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International Journal of Psychophysiology 48(2003) 1–10

0167-8760/03/$ - see front matter� 2002 Elsevier Science B.V. All rights reserved.doi:10.1016/S0167-8760(02)00156-3

N400 abnormalities in unmedicated patients with schizophreniaduring a lexical decision task

Hiroto Hokama *, Ken-Ichi Hiramatsu , Jijun Wang , Brian F. O’Donnell , Chikara Oguraa, a a b a

Department of Neuropsychiatry, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215,a

JapanDepartment of Psychology, Indiana University, Bloomington, IN 47405, USAb

Received 8 January 2002; received in revised form 7 October 2002; accepted 13 November 2002

Abstract

A lexical decision task was used to investigate semantic processing in schizophrenia. Eighteen unmedicatedschizophrenics and 18 genderyage-matched controls were tested. Subjects were visually presented with pairs of words.The target word(S2) was either a non-word, semantically related, or unrelated to preceding word(S1). Subjectsdecided whether the S2 was a word or non-word. Event related potentials(ERPs) elicited by the S2, including N350,and the late positive component(LPC) were measured. The latency of the N350 was prolonged in schizophrenia.The N400 effect, measured by the mean amplitude(300–500 ms) from difference waves(unrelated wordyrelatedword, non-wordyrelated word), was smaller in patients. Peak amplitude of the LPC was reduced and latency of theLPC was delayed in the schizophrenics. Behaviorally, control subjects responded much faster to related wordscompared to unrelated or non-words, while patients showed little difference in processing speed between wordcategories. A reduced N400 effect suggested inefficient utilization of the context, while prolonged latency of the ERPcomponents suggested a general delay of semantic information processing in schizophrenia.� 2002 Elsevier Science B.V. All rights reserved.

Keywords: N400; Priming effect; Schizophrenia; Unmedicated

1. Introduction

Many symptoms in schizophrenia reflect distur-bances of language processing(e.g. auditory hal-lucination, loose association, thought disorder,neologism). These linguistic disturbances havereceived extensive evaluation using behavioral par-adigms(e.g. Koh et al., 1974; Russell and Beek-

*Corresponding author. Tel.:q81-98-895-1157; fax:q81-98-895-1419.

E-mail address: hhokama@med.u-ryukyu.ac.jp(H. Hokama).

huis, 1976; Kwapil et al., 1990; Spitzer et al.,1994; Spitzer, 1993). More recently, event relatedpotentials(ERPs) have been used to investigatethe physiological mechanisms involved in seman-tic priming in both normal subjects and patientswith schizophrenia. Most ERP studies havefocused on the N400 component of the visual orauditory ERP, which reflects lexical processes.Initial studies by Kutas and Hillyard(1980, 1984)focused on the relation of N400 amplitude toviolations of expectancies in reading. In thesestudies, the N400 was larger in amplitude to

2 H. Hokama et al. / International Journal of Psychophysiology 48 (2003) 1–10

terminal words in a sentence, which were incon-gruous or nonsensical with respect to the precedingsemantic context. For example, in the sentence,‘HE SPREAD THE WARM BREAD WITHSOCKS’, the word ‘socks’ elicits a more negativeN400 than the word ‘Butter’. This N400 primingeffect is typically analyzed by subtraction of thecongruent from the incongruent(or unassociated)word. N400 has subsequently shown to be elicitedby various paradigms including lexical decision-making (Rugg, 1985; Bentin et al., 1985; Bentin,1987) and semantic categorization(Polich et al.,1980; Polich, 1985; Holcomb, 1988; Barrett andRugg, 1990).Both sentence and word pair priming studies

have been used to study lexical processing inschizophrenia. We summarize these results, usingthe term ‘incongruent’ to indicate words whichelicit a prominent N400 component, and the term‘congruent’ for a condition with a small or absentN400 component. N400 effect refers to a measurederived by subtracting the ERP to the congruentword from the ERP to the incongruent word.Previous findings with respect to N400 amplitudeinclude (1) a reduced N400 effect observed inincongruent–congruent subtraction waveforms inschizophrenia by many(Hokama et al., 1990;Koyama et al., 1991; Grillon et al., 1991; Bobeset al., 1996; Olichney et al., 1997; Ohta et al.,1999) but not all investigators(Nestor et al.,1997); (2) Lack of reduction of the N400(Hoka-ma et al., 1990; Koyama et al., 1991, 1994;Andrews et al., 1993; Bobes et al., 1996; Strand-burg et al., 1997), or enhanced N400 to theincongruent word(Nestor et al., 1997; Niznikiew-icz et al., 1997); and (3) enhanced negativity ofN400 in the congruent condition compared tonormal group(Bobes et al., 1996; Nestor et al.,1997; Niznikiewicz et al., 1997; Strandburg et al.,1997; Ohta et al., 1999). N400 latency findingshave been more consistent than amplitude findings,with a prolongation of N400 latency in schizo-phrenia reported in the majority of studies(Hok-ama et al., 1990; Grillon et al., 1991; Koyama etal., 1991, 1994; Mitchell et al., 1991; Adams etal., 1993; Andrews et al., 1993; Bobes et al., 1996;Nestor et al., 1997; Niznikiewicz et al., 1997;Olichney et al., 1997; Strandburg et al., 1997;

Ohta et al., 1999; Salisbury et al., 2000). N400abnormalities have been interpreted as electrophy-siological evidence of inefficient utilization of thecontext due to disruptions in spread of activationin semantic networks, coupled with a general delayof semantic information processing in schizo-phrenia.It is possible that medication may contribute to

abnormalities in the N400 component. Anti-psy-chotic medications may have acute effects(Herrm-ann et al., 1981; Boids-Wollner et al., 1981), aswell as long-term effects on ERPs(Blackwood etal., 1987; Pfefferbaum et al., 1989; Radwan et al.,1991; Hirayasu et al., 1998). Few studies haveevaluated N400 in unmedicated patients, and theresults of these studies were inconsistent(Koyamaet al., 1991; Condray et al., 1999). Condray et al.(1999) found a reduced N400 priming effect bothin patients medicated with haloperidol, as wellunmedicated patients, but N400 latency was onlyprolonged in medicated patients. Koyama et al.(1991) found that unmedicated patients showedno reduction in N400 to either congruent or incon-gruent words, but did show prolonged latency ofN400.The purpose of the present study was to evaluate

N400 amplitude, latency and topography elicitedduring a lexical decision task in patients withschizophrenia who were not receiving anti-psy-chotic medication. The P200 component whichprecedes the N400 component, and the late posi-tive component(LPC) which follows the N400component were also evaluated.

2. Methods and materials

2.1. Subjects

Eighteen patients with schizophrenia were test-ed. All but 1 were outpatients. Patients had beenfree from anti-psychotic medication for at least 1month at the time of ERP recordings, and all metthe DSM-III-R criteria for schizophrenia(Ameri-can Psychiatric Association, 1987). Clinical symp-toms were evaluated using the Brief PsychiatricRating Scale(BPRS; Overall and Gorham, 1980).Eighteen healthy subjects were used as a compar-ison group. Group characteristics are shown in

3H. Hokama et al. / International Journal of Psychophysiology 48 (2003) 1–10

Table 1Background profiles of schizophrenic group and control group

Schizophrenic Controlgroup group

Cases 18 18Age (years) 28.9"8.0 25.2"4.4Maleyfemale 9y9 9y9Handedness Right, 18 Right, 18BPRS 36.2"11.6 –

SubtypesParanoid 12 –Undifferentiated 4 –Catatonic 1 –Disorganized 1 –

Illness duration(years) 7.3"3.2 –

Table 1. The groups did not differ in age or gendercomposition. All subjects were right-handed(Edin-burgh Handedness Inventory, Oldfield, 1971) andfree of known neurological diseases, and alcoholand drug abuse. Informed consent had beenobtained from each individual subject before ERPtest.

2.2. Procedure

ERPs were recorded during a lexical decisiontask. In each trial, S1(a word) and S2(a word ornon-word) were presented. Subjects were requiredto determine whether the S2 was a word or non-word. Three types of S1–S2 pairs were presentedwith equal probability:(1) S2 as the antonym orantithesis of S1(‘related word’ condition), (2) S2as semantically unrelated to S1(‘unrelated word’condition), and(3) S2 as a non-word(‘non-word’condition) (Table 2).

The two response categories of wordynon-wordthus had respective probabilities of 0.67 and 0.33.The S1 words selected for the related word con-dition were also used for the unrelated word andnon-word conditions. All the S1–S2 pairs werepresented twice. Six blocks of 30 trials were usedfor each subject. Within each block the three typesof S2 were presented in random sequence. EachS1–S2 pair appeared only once within a block.Subjects were seated approximately 80 cm from avideo display in a sound attenuated room and wereinstructed to depress the ‘Yes’ key if they consid-ered S2 a word, or the ‘No’ key if they consideredit a non-word. Both the left and right hand wereused to make responses in each subject and coun-terbalanced across conditions. The middle andindex fingers were used to make responses. Thesubjects were also requested to minimize eyeblinks.Each trial consisted of the following sequence

of events:(1) A warning stimulus consisting of a5=12 cm rectangle was presented for 500 ms the2

center of the video display,(2) after the warningstimulus, S1 was exposed in the center of therectangle for 500 ms,(3) after a 1000 ms blankinterval, S2 was presented until a response wasmade. The maximum duration of each S2 presen-tation was 1500 ms. Responses later than 3000 msfollowing S2 were rejected from the averaging andclassified as ‘no response’. Stimuli were presentedat a visual angle of 1.98 vertically and 4.68 hori-zontally. ERPs were recorded after 60 practicetrials which differed from those words used in theERP recording session. Subjects were retested forapproximately 5 min between blocks.

4 H. Hokama et al. / International Journal of Psychophysiology 48 (2003) 1–10

2.3. ERPs recording

The EEG was recorded from 17 scalp sites(Fp , Fp , F , F , Fz, F , F , C , Cz, C , T , P ,1 2 7 3 4 8 3 4 5 3

Pz, P , T , O , O ; 10y20 system) using AgyAgCl4 6 1 2

electrodes. Eye movements were monitored froman electrode placed at the left supraorbital ridge.All the electrodes were referred to linked earlobes(impedances(5 kV). EEG was recorded from200 ms prior to the warning stimulus to 1000 msafter the presentation of S2. The EEG was digitizedon-line at 100 samplesys in each channel with aband pass of 0.16–30 Hz, and stored for lateranalysis with a microcomputer(NEC-SANEI,7T18). Trials in which the EOG deflection exceed-ed "100 mV and trials in which there was anerror response or a response omission(includingresponses longer than 3000 ms) were excludedfrom ERP averaging. Eighteen percent of the trialshad to be excluded for patients and 8% for controlssubjects, primarily because of EOG artifact.

2.4. Data analysis

The peak amplitude and latency of the ERPcomponents elicited by S2 were measured withrespect to the 400-ms pre-S2 baseline. P200 wasmeasured at the maximum positive voltage in thelatency range of 140–320 ms in order to assessearly perceptual and cognitive processes elicitedby S2. N350 was measured at the maximumnegative voltage in the latency range of 200–480ms. LPC was measured at the maximum positivevoltage in the latency range of 350–800 ms. Toassess the difference of the priming effect on N350between the two groups in more detail, the meanamplitudes(300–500 ms) of the difference waves(unrelated wordyrelated word, non-wordyrelatedword) were obtained. These difference measuresare referred to as N400 effects.The ERP data were assessed by a three-way

ANOVA {Group=(patient, control)=Condition(related word, unrelated word, non-word)=Electrode position(Fp , Fp , F , Fz, F , F , F ,1 2 3 4 7 8

C , Cz, C , T , T , P , Pz, P , O , O)} . In order3 4 5 6 3 4 1 2

to identify the nature of interactions among factors,post hoc tests were conducted using one-wayANOVAs at a significance level ofP-0.01. In

order to control type I error, allF ratios on therepeated measures were evaluated with degrees offreedom adjusted with epsilon estimates(Jenningsand Wood, 1976).

3. Results

3.1. Behavioral performance

The patients with schizophrenia were slowerthan the control subjects in all stimulus conditions,and the difference between groups was largest inthe non-word condition. The reaction time(RT)in the related, unrelated and non-word conditionwas 791.7"147.9, 876.5"134.9 and1269.4"292.1 ms for the schizophrenic patients,and 599.7"102.9, 679.6"100.2 and 796.6"143.1ms for the normal controls, respectively. ANOVAwith repeated measures on RT revealed maineffects of group(F s36.0,P-0.001), stimulus1,34

condition (F s104.0,P-0.001) and a signifi-2,68

cant interaction group=condition (F s21.7,2,68

P-0.001).While the control subjects showed error rates of

0.6"0.7% for the related condition, 1.7"1.8% forthe unrelated condition, and 3.7"3.5% for thenon-word condition, the patients showed their cor-responding error rates of 4.1"8.1%, 6.6"7.0%and 16.7"17.0%, respectively. The main effect ofgroups and conditions were significant. Thepatients reacted less accurately for both unrelated(F s8.3, P-0.01) and non-word conditions1,34

(F s10.1, P-0.01) as compared to control1,34

subjects.

3.2. Event-related potential measures

The grand average ERPs to related, unrelatedand non-word S2, and difference waveforms at Fz,Cz, Pz, T and T are shown in Fig. 1. Inspection5 6

of ERPs waveforms suggested that a marked N400effect between related word condition and the twoother conditions began approximately 300 ms afterS2 onset, reached a maximum at approximately400 ms, and resolved at approximately 500 ms.

5H

.H

okama

etal.

/International

Journalof

Psychophysiology

48(2003)

1–10Fig. 1. The grand average ERP waveforms of control subjects and schizophrenic patients at Fz, Cz, Pz, T5 and T6.(a) The grand average waveforms elicited byrelated, unrelated and non-word conditions.(b) The grand average difference waveforms, obtained by subtracting the ERPs to related condition from the ERPs to theunrelated condition, and from the ERPs to the non-word condition. A clear separation between the related condition and two other conditions began nearly 300 msafter S2 onset, reached a maximum at about 400 ms, and resolved at approximately 500 ms. The waveform of this time epoch for either the unrelated or the non-word conditions was more negative than that for the related condition, and this difference was prominent at Pz. This negativity apparently corresponds to the N400component, which was shown more clearly in the difference waveforms. This N400 effect in the schizophrenic patients was reduced. The LPC in the 500–800 msrange was the largest at Pz, and was remarkably smaller in the patient group than in the control group for all three conditions.

6 H. Hokama et al. / International Journal of Psychophysiology 48 (2003) 1–10

Table 3Means (S.E.) of ERP measurements from 17 electrodes inschizophrenic group and control group

Schizophrenic Controlgroup group

Peak P200 amplitude (mV)Related condition 5.92(0.61) 6.89 (0.81)Unrelated condition 5.97(0.71) 6.12 (0.66)Non-word condition 5.59(0.61) 6.11 (0.52)

Peak P200 latency (ms)Related condition 230(6) 236 (7)Unrelated condition 217(5) 212 (3)Non-word condition 214(6) 209 (4)

Peak N350 amplitude (mV)Related condition 1.05(0.82) 3.20 (0.74)Unrelated condition 0.22(0.71) 1.49 (0.65)Non-word condition y0.42 (0.69) 1.19 (0.52)

Peak N350 latency (ms)Related condition 339(11) 300 (7)Unrelated condition 362(10) 330 (10)Non-word condition 366(13) 333 (9)

Peak LPC amplitude (mV)Related condition 6.89(0.83) 10.98(0.85)Unrelated condition 5.67(0.81) 11.09(0.85)Non-word condition 6.70(0.93) 10.37(0.83)

Peak LPC latency (ms)Related condition 601(21) 539 (20)Unrelated condition 643(15) 590 (17)Non-word condition 708(16) 646 (21)

Mean N400 amplitude (mV)Unrelatedyrelated y1.32 (0.42) y2.94 (0.30)Non-wordyrelated y1.82 (0.54) y3.68 (0.68)

The N350 component for both the unrelated andnon-word conditions was more negative than thatfor the related condition. This N400 effect forschizophrenic patients appeared to be reduced. TheLPC in the 500–800 ms range was largest at Pz,and appeared smaller in the patient group than inthe control group. In the difference waveforms ofunrelatedyrelated and non-wordyrelated, theN400 effect was remarkably decreased in thepatient group as compared to the control group.Means of ERP measurements from 17 electrodesin schizophrenic group and control group areshown in Table 3 and the ANOVA results areshown in Table 4.

3.2.1. P200 peak amplitude and latencyP200 amplitude and latency showed no Group

effect. The Condition effect was detected withP200 latency but not with P200 amplitude. P200latency to the related words was longer than to theunrelated and non-words. The Electrode effect wassignificant to both P200 measurements. An inter-action of Group=Electrode was detected for P200amplitude, which resulted from a lower amplitudeat O in the patients than in the controls.1

3.2.2. N350 peak amplitude and latencyN350 amplitude was more negative, and the

N350 latency was longer for the incongruouswords (the unrelated or the non-word condition)compared to the congruous words(the relatedcondition). Schizophrenic patients showed pro-longed N350 latency for all three conditions, asindicated by the main effect of group.For N350 amplitude, an Electrode=Group inter-

action was detected. N350 amplitude comparisonsat the individual electrodes using one-way ANOVAsuggested that N350 was more negative in thepatient group at T , P , Pz, P , O and O than in5 3 4 1 2

the control group. The factor of Condition alsohad an interaction with the Electrode factor, indi-cating that the N400 effect was largest at Fz, F ,4

C , Cz, C , P , Pz, P , T and T .3 4 3 4 5 6

For N350 latency, the Group=Electrode inter-action was significant, and the further comparisonat each electrodes indicated that it was particularlyprolonged in patients at F , F , Fz, F , C and Cz.7 3 8 3

An interaction of Condition=Electrode indicatedthat the peak N350 latency was particularly pro-longed at Fz, F , Cz, C , T , P , Pz, P , T , O4 4 5 3 4 6 1

and O in the unrelated and non-word conditions.2

In summary, peak N350 latency was delayed inschizophrenia. N350 amplitude was larger(morenegative) at posterior electrode sites in the patientgroup.

3.2.3. N400 effect measured from differencewaveformsFor both types of difference waveforms, N400

amplitude was decreased in schizophrenia. Differ-ence waveforms were used to isolate the N400priming effect in the 300–500 ms range. A maineffect of electrode indicated that the magnitude of

7H. Hokama et al. / International Journal of Psychophysiology 48 (2003) 1–10

Fig. 2. Topography of the N400 in the difference wave(unrelatedyrelated) in the two groups. Schizophrenics show a more reducedN400 than controls. Maxima of the negativity were seen at Pz and deviated slightly to the right hemisphere in both the controlsand schizophrenics.

the N400 effect differed among recording elec-trodes. The interaction of group with electrode wasinsignificant, suggesting a similar scalp distribu-tion of N400 between the subject groups. Thetopography of N400 in the difference waveforms(unrelated wordyrelated word) were shown Fig.2. N400 amplitude was largest at Pz, and thedistribution showed a slight right hemisphere bias.

3.2.4. LPC peak amplitude and latencyA significant group difference was found for

both LPC amplitude and LPC latency. Additionalanalyses of data separately for the related, unrelat-ed and non-word conditions showed decreasedLPC amplitude and prolonged LPC latency in thepatient group for all three stimulus conditions ascompared to the control group. The conditioneffect was evident for LPC latency, but not forLPC amplitude. For both groups, LPC latency was

longer in the incongruent conditions(unrelated ornon-word) than in the congruent condition(relatedword). A group by electrode interaction for LPCamplitude was significant. Further comparison ateach electrode revealed that the LPC amplitudedeficit in patients was largest at C , Cz, C , P , Pz3 4 3

and P .4

4. Discussion

ERP measures sensitive to semantic processingshowed pervasive abnormalities in unmedicatedpatients with schizophrenia, consistent with previ-ous ERP and behavioral evidence in this disorder.In terms of processing speed, the N350 and LPCmeasures were delayed in all conditions whileP200 remained within normal range. N350 ampli-tude was more negative at posterior sites, and LPCamplitude was reduced, to each type of word in

8 H. Hokama et al. / International Journal of Psychophysiology 48 (2003) 1–10

Table 4Summary of ANOVA results

Groups Condition Electrodes C=G E=G C=E C=E=G(G) (C) (E)

ERP waveforms in each conditiond.f. 1,34 2,68 16,544 2,68 16,544 32,1088 32,1088P200 amplitude 0.40 2.17 10.15** 1.16 2.74* 1.14 1.23P200 latency 0.05 16.73** 15.71** 1.40 1.62 1.08 1.56N350 amplitude 3.37 17.25*** 6.50*** 1.06 3.05* 2.32* 0.96N350 latency 7.53** 16.90*** 7.16*** 0.19 2.81* 3.30*** 2.03*

LPC amplitude 15.93*** 0.95 24.85*** 2.44 7.75*** 1.68 0.98LPC latency 8.50** 28.11*** 3.24** 0.07 0.53 1.51 1.34

Difference waveformsd.f. 1,34 1,34 16,544 1,34 16,544 16,544 16,544Mean amplitude 7.59** 3.52 14.64*** 0.13 1.56 0.46 2.01

P-0.05.*

P-0.01.**

P-0.001.***

schizophrenia. The N400 priming effect, whichwas measured from difference waveforms betweenconditions, was reduced in schizophrenia. Unlikethe majority of previous studies of N400 in schiz-ophrenia, the patients were unmedicated. Conse-quently, these abnormalities are unlikely to besecondary to anti-psychotic medication.Schizophrenic patients showed delayed N350

and LPC latency in three different linguistic con-ditions. Both the LPC and N400 amplitudes in thedifference waveform were reduced. Consequently,it appears that the prolongation of N400 latencyand reduction of the N400 priming effect reportedby numerous investigators in medicated patients(Adams et al., 1993; Grillon et al., 1991; Koyamaet al., 1994; Bobes et al., 1996; Olichney et al.,1997; Ohta et al., 1999) is unlikely to be due toanti-psychotic medication. The finding of pro-longed N400 latency in unmedicated patients isconsistent with a study by Koyama et al.(1991),but not with Condray et al.(1999). The reducedN400 effect in patients in the present study wasalso reported by Condray et al.(1999) in unme-dicated patients.Since N400 is thought to reflect spread of

semantic activation through semantic networks, theprolongation of this component in this and otherstudies is consistent with a slowed semantic searchprocess in schizophrenia, regardless of whether a

word is congruent or incongruent with the preced-ing context(Grillon et al., 1991; Koyama et al.,1991, 1994; Nestor et al., 1997; Niznikiewicz etal., 1997; Strandburg et al., 1997). Slowing of thisprocess may contribute to the slowing of RTobserved in lexical decision tasks in schizophrenia(Koyama et al., 1994). Most studies of N400 havefocused on the priming effect or differencebetween the N400 amplitude to related and unre-lated words. We also evaluated peak N350 towords and non-words in each condition of thisstudy, and found that N350 amplitude to thesestimuli was larger(more negative) at posteriorelectrode sites. This finding is similar to that byNestor et al. (1997) and Niznikiewicz et al.(1997), who measured N400 to terminal words insensible and nonsensical sentences. These investi-gators suggested that N400 to words in generalmay elicit inappropriate, diffuse semantic activa-tion in schizophrenia, possibly due to increasedactivation or decreased inhibition within semanticnetworks (Nestor and O’Donnell, 1998; Spitzer,1993; Spitzer et al., 1994). This increase in N400amplitude has not been a consistent finding acrossstudies, however. Semantic hyperactivation maybe specific, as Spitzer(1993) and Spitzer et al.(1994) suggest with respect to RT studies, topatients with marked thought disorder.

9H. Hokama et al. / International Journal of Psychophysiology 48 (2003) 1–10

The N400 priming effect was measured fromthe voltage values in the difference waveforms.The N400 priming effect in the schizophrenicpatients was reduced for both the unrelatedyrelated waveforms and the non-wordyrelatedwaveforms. A decreased N400 priming effect hasbeen consistently reported in the schizophrenicpatients, especially when they were asked to judgethe semantic relatedness of the stimuli(Grillon etal., 1991; Mitchell et al., 1991; McCarley et al.,1991; Olichney et al., 1997; Ohta et al., 1999).This abnormality in schizophrenic patients mayindicate a lack of differential processing betweenthe associated and the unassociated words, and isconsistent with the hypothesis that schizophrenicpatients may experience a pattern of indiscriminateactivation in their semantic network, with weak-ened influence of prior context.LPC was reduced in amplitude in schizophrenia,

and prolonged in latency. LPC amplitude reduction(Grillon et al., 1991; Niznikiewicz et al., 1997;Strandburg et al., 1997) and latency prolongation(Grillon et al., 1991; Niznikiewicz et al., 1997)have also been reported in medicated patients withschizophrenia. The functional significance of theLPC component is still unclear, but it may indexsyntactic rather than semantic anomalies, or theoperation of attentional mechanisms not specificto language(Kutas and Van Petten, 1994; Oster-hout et al., 1997). The priming effect had alsobeen detected with the LPC component by someresearchers(for instance, Andrews et al., 1993;Ohta et al., 1999). In those studies, LPC compo-nent was found inversely larger to the incongruentstimuli than to the congruent stimuli. This is notthe case in this study as well as in our previousstudies, possibly due to the characteristics of thelexical decision task we used.In conclusion, these findings suggest that schizo-

phrenic patients show marked slowing of neuralprocessing of linguistic stimuli in the unmedicatedstate. The reduced N400 priming effect is consis-tent with a reduction in contextually appropriateactivation within semantic networks. Further inves-tigation of the N400 abnormality in various sub-types of schizophrenia is necessary to clarify theneural substrates of language related symptoms ofschizophrenia as well as follow up study of the

patients for the assessment of medication effect onN400.

Acknowledgments

The authors sincerely thank Makoto MiyataniPh.D.(Department of Psychology, Faculty of Edu-cation, Hiroshima University, Japan), SachikoKoyama Ph.D.(Department of Integrative Physi-ology, National Institute for Physiological Sci-ences, Japan), Yasuhiro Nageishi Ph.D.(the Centerof Teaching Professor, Asahi University, Gifu,Japan) and Simokochi Minoru Ph.D.(Departmentof Human Science, Osaka University, Osaka,Japan) for their kind guidance and support for theresearch.

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