Probing attentional dysfunctions in schizophrenia: Startle

modification during a continuous performance test

ERIN A. HAZLETT,a MICHAEL E. DAWSON,b ANNE M. SCHELL,c andKEITH H. NUECHTERLEINd,e

aDepartment of Psychiatry, Mount Sinai School of Medicine, New York, New York, USAbDepartment of Psychology, University of Southern California, Los Angeles, California, USAcDepartment of Psychology, Occidental College, Los Angeles, California, USAdDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California, USAeDepartment of Psychology, University of California, Los Angeles, California, USA

Abstract

Startle eyeblinkmodification wasmeasured in 20 relatively asymptomatic medicated schizophrenia outpatients and 18

matched controls in order to test for deficits in early and later stages of attentional processing during a memory-load

version of the Continuous Performance Test. Participants viewed a series of digits and pressed a button after the digit 7

of each 3–7 sequence. On some trials, a startling noise burst was presented either 120 or 1200 ms following cues that a

response might be needed soon (the digit 3) and also following noncues. Controls showed greater startle inhibition at

120 ms following cue than noncue prepulses, whereas patients showed equal inhibition to both, suggesting a deficiency

in allocation of controlled attentional resources in early stages of processing. The patients, however, did show large

startle inhibition at 120 ms when a distracting stimulus accompanied the task-relevant cue, unlike the controls, who

ignored the distracting stimulus. In contrast, both groups showed equal startle inhibition 1200 ms following cue and

noncue prepulses, indicating that later modality-specific attention processes are not impaired in patients during this

paradigm. Both groups also showed equal inhibition at 120 ms during passively attended prepulses, suggesting that

automatic attentional processes were not impaired in these patients.

Descriptors: Schizophrenia, Selective attention, Prepulse inhibition, Startle eyeblink modification, Continuous per-

formance test, Controlled processing, Automatic processing

Continuous performance tasks (CPTs) are often used to index the

attentional dysfunctions well known to be associated with

schizophrenia (Nuechterlein, 1991). In such tasks, participants

must detect and respond to target stimuli in a continuous train of

rapidly and briefly presented stimuli, for instance by pressing a

button whenever a ‘‘7’’ appears in a series of rapidly and ran-

domly visually presented single digits. CPTs that add a working

memory load to the task, such as instructing the participant to

respond only when a ‘‘3’’ (cue) precedes a ‘‘7’’ (target), are more

difficult than always responding to a single target (Beck, Bran-

some, Mirsky, Rosvold, & Sarason, 1956; Nuechterlein, Edell,

Norris, & Dawson, 1986). Deficits in schizophrenia patients’

performance on memory-load CPTs occur during symptomatic

remission and become more marked during a psychotic episode

(Nuechterlein et al., 1992). This pattern of deficits, present in the

remitted state and becoming greater in symptomatic states, sug-

gests that the impairment is related to the vulnerability to schizo-

phrenia and may reflect cognitive deficits that mediate symptom

formation (Nuechterlein & Dawson, 1984a).

Memory-load CPTs are complex tasks involving a number of

cognitive processes. Selective attention must be sustained on the

sensory modality (usually visual) in which the stimuli are being

presented, external distracting stimuli must be ignored, and the

task instructions must be maintained in working memory. Each

stimulus must be rapidly detected, encoded as a cue, an approri-

ate target (i.e., one that was preceded by the cue), an inappro-

priate target (one that was not preceded by a cue), a noncue or a

nontarget. Thus, in the flow of information processing, both

early predominately automatic processes (single stimulus detec-

tion) and later, predominately controlled processes (modality

focus, discrimination between cue, target, and noncue/nontarget

stimuli, and overall task instructions) must function effectively;

impaired performance could result from a breakdown at any

point. Cognitive impairments in schizophrenia have been

hypothesized to involve automatic processes (Frith, 1979),

This research was supported by grants from the National Institute of

Mental Health (MH10381 and MH073911 to E.A.H., MH46433 and

K02MH01086 toM.E.D., MH37705 to K.H.N., andMH30911 to R.P.

Liberman at UCLA). We thank Dr. Diane Filion for consulting on var-

ious technical aspects of this research, William Troyer for software de-

velopment, and Sally Friedlob and Craig Childress for assistance with

recruitment of study participants.Address reprint requests to: Dr. Erin A. Hazlett, Department of

Psychiatry, Box 1505, The Mount Sinai School of Medicine, 1 GustaveL. Levy Place, New York, NY 10029, USA. E-mail: erin.hazlett@mssm.edu.

Psychophysiology, 45 (2008), 632–642. Wiley Periodicals, Inc. Printed in the USA.Copyrightr 2008 Society for Psychophysiological ResearchDOI: 10.1111/j.1469-8986.2008.00653.x

632

controlled processes (Callaway & Naghdi, 1982), or both (Nu-

echterlein & Dawson, 1984b). In the impaired CPTperformance

seen in schizophrenia, both early automatic processes such as

those involved in stimulus detection and controlled processes

such as those involved in cue/noncue discrimination and sus-

tained focused attention may be dysfunctional.

The startle eyeblink modification technique can be used to

identify individual processes that may be impaired. Startle eye-

blink is a component of the general startle reflex elicited by any

rapidly onsetting and intense stimulus, particularly a loud noise.

This automatic reflex can be reliably modified by preceding the

startle stimulus with a nonstartling stimulus, usually called a lead

stimulus or prepulse. If the lead interval between the two stimuli

is short (30–500 ms), the startle response is reliably attenuated, a

phenomenon called prepulse inhibition (for reviews, see Blu-

menthal, 1999; Graham, 1975). Prepulse inhibition (PPI), which

typically maximizes 120–250 ms after prepulse onset, is thought

to reflect protection of the processing of the prepulse from dis-

ruption by the startle stimulus, or sensorimotor gating (Braff &

Geyer, 1990; Graham, 1975). PPI occurs whether the startle

stimulus and the prepulse are in the same sensory modality or

different modalities. Although PPI is considered to be an auto-

matic process, it can be modified by controlled selective atten-

tion. Directing attention to prepulses by making them task

significant enhances PPI relative to that elicited by prepulses that

are not task significant and that can be ignored (DelPezzo &

Hoffman, 1980; Filion, Dawson, & Schell, 1993). In selective

attention paradigms, the difference in PPI to attended versus

ignored prepulses has been interpreted as reflecting controlled

processing, or top-down modulation of the automatic PPI pro-

cess (Dawson, Schell, Swerdlow, & Filion, 1997). On the other

hand, PPI in passive attention tasks is thought to reflect pre-

dominantly automatic processing (Braff et al., 1978; Braff,

Grillon, & Geyer, 1992).

When the lead interval is longer (�1000 ms), other startle

modulation effects appear. In a passive attention task, long-lead

interval facilitation is seen that is attributed to a simple arousal

process (Graham, 1975). When attention is directed to the pre-

pulse, controlled attentional processing may produce either startle

facilitation or inhibition, depending on the experimental condi-

tions. When participants are asked to attend to prepulses and the

prepulse and the startle stimulus are in the same modality (usually

auditory), startle is facilitated at long-lead intervals, more to an

attended or task-relevant stimulus than to an ignored or task-

irrelevant stimulus (Bohmelt, Schell,&Dawson, 1999; Filion et al.,

1993; Jennings, Schell, Filion, & Dawson, 1996; Lipp & Hard-

wick, 2003). However, when the prepulse and the startle stimulus

are in different modalities and the task requires continuous, un-

wavering attention to the briefly and rapidly presented prepulses as

in a CPT, as opposed to a discrete-trial task with relatively long

prepulses and intertrial intervals, startle may be inhibited (Hazlett,

Dawson, Schell, & Nuechterlein, 2001; Lipp & Neumann, 2004;

Neumann, 2002; Rissling, Dawson, Schell, & Nuechterlein, 2005).

Several studies have found startle modification to be abnor-

mal in schizophrenia and in persons at elevated risk for schizo-

phrenia. PPI in a passive attention task, where participants are

not specifically instructed to attend to prepulses, has been re-

ported to be deficient in patients (Braff et al., 1978, 1992; Swerd-

low et al., 2006), individuals with schizotypal personality

disorder (Cadenhead, Geyer, & Braff, 1993; Cadenhead, Swerd-

low, Shafer, Diaz, & Braff, 2000), and biological relatives of

patients (Cadenhead et al., 2000). This finding has been inter-

preted as a breakdown in sensorimotor gating processes in

schizophrenia-spectrum disorders. Studies have indicated that

passive PPI deficits in schizophrenia are associated with thought

disorder (Perry, Geyer, & Braff, 1999) and both positive and

negative symptoms (Braff, Swerdlow, & Geyer, 1999), whereas

others have found no symptom correlates (Swerdlow et al.,

2006). Wynn, Sergi, Dawson, Schell, and Green (2005) found

that schizophrenia patients with lower PPI were poorer at de-

tecting relevant social cues than patients with better PPI. Wynn

et al. (2004) also reported reduced long-lead interval startle fa-

cilitation in a passive-attention task with auditory prepulses and

startle stimuli in both patients and first-degree relatives, theo-

rized to reflect reduced orienting and reduced availability of

cognitive processing resources.

We (Dawson, Hazlett, Filion, Nuechterlein, & Schell, 1993;

Dawson, Schell, Hazlett, Nuechterlein, & Filion, 2000; Hazlett &

Buchsbaum, 2001; Hazlett et al., 1998, 2007) have reported that

attentional modulation of both PPI and long-lead interval startle

modification is impaired in schizophrenia during an active-at-

tention paradigm in which attended stimuli and startle probes

were in the same (auditory) modality. Unlike healthy controls,

patients failed to show greater PPI or long-lead interval facili-

tation following task-relevant attended auditory prepulses than

following task-irrelevant ignored prepulses. We have also re-

ported that deficient PPI during attended prepulses is correlated

with heightened delusions, conceptual disorganization, and sus-

piciousness (Dawson et al., 2000) and overall positive and neg-

ative symptom severity (Hazlett et al., 2007). This failure to

attentionally modulate startle has also been reported in individ-

uals with schizotypal personality disorder (Hazlett et al., 2003,

2007) and putatively at risk for psychosis as assessed by Chap-

man scale scores (Schell, Dawson, Hazlett, & Filion, 1995).

Attentional modulation of startle can also be seen during the

CPT. For example, Hazlett, Dawson et al. (2001) measured

startle modification while college student participants performed

a memory-load visual CPT in which they pressed a button

whenever a ‘‘7’’ (the target) appeared following a ‘‘3’’ (the cue).

The digits served as prepulses for an acoustic startle stimulus

(white noise burst) that was presented at lead intervals of 120 and

1200 ms following some cue prepulses (‘‘3’’), noncue prepulses,

and combinations of cue prepulses and distractor stimuli (tones).

We found greater PPI 120 ms following cue than noncue pre-

pulses, reflecting greater controlled processing of the more task-

relevant stimuli of the CPT. At the long-lead interval, significant

inhibition of acoustic startle was seen during both cue and non-

cue prepulses, which we attributed to a strong focus of attention

toward the visual modality and away from the auditory startle

stimuli. PPI and long-lead interval startle modification did not

differ between cue and cue1distractor trials, indicating an ability

of the participants to prevent attention from being captured by

the distractor stimulus.

The present study extends the methods previously used with

college student participants (Hazlett, Dawson, et al., 2001) to the

study of CPT deficits in schizophrenia. The ‘‘3–7’’ memory-load

CPT, adapted fromNuechterlein et al. (1986), was performed by

schizophrenia patients and matched healthy controls while star-

tle probeswere delivered at both early (120ms) and late (1200ms)

time points after digit prepulse onset. Using startle modification

measures of attentional processing, we tested three hypotheses

that, compared with the healthy controls, the schizophrenia pa-

tients would (1) fail to attentionally modulate PPI during the

CPT, (2) show reduced startle modification at long-lead intervals

Deficient attentional startle in schizophrenia 633

during the CPT, and (3) be less able to avoid attention capture by

a distracting stimulus during the CPT. We also explored whether

schizophrenia-related CPT deficits were associated with mea-

sures of startle modification.

Method

Participants

Twenty schizophrenia outpatients (17 men) and 18 age- and sex-

matched healthy controls (15 men) comprised the final sample of

paid volunteer participants in this study. Each was paid $25 for

participation. Data from 2 additional controls were discarded

from analysis because of equipment problems (n5 1) and exces-

sive muscle artifact (n5 1). In addition, data from 2 patients and

3 additional controls were eliminated for failure to exhibit eye-

blinks on over 25% of the baseline startle stimulus presentations.

The schizophrenia patients were outpatients from the UCLA

Aftercare Research Program and participants in a longitudinal

study of the early phases of schizophrenia (Nuechterlein et al.,

1992). The patients met both Research Diagnostic Criteria

(Spitzer, Endicott, & Robins, 1978) and DSM-IV criteria for

schizophrenia (n5 18) or schizoaffective disorder, mainly schizo-

phrenic (n5 2). The first psychotic episode began not longer than

2 years before entry into the main longitudinal project and oc-

curred an average of 6.5 years (SD5 4.1 years) before testing in

the present study. The patients were either off all psychoactive

medication (n5 1), on a low–to–moderate dose of the antipsy-

chotic fluphenazine (Prolixin), injectable (n5 16) or oral (n5 3).

The outpatients were relatively asymptomatic at the time of

their testing as assessed by independent ratings on the Brief Psy-

chiatric Rating Scale (BPRS; Overall & Gorham, 1962); the 18–

item BPRS Total Psychopathology scores ranged from 18 to 43

(M5 28.4, SD5 6.8), where the minimum possible rating is 18.

Ratings for the three psychotic symptom items of the BPRS (i.e.,

unusual thought content, hallucinations, and conceptual disor-

ganization) were in the nonpathological range (i.e., � 3 on a

7-point scale) with the exception of 3 patients who received a

rating of 4 on unusual thought content and 1 patient who re-

ceived a 4 on conceptual disorganization. More details regarding

the inclusionary and exclusionary criteria and patient demo-

graphics are found in Nuechterlein et al. (1992).

The healthy controls also were drawn from participants in the

longitudinal research project. These participants were matched

to the patients on age, sex, and educational level. Thus, the final

sample of patients and the healthy controls did not differ in age

(patients: M5 30.6, SD5 6.3; controls: M5 28.3, SD5 5.3,

t[36]5 1.2, p5 .24) or years of education (patients: M5 13.2,

SD5 2.1; controls: M5 13.2, SD5 1.6, t[36]5 0.04, p5 .97).

The healthy controls were interviewed with a lifetime version of

the Present State Exam (PSE;Wing,Nixon,Mann, &Leff, 1977)

to exclude those with a history of significant psychiatric illness in

self or first–degree relatives.

The psychophysiology research procedure was fully explained

and participants read and signed an informed consent form that

provided a general description of the study and the physiological

responses being recorded and was approved by the Institutional

Review Board.

Design

To examine the effects of different types of CPT prepulses, a 2 �3 � 3 mixed-design ANOVA was employed for the short

(120 ms) and long-lead (1200 ms) intervals separately. The first

variable consisted of group (healthy controls vs. schizophrenia

patients), the second variable consisted of prepulse type (cue,

noncue, and cue1distractor), and the third variable consisted of

three CPT trial blocks. Data from the short- and long-lead in-

terval responses were analyzed separately because they are

thought to reflect quite different processes, PPI and arousal pro-

cesses, respectively.

To examine the effects of the distractor stimulus when pre-

sented alone as a prepulse, a one-wayANOVAwas employed for

the short- and long-lead intervals separately, with startle re-

sponses at each lead interval being averaged over the baseline

periods.

Procedure

The procedure for this experiment was identical to that published

in our previous study of college students (Hazlett, Dawson, et al.,

2001). The experimental session consisted of five phases: the au-

diology test, electrode placement and task instructions, rest pe-

riod, CPTpractice, and the CPT-startlemodification experiment.

A brief audiology test was performed to ensure that all partic-

ipants had normal hearing within the frequency range of the

1000-Hz 70-dB(A) distractor tone. Participants were presented

tape-recorded instructions that provided information about the

nature of the stimuli to be used and a description of their task.

They were instructed that their task was to concentrate on the

numbers appearing on the screen, to press a response button

every time they saw the digit 3 followed by the digit 7, and to

refrain from pressing the button at any other time. Participants

were also instructed that two types of auditory stimuli (a pure

tone and/or a brief burst of static noise) would be presented

occasionally throughout the experiment and that they should

simply ignore these stimuli and concentrate on the visual task.

Following detailed instructions regarding the task, 10 examples

of the 3–7 sequence were shown to the participants. They were

asked to practice pressing the button after each of these 3–7

sequences. Next, participants performed one block (160 trials) of

the CPT, which served as practice to familiarize them with the

visual task and ensure that they understood the task instructions.

No distractors or startle stimuli were presented during this prac-

tice block. Participants were then given three warned examples of

the startle stimulus. Following the examples of the startling noise

bursts, the CPT-startle modification portion of the experimental

session began.

The CPT-startle modification phase lasted 21.5 min and con-

sisted of three CPT blocks with a baseline period preceding and

following each block. Each CPT block consisted of 160 stimulus

presentations or ‘‘trials’’ made up of 20 3–7 sequences (40 stim-

uli), 80 noncues, 20 3s not followed by a 7, and 20 7s not preceded

by a 3 over a continuous observation period of approximately

4.5 min (interstimulus interval5 1.65 s). On 20% of the CPT

trials in each block (32 trials), a tone distractor was presented

through headphones simultaneously with a CPT stimulus (both

cues and noncues). To measure eyeblink modification during

the processing of the CPT stimuli, 12 preselected trials were

‘‘probed’’ with an acoustic startle-eliciting stimulus. Throughout

the entire experimental session, participants were monitored

through a one-way mirror for any movements.

A schematic of a portion of the trial sequence during the

baseline and CPT periods is shown in Figure 1. To measure

eyeblink modification effects to task-related stimuli without in-

terference from the task motor response (see right portion of

634 E.A. Hazlett et al.

Figure 1), the startle-eliciting stimulus was presented at one of

two possible lead intervals following the onset of the cue (digit 3)

of a 3–7 trial sequence, while the participant was to press the

response button after the digit 7 of the same sequence. Startle-

eliciting stimuli were also presented at times following the digit 3

when the 3 was not followed by a 7. To determine eyeblink

modification effects of noncue stimuli, the startle-eliciting stim-

ulus was presented following the onset of noncue digits (i.e., 0s

and 1s were chosen to be the least easily confused with the cues).

Last, to determine the eyeblink modification effects of the pres-

ence of a distracting stimulus, startle-eliciting probes were pre-

sented on cue trials that had the simultaneously presented

auditory distractor. In sum, during each CPT block, there were

two startle-eliciting probes presented at both the short (120 ms)

and long (1200 ms) lead intervals following the preselected cue,

noncue, and cue1distractor stimuli (‘‘prepulses’’), yielding a to-

tal of 12 probe trials.

Six of the probe trials were presented during the first 80 CPT

stimuli of each block and the remaining six were presented during

the last 80 stimuli. The amount of time between the startle-elic-

iting probes varied from 13 to 36 s, with a mean interval of 24 s.

The CPT trial sequence was varied across the three CPT blocks.

The order of probed CPT trials was pseudorandom within each

participant’s test session and did not vary across individuals.

However, probe position (120 ms vs. 1200 ms) order was coun-

terbalanced across participants.

Each of the CPT blocks was preceded and followed by a

baseline period, which resulted in a total of four baseline periods

(see left portion of Figure 1). The purpose of the 2-min baseline

periods was twofold. First, to determine whether participants

showed eyeblink modification during the distractor prepulse

alone (i.e., tone prepulse without the presence of a visual CPT

prepulse) during each baseline period, a startle probe was pre-

sented at both the short- and the long-lead interval following the

onset of the distractor prepulse. PPI and long-lead interval startle

modification data were averaged across the baseline periods for

data analysis. Second, during each baseline period, two startle

stimuli were presented at preselected times in the absence of a

prepulse. Responses to these probes served as baseline measures

with which to compare eyeblink modification produced by the

prepulses. No stimuli were presented for at least 15 s before the

distractor prepulses that contained probes or before the baseline

probes.

Tomatch arousal level during the baseline andCPTperiods as

closely as possible, CPT digits were presented during the baseline

periods. These CPT digits usually had the same interstimulus

interval as those presented during the CPTproper (1.65 s); how-

ever, occasionally there were relatively longer interstimulus in-

tervals (varying from 3 to 24 s with a mean interval of 13 s) to

allow for the presentation of distractor plus startle stimuli and

startle stimuli alone. There was no interruption between the

baseline and CPT phases of the experiment, so from the partic-

ipant’s point of view, the baseline periodwas identical to the CPT

except for the occasional longer-than-usual gap between CPT

stimuli. The participants were told that occasionally there would

be brief periods where no numbers would appear, but they

should continue to focus their gaze on the computer monitor and

wait for the next number to appear. In sum, during each baseline

period, there was one startle-eliciting probe presented at the

short- (120 ms) and long- (1200 ms) lead intervals following the

onset of the distractor tone and two startle probes presented in

the absence of any prepulse stimuli, yielding a total of four

probes.

Stimulus Materials and Apparatus

The CPTwas administered using a computer with a NEC-Mul-

tisync-3Dmonitor. The computerized version of the CPTused in

this project was a modification of the 3–7 CPT program devel-

oped by Nuechterlein and Asarnow (1993). CPT stimuli con-

sisted of a series of single digits (0–9) presented visually one at a

timewith an exposure time of 33 ms and an interstimulus interval

of 1.65 s. The computer recorded correct target detections, false

positive responses, and reaction time in milliseconds.

The auditory distractor stimulus was a 1000-Hz 70-dB(A)

tone, 1400ms in duration with a controlled rise/fall time of 25ms

with the frequency controlled by the VCO input to a Coulbourn

tone generator. The startle-eliciting stimulus was a 100-dB(A)

white noise burst 40 ms in duration with a near instantaneous

rise/fall time generated by a Grason Stadler Model 901B noise

generator. All auditory distractors and startle-eliciting stimuli

were presented throughheadphones (RealisticNOVA-40Model).

The onsets, durations, and intervals between stimuli were con-

trolled online by ASYSTcomputer software.

Electromyographic (EMG) eyeblink responses were recorded

using a Grass Model-7 polygraph equipped with a wide-band

integrator/preamplifier (Model 7P3). Startle eyeblink was re-

corded as EMG from a pair of 4-mm silver–silver chloride elec-

trodes filled with TECA electrode paste and placed directly over

the orbicularis oculi muscle, the flexor muscle responsible for

eyelid closure. These electrodes were placed just below and to the

left of the lower left eyelid. All impedenceswere less than or equal

to 5 KO. The EMG signal was recorded at full wave rectification

with an integration time constant of 20 ms. The eyeblink re-

sponses were recorded and digitized at a rate of 1000 Hz for a

period of 200 ms before to 300 ms following the presentation of

each startle-eliciting stimulus.

Dependent Measures

The two primary dependent variables were the modification of

eyeblink magnitude and behavioral performance on the CPT

(indexed by a transformed A0 score). Startle eyeblink amplitude

was measured under five stimulus conditions: probe-alone pre-

sentations (i.e., baseline magnitude) and probes presented at the

two lead intervals following cue, noncue, cue1distractor, and

distractor-alone presentations.

Eyeblink amplitude was computer scored off-line based on

the criteria suggested by Balaban, Losito, Simons, and Graham

Deficient attentional startle in schizophrenia 635

Figure 1. Schematic of a portion of the experimental session. During the

baseline blocks, there were two stimulus conditions (startle probe alone,

distractor tone with a startle probe presented at either the 120 ms or 1200

ms lead interval). During the CPT blocks, there were three stimulus

conditions (cue, noncue, and cue1distractor tone) that had a startle

probe presented at either the 120 ms or 1200 ms lead interval.

(1986). Blink amplitude was scored in microvolt units for re-

sponses beginning within a latency window of 21–120 ms and

reaching a peak within 150 ms of response onset. Scores for

individual trials with an unstable prestimulus EMGbaseline were

replaced with the score for the nearest trial in the same condition.

Outlier scores (any score greater than three standard deviations

above the mean and greater than two standard deviations above

the next highest score) were also replaced. Fewer than 1%of data

points in either group were replaced.

To examine eyeblink modification across the three CPT

blocks, separate baseline eyeblink amplitudes were calculated for

comparison with each CPT block. Specifically, the two baseline

probes preceding and following each CPT block were averaged

together, which resulted in three baseline mean values (i.e.,

Baseline 15mean of probes presented during baselines 1 and 2,

Baseline 25mean of probes presented during baselines 2 and 3,

and Baseline 35mean of probes presented during baselines 3

and 4).

The magnitude of each startle eyeblink elicited under a pre-

pulse condition was expressed as a percent change score from the

average response to the startle-alone stimuli presented during the

appropriate baseline period, using the formula: percentage

change5 [(magnitude during prepulse�mean baseline)/mean

baseline)] � 100. A positive startle modification score indicates

facilitation relative to baseline, and a negative score indicates

inhibition relative to baseline.

To determine behavioral performance on the CPT, the

hit rate and false alarm rate were used to calculate A0 (i.e.,

sensitivity; Grier, 1971) values across the three CPT blocks. In

signal detection theory, ‘‘sensitivity’’ refers to an individual’s

ability to discriminate the target (signal) stimuli from the non-

target (noise) stimuli independent of any response bias (Green &

Swets, 1966). When an individual has a high perceptual sensi-

tivity score he/she typically has a relatively high hit rate (few

errors of omission) and a relatively low false alarm rate (few

errors of commission). Each participant’s A0 was transformed

using the formula: 2 � arcsin (pA0) in order to create a more

normally distributed variable (McNicol, 1972). In addition, this

transformation creates a variablewith a nearly linear relationship

to d0, which is another commonly used index of sensitivity

(McNicol, 1972). These transformed A0 scores were used in

all subsequent data analyses to index behavioral performance on

the CPT.

Statistical Analyses

Analyses involving repeated measures with more than two levels

used Greenhouse–Geisser epsilon corrections to adjust proba-

bilities for repeated measures F values. The uncorrected degrees

of freedom for these analyses and for t tests that required cor-

rection due to heterogeneity of variance are reported.

Results

Baseline Startle

To determine whether there were group differences in baseline

startle, we examinedmean startle eyeblink amplitude in response

to the startle alone stimulus that was presented during the base-

line period. The healthy control and schizophrenia patient

groups showed no difference in baseline startle amplitude (con-

trols: M5 24.89, SD5 32.29 mV; patients: M5 19.98,

SD5 19.79 mV; t[36]5 0.56).

Startle Modification during the CPT

Short-lead interval (PPI) effects. Figure 2 shows the PPI

scores for each prepulse type averaged over trial blocks for the

patient and control groups. A 2 (group) � 3 (prepulse type) � 3

(trial block) mixed-design ANOVA on PPI during the CPT re-

vealed no group effect, F(1,36)5 0.72, p5 .40, indicating that the

patients did not differ from healthy controls in overall PPI aver-

aged over prepulse type and trial block. More important, this

analysis revealed a significant Group � Prepulse Type interaction,

F(2,72)5 4.02, po.03, epsilon5 .93. This effect indicates that the

patients and controls differed significantly in their differential eye-

blink responses to the different prepulse types averaged over trial

blocks. Because the trial block effect, F(2,72)5 2.04, p5 .15,

Group � Trial Block interaction, F(2,72)5 1.17, p5 .31, Pre-

pulse Type � Trial Block interaction, F(4,144)5 1.62, p5 .18,

and Group � Prepulse Type � Trial Block interaction,

F(4,144)5 1.59, p5 .18, were all nonsignificant, the PPI scores

were averaged over the three trial blocks for further analysis.

As can be seen in Figure 2, the matched controls showed

significantly greater PPI following the cue prepulse than follow-

ing the noncue prepulse at the short-lead interval, t(17)5 3.41,

po.004, d5 0.80. They also showed significantly greater eye-

blink PPI following the cue1distractor prepulse compared to the

noncue prepulse, t(17)5 2.40, po.03, d5 0.57. The degree of

eyeblink inhibition for the cue and the cue1distractor conditions

did not differ significantly, t(17)5 0.70.

In contrast, the patients failed to show differential inhibition to

the cue and noncue prepulses. Instead, the patients exhibited more

eyeblink inhibition to the cue1distractor prepulse compared to the

cue prepulse, t(19)5 4.70, po.001, d51.06 and compared with

the noncue prepulse, t(19)5 4.34, po.001, d50.97.

Between–group comparisons were conducted on the differ-

ential eyeblink inhibition scores (i.e., cue minus noncue and

cue minus cue1distractor difference scores). These analyses

confirmed that the patients, compared to the controls, exhibited

significantly less differential eyeblink inhibition between the cue

and noncue prepulse, t(36)5 2.65, po.02, d5 0.87. In addition,

the patients compared to the controls exhibited significantly

636 E.A. Hazlett et al.

Figure 2. Prepulse inhibition at the 120 ms lead interval during the CPT.

A significant Group � Prepulse Type interaction is shown. nControls

showed cue4noncue prepulse inhibition (po.004). nnControls showed

cue1distractor4noncue prepulse inhibition (po.03). nnnIn contrast, the

schizophrenia patients showed cue1distractor4cue (po.001),

suggesting they allocated excessive controlled processing to the task-

irrelevant distractor.

greater differential eyeblink inhibition between the cue and the

cue1distractor prepulse, t(36)5 2.50, po.02, d5 0.81. These

findings demonstrate that the patients are capable of showing

normal amounts of attentional modulation of PPI; however, the

attentional modulation was driven by capture of attention by the

distractor prepulse rather than the voluntary allocation of at-

tention to the cue prepulse.

Long-lead interval effects. To determine whether patients ex-

hibited deficits in controlled processing at the long-lead interval,

the startle modification scores were submitted to a 2 (group) � 3

(prepulse type) � 3 (trial block) ANOVA. As seen in Figure 3,

this analysis revealed that the overall effect of startlemodification

was significant, F(1,36)5 490.26, po.001, with participants re-

sponding less to the startle stimulus during the CPT prepulses

than during the startle alone baseline trials (overall

mean5 � 63.4, SD5 31.8). However, the group effect, F

(1,36)5 1.82, p5 .19, prepulse type effect, F(2,72)5 1.23,

p5 .29, trial block effect, F(2,72)5 1.44, p5 .24, Group � Pre-

pulse Type interaction, F(2,72)5 1.26, p5 .29, Group � Trial

Block interaction, F(2,72)5 0.84, p5 .43, Prepulse Type � Trial

Block interaction, F(4,144)5 2.00, p5 .10, and Group � Pre-

pulse Type � Trial Block interaction, F(4,144)5 1.05, p5 .38,

were all nonsignificant. Thus, long-lead interval startle modifi-

cation to the CPT prepulses did not differ between the patients

and the controls, or between cue and noncue prepulses.

Startle Modification during the Distractor Prepulse

in Baseline Period

Short lead–interval (PPI) effects. PPI during the distractor-

alone prepulse presented during baseline when there was an oc-

casional longer-than-usual gap betweenCPTstimuli was thought

to provide a measure of predominantly automatic attentional

processes to a passively attended stimulus. To determine if pa-

tients exhibited a deficit in automatic sensorimotor processing of

the distractor prepulse, the PPI scores were submitted to a be-

tween-groups ANOVA. This analysis revealed that there was a

significant overall level of PPI, F(1,36)5 303.38, po.001, and no

groupmain effect, indicating that both groups showed significant

overall eyeblink inhibition and patients did not differ from

healthy controls (controls: M5 � 71.5, SD5 22.5; patients:

M5 � 67.0, SD5 41.5), F(1,36)5 0.38, p5 .54. These results

indicate that during the baseline period, patients exhibited nor-

mal PPI during the passive distractor prepulse.

Long-lead interval effects. It was anticipated that startle

modification to the distractor alone prepulse at the long-lead

interval would provide a measure of predominantly automatic

arousal processes (Graham, 1975). The long-lead interval startle

modification scores for the distractor prepulse were submitted to

a between-groups ANOVA which revealed startle modification

was not significant (for either facilitation or inhibition) in either

group at 1200 ms (M5 � 6.21 for patients, SD5 60.29, and

M5 21.00 for controls, SD5 91.74; patients and controls did

not differ, F [1,36]5 1.19, p5 .28).

Behavioral Performance

As predicted, the groups differed significantly in CPT perfor-

mance, t(36)5 2.46, po.05, d5 .79. The mean transformed A0

score was 2.99 (SD5 0.09; range: 2.71–3.03) for the matched

controls and 2.89 (SD5 0.15; range: 2.54–3.03) for the patients.

It is noteworthy that 5 of the 20 patients had perfect A0 scores.

Eleven of the 18 control participants obtained perfect A0 scores;

however, 2 of the controls performed well below the rest of the

healthy controls (their scores were 2.71 and 2.80). Because the A0

scores of both groups, particularly the controls, showed ceiling

effects, we performed a nonparametric test (the Mann–Whitney

U test) on the group difference in addition to the t test. This was

also highly significant, z5 2.68, po.01. Taken together, there

was a fair amount of overlap in performance scores for the two

groups even though the patients as a group performed signifi-

cantly more poorly than the controls.

Although patients and controls did differ on accuracy of sig-

nal detection, they did not differ in reaction time on trials on

which targets were detected, t(36)5 0.62, p5 .54. Mean reaction

time for patients was 425 ms (SD5 78 ms) and mean RT for

controls was 441 ms (SD5 83 ms).

Relationship between Behavioral Performance

and Startle Modification

To test for relationships between performance on the CPT task

and startle modification, we computed the Pearson correlation

coefficients between A0 and startle modification during the cue,

noncue, and cue1distractor prepulses at 120 ms and 1200 ms,

averaged over trial blocks, and cue minus noncue differences at

120 and 1200 ms averaged over trial blocks. Because of the lim-

ited variability of A0 measures in the control group, correlations

were computed separately for the two groups (eight correlations

per group). No significant correlation was found between startle

modification scores during any of the prepulse types or cueminus

noncue difference scores and CPT performance in either group.

Correlations among controls ranged between� .12 and .34

(df5 16), and correlations among patients ranged from� .43

and .10 (df5 18).

Discussion

Startle Modification during the CPT

The finding of performance deficits in the patient group is con-

sistent with the CPT literature on schizophrenia (Nuechterlein,

1991; Nuechterlein et al., 1992). In particular, Nuechterlein et al.

(1992) reported that signal/noise discrimination level (d0) in a

memory–load CPT similar to the one employed in the present

study was significantly lower in patients during remission and

even more deficient during psychotic states compared to healthy

controls. The present study extends these seminal findings by

using a startle paradigm to shed light on the nature of attentional

deficits observed during a memory-load CPT.

Deficient attentional startle in schizophrenia 637

Figure 3. Startle modification at the 1200 ms lead interval as a function of

Group and Prepulse type shows no healthy control-schizophrenia differences.

Our first hypothesis, that schizophrenia patients would fail to

attentionally modulate PPI during the CPT, was confirmed. The

healthy control group showed significantly greater PPI to the cue

than to the noncue prepulse, whereas the patient group did not.

Our second hypothesis, that patients would show reduced startle

modification at long-lead intervals, was not confirmed, as pa-

tients and controls both showed significant startle inhibition that

was not different across prepulse types. Our third hypothesis,

that patients would be less able to avoid attention capture by the

distractor prepulse, was supported for the short-lead interval

measure. The patient group showed significantly greater PPI to

the cue1distractor than to the cue prepulse, whereas the healthy

control group did not. Finally, startle modification measures

were found to be uncorrelated with schizophrenia-related CPT

deficits.

Consistent with our earlier results with college student par-

ticipants (Hazlett, Dawson, et al., 2001), the matched controls in

the present study showed greater PPI to the cue than the noncue

prepulses at the short-lead interval. This attentional modulation

of startle at the short-lead interval indicates that approximately

120 ms following the prepulse, an early evaluation of the signifi-

cance of the cue prepulse has occurred. This finding is consistent

with other work showing that startle inhibition at short-lead in-

tervals can be modulated by attention in healthy individuals in a

discrete–trial selective attention task (Bohmelt et al., 1999; Filion

et al., 1993; Hawk, Pelham, & Yartz, 2002; Rissling et al., 2005).

In contrast, the patients failed to show attentional modulation of

PPI during the cue compared with the noncue prepulses.

This result is consistent with previous research showing both

medicated (Dawson et al., 1993, 2000) and unmedicated

schizophrenia patients (Hazlett et al., 1998, 2007) exhibit defi-

cient attentional modulation of PPI during an auditory selective

attention task. Previous work suggests that attentional modula-

tion of PPI at a lead interval of 120 ms reflects stimulus discrim-

ination and greater allocation of limited controlled processing

resources to a stimulus identified as task significant (Dawson et

al., 1993, 1997). Thus, the finding in the present study of non-

differential eyeblink inhibition to the cue and noncue prepulses in

the patient group is interpreted as a deficit in controlled attent-

ional processing, more specifically, the failure of voluntary mod-

ulation of an automatic process.

With respect to attention capture by the distractor prepulse,

in the patient group, the greater PPI produced by the cue1dis-

tractor than by the cue alone demonstrates an inefficient allo-

cation of attentional processing. In contrast to the patients, the

controls appeared to effectively ignore the distractor as indicated

by an equal amount of eyeblink inhibition to the cue prepulse and

the cue1distractor prepulse. This finding is consistent with the

hypothesis of Nuechterlein and Dawson (1984b) that CPT defi-

cits in schizophrenia may be caused at least in part by devoting

more of the available limited processing capacity to task–irrel-

evant stimuli. The fact that controls showed equal levels of PPI to

the cue and the cue1distractor, both of which were greater than

the PPI to noncues, suggests that their allocation of controlled

resources to the cue1distractor is dominated by their voluntary

controlled allocation to the cue, and this allocation represents a

‘‘there it is’’ response to a cue whose template has been main-

tained in working memory. The presence of the distractor does

not cause any additional allocation of attentional resources. The

fact that the patients show greater PPI to cue1distractor than to

cue alone suggests that their processing of the cue1distractor

reflects largely an automatic allocation of resourcesFa ‘‘what is

that?’’ response that they cannot suppress. However, it is also

true that PPI among both the controls and the patients during the

cue1distractor is very strong (470% in both groups). It is pos-

sible that the failure of the controls to show greater PPI to the

cue1distractor than to the cue alone may represent a ceiling

effect on startle suppression.

At the long-lead interval, both patients and controls showed

significant and nondifferential eyeblink inhibition. These results

for the controls replicate the results of Hazlett, Dawson, et al.

(2001) and Rissling et al. (2005). This finding suggests that this

particular patient group may not be deficient in the later, mo-

dality specific attentional processes activated by the CPT. This

finding differs from our prior work (Dawson et al., 1993, 2000;

Hazlett et al., 1998, 2007) that found differences in attentional

modulation of long-lead interval prepulse facilitation in a selec-

tive attention tone length-judging task, with controls showing

greater facilitation to an attended than to an ignored stimulus,

whereas patients did not. This result was interpreted as reflecting

decreased sustained attention to the attended stimulus compared

with the ignored stimulus among patients. However, this task

employed discrete trials with relatively long interstimulus inter-

vals (20–30 s) with both task-relevant and startle stimuli in the

auditory modality and the tones to be judged as either 5 s or 7 s (5

s or 8 s inHazlett et al. studies) in duration. In contrast, long-lead

interval startle modification in the CPT task was measured while

no task-related stimulus was physically present (CPT digits were

33 ms in duration). At this point, startle may be dominated by

general (as opposed to cue-specific) modality-specific attention

processes aimed at screening out cross-modality stimuli, pro-

cesses in which these patients may not be deficient.

Taken together, these findings suggest that startle modifica-

tion at the short- and long-lead intervals reflects a sequence of

two processes activated by the CPT; one is impaired in the patient

group and the other does not appear to be impaired. First, pa-

tients are deficient in the allocation of controlled resources in-

volved in the encoding and discrimination of the cue and noncue

stimuli at approximately 120 ms. This deficiency is reflected by

the lack of differential eyeblink inhibition to the cue and noncue

prepulses. Further, the finding of more eyeblink inhibition to the

cue1distractor prepulse than to the cue alone in the patient

group indicates that controlled resources are being inappropri-

ately allocated to task–irrelevant stimuli, suggesting an inability

to ignore distracting stimuli. Second, at the long-lead interval, a

more general anticipatory attention process occurs while atten-

tion is focused on the visual modality following both cue and

noncue prepulses. Both the controls and patients showed sig-

nificant yet nondifferential eyeblink inhibition following the cue

and noncue prepulses. According to this hypothesized sequence

of events, relatively asymptomatic schizophrenia outpatients

may not be deficient in the later modality-specific anticipatory

attention process.

These results suggest that a major source of the schizophrenia

patients’ impaired CPT performance has to do with encoding of

the task-related stimuli and perhaps not with maintenance of the

task instructions in working memory. At 120 ms following stim-

ulus onset, the patients show no evidence of having discriminated

the differential task relevance of the cue compared to the noncue.

Normal participants, on the other hand, have made the discrim-

ination between the cue and noncue and are inhibiting the startle

reflex more following the cue. In contrast, at the long-lead

interval following the cue, both patients and controls are exhib-

iting equal startle inhibition to both the cues and noncues. To the

638 E.A. Hazlett et al.

extent that the startle modification at the long-lead interval re-

flects anticipation of the target following the cue, the patients are

not abnormal in this anticipation and, therefore, do not appear

abnormal in maintenance of task instructions and modality-

selective attention.

Startle Modification during the Distractor Alone

In terms of the startle effects during the passively attended dis-

tractor prepulse, the patients did not differ from healthy controls

at either the short-lead interval or the long-lead interval. In

the present study, startle to the distractor alone is considered

a measure of predominantly automatic processing to a passively

attended prepulse, one that is presented when a task-relevant

stimulus is not present. It is important to remember that these

(auditory) distractor-alone prepulses were in a differentmodality

from the primary visual vigilance task, and they did not require

processing in order to perform the primary task. Thus, the find-

ing that patients and controls did not differ in the amount of PPI

produced by the distractor prepulse presented alone during

the baseline period suggests that the patients do not have a deficit

in automatic sensorimotor gating under these experimental

conditions.

The finding of normal short-lead interval PPI in the patient

group during these passively attended distractor prepulses con-

trasts with several previous findings (e.g., Braff et al., 1978; Braff,

Geyer, & Swerdlow, 2001; Swerdlow et al., 2006). Across all of

these studies employing passive attention paradigms, as well as in

other studies, the schizophrenia patients exhibited impaired PPI

compared with healthy controls. The failure of the present study

to confirm previous observations of PPI deficits in schizophrenia

to nontask stimuli may stem from some combination of the fol-

lowing factors.

First, several paradigmatic characteristics in the present study

differ from those employed in previous research. Potentially im-

portant sources of variance include the use of explicit instructions

regarding the nature of the prepulses in the present study, in

contrast to an uninstructed passive attention paradigm that was

most often previously employed. In addition, the distractor pre-

pulses used in the present study were continuous 1000-Hz

70-dB(A) tones without imposed background noise, whereas

previous reports of reduced PPI during a passive task utilized

primarily brief discrete white noise prepulse stimuli (e.g., 75–90

dB(A) of white noise), which were presented over a constant

background white noise of 70 dB(A), making the prepulses diffi-

cult to detect. Braff, Geyer, Light, et al. (2001) found that

schizophrenia patient–control differences in passive PPI maxi-

mize when brief discrete white noise prepulses are used. More-

over, Hsieh, Swerdlow, and Braff (2006) have demonstrated that

PPI is greater among normal participants (with an 86-dB(A)

prepulse) when background noise is 54 dB(A) versus 70 dB(A),

suggesting that discriminability of the prepulse is critical. Wynn

et al. (2004) and Ford, Roth, and Pfefferbaum (1999), who did

not use a background noise, failed to find passive PPI deficits in

schizophrenia patients using brief white noise prepulses. PPI

deficits in schizophrenia patients may appear only when the sen-

sory gating system is in some sense taxed, either by prepulses that

are difficult to detect or by the requirements of a selective atten-

tion task that requires top-down control of the process, and may

not occur when single, easily detected prepulses are presented

with relatively long intertrial intervals.

Second, the patient population in the present study differs

from those tested in previous startle modification research using

passive attention tasks. Specifically, the patients in the present

study had a relatively recent onset of schizophrenia and were in a

relatively asymptomatic period at the time of testing, whereas

previous research with passive attention tasks involved more

heterogeneous groups of patients in terms of chronicity of illness,

years of neuroleptic treatment, number of hospitalizations, and

concurrent psychotic symptoms. However, the findings of startle

modification abnormalities similar to those seen in patients

among persons with schizotypal personality disorder (Caden-

head et al., 1993, 2000) and relatives of schizophrenia patients

(Wynn et al., 2004) raise doubt that differences between the

present findings and those of previous research are due to lower

levels of symptoms in the patients in the present study.

Startle modification to the distractor-alone prepulse at the

long-lead interval was used as a measure of predominantly au-

tomatic processing. The long-lead interval facilitation of eyeblink

frequently seen in passive paradigms (e.g., Graham, 1975, 1979,

1980) is hypothesized to reflect what Graham (1975, p. 243)

described as an automatic arousal effect that is considered to be

independent of controlled processes. In an earlier study of startle

modification during this CPTparadigm (Hazlett, Dawson, et al.,

2001), college students showed significant eyeblink facilitation

during baseline periods to the distractor prepulse at the long-lead

interval, which is consistent with the previous work employing

passively attended prepulses at long-lead intervals. The failure of

the patients and controls in the present study using the same

paradigm to show reliable startle modification at this point may

reflect a tendency of college students to show stronger orienting

activity than the present participants, few of whom had attended

college. The discrepancy between the previous findings with col-

lege students and the present results with patients and matched

controls using the same paradigm may reflect a tendency of col-

lege students to show stronger arousal during the distractor-

alone prepulse.

General Conclusions

Do schizophrenia patients have deficits in startle modification

consistent with deficits in automatic processing, or deficits in

controlled processing, or both? The present study included mea-

sures of automatic and controlled processing of startle during

both ‘‘actively’’ and ‘‘passively’’ attended prepulses on a within–

subject within–task basis. The results of this study suggest that

during this task, patients exhibit deficits in predominantly con-

trolled processes. Predominantly automatic sensorimotor gating

processes appear to be normal in the patients under the present

experimental conditions.

The finding that schizophrenia patients failed to show greater

PPI to a task-relevant cue than to a noncue in the CPT task is

consistent with our previous research using a continuous pre-

pulse tone (Dawson et al., 1993, 2000; Hazlett et al., 1998, 2007)

and suggests that patients are deficient in early stimulus encoding

and discrimination and the allocation of controlled resources to

task-relevant stimuli (Nuechterlein & Dawson, 1984a). The

present study extends earlier work by showing that patients’ fo-

cus of attention is more vulnerable than that of controls when a

task–irrelevant distracting prepulse is included in the paradigm.

Specifically, the patients showed increases in PPI in response to

the cue1distractor stimulus compared to the cue stimulus alone.

This differential PPI suggests that differential automatic alloca-

tion of attention is possible for schizophrenia patients, but im-

plies that allocation is not governed by task significance in a

normal voluntary fashion.

Deficient attentional startle in schizophrenia 639

A potential limitation in interpreting these data occurs be-

cause the patients (except for one) were receiving antipsychotic

medication. However, recent work suggests antipsychotic med-

ications may, if anything, improve PPI deficits, at least in passive

attention tasks (Weike, Bauer, & Hamm, 2000; Kumari &

Sharma, 2002; Quednow et al., 2006), thus reducing the appear-

ance of patient–control differences. However, the improvement

in PPI is much more marked with the atypical antipsychotics

(e.g., Swerdlow et al., 2006), and the present patients were re-

ceiving a typical antipsychotic, fluphenazine. In addition, we

have reported deficient attentional modulation of PPI in un-

medicated schizophrenia patients during a tone discrimination

paradigm (Hazlett et al., 1998, 2007). Whether the attentional

modulation of PPI is also improved by atypical antipsychotic

medication is a subject for future research. It is also clear that the

CPT deficits in schizophrenia are, if anything, partially alleviated

by antipsychotic medication (Orzack, Kornetsky, & Freeman,

1967; Sax, Strakowski, & Keck, 1998; Spohn, Lacoursiere,

Thompson, & Coyne, 1977). Therefore, it is highly unlikely that

medications can account for the present results.

Another limitation of the present study is that we probed the

CPT process at only 120 ms and 1200 ms after the CPT stimuli.

We felt that probing more often to include more probe latencies

might have distorted the CPTprocess by focusing attentionmore

on the probe stimuli and disrupting CPTperformance. This study

leaves open the question of whether development of PPI on the

part of the patients simply lags that of controls, so that attent-

ional modulation of PPI might have appeared at a later point.

However, in our earlier studies of PPI in schizophrenia (e.g.,

Dawson et al., 1993, 2000), which found attentional modulation

of PPI at 120ms in controls but not in patients, we also probed at

240 ms after prepulse onset. PPI at this later point was reduced in

both groups compared to that seen at 120 ms, and neither group

showed attentional modification at this point, so the schizophre-

nia patients did not ‘‘catch up’’ to controls in terms of developing

greater PPI to an attended than to an ignored prepulse. On the

other hand, the prepulses in these studies were auditory, and PPI

to visual prepulses shows a somewhat longer latency, so we can-

not be sure that at a slightly longer probe latency, patients might

not have shown attentional modulation in the present study. The

startle probe paradigm could be fruitfully used in further research

to more fully track the allocation of attentional resources

throughout the sequence of stimulus presentation in the CPT.

In conclusion, the present startle modification results indicate

that deficits in CPTperformance may be caused by two different

factors suggested by Nuechterlein and Dawson (1984b). First, as

indicated by the lack of differential eyeblink inhibition to cue and

noncue prepulses at the short-lead interval, the patients failed to

allocate controlled resources appropriately to task-relevant cues.

This would appear to reflect a failure of top-down controlled

attention processes to modify what may be, in other circum-

stances, a largely automatic mechanism (basic PPI). Second, as

indicated by greater eyeblink inhibition to the cue1distractor

prepulse compared to the cue prepulse at the short-lead interval,

the patients’ attention is captured by task–irrelevant stimuli that

were not even in the same sensory modality.

Startle modification measures were not correlated with be-

havioral performance in either of the groups in the present re-

search, nor did we find them to be correlated in our previous

study (Hazlett, Dawson, et al., 2001) with college student par-

ticipants. One factor that would mitigate against such a corre-

lation is a restricted range of performance scores in both the

patient and matched control groups, with performance being

quite good in both groups, as it was with the college students.

Rissling et al. (2005), on the other hand, found performance to

be more variable in a more demanding CPT with perceptually-

degraded stimuli in college students and reported a significant

correlation among normal participants, with greater PPI asso-

ciated with better performance. The use of the more difficult

perceptually degraded stimulus CPTwith schizophrenia patients

may also reveal a correlation between PPI and behavioral per-

formance deficits. However, previous investigations have also

failed to find correlations between schizophrenia-related PPI

deficits and behavioral measures of neurocognitive functioning

(e.g., Swerdlow et al., 2006).

The results of the present research suggest that the measure-

ment of startle modification is a useful tool to quantify both

automatic and controlled attentional impairments in schizophre-

nia. Previous startle modification research in schizophrenia has

focused solely on discrete–trial paradigms. However, the results

of this study offer encouragement to investigators interested in

using startle modification to explore specific time-linked phases

of attentional processing in continuous tasks known to reveal

deficits in schizophrenia.

As we begin to understand the cognitive processes underlying

CPT deficits in schizophrenia, it will also be important to under-

stand the neural circuits that subserve these attention processes.

Compared with healthy controls, FDG-PETscans in schizophre-

nia patients show abnormally low relative glucose metabolism in

dorsolateral prefrontal cortex (DLPFC) and ventral caudate

(Buchsbaum et al., 1990; Siegel et al., 1993), as well as, a lack of

thalamo-cortical intercorrelations (Katz et al., 1996) during de-

graded stimulus CPT performance, suggesting circuitry dysfunc-

tion. More recent work using functional magnetic resonance

imaging during amemory-load CPTsimilar to the one used in the

current study confirms DLPFC and thalamic dysfunction in pa-

tients (e.g., Barch et al., 2001; Salgado-Pineda et al., 2003). These

findings converge with animal (e.g., Swerdlow, Geyer, & Braff,

2001) and human (Hazlett et al., 1998; Hazlett, Buchsbaum,

et al., 2001; Kumari et al., 2003) work indicating PPI is mod-

ulated by cortical-striato-thalamic circuitry. Thus, the observed

deficiencies in controlled processing measured with startle mod-

ification and poor CPTperformance in schizophrenia may have a

common neural substrate. Given its known neurobiological sub-

strates and genetic loading related to schizophrenia, a combined

startle-CPT paradigm may be an excellent candidate measure to

use in clinical studies to examine how different antipsychotics

normalize these neural substrate deficits.

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(Received April 25, 2007; Accepted October 26, 2007)

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