Abnormal timing of visual feedback processing in young adults with schizophrenia.

Abstract

Recent studies have shown that schizophrenia is characterized by visual perceptual deficits, especially in the ability to integrate stimulus details into a global percept. Also, several studies have found amplitude attenuation of the visual P1 component of the event-related brain potential (ERP), probably indicating impaired visual feedforward processing in schizophrenia. However, there is little knowledge on the role of feedbackward processing in this group. This question is of importance, as recent studies indicate that feedback processing is critical in stimulus integration.
In the present study we tested whether there is evidence for atypical recurrent processing in a group of 14 young adults with recent-onset schizophrenia (mean age 21.7 years, mean TIQ 92.7) and 17 age and IQ matched control subjects, all males. To achieve this aim, we used a texture segregation task and measured ERP activity concurrently.
We found normal amplitudes, but longer latencies of activity related to feedbackward processing in the schizophrenia group. In addition, we found enhanced occipito-temporal activity around 160 ms that is probably the reflection of increased detail processing.
We show for the first time evidence for abnormal timing in feedback activity related to visual perception in subjects with schizophrenia. It is hypothesized that this latency effect is the functional reflection of abnormal structural connectivity in this group, and might result in increased processing of stimulus detail.

Full text

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Neuropsychologia 47 (2009) 3105–3110
Contents lists available at ScienceDirect
Neuropsychologia
journal homepage: www.elsevier.com/locate/neuropsychologia
Abnormal timing of visual feedback processing in young adults with
schizophrenia
Chantal Kemnera,b,c,∗, John J. Foxed,e, Judith E. Tankinkb, René S. Kahna,b, Victor A.F. Lammef,g
aRudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands1
bDepartment of Child and Adolescent Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands
cDepartment of Developmental Psychology, Faculty of Social Sciences, Utrecht University, Utrecht, The Netherlands
dProgram in Cognitive Neuroscience, Department of Psychology, The City College of the City University of New York, New York, NY 10031, USA
eThe Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA
fDepartment of Psychology, University of Amsterdam, Amsterdam, The Netherlands
gThe Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands
a r t i c l e i n f o
Article history:
Received 20 February 2009
Received in revised form 14 July 2009
Accepted 15 July 2009
Available online 23 July 2009
Keywords:
Schizophrenia
Texture segregation
Recurrent processing
Connectivity
P1
Visual perception
a b s t r a c t
Background: Recent studies have shown that schizophrenia is characterized by visual perceptual deficits,
especially in the ability to integrate stimulus details into a global percept. Also, several studies have found
amplitude attenuation of the visual P1 component of the event-related brain potential (ERP), probably
indicating impaired visual feedforward processing in schizophrenia. However, there is little knowledge
on the role of feedbackward processing in this group. This question is of importance, as recent studies
indicate that feedback processing is critical in stimulus integration.
Methods: In the present study we tested whether there is evidence for atypical recurrent processing in a
group of 14 young adults with recent-onset schizophrenia (mean age 21.7 years, mean TIQ 92.7) and 17
age and IQ matched control subjects, all males. To achieve this aim, we used a texture segregation task
and measured ERP activity concurrently.
Results: We found normal amplitudes, but longer latencies of activity related to feedbackward processing
in the schizophrenia group. In addition, we found enhanced occipito-temporal activity around 160ms
that is probably the reflection of increased detail processing.
Discussion: We show for the first time evidence for abnormal timing in feedback activity related to visual
perception in subjects with schizophrenia. It is hypothesized that this latency effect is the functional
reflection of abnormal structural connectivity in this group, and might result in increased processing of
stimulus detail.
© 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Several studies have demonstrated that abnormal visual per-
ception is a hallmark of schizophrenia (Butler et al., 2005, 2007;
Doniger, Foxe, Murray, Higgins, & Javitt, 2002; Laycock, Crewther, &
Crewther, 2006; Malaspina et al., 2002), but little is known about
the underlying brain mechanisms. Studies of brain activation to
visual stimulation have consistently shown attenuation of the P1
peak of the visual ERP in patients (Butler et al., 2007; Donohoe
et al., 2008; Foxe, Doniger, & Javitt, 2001; Foxe, Murray, & Javitt,
2005; Haenschel et al., 2007; Yeap, Kelly, Sehatpour, et al., 2008),
∗
Corresponding author at: Dept. of Child and Adolescent Psychiatry, UMCU
B01.324, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Tel.: +31 88 7557462; fax: +31 88 7555444.
E-mail address: C.Kemner@umcutrecht.nl (C. Kemner).
1Institution where the study was carried out.
first-episode psychosis (Yeap, Kelly, Thakore, et al., 2008), as well
as in unaffected first-degree relatives (Yeap et al., 2006), and this
has been directly related to abnormal behavior on visual percep-
tion tasks (Haenschel et al., 2007). In addition, the results of the
latter study suggest that abnormal neuronal activity in extrastriate
brain areas underlies the ERP P1 deficit (Haenschel et al., 2007).
Activity in extrastriate areas at this latency is usually associated
with early sensory-level processing of relatively simple stimulus
features, which are transferred via feedforward cortico-cortical
connectionstowardhighercorticallevels.Abnormalitiesatthelevel
of the P1 would, therefore, suggest abnormal bottom-up, or feed-
forward,visualprocessinginsubjectswithschizophrenia(Butleret
al., 2007; Lalor, Yeap, Reilly, Pearlmutter, & Foxe, 2008).
An important question, however, concerns the role of recurrent
processing in visual perception in schizophrenia. This topic is espe-
cially interesting, as there are indications that visual processing
in schizophrenia is characterized by an over-focusing on the local
details of stimuli, and a reduced capability to integrate the ele-
0028-3932/$ – see front matter © 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neuropsychologia.2009.07.009

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C. Kemner et al. / Neuropsychologia 47 (2009) 3105–3110
ments of a visual scene into a global percept (Silverstein, Kovács,
Corry, & Valone, 2000; Uhlhaas et al., 2006). Early visual stimulus
processing involves the processing of stimulus elements (details)
in hierarchically early visual areas. It has long been assumed that
the integration of these elements occurs through feedforward pro-
cesses in higher cortical areas. However, feedforward connections
are nearly universally reciprocated by large-scale feedback fibres,
and there is increasing evidence that recurrent processing, includ-
ing both lateral and feedback processing, is essential for stimulus
integration (Lamme & Roelfsema, 2000). It has therefore been sug-
gested that recurrent processing might be specifically impaired in
schizophrenia (Lamme, 2003; Laycock et al., 2006). One study has
previously tested ERP activity related to boundary segmentation in
subjects with schizophrenia, and these authors found essentially
normal amplitudes in their patient group (Foxe et al., 2005). This
activity had been theoretically linked to feedback processes in a
series of earlier studies in healthy adults (e.g. Murray et al., 2002;
Murray, Foxe, Javitt, & Foxe, 2004). However, since the Foxe et al.
study (2005) is the only study to assess this feedback activity in
schizophrenia thus far, and the timing of these processes was not
explicitly tested in that study, the issue of the role of feedback
processing in schizophrenia clearly warrants further investigation.
Recurrent connectivity related to visual perception has often
been studied in both monkeys and humans by using so-called
texture segregation tasks (Lamme, Van Dijk, & Spekreijse, 1992).
Texture segregation involves the pre-attentive processing of (tex-
ture)differencesbetweenadjoiningregionsinthevisualfieldandis
essentialtothesegmentationofasceneintofigureandbackground.
Recurrent activity related to texture segregation can be isolated by
subtracting the ERP in response to homogeneous textured visual
stimuli from ERP responses to stimuli with texture differences. This
will result in activity at occipital sites that reflects the re-entry
of visual information related to the processing of texture differ-
ences at higher cortical areas (Fahrenfort, Scholte, & Lamme, 2007;
Vandenbroucke, Scholte, Engeland, Lamme, & Kemner, 2008). The
role of feedback in texture segregation has been shown directly in
severalanimalstudies;whenextrastriateareasinthemonkeybrain
were silenced, the signal related to texture segregation in V1 was
no longer apparent. Also, the animals were no longer able to detect
texture differences (Hupé et al., 1998; Lamme, Zipser, & Spekreijse,
1998; Supèr & Lamme, 2007).
The present study was designed to directly test recurrent
processingrelatedtovisualperceptioninyoungadultswithrecent-
onset schizophrenia and a group of age and IQ matched controls, by
measuring ERPs in a task that was effective in indicating recurrent
activityinearlierstudiesinhumansandmonkeys(Kemner,Lamme,
Kovacs, & van Engeland, 2007; Lamme et al., 1992). We hypoth-
esized that impaired recurrent processing would be reflected in
smaller amplitude and/or delayed latency of EEG activity related
to texture segregation. We also tested the amplitude of the P1, to
determine how the present study related to previous studies of
visual processing using ERPs in schizophrenia. In addition, as we
have previously shown in subjects with autism that reduced occip-
italvisualERPscanbeconcomitantwithincreasedactivityinhigher
visual areas (Vandenbroucke et al., 2008), we inspected the data for
the presence of such activity in the schizophrenia group and tested
this.
2. Methods and materials
2.1. Participants
Nineteen healthy control subjects and 14 clinical subjects with schizophrenia,
all male, participated in the study. All patients were recruited from the (out) patient
clinic of the Adult Psychiatry Unit of the University Medical Center Utrecht, and
had received a diagnosis of schizophrenia or a related disorder less than half a
year before the experimental testing. The psychiatric diagnosis was verified with
the results of the Comprehensive Assessment of Symptoms and History (CASH) by
two independent raters (Andreasen, Flaum, & Arndt, 1992). Severity of illness was
measured with the Positive and Negative Syndrome Scale (PANSS) (Kay, Fiszbein,
& Opler, 1987). Means for the PANSS Negative symptoms scale (total N) was 16.8,
for the Positive symptoms scale (total P) 13.8, and for the General psychopathology
scale (total G) 31.9. Thirteen clinical subjects used psychotropic medication (atypi-
cal antipsychotics in 12 cases). All subjects reported normal or corrected to normal
vision and were free of substance abuse in the past month, seizure disorders, neuro-
logical diseases, head trauma or mental retardation. Healthy controls had no history
ofpsychiatricdisorder,andweremedicationnaive.Twocontrolswereexcludedfrom
analysis because of extreme alpha-ringing in the EEG.
Thefinalgroupsconsistedof17controls(M=20.1years,SD=2.2)and14patients
(M=21.7years,SD=3.3).AllindividualswereadministeredtheWechslerAdultIntel-
ligence Scale, Dutch edition (WAIS-III-NL). Mean total IQ for the control group
was 101.3 (SD=15.0), and for the schizophrenia group 92.7 (SD=14.7). There were
no significant differences in either age or IQ between the control group and the
schizophrenia group.
ThemedicalethicscommitteeoftheUniversityMedicalCentreUtrechtapproved
of this study, in accordance with the Declaration of Helsinki. All participants gave
informed consent after explanation of the procedure and received a monetary
reward.
2.2. Stimuli
The task consisted of full-screen presentations of 900 stimuli, alternating every
550ms, on a 21in. computer screen (42cm×32cm) approximately 1m from the
subject. The stimuli consisted of homogeneously textured fields of either 45◦or
135◦oriented, randomly positioned line segments (total 450), or of checkerboards
consistingofthesamelinesegments(total450)(17)(seeFig.1).Duringpresentation
a red dot was shown in the middle. Randomly during the task, cartoon (Pokemon)
stimuliwerealsopresentedfor550ms(intotal39stimuli,19ofwhichweretargets).
Subjects were required to press a button with the right index finger in response to
thetargetstoensureattentiontothetask.Therewerenodifferencesbetweengroups
in number of hits (schizophrenia 97.5%, SD=3.2, controls 98.6%, SD=2.7). Data for
the first two trials after each cartoon presentation were not included in the analysis.
2.3. Data recording and ERP acquisition
Electroencephalographic recordings were obtained from 32 electrode positions
at standard EEG recording locations of the international 10/20 system by using a
Fig. 1. Examples of the stimuli used: left panel, homogenous stimulus; right panel, checkerboard stimulus.

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BioSemi Active Two EEG system (Biosemi, Amsterdam), while participants were sit-
ting in an acoustically shielded room. The EEG was sampled at a rate of 2048Hz and
stored offline as continuous signals. A left mastoid electrode was used as a refer-
ence. Horizontal EOG was recorded from electrodes on the outer canthi of the eyes
by means of adhesive rings. Vertical EOG was recorded from electrodes placed infra-
and supra-orbital to the left eye. The raw data were resampled offline at 500Hz and
filtered with a high-pass filter of 1Hz, a low-pass filter of 30Hz, and a notch filter of
50Hz. The resulting data were segmented into epochs from 100ms pre-stimulus to
400ms post-stimulus. After baseline correction, ocular correction (Gratton, Coles, &
Donchin,1983)andartifactrejectionwereperformed.Next,segmentswereaveraged
separatelyforthehomogenousandthecheckerboardstimuli.Adifferencewavewas
created by subtracting the average ERP to homogenous stimuli from the average ERP
to checkerboard stimuli. Electrode sites of interest were determined on the basis of
the existant literature and the observed topographies in the data. ERP peaks were
scored as the maximum amplitude in the indicated time window. The latency of the
texture negativity was based on the latency of this peak.
3. Results
Repeated measures analyses were done, using as within-
subjects factors of stimulus (homogeneous, checkerboard) and
electrode (specific levels dependent on the peak) and a between-
subjects factor of group (control, schizophrenia). The alpha value
was set at .05. Only group main effects or interactions with group
are reported.
P1. The P100 showed a right sided, occipital distribution and
thereforetheanalysesincludedelectrodelocationsOz,O2andPO4.
The P1 was determined as the largest peak in the period between
80 and 130ms. One outlier (clinical subject) was excluded from
the analysis. Only a marginally significant main effect of group was
found (F(1,28)=1.9, p=.09, one-sided) indicating that subjects with
schizophreniashowedatendencyforsmalleramplitudesthancon-
trols (see Fig. 2).
Texture negativity. The texture negativity was determined in the
difference wave as the largest negativity within 130–190ms at
occipitalelectrodesO1,OzandO2.Agroupmaineffect(F(1,29)=6.2,
Fig.2. ERPsatoccipitalsitestohomogenous(upperpanel)andcheckerboard(lower
panel) stimuli. Blue lines represent the control group, red lines the schizophrenia
group. (For interpretation of the references to color in this figure legend, the reader
is referred to the web version of the article.)
Fig. 3. ERPs at Oz and voltage maps, both representing the difference wave between
checkerboard and homogenous stimuli (130–190ms window for the voltage maps).
Blue lines and lower voltage map represent the control group, red lines and upper
voltage map the schizophrenia group. Arrows indicate the peak of the texture neg-
ativity. (For interpretation of the references to color in this figure legend, the reader
is referred to the web version of the article.)
p<.05) indicated that subjects with schizophrenia showed longer
latencies than controls (resp. 167.7, SE 2.7 and 158.4, SE 2.5) (see
Fig. 3). There was no difference in amplitude between the clinical
and control groups.
N160 amplitude. Visual inspection of the data for increased
amplitudes in the schizophrenic group showed larger negativity in
the clinical group over right occipito-temporal sites around 160ms
(see Fig. 2). This activity was scored as a negative peak (N160)
between130and190msatPO4,P4,CP6andP8.Agroupmaineffect
(F(1,29)=11.4, p<.005) showed that subjects with schizophrenia
had larger amplitudes than controls (see Fig. 4).
3.1. Covariance analyses
We tested whether the marginally smaller P1 in the schizophre-
nia group was related to the group effects on the texture negativity
and N160 by using the P1 amplitude as a covariate in the analy-
ses of the latter peaks. Additionally, we tested whether the larger
N160 amplitude was a consequence of the delayed latency of the
texture activity in the clinical group, by using the latency of the
texture activity as a covariate in the analysis of the N160 ampli-
tude. However, all group effects remained significant (group effect
of the latency of the texture activity after covariance analysis for
the P1 amplitude: F(2,27)=4.5, p<.05, group effect of the ampli-
tude of the N160 after covariance analyses for resp. the amplitude
of the P1: F(2,27)=5.4, p=0.01, and the latency of the texture activ-
ity: F(2,27)=5.5, p=0.01). This indicates that there is no evidence
for a relationship between the marginally smaller P1, the longer
latency of the texture negativity, and the larger N160 seen in the
group with schizophrenia.
4. Discussion
In the present study we tested whether young adults with
schizophrenia showed indications of abnormal recurrent activity
duringvisualprocessing.Toachievethis,weusedawell-established
texture segregation task wherein homogeneous and texture-
defined checkerboard stimuli were presented to participants. By

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Fig. 4. Voltage maps of activity to homogenous stimuli in the N160 latency window (130–190ms). Please note that group effects were also seen to checkerboard stimuli (not
shown). Upper row: controls, lower row: subjects with schizophrenia.
subtracting ERP activity to homogeneous stimuli from activity
in response to the textured checkerboard stimuli, feedback pro-
cesses from higher to lower-order cortical visual areas related
to the processing of these texture differences were isolated in
the so-called texture negativity. We found normal amplitudes,
but abnormal latencies of recurrent activity in subjects with
schizophrenia. In addition, we found an increased right-lateralized
occipito-temporal negativity that peaked at approximately 160ms
in this group.
Since several studies have shown that subjects with schizophre-
nia show smaller amplitudes of the occipital P1 (e.g. Butler et al.,
2007; Donohoe et al., 2008; Foxe et al., 2001, 2005; Yeap, Kelly,
Thakore, & Foxe, 2008), we first tested whether we could repli-
cate this effect in our population. We found that the schizophrenia
group had attenuated P1 amplitudes relative to the control group,
althoughthiswasonlymarginallysignificant,probablybecausethe
number of subjects included was smaller than the N in earlier stud-
ies. Data from an earlier study (Lamme et al., 1998) indicated that
the P1 is not modulated by feedbackward activity during boundary
segmentation tasks (see also Murray, Imber, Javitt, & Foxe, 2006).
Therefore,wesuggestthatthemarginallyreducedamplitudeofthe
P1 in schizophrenia patients in the present study is likely related to
abnormalprocessingofvisualinformationintheinitialfeedforward
sweep.
Wewerespecificallyinterestedintheintegrityofrecurrentcon-
nectionsinthevisualcorticalsystem,andtothisendwedetermined
both the amplitude and the latency of the texture negativity. A sig-
nificant effect was noted for the peak latency of this wave, which
reached its peak amplitude significantly later in the schizophrenia
group than in the controls. With respect to the theoretical meaning
of the delayed latency, long range interactions between and within
corticalregionshavebeenassociatedwithgeneralfunctionsrelated
to coordinated activity of different brain areas and integration of
stimulus detail (Phillips & Silverstein, 2003; Silverstein et al., 2000;
Uhlhaas et al., 2006). As such, the finding of abnormal timing of
the texture negativity could be related to the abnormal detail and
Gestalt perception that is consistently reported in schizophrenia
(Phillips & Silverstein, 2003).
Thelatencydifferencesuggestseitherabnormaltimingoflower-
order activity that serves as input to the generator(s) of the texture
negativity, or abnormal transmission times from higher to lower
cortical areas. There were no latency differences between groups
with respect to the P1, so the timing of the (lower-order) P1 input
is probably normal. It is possible, though, that onset of recurrent
processing is dependent on the amplitude of the P1 input, and
this tended to be smaller in the schizophrenic group. However, we
specifically tested whether there was a relationship between P1
amplitude and texture negativity latency by performing a covari-
ance analysis, and this was not seen. It is therefore more likely that
thedelayedpeaklatencyofthetexturenegativityintheschizophre-
nia group reflects altered transmission times from higher to lower
visual areas, perhaps due to abnormal structural connectivity. Such
structural abnormalities have been consistently found in visual
areas in subjects with schizophrenia (e.g. Agartz, Andersson, &
Skare, 2001; Ardekani, Nierenberg, Hoptman, Javitt, & Lim, 2003;
Ashtari et al., 2007; Butler et al., 2006; Kumra et al., 2004). In con-
trast, the normal amplitude of the texture negativity suggests that
the higher order areas that are involved in the generation of this
activityfunctionrelativelynormallyinthisgroup.Theresultsofthe
current study are in agreement with a recent study in which activ-
ity related to boundary completion processing of so-called Kanisza
figures, which produce illusory contours, was measured in subjects
withschizophreniaandcontrols(Foxeetal.,2005).Inearlierpapers
from the same group (Doniger et al., 2000; Murray et al., 2002),
it was argued that enhanced activity to illusory contours reflected
feedbackactivityfromhigherordertolower-ordervisualareas,very
much in line with the central thesis of the present work. In the Foxe
et al. (2005) study, both controls and subjects with schizophrenia

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showed activity that can be related to feedback processing. There
were no between-groups differences in amplitude of this activity,
in close agreement with the results of the present study.
In addition to the P1 component and the texture negativity, we
also analysed a right-lateralized occipito-temporal negativity that
peaked at approximately 160ms. Several studies have shown that
subjects with schizophrenia have normal amplitudes of a negativ-
ity seen in this latency range, even though the P1 is found to be in
deficit at the same time (Butler et al., 2005; Foxe et al., 2001, 2005).
In our study, patients with schizophrenia showed stronger N160
responses to both types of stimuli. As to the meaning of the large
N160 in this study, a right-lateralized negativity over lateral occip-
ital scalp in this latency range is usually associated with the initial
perceptual processing of meaningful visual stimulus patterns, such
as faces and letters (Hillyard, Teder-Sälejärvi, & Münte, 1998;
Treisman & Kanwisher, 1998). It is also often referred to as N170 in
face processing studies, but comparable activity has certainly also
been noted to textures (Itier & Taylor, 2007). It has been suggested
that an increase in N170 amplitude to faces might reflect more
fine-grained analysis of features following face detection (Anaki,
Zion-Golumbic, & Bentin, 2007). Analogously, the N160 group dif-
ference herein might indicate that subjects with schizophrenia are
engaged in increased processing of stimulus detail, even for stim-
uli that are relatively non-meaningful like the textures used in the
current study. It is plausible that this increased processing of stim-
ulusdetailisaconsequenceofthetimingabnormalitiesinfeedback
connections, as feedback processing has been previously related to
detailintegration(Lamme&Roelfsema,2000).Howevercovariance
analysis did not show evidence for a relationship between N160
activityandthetimingoffeedbackactivity,althoughthislackofcor-
relationcouldwellbeduetotherelativelysmallsamplesize,which
stresses the importance of increasing group size in future studies of
this topic. In addition, the role of medication and symptomatology
should be addressed.
In conclusion, the current study revealed normal amplitudes of
activitythatreflectsfeedbackprocessesrelatedtovisualperception
in a group of young adults with schizophrenia, in close agreement
with an earlier study (Foxe et al., 2005). However, we also uncov-
ered significantly delayed timing of this activity in our patient
group, as well as evidence for increased activity over occipito-
temporal sites that might be related to increased detail processing.
Future studies on this topic should be aimed at further under-
standing the relationship between these latter two phenomena. An
important next step will be to directly test structural connectivity
and the timing of the texture negativity within the same patient
group.
Acknowledgements
We would like to thank Emmie van Schaffelaar for testing of the
subjects, Ivo Heitland for data processing, and Gert Camfferman for
technical assistance.
The work described was supported by an Innovational Research
Incentives grant (VIDI-scheme, 402-01-094) of the Netherlands
OrganizationforScientificResearch(NWO)toChantalKemner.John
Foxe receives support from the US National Institute of Mental
Health (MH65350 & MH85322).
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