Increased

Distractibility in Schizophrenic Patients Electrophysiologic Christian Grillon,

and Behavioral Evidence

PhD; Eric Courchesne, PhD; Rezvan Ameli, PhD; Mark A. Geyer, PhD; David L. Braff, MD

\s=b\ The inability of schizophrenics to filter irrelevant information has often been implicated in the psychopathology of schizophrenia. Despite numerous attempts at characterizing the behavior of schizophrenics in the presence of distractors, evidence of increased distractibility has been equivocal due to the difficulty of assessing simultaneously the behavioral and neurophysiological effects of distracting stimuli. We report the results of an experiment in which event-related potential and performance measures were used to assess distractibility during reaction time tasks under different distracting conditions. The results supported the view of an increased distractibility in schizophrenic patients. Event-related potential data suggested that in schizophrenic patients, a reduced amount of processing resources is allocated to process external stimuli and attention is abnormally apportioned to task-irrelevant vs task-relevant stimuli. (Arch Gen Psychiatry. 1990;47:171-179)

in attention and information have fre¬ been in an to understand the of Relevant theories have often emphasized the schizophrenics' inability to filter or "gate" irrelevant information.3,4 Conceptually, such a defect leads to trivial stimuli inundating schizophrenic patients, causing information overload and cognitive fragmentation.16,6 Consistent with the gating deficit theory is the prediction that schizophrenic patients should show increased distractibility due to their impaired ability to screen out irrelevant stimuli. Our understanding of the capacity of schizophrenic patients to process relevant information when irrelevant information is simultaneously presented has been advanced by a series of studies. These studies, which explore performance on distrac¬ tion-laden tasks, have usually confirmed that schizophrenics are vulnerable to distraction.7"11 This vulnerability is particu¬ larly evident among severely ill, hebephrenic and chronic schizophrenic patients.8,12 It has also been noted that distracti¬ bility is pronounced in the auditory modality, where schizo¬ phrenics show maximal hallucinatory phenomena.8,12 However, in these studies, the criticism could be raised that poorer schizophrenic performance may have been due to the in-

processing quently Deficits implicated attempt psychopathology schizophrenia.1,2

Accepted for publication May 10,1989. From the Department of Psychiatry, Yale University School of Medicine, Genetic Epidemiology Research Unit, New Haven, Conn (Drs Grillon and Ameli); Departments of Neurosciences (Dr Courchesne) and Psychiatry (Drs Geyer and Braff), School of Medicine, University of California San Diego, La Jolla; and Neuropsychology Research Laboratory, Children's Hospital Research Center, San Diego, Calif (Dr Courchesne). Reprint requests to Department of Psychiatry, Yale University School of Medicine, Genetic Epidemiology Research Unit, 40 Temple St (Lower Level), New Haven, CT 06510-3223 (Dr Grillon).

creased difficulty in the with-distractor vs the without-distractor conditions.13 In addition, monitoring performance alone does not provide information about the different man¬ ners in which subjects process relevant and irrelevant infor¬ mation. The technology now exists to examine brain activity

during information processing. Event-related potential (ERP) methods allow investigators to sample the brain physiologic activity that underlies information processing operations even in the absence of apparent behavioral responses. Among the several ERP components that have been associ¬ ated with cognitive processes is the P3 complex, which has a latency of about 300 ms after stimulus. The P3 complex is composed of multiple components, including P3b and P3a.14 P3b is a positive potential, 300 ms, largest at parietal sites; it is well known and has predictable characteristics under many task-related conditions.15,16 For example, when infrequent tar¬ get stimuli are randomly inserted into a sequence of frequent stimuli, the P3b is evoked whenever the subject detects the target stimulus." P3a is an earlier component distributed centrofrontally that is elicited by surprising and orienting stimuli, whether or not the subjects are told to attend to the stimulus.14,18"25 P3a is typically recorded in conditions where

unexpected task-irrelevant stimuli are inserted in a back¬ ground ofrelevant stimuli.26"28 P3a has been associated with the orienting response14 and with the utilization of processing resources.2"1 Our recent findings lend support to these hy¬ potheses. In normal controls, we demonstrated that the pro¬ cessing of information that immediately followed these taskirrelevant stimuli was disrupted.26 We reported that, in a reaction time experiment, the reaction times were longer when the target stimuli followed rare, unexpected task-irrele¬ vant stimuli (which elicited large P3a components) than when they followed frequent expected task-irrelevant stimuli (which did not elicit P3a components). We also reported that the more surprising the unexpected task-irrelevant stimuli, the larger the P3a components and the more delayed the reaction time to the following target stimulus. Furthermore, we found that the cognitive processing ofthe stimulus that immediately followed unexpected task-irrelevant stimuli was different from the cog¬ nitive processing of the stimulus that followed frequent ex¬ pected stimuli, as indicated by ERPs to these stimuli. We concluded that the unexpected task-irrelevant stimuli im¬ paired ongoing cognitive activity and that the P3a component could be used as a sign of distraction. The purpose of the present investigation was to further explore the vulnerability of schizophrenic patients to distrac¬ tion by using both overt (eg, reaction time) and covert (eg, ERPs) measures. More specifically, our goal was to assess how

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process and integrate relevant and information, and to relate these findings to their performance in distraction-laden tasks. The basic experiment was a reaction time task in which subjects had to press a button on detection of rare target stimuli among frequent identical nontarget stimuli. In the distraction condition, rare distractors were administered along with the target and nontarget stimuli. As noted above, such an experimental design has been criticized on the grounds that the distraction condi¬ tion is more difficult than the nondistraction condition and, therefore, performance deficits in the distraction condition

schizophrenic patients

irrelevant

necessarily caused by distraction.13 Our recent findings an experimental design confirmed the increased global difficulty of the with-distractor task.26 However, we also showed that the distractors provoked short and transient distracting effects that can be assessed with appropriate ana¬ lyses. In other words, we were able to separate the effects of task difficulty from distraction in the performance of our subjects. Similarly, in the present experiment, we carried out two types of analysis designed to assess both the increased difficulty of the with-distraction task and the effects of the distractors per se. In the first analysis, the reaction time and the ERP data recorded during the with- and without-distractor conditions were directly compared. In the second analysis, the transient effects of the distractors were investigated dur¬ ing the with-distractor condition. are not

with such

SUBJECTS AND METHODS

Subjects Schizophrenic Patients.—Patients were diagnosed as schizo¬ phrenic on the basis of the Research Diagnostic Criteria.32 A trained research assistant and an experienced psychiatrist (D.L.B.) per¬ formed the diagnosis on the basis of chart review, individual inter¬ views, and the Schedule for Affective Disorders and Schizophrenia, Lifetime version.33 Twenty-five patients participated in this experi-

No-Distraction Condition

Distraction Condition

1

1

some patients were excluded because of excessive eye and/or muscle artifacts (5 patients), lack of cooperation (2 patients), or equipment malfunction (3 patients). The 15 remaining patients consti¬ tuted our experimental schizophrenic group. The mean age of the schizophrenic group was 31.6 ±6.7 years (range, 18 to 41 years). There were three women and 12 men. The patient group was studied for diagnostic subtype, medication, and psychological state. Thirteen schizophrenic patients were para¬ noid and two were nonparanoid according to Research Diagnostic Criteria. All but one of the schizophrenic patients were taking anti¬ psychotic medication at the time of the recording. The average dosage was 1200 mg (range, 100 to 5000 mg) chlorpromazine equivalent daily. Brief Psychiatric Rating Scale34 and Global Assessment Scale85 scores were obtained for all but one patient. Their mean scores were 42.2 ± 11.9 and 36.1 ± 12.2 for the Brief Psychiatric Rating Scale and the Global Assessment Scale, respectively. Normal Controls.—Fifteen adult volunteers participated in this study. They were matched for gender and age to the schizophrenic patients. Their ages ranged from 19 to 43 years (mean, 29.1 ±6.7 years). No subject had a history of psychiatric illness, drug abuse, seizure disorder, head injury, or hearing problems.

ment, but

Procedure The experiment consisted of auditory reaction time (RT) tasks in which ERPs were recorded. Three kinds of auditory stimuli were used: frequent standards, rare targets, and rare distractors. The target and the standard stimuli were 1600-Hz and 900-Hz tones, respectively. Both types of stimuli had a duration of 50 ms. The distractors (called "novel" in Fig 1) were a collection of buzzes, filtered noises, and other unusual, computer-generated sounds that were different from each other. The duration of each distractor was 100 ms. The intensity of each stimulus was 65 dB normal hearing level. There were two experimental conditions: a no-distraction (ND) and a distraction (D) condition (Fig 1). In the ND condition, the standard (900 Hz, .85) and the target (1600 Hz, =. 15) stimuli were used. In the D condition, the standard (900 Hz, =. 70), the target (1600 Hz, =.15), and the novel distractor ( =. 15) stimuli were used. In each condition, 150 stimuli were randomly presented with a 1-s interval between stimuli. Before the experiment, an informed consent was obtained from all subjects. During the entire recording period, the subjects had their eyes open and sat in a comfortable reclining chair in a dimly lit room. The subjects were told to press a button with the thumb of their preferred hand as quickly as possible to the target tones. They were also told that the targets would be the same stimulus during the entire session, but that in some conditions the nontarget stimuli could differ from one another. Some practice trials from the ND condition were initially administered to all subjects before the recording to ensure that they understood the task. Each condition was given three times. The order of presentation of the conditions was random. =

ERP Recording

Fig 1.—Schematic diagram for

types used in each condition. In the no-distraction condition, only target (closed squares) and standard (open squares) stimuli were presented. In the distraction condition, target, standard, and distractor (novel; stimulus

circle with cross) stimuli were presented. In the specific analysis of the distraction condition, the reaction times to the target stimuli that followed at least five standard stimuli were compared with the reaction time to the target stimuli that followed a novel stimulus. Table 1.—Global

The ERPs were recorded with nonpolarizable electrodes placed at Fz, Cz, and Pz according to the 10-20 system. Two electrodes were also

placed above and below the right eye to detect eye artifacts; one was located just below the infraorbital ridge of the eye (LoE), and the other was located above the eyebrow (UpE). All electrodes were

referenced to the right mastoid. The ground electrode was located on the left mastoid. The impedance of each electrode was below 5 kO. The ERPs were amplified by means of bandpass settings at 0.15 and 100 Hz and digitized at a rate of 195 Hz for 1200 ms with 200-ms prestimulus baseline.

Analysis of Performance in the No-Distraction and Distraction Conditions*

No Distraction

RT, Controls Patients

ms

347.8±53.6 404.9 + 63.3

Distraction

SFA, %

TM, %

0.4±0.4 0.6±0.9

2.2±2.6 3.6±6.5

RT,

ms

432.9±73.6 535.3±73.2

sFA, %

TM, %

dFA, %

0.3±0.4 0.5±0.6

3.1 ±3.1 10.1 ±9.7

2.1 ±3.0 4.7±3.9

•"Values are means ± SDs. RT indicates reaction time; sFA and dFA, false alarms to standard and dlstractor stimuli, respectively; and TM, targets missed. There 85.1-millisecond and a 130.4-millisecond increase In RT In the distraction condition in the control and patient groups, respectively. This differential RT increase was statistically significant. In addition, the percentage of TM increased statistically significantly more in the patients than In the controls (see text).

was an

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Analysis The RT as well as the number of false alarms and target misses were calculated for each subject in each condition. A false alarm was a response to a nontarget stimulus. A target miss was a target not followed by a response. In the ERP analysis, the same trial was merged across the same conditions. The ERPs were separately aver¬ aged for each condition and each type of stimulus. False alarm and target miss trials were excluded from the average. The P3 component was defined as the most positive peak between 270 and 550 ms. P3 amplitude was measured baseline to peak, with 200 ms of the average preevent electroencephalogram tracing serving as baseline. P3 laten¬ cy was calculated from stimulus onset. Trials with eye blinks, eye movements, or excessive muscle artifact were detected and excluded

Table 2.—Specific

Analysis of Reaction Time in Distraction

After Novel Stimulus

429.3 + 81.1 512.8±63.8

504.1 ±102.5 669.1+162.3

Schizophrenics

amplitude and latency data were analyzed by means of of variance techniques (ANOVA). All statistical analyses were carried out with the use of a statistical package.M The

RESULTS Behavioral Data

*Mean±SD reaction time to the target stimuli that followed either five standard stimuli or a distractor in the distraction condition. Note that the mean reaction time to the targets that followed a standard stimulus was similar to the mean reaction time for that condition (Table 1 ). This was because many more targets followed a standard stimulus than a distractor. There was a 74.8-ms and a 156.3-ms Increase in reaction time in the distraction condition In the control and patient groups, respectively. This differential reaction time increase was

raw

analysis

Time, ms

After Standard Stimulus Controls

This method ensured that no artifact contaminated the ERPs. Two types of analyses of the performance data were performed: (1) aglobal analysis, in which the performance (RT and numbers of false alarms and target misses) during the ND and the D conditions were compared, and (2) a specific analysis in the D condition, in which the transient effect of the distractors was assessed. The transient effect was assessed by separately analyzing the performance to the target stimuli that followed a distractor and the performance to the target stimuli that followed at least five standard stimuli (Fig 1). The situa¬ tion in which a target stimulus followed a distractor occurred between 6 and 11 times during the D condition for each group (mean, 7.9 ± 1.8 times in the control group and 8.6 ±1.4 times in the schizophrenic

group).

Condition* Reaction

by computer algorithms. The artifact rejection level was set at 100 µ for most of the subjects. However, this criterion was lowered when eye artifacts were present in the UpE or LoE electrodes. The average for each rare stimulus was based on at least 15 trials. Subjects were excluded from the final analysis if the 15-trial criterion could not be reached. Five schizophrenic subjects were eliminated for that reason.

statistically significant (see text).

Global Analysis. —The performance in the ND and in the D condi¬ tions is presented in Table 1. The RT data were analyzed by a two-way ANOVA with group (controls, schizophrenics) and condition (ND, D) as the two factors. The schizophrenic patients were slower than the control subjects in both conditions (group main effect; F[l,28] 12.06, P-S.002). The RTs were slower during the D condition in the two =

No Distraction LoE

v--.wV/.-

i\A/v/-

UpE

-

Targets C,

^

Fig 2.—Event-related po¬ tential responses elicited by the target and the distractor stimuli at LoE, UpE, F„ C2, and Pz electrodes in a represen¬ tative control subject. The target and the distractor stimuli elicited P3b and P3a responses, respec¬ tively. Positive is up.

Distraction

L?E ~%VY^

UpE

Targets

LoE -o-¡ Distractors

F,

V--

'

Í

5µ [_ 200 ms

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No Distraction LoE -*y\^*—-

UpE

,

No Distraction

-^ P3b

Targets c,

z

Targets

P3b

f;-î

-

f

C2

Distraction

UpE

LoE

Distraction

^\ ·^-~

LoE P3b

Targets

Targets

F--tvV

P3b

c,-^·

?.*

LoE-**-^-

UpE

-^^ --

LoE P3a

Distractors

Distractors

P3a

C2

C2

5µ -

z

(

5µVL

200 ms

200 ms

Fig 3.—Grand average event-related potentials to the target and the distractor stimuli in the control (left) and schizophrenic (right) groups. Note the dramatic reduction in schizophrenic patients' P3b response to the target

stimuli in the distraction condition. Note also the difference between the P3b response to the target stimuli and the P3a response to the distractors in the schizophrenic group. Positive is up.

groups (condition main effect; F[l,28] 186.88, P-s.001). However, the schizophrenic patients were more impaired than the control sub¬ jects by the presence of distractors (group condition interaction effect; F[l,28] 8.27, P=s.008). The error rate (false alarms and target misses) was also higher in the schizophrenic than in the control group. The error rate data were analyzed by a three-way ANOVA with group (two), type of errors (false alarm to standard, target miss), and condition (ND, D) as the three factors. There was a main effect of condition (F[l,28]=4.9, P-s.036) due to the increased number of total errors in both groups and a main effect of type of errors (F[l,28] 34.3, P-S.0009) due to the higher number of target misses than false alarms. In addition, both the condition group and type of errors group interaction were significant (F[l,28] 4.8, P=s.036 and F[l,28] 34.3, P-S.0009, respectively). These interactions mean that the increase in error rate in the D condition was larger in the patients than in the controls and that the patients made more errors of target miss than false alarms, compared with the controls. Specific Analysis.—Table 2 presents the RTs to the target that followed either a distractor or a minimum of five standard stimuli in the D condition. When a target followed a distractor, the RT was greatly delayed in both groups. This RT increase was greater in the schizophrenic than in the control group (156.3 ±119.5 msec [29.5%] and 74.7 ±56.9 msec [17.7%], respectively). This differential group effect of the position of the target stimuli on RTs was confirmed in two ways, first by an ANOVA (group position of target interaction; F[l,28] 5.70, Ps.024) and second by a t test on the difference in RT scores (RT to target following a distractor minus RT to targets following standards; 7T28] 2.38, P-s.024). The rate of target misses for targets following a distractor was also different in the two groups. We calculated the rate of target misses when a target followed a distractor relative to the total number of target misses. This rate was 4.4% and 29.9% in the control and in the patient group, respectively (7T28] 1.56, P-S.018). Thus, in the schizophrenic group, 30% of the target misses were due to the immediate presence of a distractor.

30

=

tzzi

Controls

zza Patients

=

>

20

,i

=

V

10

=

=

=

Targets

C2

Targets

P2

F2

C, P,

Distractors

No Distraction

Distraction of P3b response to the targets (in the nodistraction and distraction conditions) and P3a response to distractors (in the distraction condition).

Fig 4.—Amplitude

=

=

Electrophysiologic Data Description of the Data.—Figure 2 illustrates the different ERP responses elicited by target and distractor stimuli in a control subject

in the LoE, UpE, F2, C2, and P2 electrodes. The grand average waveforms for the control and the schizophrenic groups are presented in Fig 3. Both target and distractor stimuli elicited Nl and P2 compo¬ nents followed by a large positive deflection, P3. The amplitude and SD of the P3 responses for each group are presented in Fig 4. The P3 responses to each type of stimuli in each condition and each group were analyzed by means of two-way ANOVAs with (1) electrode (Fz, C2, P2) and condition (ND, D) for P3 to targets as the two factors and (2) electrode and stimulus type (targets, distractors) in the D condi¬ tion as the two factors. In the control group, the P3 responses to the target stimuli were

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reduced in the D condition compared with the ND condition (F[l,14] 9.6, P-S.008) (Figs 3 and 4). This amplitude reduction in the D condition was accompanied by a latency increase (F[l,14] 19.7, Ps.001) (Table 3). In the D condition, P3 responses to the distractors were larger than the P3 responses to the targets (F[l,14] 23.6, P-S.0009). More importantly, P3 responses to the targets were larger parietally, whereas P3 responses to the distractors were distributed more (electrode condition interaction: frontocentrally F[l,28] 14.0, P-S.0009). This more frontocentral distribution of the P3 response to the distractors were not due to eye artifact, as can be seen in the LoE and UpE electrodes of the grand average (Fig 3). In addition, the P3 response to the distractors was earlier than the P3 response to the targets (F[l,14] 18.0, P-s.001). In the remainder of this article, we will use the terminology given by Squires et al14 to label P3 components. "P3b" will refer to the parietal P3 responses to the target stimuli and "P3a" to the earlier frontocentral P3 responses to the distractors. Qualitatively, the results were about the same in the patient group. The P3b responses to the targets were smaller (F[l,14] 28.8, P«.0009) and later (F[l,14] 10.4, P«.006) in the D condition than in the ND condition. In the D condition, P3a responses to the distractors were earlier (F[l,14] 17.2, Ps.001) and larger (F[l,14] 43.9, Ps.0009) than P3b responses to the targets. Comparison Control/Patient Groups.—In all conditions, the schizophrenic patients had significantly reduced P3 responses com¬ pared with those of controls regardless of the stimulus type. Separate two-way ANOVAs (group electrode) on amplitude measures for each rare stimulus in each condition showed the schizophrenic group to have an overall lower P3 amplitude than the normal group (ND condition: targets, F[l,28] 8.3, P=s.007; D condition: targets, F[l,28] 29.8, P-s.OOOl; distractors, F[l,28] 8.1, P-s.008). In addi¬ tion, for the target stimuli in both the ND and the D conditions, there were significant electrode x group interaction effects (F[2,56] 3.73, P-S.03, and F[2,56] 7.53, Ps.001, respectively). These interaction effects were due to the gradient of P3b amplitude from the front to the back of the head. This gradient was steeper in the control than in the

latency to the target than did control subjects. However, this differ¬ ence was not statistically significant (F[l,28] 3.3, P-s.079, and F[l,28] 2.7, P-S.112 in the ND and D conditions, respectively). The latency of P3a response to the distractors was very similar in the two

=

=

=

=

groups (Table 3).

=

Although the patterns of P3 amplitude responses in the different conditions were qualitatively similar in the schizophrenic and the control groups, there were, as hypothesized, important quantitative differences. PSb to Targets.—From the ND condition to the D condition, P3b responses to targets were reduced by 24.7%, 20.6%, and 15.5% in the control group at F2, C2, and P2, respectively. In the schizophrenic group the P3b reductions were more than twice these numbers (45.4%, 54.4%, and 36.5% at F„ C2, and Pz, respectively). These differences were statistically significant (F[l,28] 4.9, P-s.035). P3a to Distractors.—\n the D condition, the distractors elicited a large P3a response in both groups (Figs 3 and 4). In the schizophrenic group, these P3a responses contrasted with the small P3b components elicited by the target stimuli. In the control group, the P3b responses were 38.2%, 35.2%, and 12.2% smaller than the P3a responses at F2, C2, and P2, respectively. These differences were almost twice as large in the patient group (P3b responses were 58.7%, 62.6%, and 38.0% smaller than P3a responses, respectively) (F[l,28] 9.8, P=£.004). Correlations. —Table 4 and Fig 5 present the within-group correla¬ tions between (1) P3b responses in the ND and D conditions and (2) P3b and P3a responses in the D condition. In the control group, there was a high correlation at C2 and P2 between the P3b elicited by the target stimuli in the ND and D conditions. In the schizophrenic group, these correlations were found at F2 and C2. The main difference between the two groups was that there were positive correlations between P3b responses to the targets and P3a responses to the distractors in the D condition in the control group, whereas these correlations were not significant in the patient group. Thus, one might

=

=

=

=

=

=

=

=

=

=

=

=

=

20 r

schizophrenic group. The schizophrenic patients tended to have a longer P3b response

10

Ok 20

Table 3.—Latency of P3

Responses* Latency, ms

Controls

Patients

F, C2 P2 F,

No-Distraction Condition, P3b 324 + 27 324 + 34 327 ±26 334 ±23

12

"

co

o.

Distraction Condition Electrode Location

25

25

>

345 ±33

315 + 35

347 ±34

360 + 35

360 ±35

331 ±20

369 ±47

321 ±30

339±23

377±46

314±31

351 ±22

371+41

320 ±31

25

25

P3a

P3b

-4L,

40

*-'-

10

25

16

P3a, µ

Fig 5.—Scatterplots of P3b amplitude as a function of P3a amplitude in the distraction condition in controls (left) and patients (right). Control subjects had a significant positive correlation between P3a and P3b amplitude at each electrode site (Table 4). No significant correlations were found in the patient group.

'Values are means + SDs. Note that in both groups there was an increased latency of P3b responses to the target from the no-distraction to the distraction condition and that, in the distraction condition, P3a responses to distractors were earlier than were P3b responses to targets. There were no significant latency differences between the two groups.

Table 4.—Correlations* Between P3b in No-Distraction and Distraction Conditions

Controls Electrode Location

F2 C,

Correlation .23 .65

Patients

significant.

Controls

Correlation

Patients Correlation

Correlation

NS

.71

;.001

.47

£.05

.34

£.01

.81

-.001

.71

.27

.13

NS

-£.01 £.001

£.01

*NS indicates not condition.

Between P3a and P3b ¡n Distraction Condition

Note that, unlike control

subjects, schizophrenics

had

.81 a

.15

NS NS NS

very low correlation between P3b and P3a responses in the distraction

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No Distraction LoE

-

UpE

Targets '

*t Distraction

UpE A*

LoE

Fig 6.—Event-related po¬ tentials to the target and the distractor stimuli in a

Targets

schizophrenic patient showing a clear dissoci¬ ation between P3b and P3a responses in the distraction condition. Pos¬ itive is up.

LoE --^v

UpE

W^ *\aV-

*

Distractors

P2 -V 5µ L 200 ms

that during the D condition P3b responses to the target stimuli were good predictors of P3a responses to the distractors for the control subjects, but not for the schizophrenic group. At the P2 electrode location in the D condition, P3b amplitude accounted for 65% of the variance of P3a amplitude in the control group but only for 0.02% in the schizophrenic group. The absence of a significant correla¬ tion between P3b and P3a responses in a schizophrenic individual is illustrated in Fig 6. During the ND condition, the target stimuli elicited a large P3b response (12 µ at C2) in this schizophrenic patient. This P3b response was dramatically reduced by 55% by the presence of distractors in the D condition. However, the P3a response elicited by the distractors was very large (17 µ ). Such a difference suggests a dissociation—not seen in control subjects—between the ERPs to target and distractor stimuli. assume

COMMENT

We compared the effects of distractors on performance and brain electrophysiologic activity of schizophrenic patients in an attempt to further characterize the schizophrenic patients' vulnerability to distraction. The behavioral data indicate that the psychomotor performance of schizophrenic patients was abnormally vulnerable to the effects of distractors. The ERP data suggest that this vulnerability was due to (1) a reduced total amount of processing resources available to the schizo¬ phrenic patients to process external stimuli, as indicated by their smaller P3 responses to both the target and the distractor stimuli, and (2) the schizophrenics' inability to apportion adequately their attentional resources to target vs distractor stimuli, as indicated by their abnormally small P3 responses

targets compared with their P3 responses to the distractors. There have been numerous attempts to assess the vulnera¬ bility of schizophrenic patients to the performance-deteriorat¬ ing effects of distraction.2,8"12,37 In such a paradigm, it could be argued that the poorer schizophrenic performance is due to the increased global difficulty in the D vs ND conditions.13 Although in the present study we did not use ND and D conditions of equal discriminative power, we believe that we were able to assess the distracting effects of the distractors. In what follows, before discussing the results, we will com¬ ment on the validity of the technique used to investigate distraction. In our experiment, the presence of distractors induced two types of changes, ie, global and transient (or specific). This was true for both the control and the schizophrenic groups. Globally, the distractors increased task difficulty due to shift¬ ing from a two-item to a three-item RT condition. This re¬ sulted in a global performance impairment and an amplitude reduction and latency increase ofthe P3b responses to targets (Figs 3 and 4; Table 3). The transient changes were the change in performance due to the immediate presence of a distractor. These included slower RTs (Table 2) and increased target miss. Distraction occurs when the efficiency of an ongoing cogni¬ tive activity is affected by stimuli irrelevant to such activity.31 Tecce et al38 considered distraction as a process that directs attention toward task-irrelevant stimuli and interferes with the processing of task-relevant stimuli. Their criteria for dis¬ traction were (1) evidence that the distracting stimuli have to the

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been cognitively processed and (2) evidence that the process¬ ing of the ongoing central task has been impaired. These criteria were fulfilled in the present experiment. First, the distractors were cognitively processed, as indicated by the large P3 response they elicited. The distractors elicited an early frontocentral P3 response that differed from the later, parietally distributed P3 response to the target. Squires et al14 reported similar results between a "P3b" response to rare attended targets and a "P3a" response to rare nonrelevant stimuli presented out of the focus of attention. The frontocen¬ tral P3a response has been associated with the orienting response.14,22 It can be viewed as a sign of distraction, since orienting has been conceptualized as a passive shift of atten¬ tion that diverts attentional resources from the processing of the central task.39 Second, the distractors induced an impair¬ ment in ongoing cognitive activity. Proof of this impairment was given in the specific analysis where the transient effects of the distractors were assessed. This assessment was made possible by comparing the performance ofboth subject groups to targets that followed standard stimuli vs their performance to targets that followed a distractor in the same condition (the D condition). In both groups, the performance to targets that followed standard stimuli was significantly better than the performance to targets that followed a distractor. Since the only difference between these two types of performance was the immediate presence of a distractor vs the presence of standard stimuli, it seems logical to attribute the difference in performance to the effects of the distractor. The comparison between the performance (RT and target misses) to target stimuli that followed a distractor with the performance to target stimuli that followed a standard stimu¬ lus in the D condition demonstrates the effects of the distrac¬ tors on performance for both groups. These effects were significantly more pronounced in the schizophrenic group. In the control subjects, the distractors induced a 74-ms (17%) RT increase, whereas in the schizophrenic patients, the RT in¬ crease was 156 ms (31%), which is significantly longer. Fur¬ thermore, the schizophrenic patients were more likely to miss a target that followed a distractor than one that followed a series of standards. This detrimental effect of distractors on performance is also supported by various authors' findings reported in a review article on RT in schizophrenia.40 Nuech¬ terlein40 reported a number of "time-linked" variations in RT in schizophrenia that suggest that attention and information processing may be disturbed immediately after the presenta¬ tion of irrelevant stimuli. Among the possible causes of dis¬ traction are the use of (1) irregular interstimulus interval, (2) cross-modality stimuli, and (3) irrelevant stimuli presented before the target stimuli. For example, Steffy and Galbraith41 demonstrated that irrelevant stimuli presented before the target stimuli delayed schizophrenics' RT. An important aspect of this study was to assess and com¬ pare the electrophysiologic responses of the brain to taskrelevant and task-irrelevant information to attempt to under¬ stand the cognitive deficits underlying the impaired performance of the schizophrenic patients. Strikingly, all the P3 responses were significantly reduced in the schizophrenic group. Others have reported similar findings in a wide variety of experimental contexts.25,42'48 These smaller P3 responses to both the targets and the distractors in the schizophrenic group can be explained in two ways. First, it is possible that the widely reported P3 reduction in a number of experimental paradigms denotes a decreased total amount of processing resources in schizophrenic individuals. Alternatively, it might be that the processing capacity of schizophrenic patients is normal, but that they are mainly used for sources of stimula¬ tion other than the stimuli provided by the experimenters. Internal stimuli are an example of such stimuli. Although the P3 responses were reduced in the schizo-

phrenic group, the reduction was not uniform across stimulus types. In the D condition, the P3b responses of schizophrenic patients to the target stimuli were very small, whereas rela¬ tively large P3a responses to the distractors were recorded.

Such results were in contrast with the small P3a/P3b response differences recorded in the control group. Specifically, across electrode sites, P3a response was only 28.6% larger than P3b response to the target stimuli in the control group, whereas it was 59.3% larger in the schizophrenic group. These results suggest that target and distractor stimuli were processed differently by the control and schizophrenic subjects. This differential stimulus processing between the two groups was further confirmed by the significant positive correlation be¬ tween P3a and P3b responses in the D condition found in the control group but not in the schizophrenic group. Insofar as P3 amplitude reflects the amount of stimulus processing, it can be suggested that, compared with the control subjects, the schizophrenic patients allocated more processing resources to the distractor than to the target stimuli. It could be argued that in the schizophrenic patients, there is an imbalance in the way in which task-relevant and task-irrelevant stimuli access the brain. It is possible that this imbalance disturbs the flow of sensory information and leads or contributes to disturbances in thought processes. In the present study, target and distractor stimuli were presented in the same modality where attention was directed. There have been studies in which task-irrelevant stimuli have been presented out of the focus of attention. Roth and Can¬ non48 reported that in a passive situation when subjects were asked to "ignore [the stimuli] as much as possible," the P3 response to rare stimuli was smaller in the patient group than in the control group. However, in a recent study, Scrimali et al49 showed that schizophrenic patients had a reduced P3b response to target stimuli but a normal P3a response to rare stimuli when subjects were instructed to "listen passively." Similarly, we have shown (C.G.,R.A., E.C., D.L.B.,unpub¬ lished data, 1988) that when the distractors used in the pre¬ sent experiment where presented out of the focus of attention, they elicited a P3 response that did not differ between control and schizophrenic subjects. At the present time, the question of the nature of the P3 response to task-irrelevant stimuli presented out of the focus of attention in schizophrenic pa¬ tients remains unclear. However, it is possible that different subtypes of schizophrenic patients have different P3 respons¬ es to task-irrelevant stimuli. Indeed, it has been argued that acute and paranoid schizophrenic patients are responsive to a broad range of stimulation, and that chronic schizophrenic patients show narrowed responsivity.50,51 It could be expected that more acute and paranoid schizophrenic patients have a larger P3 response to task-irrelevant stimuli delivered out of the focus of attention than do chronic and nonparanoid schizo¬

phrenic patients.

were also group differences in global ERP, RT, and rate changes from the ND to the D condition. P3b response reduction, induced by the distractors, was larger in

There

error

the schizophrenic patients than in the control subjects. Across electrodes, P3b reduction from the ND to the D condition was 22.5% in the control group and 52.3% in the schizophrenic group. This pattern of ERP responses was accompanied by a performance impairment. We previously demonstrated that, in control subjects, distraction was transient and had little influence on these global P3b and performance changes.26 Instead, the global P3b reduction and performance impair¬ ment in the D condition were due to an increased level of task difficulty. This explanation, certainly, still holds for the con¬ trol subjects in the present experiment. However, it is possi¬ ble that in the schizophrenic group distraction lasted longer than in the control group and contributed significantly to the global P3b and RT changes. In support of this view is the work

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of Steffy and Galbraith41 cited earlier. These authors found that irrelevant stimuli presented 1, 3, or 9 s before the target stimuli delayed schizophrenics' RT. Future studies should focus on the assessment ofthe duration ofdistraction effects to attempt further to separate task difficulty from distraction effects on these global changes. Unlike the amplitude data, the latency data did not signifi¬ cantly differ between the two groups. The latency of P3b to targets from the ND to the D condition increased in both groups, but this increase was not significantly different be¬ tween groups. Thus, P3 latency cannot explain the differential RT increase between the control and the schizophrenic groups. Although P3b latency has been shown to correlate with RT,52 it is now clear that another component, N2, is a better indicator of stimulus evaluation than P3.53,54 N2 is a negative component with a latency of 100 to 200 ms that has been associated with a mismatch between two stimuli.55 Brecher et al56 reported that the N2 component is delayed in schizophrenic patients. We have preliminary data that sup¬ port this finding and suggest that sensory information is transmitted with delay and that this delay increases with distraction in schizophrenic individuals. Some ERP studies have failed to report increased distracti¬ bility in schizophrenic patients. Pass et al,46 for example, did not find that schizophrenic patients were abnormally impaired by distractors in a visual continuous performance task with visual and auditory distractors. There are at least two expla¬ nations for this result. First, Pass et al46 performed a global analysis, which, as we have seen, can provide information about only the task difficulty effects but not the distraction effects. In addition, they did not compare the ERPs elicited by the target and the ones elicited by distractor stimuli. Second, distraction could be modality specific in schizophrenia. There is evidence that the auditory and visual modalities are differ¬ entially affected by distraction in schizophrenic patients. In¬ deed, hallucinations are usually more frequent in the auditory than in the visual modality in schizophrenic patients (auditory hallucinations are one of the symptoms of schizophrenia as defined by DSM-III). It could be argued that this modality difference could explain why Pass et al,46 who used a visual task, did not find a differential effect of distraction between control and schizophrenic subjects. Recently, there has been some attempt to identify the anatomic structures and physiologic mechanisms underlying P3 responses with the use of animal models.57"60 Pineda et al60 recorded late positive P3-like potentials to rare stimuli in¬ serted among frequent stimuli in squirrel monkeys. They re¬ ported that after lesion of the locus ceruleus, the P3-like responses were dramatically reduced. The locus ceruleus, which releases norepinephrine onto target neurons in numer¬ ous brain regions including the neocortex, has been thought to be involved in mediating orienting behaviors.61 Abnormal functioning of the norepinephrine neurons of the locus ceru¬ leus, therefore, would be expected to result in inadequate behavioral responsitivity to novel and informative stimuli. These data suggest a very speculative but plausible associa¬ tion between the abnormal functioning of the norepinephrine neurons of the locus ceruleus and the schizophrenic disorders. In concert with this hypothesis, the relevance of norepineph¬ rine system imbalance in the pathogenesis of schizophrenia has been argued.62,63 On the basis of cerebrospinal fluid studies of monoamine metabolism, van Kämmen et al63 suggested a

dysregulation of dopamine as well as norepinephrine tone in schizophrenic patients. The results of startle habituation and sensorimotor gating studies in schizophrenic patients and in a

related animal model have also added support to the idea of abnormal functioning of norepinephrine and dopamine sys¬ tems in schizophrenia.64 These results emphasize the need for a theory of schizophrenia involving dysfunction of a number of neurotransmitters, including dopamine and norepinephrine. The use of antipsychotic medication by the schizophrenic group may have contributed to the group differences observed in this study. However, RT's are known to be largely unaf¬ fected by drug treatment40 in schizophrenic patients. Also, a number of studies have assessed the effects of antipsychotic medication on ERPs.46,65,66 More specifically, it has usually been found that the P3 component seems to be independent of drug-related effects.46,66 In fact, there is reason to believe that antipsychotic medications tend to reduce the "disrupting in¬ fluence of distracting stimuli."67 As such, the detrimental effects of distractors might have been even larger in the patient group if they did not take medications. Reduced P3 ERP responses and slower RT in schizophrenic subjects compared with control subjects are among the most consistent electrophysiologic and behavioral findings in schizo¬ phrenia research. It has been suggested that the general P3 and RT deficits in schizophrenic individuals could be nonspecific effects due to a lack of motivation.68 Such an explanation does not appear to be supported by our P3 and RT findings. The pattern of electrophysiologic (ERP) and behavioral (RT) changes in¬ duced by the distractors were similar in both the schizophrenic and the control groups. Only the extent to which these changes occurred differentiated the two populations. In conclusion, we have attempted to assess the effects of distractors on schizophrenic patients. We have shown that performance to target that immediately followed a distractor was more impaired in schizophrenic than in control subjects. We have indicated that the P3 responses to targets and dis¬ tractors suggest that schizophrenic patients inadequately ap¬ portion their processing resources to task-irrelevant and taskrelevant external stimuli. On the basis of the global decreased P3 responses to both the targets and distractors, we have also proposed that schizophrenic patients either (1) have a reduced total amount of processing resources or (2) in addition to inadequately allocating their processing resources to irrele¬ vant external stimuli, inadequately allocate processing re¬ sources to internal stimuli. This study points out the advan¬ tage of combining behavioral and electrophysiologic data. The behavioral data allowed us to identify a specific cognitive deficit in schizophrenic individuals that was subsequently investigated with ERP techniques. It is hoped that by using the approach of combining multiple techniques, a more inte¬ grated view of cognitive deficits in schizophrenia could emerge. Such a study, for example, would examine sensori¬ motor gating,3,5 P3 responses, and performance in the same subject. However, before such a study could be advanced, attempts should be made to (1) use more homogeneous groups of schizophrenic patients, preferably not receiving medica¬ tion, and (2) identify nonschizophrenic patients who could serve as a control group. This research was supported in part by a National Alliance for Research on Schizophrenia and Depression Fellowship Extension Award (Dr Grillon) and by National Institute of Mental Health (Bethesda, Md) grants 1-RO1-MH36840 (Dr Courchesne), MH42228, and MH00188 (Research Scientist Development Award, Dr Geyer).

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Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence.

The inability of schizophrenics to filter irrelevant information has often been implicated in the psychopathology of schizophrenia. Despite numerous a...
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