7
~ Pergamon PII: S0028 3932(97)00087-0 Neuropsychologia, Vol. 35, No. 12, pp. 1519-1525, 1997 ~'i~ 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0028 3932/97 $17.00+0.00 Lateralized attentional deficits in drug-free and medicated schizophrenic patients SHARON B. WIGAL, *+ JAMES M. SWANSON* and STEVEN G. POTKINt *Department of Pediatrics, University of California, Irvine, CA 92612-2418, U.S.A.; tDepartment of Psychiatry, University of California, lrvine, CA 92612-2418, U.S.A. (Received 9 March 1997; accepted 28 May 1997) Abstract--Performance on a cued reaction time (RT) task, theoretically linked to posterior and anterior neuroanatomical systems in the brain (Posner, M. I. et al., Science, 1988, 210, 1627-1631; Archives qJGeneral Psychiatry, 1988, 15, 811 821), was used to assess sensory orienting and maintenance of attention. In schizophrenic patients, Posner et al. found a lateralized abnormality in RT (longer RTs to uncued targets in the right visual field than in the left visual field), as did Maruff et al. (Neuropsychologia, 1995, 33, 1205-1223), but Strauss et al. (Journal of Psychiatric Research, 1991, 37, 139-146), among others, did not replicate this effect. However, the subjects in these studies differed in the percentage of schizophrenic patients taking neuroleptic medication at the time of testing and in the chronicity of the illness. In the present study, we used two groups of schizophrenic subjects to control for the use of neuroleptic medication. The lateralized abnormality in RT was observed in the drug-free group of schizophrenic subjects, but not in the group of drug-treated schizophrenic subjects. © 1997 Elsevier Science Ltd. All rights reserved Key Words: attention; schizophrenia; lateralized effect; neuroleptics; reaction time (RT) task. Introduction Attentional deficits in schizophrenic patients were first suggested by Bleuler [2], who viewed 'passive' or auto- matic attentional processes as defective in schizophrenic subjects. Recently, neuroanatomical network theories of visual-spatial attention have been developed. Posner et al. [17, 18] described two distinct but linked attentional systems: a posterior system, dealing with sensory arousal and automatic processing; and an anterior system, deal- ing with motor activation and effortful processing. In this theory, both the parietal lobe (as part of the posterior attentional system) and the frontal lobe (as part of the anterior attentional system) are important in the direction and maintenance of visual-spatial attention. Posner et al. [18] developed a cued reaction time (RT) task in which the detection of an asterisk presented in the periphery was required at specific time intervals (100 and 800 msec) after the presentation of valid and invalid vis- ual-spatial cues (the brightening of a target box). The task was used to study abnormal lateral RT differences manifested by neurological patient groups selected on the +Address for correspondence: Department of Pediatrics, Child Development Center, University of California, Irvine, 19722 MacArthur Blvd., lrvine, CA 92612-2418, U.S.A. basis of specific brain injury. (A refined description of the series of studies on these patient groups is provided by Petry et al. [15], Posner et al. [17] and Swanson et al. [27].) Although patients with right parietal as well as left parietal lesions showed slower responding to trials on the contralateral side, the neurological group with left parietal lesions manifested a specific lateralized abnor- mality in performance of note. One way to describe this RT pattern emphasizes covert shifts of attention after short (100msec) cue-target intervals, which produced larger validity effects (the difference in RT after valid and invalid cues) for responses to right visual field (RVF) targets than for responses to left visual field (LVF) targets. In other words, the tendency to respond more quickly to valid than invalid trials was lateralized. Posner et al. [18] found that a psychiatric group of schizophrenic subjects showed the same pattern of performance as the neurological group of left parietal subjects on the covert visual-spatial attention tasks (i.e. after short cue-target intervals, an abnormal lateral difference in RT following invalid cues, which resulted in a larger validity effect for RVF than LVF targets). Three additional reports which replicate some of these lateralized findings in patients with schizophrenia are those by Carter et al. [6], Maruff et al. [12] and Potkin et al. [19], but the specifics differ about which visual field or hemisphere is affected. 1519

Lateralized attentional deficits in drug-free and medicated schizophrenic patients

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~ Pergamon PII: S0028 3932(97)00087-0

Neuropsychologia, Vol. 35, No. 12, pp. 1519-1525, 1997 ~'i~ 1997 Elsevier Science Ltd. All rights reserved

Printed in Great Britain 0028 3932/97 $17.00+0.00

Lateralized attentional deficits in drug-free and medicated schizophrenic patients

SHARON B. WIGAL, *+ JAMES M. SWANSON* and STEVEN G. P O T K I N t

*Department of Pediatrics, University of California, Irvine, CA 92612-2418, U.S.A.; tDepartment of Psychiatry, University of California, lrvine, CA 92612-2418, U.S.A.

(Received 9 March 1997; accepted 28 May 1997)

Abstract--Performance on a cued reaction time (RT) task, theoretically linked to posterior and anterior neuroanatomical systems in the brain (Posner, M. I. et al., Science, 1988, 210, 1627-1631; Archives qJGeneral Psychiatry, 1988, 15, 811 821), was used to assess sensory orienting and maintenance of attention. In schizophrenic patients, Posner et al. found a lateralized abnormality in RT (longer RTs to uncued targets in the right visual field than in the left visual field), as did Maruff et al. (Neuropsychologia, 1995, 33, 1205-1223), but Strauss et al. (Journal o f Psychiatric Research, 1991, 37, 139-146), among others, did not replicate this effect. However, the subjects in these studies differed in the percentage of schizophrenic patients taking neuroleptic medication at the time of testing and in the chronicity of the illness. In the present study, we used two groups of schizophrenic subjects to control for the use of neuroleptic medication. The lateralized abnormality in RT was observed in the drug-free group of schizophrenic subjects, but not in the group of drug-treated schizophrenic subjects. © 1997 Elsevier Science Ltd. All rights reserved

Key Words: attention; schizophrenia; lateralized effect; neuroleptics; reaction time (RT) task.

Introduction

Attentional deficits in schizophrenic patients were first suggested by Bleuler [2], who viewed 'passive' or auto- matic attentional processes as defective in schizophrenic subjects. Recently, neuroanatomical network theories of visual-spatial attention have been developed. Posner et

al. [17, 18] described two distinct but linked attentional systems: a posterior system, dealing with sensory arousal and automatic processing; and an anterior system, deal- ing with motor activation and effortful processing. In this theory, both the parietal lobe (as part of the posterior attentional system) and the frontal lobe (as part of the anterior attentional system) are important in the direction and maintenance of visual-spatial attention.

Posner et al. [18] developed a cued reaction time (RT) task in which the detection of an asterisk presented in the periphery was required at specific time intervals (100 and 800 msec) after the presentation of valid and invalid vis- ual-spatial cues (the brightening of a target box). The task was used to study abnormal lateral RT differences manifested by neurological patient groups selected on the

+Address for correspondence: Department of Pediatrics, Child Development Center, University of California, Irvine, 19722 MacArthur Blvd., lrvine, CA 92612-2418, U.S.A.

basis of specific brain injury. (A refined description of the series of studies on these patient groups is provided by Petry et al. [15], Posner et al. [17] and Swanson et al.

[27].) Although patients with right parietal as well as left parietal lesions showed slower responding to trials on the contralateral side, the neurological group with left parietal lesions manifested a specific lateralized abnor- mality in performance of note. One way to describe this RT pattern emphasizes covert shifts of attention after short (100msec) cue-target intervals, which produced larger validity effects (the difference in RT after valid and invalid cues) for responses to right visual field (RVF) targets than for responses to left visual field (LVF) targets. In other words, the tendency to respond more quickly to valid than invalid trials was lateralized. Posner et al. [18] found that a psychiatric group of schizophrenic subjects showed the same pattern of performance as the neurological group of left parietal subjects on the covert visual-spatial attention tasks (i.e. after short cue-target intervals, an abnormal lateral difference in RT following invalid cues, which resulted in a larger validity effect for RVF than LVF targets). Three additional reports which replicate some of these lateralized findings in patients with schizophrenia are those by Carter et al. [6], Maruff et al. [12] and Potkin et al. [19], but the specifics differ about which visual field or hemisphere is affected.

1519

1520 S.B. Wigal et al./Lateralized deficits in schizophrenic patients

Strauss et al. [24] examined neuroleptic-treated schizo- phrenic patients who were in remission and claimed not to replicate the Posner effect. However, they investigated a group of schizophrenic subjects, all of whom were being treated with neuroleptics, and they did not match the percentage of schizophrenic subjects in the Posner et al.

[18] study who were no t being treated (one fourth) at the time of testing. Likewise, a number of other studies

described a l ack of asymmetric findings to covert ori- enting in schizophrenic patients who were chronic or remitted [10, 11, 14, 25]. Carter et al. [5], Coppola et al.

[8], Muller et al. [13], Posner et al. [16] and Rafal et al.

[20] also contr ibute to the lack of consensus related to medicat ion status and chronici ty of illness. The present study at tempted to evaluate the difference in subject characteristics represented by the Strauss et al. and Posner et al. studies by investigating two groups of schizophrenic subjects on performance on the covert ori- enting RT task.

Methods

An IBM-compatible computer programmed with the MEL language [21, 26] was employed for the visual-spatial cued RT task used by Posner et al. [18]. Subjects were instructed to keep their eyes fixated on a central cross. Two boxes were presented on the screen 5 ° to the right and to the left of the cross, and this display remained on for the entire experiment. A simple stimulus (an asterisk) was presented as a target, which required a motor response. On some trials, one of the boxes was brigh- tened to present a cue at a specific time (i.e. either 100 or 800msec) before the target. A simple detection response was required. On each trial, subjects made the same response by pressing the space bar on the computer keyboard with the index finger of the dominant hand when the target stimulus (which was always an asterisk) was presented. RT was measured from the onset of the target to the onset of the key press. An error was recorded if RT was less than 100 msec (which was assumed to be an anticipation error or false alarm) or if no RT occurred after the target presentation (which was assumed to be a sen- sitivity error or miss). After the response, the fixation cross and the target (but not the two boxes) disappeared from the screen, with an intertrial interval of 1000 msec.

Posner et al. [18] used three blocks of 240 trials, with "...four breaks within each block and substantial breaks between each block" (p. 816). In our preliminary attempts to faithfully rep- licate the covert orienting task [30] of Posner et al. [18], we found this to be complicated because it resulted in a session that was too long (even with multiple breaks) or excessively boring (due to the vigilance effect in a long series of detection trials). To overcome this methodological limitation, we used five blocks of 60 trials for a total of 300 trials. The three types of cues (null, valid and invalid) occurred randomly within a block of trials. On 16.7% of the trials, the target appeared without a cue (brightening of the square). This is called the null cue condition, and on these trials, the target was presented 1100 or 1800 msec after the previous response. On 83.3% of the trials, a cue occurred either 100 or 800msec before the target was presented. Two types of cues were used: valid and invalid. On the valid cue trials (80% of the cued trials), the target was presented in the square that was brightened before the target was presented. On the invalid cue trials (20% of the cued trials), the target was presented in the uncued square. In each case, the

Time I ' l ~eC

RVF Tar,qet

Valid Cue Invalid Cue

Left Right

o I 1 + 1 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

'° m + l I

Fig. 1. Cue and delay conditions for right visual field targets.

target remained on until the subject made a key press response. If a response was not made before 3 sec elapsed, the trial was terminated.

Half of the targets were presented in the RVF (see Fig. 1) and half in the LVF (see Fig. 2). It should be noted that by replicating Posner et al., we used a null condition on which neither a temporal warning nor a spatial cue was provided, while in the valid and invalid conditions a temporal warning as well as a spatial cue was provided.

Subjects

Twelve normal control subjects and 24 schizophrenic patients (12 on typical neuroleptic medication and 12 drug free for at least 5 days) were the subjects for this study. The patients were referrals to the psychiatry service at the University of California at Irvine Medical Center (UCI-MC). The schizophrenic groups and normal control group were approximately matched for age and sex. Demographic and clinical information on the groups is presented in Table 1. All subjects gave informed consent to participate after the nature of the procedure was fully explained.

Patients were interviewed with the Structured Clinical Inter- view for DSM-III-R (SCID), which is tailored to a DSM-III-R [1] diagnosis. A reliability check of these diagnoses was per- formed by a research psychiatrist. Schizophrenic patients had at least a 1-year history of illness. Only those patients identified as having schizophrenia with no other major medical illness were included in the study. The majority of the drug-free schizo-

LVF Tar,qet

"[1me

Valid Cue Invalid Cue

Left" Right

0 +lJ I I + f l

'° f

Fig. 2. Cue and delay conditions for left visual field targets.

S. B. Wigal et al./Lateralized deficits in schizophrenic patients 1521

Table 1. Sample characteristics of schizophrenic patients and controls

Subjects

Medicated Drug-free Normal patients patients controls (n = 12) (n = 12) (n = 12)

Sex Males 11 9 7 Females 1 3 5

Age (years) Mean 32.6 31.2 31.7 Range 18-40 18-42 18-49

Education (years) Mean 12.9 11.5 14.75 Range 9-16 10-14 12 20

Age of first hospitalization (years) Mean 20.8 23.7 - - Range 13-27 15-38 - -

Duration of illness (years) Mean 13.7 12.2 - - Range 2-28 1.5-20

Diagnostic classification Paranoid 9 10 - - Undifferentiated 3 2 - -

Score on modified Brief Psychiatric Rating Scale (BPRS) Mean 22.1 27.4 - - Range 8-38 9 39 - -

phrenic patients were admitted as inpatients to a Research Unit at UCI-MC following an acute exacerbation of symptoms. In most cases, these subjects had stopped their neuroleptics several days prior to admission. No schizophrenic subject identified as chronically neuroleptic treatment-resistant was included in the present study in order to avoid masking or distortion of medi- cation effects [23]. A number of patients tested did not meet diagnostic criteria (see Table 2) and their data were not included in this study.

Table 3. Mean reaction time for the experimental conditions

Condition Group

Delay Normal Df Sz Med Sz (msec) Cue VF (msec) (msec) (msec)

100 V L 398 518 510 100 V R 393 506 510 100 I L 440 526 606 100 I R 444 580 579 100 N L 418 554 545 100 N R 416 501 570 800 V L 352 466 485 800 V R 338 477 479 800 I L 373 513 493 800 I R 373 480 546 800 N L 350 467 499 800 N R 355 524 465

VF, visual field; Df Sz, drug-free schizophrenic Sz, medicated schizophrenic subjects; V, valid; null.

subjects; Med I, invalid; N,

and norma l control] as a between-subject factor and three wi thin-subject factors (cue, visual field and delay). The mean RT for the 12 condi t ions defined by the levels of delay, cue and visual field are presented in Table 3 separa te ly for the normal , D f Sz and Med Sz groups. The s t anda rd errors of the mean for the 12 condi t ions defined by the levels of delay, cue and visual field are presented in Table 4 separa te ly for the normal , D f Sz and M e d Sz groups. The RT da t a are presented in Figs 3 and 4.

Both D f Sz and M e d Sz subjects ( m e a n = 5 0 9 and 524 msec, respectively) d i sp layed slower overal l RTs than con t ro l subjects (mean = 388 msec), as revealed by a sig- nificant main effect of g roup [F(2,33) = 4.22, P < 0.0234]. A mul t ip le compar i sons test (Scheffe) indica ted that Med Sz subjects differed f rom the cont ro l g roup ( P < 0 . 0 5 ) ,

Results Table 4. Standard errors of the mean (S.E.M.) for mean reaction

time for the experimental conditions

A four -way analysis o f var iance ( A N O V A ) was per- fo rmed using g roup [drug-free schizophrenic (Dr Sz), typical neuro lep t ic -medica ted schizophrenic (Med Sz)

Condition Group

Delay Normal Df Sz Med Sz (msec) Cue VF (msec) (msec) (msec)

Table 2. Screening of patients for testing on Posner paradigm

Number of Exclusion factors patients

Experimental medication 34 Medications other than neuroleptics 1 Diagnosis other than schizophrenic 35 Treatment resistant chronic schizophrenic patients 2 Repeat patients 23 Short washout period (less than 5 days) 6 Other miscellaneous exclusion factors 26

Total 112

100 V L 12.17 45.86 52.02 100 V R 11.03 48.31 49.19 100 I L 14.64 36.28 50.44 100 I R 13.11 75.95 53.33 100 N L 11.52 47.60 50.95 100 N R 8.74 35.69 57.73 800 V L 11.17 29.95 35.94 800 V R 7.55 42.68 33.44 800 I L 12.48 62.62 38.37 800 I R 18.63 51.35 52.81 800 N L 13.82 33.38 45.86 800 N R 11.56 56.22 34.49

VF, visual field; Df Sz, drug-free schizophrenic Sz, medicated schizophrenic subjects; V, valid; null.

subjects; Med I, invalid; N,

1522 S. B. Wigal et al./Lateralized deficits in schizophrenic patients

¢.j7~ m ~J

0

100 msec Dela~¢ Condition Target

Sdd~opb~e~s Scblzopl~m~ (n.12) ~ (n-12)

Nom~Rs (n-12)

Cue Condition

Fig. 3. Mean reaction times for drug-free schizophrenic subjects, normal subjects and typical neuroleptic schizophrenic

subjects at the 100-msec delay.

QJ

~0~ 0

800 msec Delay Condition Target

Dmg.Froe Typical NemJlep~ Sci~ophce~ Sclds~tcea~

(nffil2) ~ (n-12)

Non~ (n*12)

Cue Condition

Fig. 4. Mean reaction times for drug-free schizophrenic subjects, normal subjects and typical neuroleptic schizophrenic

subjects at the 800-msec delay.

In the covert orienting task, the normal pattern of RTs is characterized by a significant 'validity effect' (defined by the difference in RT to stimuli presented after invalid and valid cues) which is equal in size for LVF and RVF presentations of stimuli. For the 100-msec cue-target delay, significant validity effects were manifested by the normal subjects and the Med Sz subjects for targets in both visual fields: as expected, RTs were faster after valid than invalid cues. A significant validity effect was present for the Df Sz group, but only for responses to targets in the RVF. As shown in Fig. 5, for the LVF, the validity effect for the Df Sz group (8 msec) was not significantly different from zero and was significantly smaller than the validity effect for both normal (43msec) and Med Sz (95 msec). Based on planned comparisons derived from the Posner et al. [18] study, we tested the size of the six validity effects from the 100-msec cue target interval for the three groups (Df Sz, Med Sz and normal) and two visual fields (LVF and RVF). The group difference in validity effect for responses to LVF targets was significant (P < 0.05), but there were no statistical differences among validity effects across groups for response to targets in the RVF. Therefore, all groups displayed a validity effect in all conditions, except for the unmedicated schizo- phrenic subjects' responses to targets presented in the LVF.

In an analysis of simple effects of data for the 800-msec delay condition, the cue x visual field x group interaction was significant [F(4,66)= 3.89, P < 0.0068]. This was due to a lateral difference in the validity effect for the Med Sz group, but no other group (see Fig. 6).

Discussion

Non-lateralized differences

but the two schizophrenic groups did not differ from one another (P<0.8). The 800-msec delay resulted in RTs faster than the 100-msec delay condition (by about 55msec), and the statistical significance of this was verified in the ANOVA by a main effect of delay [F(1,33) = 44.48, P<0.00001].

The presentation of a valid cue resulted in RTs faster than an invalid cue (by about 43 msec) or a null cue (by about 19 msec), which resulted in a significant main effect of cue [F(2,66)=21.23, P<0.00001]. A multiple com- parisons test indicated that the valid cue was faster than the invalid cue condition ( P < 0.00001) and the null cue condition (P < 0.0001).

After invalid cues and a 100-msec delay, response to RVF targets was slower than to LVF targets for Df Sz subjects (580, 526 msec), but not for normal controls (444, 440 msec) or Med Sz subjects (579, 606 msec). This was statistically confirmed by a significant delay x c u e x visual field xgroup interaction [F(4,66)=3.34, P < 0.0222J. The variability was greater for schizophrenic subjects than normal controls, as expected (see Table 4).

Both Med Sz and Df Sz subjects exhibited an overall slower RT than the normal control group. This finding is consistent with others (e.g., [12, 18]) and confirms general psychomotor slowing associated with the disorder. As

.~ 80 m

6 0 - -

5 0 ~

30 m

e~ 20--

10--

0

Validity Effect for 100 msec Delay (Invalid - Valid RTs)

m l~dt Virtual Fiekl

~ - - ~ mgld Visual Fu~ld

{

{

S c h i z o p ~ (n~12)

D i a g n o s i s

Fig. 5. Validity effects at the 100-msec delay condition.

S. B. Wigal et al./Lateralized deficits in schizophrenic patients 1523

Validity Effect for 800 msec Delay (Invalid - Valid RTs)

~ Leh V~ual F~Id

I I

Diagnosis Fig. 6. Validity effects at the 800-msec delay condition.

noted earlier and shown in Table 4, schizophrenic subjects, regardless of medication condition, displayed greater heterogeneity in responses than normal control subjects. This was expected due to variability in symptom severity and in neuroleptic response at testing. However, a general pattern was evident across each of the three groups: the least variability was evident to valid cues followed by null cues and then, lastly, invalid cues.

There was no overall laterality effect, but the main effect of visual field did interact with delay and group. The normal pattern (the lack of a lateral difference in RT for responses to stimuli) at both the 100- and 800-msec delays was confined to the control group, but lateral differences were significant for the Df Sz (at the 100-msec delay) and the Med Sz (at the 800-msec delay) groups, and this pattern of RTs would equal the significant inter- action. Thus, a significant lateral difference on the detec- tion task may be interpreted as an abnormality in RT performance.

Lateralized differences

Sensory orienting. The response pattern after the 100- msec cue target interval serves as an indicator of the covert sensory orienting response to the cue in the visual- spatial detection task developed by Posner and colleagues [27]. Posner et al. [18] reported an abnormal lateral RT difference which suggested a defect in schizophrenic sub- jects for this covert process of shifting attention. The present study replicates the abnormal lateral RT effect reported in the Posner et al. [18] study and in our earlier work [19], but only for the Df Sz patients. This abnor- mality may reflect an asymmetric attentional disorder related to inefficient processing of cues in the LVF or target stimuli in the RVF when attention is misdirected to another location. Posner et al. [18] interpreted this pattern of performance at 100msec as a reflection of schizophrenic subjects having difficulty in disengaging attention when it was directed to the LVF, resulting in their being "slow in processing right visual field targets"

(p. 820). However, in both Posner et al.'s [18] study and the present study, Df Sz patients demonstrate a validity effect for RVF targets of the same magnitude as normal controls. The abnormality seems to be manifested in response to LVF targets, resulting in a validity effect that is abnormal because it is flat. Based on this interpretation of validity effects, we propose an alternative interpret- ation of the lateral difference. Drug-free schizophrenics may not respond normally to RVF cues, and thus may not perform a covert shift of visual-spatial attention to the right. As a result, there is no delay in processing LVF targets when they occur in the field opposite to the cue. Maruff et al. [12] also adopt this type of interpretation based on our presentations of these findings [29].

Neuroleptic medication normalized the abnormal lat- erality effect by increasing the validity effect for LVF targets (see Fig. 3). Thus, our findings suggest that neu- roleptic medication may normalize the early covert ori- enting response of schizophrenic subjects. The Posner et al. [18] study was not designed to evaluate the neuroleptic effect, but a post-hoc comparison was performed. The lack of a medication effect in the Posner et al. [18] study may be associated with the use of first-episode rather than chronic schizophrenic subjects or the dose or clinical effectiveness of the medication regime in use. Posner et aL [18] mentioned hallucinatory behavior of their patients during testing. A more clinically effective dosage of medi- cation may have been used in our study, as we did not observe hallucinatory behavior or other positive symp- toms during testing of subjects on medication. Strauss et al. [24] similarly did not observe lateralized RT findings in Med Sz patients. We did observe a significant effect of neuroleptic treatment on the validity effect, but since the medication effect is a between-subjects comparison, we cannot conclude that typical neuroleptic medication 'restored' the validity effect at 100msec. However, the normal pattern of RT indicating efficient processing of cues in both visual fields is present in the Med Sz subjects but not in the Df Sz subjects. Maruff et al. [12], using a between-subjects design, reported a similar finding of attentional asymmetries at 150msec as compared to medicated schizophrenic subjects. Thus, the stimulus onset asynchrony (SOA), or the time interval between the onset of the cue and target of 100 msec in the present study, resulted in similar findings to a SOA of 150 msec in their study. They additionally used a within-subjects design and did not see a normalization of attentional asymmetries when ld~21 days of neuroleptic medication reduced positive symptoms.

Maintenance o f attention. In the 800-msec cue-target interval condition, the validity effect for normal subjects, as well as both groups of schizophrenic subjects, decreased relative to the 100-msec cue-target interval condition. This decrease of the validity effect with time has been attributed to a dynamic covert attentional pro- cess which is maximal at 100 msec, and dissipates or less of an effort is made to maintain the covert attentional shift. Even though smaller than at 100 msec, the validity

1524 S.B. Wigal et al./Lateralized deficits in schizophrenic patients

effect is still symmetric and significant in the normal subjects. There were no statistical differences in laterality or validity between normal control subjects and Df Sz subjects at 800 msec. However, Med Sz subjects did show an abnormal laterality effect, due to a larger validity effect for the RVF target than the LVF target. Neuroleptic medication may correct one abnormality (at the 100-msec delay), but creates another abnormality (at the 800-msec delay). Another interpretation may be that, rather than medication 'creating' the 800-msec effect, voluntary ori- enting is responsible for this deficit, and neuroleptic medi- cation causes a slowing effect. In the Med Sz group, there was no cost associated with the RVF invalid cue, since the response to the LVF target was not different following invalid and valid cues. Strauss et al. [24] did not report their findings at 800msec, and Maruff et al. [12] only examined subjects at intervals of 150 and 550msec, so a comparison between SOA of our data and either of theirs is precluded, although a similar pattern of results would be expected.

Dopamine is thought to be lateralized in human brain tissue [29], with a greater concentration in the left than in the right hemisphere, and this has led to the prediction that dopaminergic agents may produce subtle lateral differences [7]. This lateralization was clearly dem- onstrated in the globus pallidus in cerebral blood flow studies [9]. Our data support this hypothesis, although they do not directly test it. An innate dopamine excess or a failure of dopaminergic regulation in schizophrenia (e.g., [3, 4]) may account for the specific abnormal RT performance in Df Sz subjects as compared to neu- roleptic-treated schizophrenic subjects.

A limitation of the present study is the failure to include measurements of eye movements of subjects related to these findings. However, Maruff et al. [12] reported simi- lar findings of RVF asymmetries in unmedicated schizo- phrenic patients who were neuroleptic-free for at least 1 month, and these investigators included analyses of eye movement data. They recorded eye movements with high resolution infrared oculography while subjects' heads were stabilized in a chin rest. Latency and accuracy of visually guided reflexive saccades were measured. No sig- nificant correlations were found between anti-saccadic error rate and the latency and number of catch-up sac- cades during smooth pursuit and the symmetry ratios of cueing conditions at delays of both 150 and 550msec. Therefore, they reported no relationship between non- lateralized eye movement abnormalities and covert atten- tional impairment.

In conclusion, neuroleptic medication appeared to nor- malize a lateralized sensory orienting attentional deficit in schizophrenic patients at the short cue-target interval of 100msec, while 'creating' a lateralized attentional deficit in these same subjects at a longer cue-target inter- val of 800 msec. However, the marked similarity between the drug-free subjects at 100 msec and the medicated sub- jects at 800 msec suggests that voluntary orienting may cause this deficit, and it is slowed by neuroleptic medi-

cation. This is in line with previous reports of neuroleptic drugs on attentional asymmetries (e.g., [28]). Future work related to the attentional deficits of schizophrenic patients should address other types of antipsychotic medications for specific dopaminergic receptor subtypes or other neurotransmitter systems (e.g., serotonin) whose alter- ations have also been implicated.

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