://academic.oup.com/schizophreniabulletin/article-abstract/46/4/955/5735334 by Serials Processing Library University of Canberra user on 13 July 2020
it fails even at early stages of psychosis.
Funding
Funded by National Institute of Mental Health (P50
MH103204) (David Lewis, MD, Director, DFS Project
Co-PI).
Acknowledgments
We thank the faculty and staff of the WPH Psychosis
Recruitment and Assessment Core and the University of
Pittsburgh Clinical Translational Science Institute (UL1
RR024153, Steven E.  Reis, MD) for their assistance.
None of the authors reported any biomedical financial
interests or potential conflicts of interest.
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