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ifferential Effect of HIV Infection and Alcoholismn Conflict Processing, Attentional Allocation,nd Perceptual Load: Evidence from a Stroopatch-to-Sample Task

ilman Schulte, Eva M. Mueller-Oehring, Margaret J. Rosenbloom, Adolf Pfefferbaum, anddith V. Sullivan

ackground: Alcoholism and human immunodeficiency virus (HIV) infection each can impair components of selective attention,robably through disruption of the integrity of the frontoparietal neural systems that underlie conflict processing, attentionalllocation, and perceptual load.ethods: We studied 18 patients with alcoholism (ALC) alone, 19 with HIV infection alone (HIV), 20 with both disorders (H�A), and

9 healthy control subjects (CTL). We used a novel paradigm (Stroop Match-to-Sample tasks), in which subjects saw either a valid ornvalid color cue before a target word, printed in a color that was either congruent or incongruent with the word’s meaning.esults: All groups showed a significant Stroop effect, cue–target color Match effect, and interaction between Match and Stroop, withn exaggerated Stroop effect for the Match condition. The HIV patients were comparable to CTL, whereas ALC showed mild delays, withurther delays associated with comorbidity with HIV. Although H�A profited from a valid match to Stroop stimuli, they wereompromised in disengaging attention from the invalidly cued color.onclusions: Impairment in conflict processing and attentional allocation in alcoholism suggests disruption of frontal–parietalttentional systems. Although HIV alone did not demonstrate detectable impairment in performance, HIV conferred liability on

ttentional processes when combined with alcohol abuse.

ey Words: Human immunodeficiency virus, alcoholism, selectivettention, Stroop, Match-to-Sample, frontoparietal attentionetwork

lcoholism is highly prevalent in the United States, withestimates of approximately 14 million individuals meetingcriteria for alcohol abuse or dependence (NIAAA 2001).

n addition, human immunodeficiency virus (HIV) infection haseen estimated as affecting between 720,000 and 950,000 in 2002Osmond 2003). Moreover, lifetime prevalence rates of alcohol-se disorders among HIV-positive populations are estimated toange from 29% to 60% (NIAAA 2001). The comorbidity of HIVnd alcoholism poses serious health problems for affectedndividuals and might have deleterious additive effects on cog-itive functioning (Fein et al 1998; Green et al 2004; Justice et al004). Human immunodeficiency virus and alcohol abuse eachan result in deficits in components of selective attention (Evertnd Oscar-Berman 2001; Hardy et al 2004; Rippeth et al 2004),ediated predominantly by cortical networks involving posteriorarietal and frontal association areas and the anterior cingulumDevinsky and D’Esposito 2003). Little is known, however, abouthe combined effects of alcohol abuse and HIV on selectivettention, even though primary pathology of each disease affectseural systems known to underlie component processes ofelective attention.

rom the Neuroscience Program (TS, MJR, AP), SRI International, Menlo Park;and the Department of Psychiatry and Behavioral Sciences (EMM-O, MJR,AP, EVS), Stanford University School of Medicine, Stanford, California.

ddress reprint requests to Edith V. Sullivan, Ph.D., Stanford UniversitySchool of Medicine, Department of Psychiatry and Behavioral Sciences(MC 5723), 401 Quarry Road, Stanford, CA 94305-5723; E-mail: edie@stanford.edu.

eceived May 6, 2004; revised September 9, 2004; accepted September 27,

2004.

006-3223/05/$30.00oi:10.1016/j.biopsych.2004.09.025

Selective attention refers to the ability to focus current, activethought on one of multiple available sources of information andto select relevant from irrelevant information from such an array.A paradigm used widely to study these sort and select processesof attention is the Stroop color–word interference task (Stroop1935). The Stroop effect describes the prolonged response whensubjects are asked to name the ink color of a word printed in acolor incongruent with the word’s meaning (e.g., the word BLUEprinted in red ink) relative to when the word’s meaning and inkcolor are the same (e.g., BLUE printed in blue ink). Executivefunctions of conflict monitoring and response inhibition betweencompeting stimulus attributes in the Stroop task (Bush et al 2003;Carter et al 1999; Fan et al 2003; MacDonald et al 2000; Salo et al2001) are likely dependent on the prefrontal and anterior cingu-late cortex (Carter 2000; Kerns et al 2004; MacDonald and Carter2003; Pardo et al 1990).

Compromise of the cortico-cortical circuits linking prefrontaland parietal cortices in both alcoholism (Pfefferbaum et al 1997;Sullivan et al 2003) and HIV infection (Ernst et al 2002; Winsaueret al 2002) are thought to contribute to disruption of at least asubset of component attentional processes in alcoholism (Eck-ardt et al 1996; Pfefferbaum et al 2001; Schulte et al 2001, 2002;Sharma et al 2001; Stormark et al 1997; Sullivan et al 1992; Zhanget al 1997) and HIV (Hardy and Hinkin 2002; Hinkin et al 1999,2000; Martin et al 2004; Sahakian et al 1995). Functional deficits,shown to be attributable to alcohol-related disruption of prefron-tal–parietal neural systems (Desmond et al 2003; Pfefferbaum etal 2000; Sullivan 2003), affect cognitive control (Dao-Castellanaet al 1998; Evert and Oscar-Berman 2001) and orienting ofattention (Polo et al 2003; Schulte et al 2001). Similarly, HIVaffects frontoparietal system functions, even at an early stage ofthis disease, before acquired immune deficiency syndrome isclinically diagnosed (Grant et al 1987; for review see Pfefferbaumet al 2002). In a functional magnetic resonance imaging (fMRI)study, Chang et al (2001) reported greater activation in frontal

and parietal cortices in HIV patients than in control subjects but

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imilar behavioral performance in working memory tasks requir-ng different levels of attention. Neural damage caused by HIVnfection might necessitate greater attentional modulation of theeural circuits by recruiting compensatory brain reserve (Changt al 2001; Chao et al 2003; Ernst et al 2003).

To address attentional control in HIV infection and alcoholbuse, we combined a computerized version of the Stroop taskith a novel Match-to-Sample task. In this paradigm, matchecisions were based on a color cue that directs attention to apecific color and primes the color processing of the Strooptimulus. Other researchers (Christman 2001; Egeth et al 1969;irzi and Egeth 1985) have also combined matching with thetroop task by asking subjects to decide whether a concurrentlyresented patch and a Stroop stimulus are the same color. Inontrast, we presented the two stimuli sequentially to addressttentional allocation with the color patch, which served as a cuePosner and Petersen 1990), and to engage sensory attentionechanisms associated with parietal (Corbetta et al 1991) and

isual association (Heinze et al 1994; Kastner et al 1998) cortices.hen the cue color correctly predicts the color of the Stroopord (match), visual identification of the color should be suffi-

ient to elicit a response and to reduce interference caused by theonflicting word information; however, when the color cueisdirects attention in nonmatch trials, interference should be

xacerbated.In the sequence of processing from perception to action, our

aradigm also examined the contribution of early sensory func-ions on Stroop effect by varying the sensory input with redun-ant paired (i.e., two identical Stroop stimuli) or single Strooptimulus presentations (for redundant target effects; Reuter-orenz et al 1995; Schulte et al 2004). Although redundant stimulirovide no further novel information than singly presentedtimuli, Yee (1991) found suppression effects (i.e., slowed re-ponse time), when presenting redundant word information in atroop paradigm (two irrelevant flanker words vs. a singlelanker word).

Thus, we propose that in addition to the attentional top-downnfluence, behavioral inhibition in Stroop interference can beanipulated by sensory bottom-up influence on attribute selec-

ion (Lavie 1995). Investigations of selective attention with thetroop task in patients with alcoholism or HIV have yieldedixed results, possibly owing to differences in task requirements

Salo et al 2001, 2002) and their effects on component attentionalrocesses, or to differences in disease stage or severity. Specifi-ally, alcoholics have shown enhanced Stroop-color interfer-nce, with longer reaction times (RTs) (Stormark et al 2000) andmpaired vigilance (Duka et al 2003) compared with controlubjects; however, the Stroop effect has not always been forth-oming (Noel et al 2001). Likewise, individuals with HIV exhib-ted an exaggerated Stroop effect compared with control subjectsn a computerized version of the Stroop but not on a traditionalaper-and-pencil Stroop version (Martin et al 1992), yet theyhowed the opposite pattern in another study (Hinkin et al 1999).

A further potential complication derives from the significantomorbidity of alcoholism and HIV, with potential differential asell as additive effects (Fein et al 1995, 1998; Meyerhoff 2001;fefferbaum et al 2002). For example, in an electrophysiologictudy, Fein et al (1995) found a deleterious additive effect of HIVnd alcohol abuse on the latency of the P3a, an event-relatedotential component associated with orienting that is thought toe a composite response of an early parietal and a later frontal

ubcomponent (Polo et al 2003). No study, however, has tested

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the combined effects of HIV and alcohol abuse on attentionalcomponents of interference processing.

We tested the following hypotheses. First, we assumed thatselection of stimulus attribute (color/word) information isinfluenced by sensory attentional control mechanisms. Here,priming the color system with a color cue should havefacilitating effects on RTs and reduce the Stroop conflict whenthe color cue matches the color of the Stroop stimuluscompared with nonmatch trials. Second, we proposed earlybottom-up influence of sensory input, whereby paired targetswould compound the Stroop effect if containing incongruentcues but facilitate RT if containing congruent cues (Yee 1991).Here, priming the color system with a valid/match color cueshould have facilitating effects on RTs and reduce the Stroopconflict. Third, we expected that all subjects would showStroop effects, but to different degrees, depending on theneural system compromised. Specifically, we expected thatHIV alone would lead to only mild degrees of cognitiveimpairment in Stroop performance by eliciting attentionalcontrol mechanisms (no impairment in attentional control tosensory functions) and that alcohol would have a strongereffect on Stroop conflict (compromised attentional control tosensory and executive functions), with further exacerbationfrom the combined effect of HIV and alcoholism (Table 1).Finally, we predicted three sources of interaction influencingthe Stroop effect: 1) perceptual stimulation (single vs. paired);2) sensory attentional functions (match vs. nonmatch); and3) disease comorbidity (alcoholism and HIV).

Methods and Materials

SubjectsFour groups participated in the study: 19 control subjects

(CTL), 18 patients with alcoholism (ALC), 19 with HIV infection(HIV), and 20 patients with alcoholism and HIV combined(H�A). Alcoholic and HIV patients were recruited from localrehabilitation programs and clinics, and control subjects werevolunteers from the local community. All subjects gave writteninformed consent to participate in the study, which was ap-proved by the institutional review boards at Stanford UniversitySchool of Medicine and SRI International. All volunteers werescreened by trained clinicians using the Structured ClinicalInterview for DSM-IV diagnosis (American Psychiatric Associa-tion 1994) and medical examination to exclude any with otherlifetime Axis I diagnoses, current (past 3 months) non–alcoholabuse or dependence diagnosis, or use of drugs (excludingcannabis) in the past month. Subjects were also excluded for a

Table 1. Prediction of Compromised Functions (2) in the Three PatientGroups Measured with the Stroop-Match-to-Sample Paradigm

Patient Group

AttentionalControl,

ExecutiveFunctions

(StroopInterference)

Attentional Control,Sensory Functions

(Cue–Target Match/Nonmatch)

PerceptualSelection

(Paired/SingleStimulation)

HIV 2ALC 22 22 2H � A 222 22 2

ALC, alcoholics; HIV, patients with human immunodeficiency virusinfection; H � A, patients with both HIV infection and alcoholism.

history of insulin coma, psychosurgery, head trauma, docu-

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ented compound skull fracture, clear neurologic sequelae, orny disease with potential central nervous system involvement,uch as stroke, multiple sclerosis, or epilepsy. In addition, 6 CTL,ALC, 2 HIV, and 3 H�A subjects were excluded as statisticalutliers (�3 SD) on RTs, number of errors, negative interferenceffects, failure to complete the task, or poor English skills.

All subjects used a breath-alcohol analyzer to ensure absti-ence from alcohol at the time of testing. The length of absti-ence differed significantly between the alcoholism groups, withonger abstinence in the ALC than in the H�A group (z � �2.34,

� .02, Mann-Whitney U test) (Table 2). Lifetime alcoholonsumption (kg) was assessed with a semistructured interviewPfefferbaum et al 1988). Drinks of each type of alcoholiceverage were standardized to units containing approximately3.6 g of absolute alcohol and summed over the lifetime. Thetudy groups did not differ by age or gender but did by educationnd lifetime alcohol consumption, with both alcohol groups, asxpected, having consumed significantly more alcohol than theontrol and the HIV group. Although alcohol was the preferredubstance for the ALC and H�A subjects, nonalcohol substancesamphetamine, opiates, cocaine, hallucinogens, and sedative-ypnotics) were abused by 56% of the ALC and 75% of the H�Aroup (�2 � 1.59, p � .21). In the HIV group, 32% usedonalcohol substances, which was significantly less than in the�A group (�2 � 39.0, p � .0001). Control subjects had no pastr current abuse or dependence diagnoses. The HIV and the�A groups did not differ in CD4 and viral load for disease

everity. We used the Karnofsky scale (Karnofsky et al 1948) tostimate each patient’s current disease stage; 10.8% of patientsere scored 80 (i.e., normal activity with effort and some signs ofisease), 32.4% 90 (i.e., normal activity; minor signs of disease),nd 56.8% had no evidence of disease (score 100). RegardingIV medication, 68.4% in the HIV group and 55% in the H�Aroup were taking highly active antiviral treatment (HAART).here was no significant difference in medication status betweenhese two study groups (�2 � .74, p � .39).

timuliEach block included 192 stimuli randomly presented on a

1-in monitor of a Macintosh computer (Apple, Cupertino,alifornia) using PsyScope 1.2.5 (http://psyscope.psy.cmu.edu)

or stimulus delivery and reaction time (RT) acquisition. Subjectsixated on a point displayed in the middle of the computer screent the beginning of each trial. Stimuli were presented at 4° visualccentricity (distance of approximately 50 cm) radially distrib-ted around the fixation point, positioned in the visual fielduadrants.

atch-to-Sample TaskIn the Match-to-Sample task, target stimuli were four colored

able 2. Demographic Data and Statistical Results for the Four Groups

nGender

(men/women)Age

(years)Education

(years)Lif

TL 19 8/11 41.4 (9.38) 15.6 (1.92)LC 18 10/8 46.7 (8.4) 13.7 (2.4)IV 19 12/7 41.58 (9.92) 14.4 (2.46)� A 20 15/5 43.5 (6.67) 12.7 (1.3)

ns (�2) ns .001

Data are presented as mean (SD). CTL, control subjects; ALC, alcoholics;oth HIV infection and alcoholism; NA, not applicable.

s following cue stimuli (XXXX) by 150 msec (Figure 1). This

task had two conditions: 1) match versus nonmatch; and 2) singleversus paired targets. It was designed to test whether subjectswere able to perform simple color matching independent ofStroop performance and was given before the Stroop Match-to-Sample task.

Stroop Match-to-Sample TaskThe Stroop Match-to-Sample task was developed to test

sensory and attentional processes of Stroop conflict. Subjectsmatched the color of a cue stimulus (four colored Xs), displayedfor 800 msec in the lower visual field, to the color of a targetstimulus, appearing 300 msec later for 1000 msec, above thefixation point. Target stimuli were color words 1) written in anink either congruent or incongruent with the word’s meaning;2) either single (left or right visual field) or paired (identicalstimuli appearing simultaneously in both fields; i.e., redundanttargets); and 3) either matched or nonmatched to the cue color(Figure 1). In both tasks, subjects were instructed first to sayaloud the color of the target stimulus, then to say either “Yes” or“No,” depending on whether the target color matched the cuecolor, and finally to press the corresponding YES or NO key withtheir right hand. Naming the target color was required becauseneuroimaging data provide evidence that executive control in theStroop task is associated with vocal control regions (Paus et al1993; Picard and Strick 1996), and manual responses are knownto produce reduced Stroop effects (MacLeod 1991).

In the Stroop task, using a neutral condition for detailedanalysis of facilitation and inhibitory effects is difficult becausedifferent neutral conditions produce different results (Jonidesand Mack 1984; MacLeod 1991; Salo et al 2001). For this reason,we examined Stroop effect by comparing congruent and incon-gruent conditions (Koch and Brown 1994); however, we admin-istered the Match-to-Sample task in a block separate from theStroop-Match-to-Sample task, which can be used as a referencecondition to investigate whether Stroop effects are driven bycongruent or by incongruent word types.

Statistical AnalysesMedian RTs for correct YES and NO responses and the

number of errors were computed for each subject for eachcondition. Analyses of variance (ANOVAs) for repeated measureswere carried out to test for effects of group, cue–target match(match–nonmatch), target stimulation (single–paired) in theMatch-to-Sample task (4 � 2 � 2 mixed factors), and additionallyfor a Stroop target effect (congruent–incongruent) in the StroopMatch-to-Sample task (4 � 2 � 2 � 2 mixed factors). For furtherexamination of the Stroop � match interaction, Stroop effectswere calculated by subtracting congruent from incongruent trialsfor match and nonmatch conditions separately. The resulting twovariables, Stroop–match and Stroop–nonmatch, were subjected

Alcohol Intake(kg)

Sobriety(days)

CD4(cells/mm3)

Viral Load(copies/mL)

.41 (52.88) NA NA NA

.89 (426.56) 336.67 (310.5) NA NA9.7 (42.01) NA 495.6 (241.7) 11,311 (19,725)3.1 (553.86) 196.1 (350.9) 511.3 (287.6) 13,010 (18,388)

.0001 .019 ns ns

atients with human immunodeficiency virus infection; H � A, patients with

etime

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378

to a multivariate ANOVA testing for group differences. Spear-

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an’s rho correlation (two-tailed) examined the relationshipetween Stroop and education, Stroop and overall RTs, andtroop and errors in the four study groups. Spearman rhoone-tailed) tested whether HIV disease severity (CD4 T cells)orrelated with Stroop–match performance. The � level was sett .05 for all statistical tests.

esults

In the Match-to-Sample task, there was a significant matchffect, with faster RTs in match than in nonmatch trials [F (1,72) �37.2, p � .0001] but no difference between single and pairedarget stimulation [F (1,72) � .26, p � .61]. The group effect wasignificant [F (3,72) � 5.76, p � .001], with ALC and H�A havingonger RTs than CTL. Moreover, the group � match interactionas significant [F (3,72) � 3.39, p � .022] (Figure 2). Analysis ofariance of nonmatch–match differences yielded a significantroup effect [F (3,72) � 3.03, p � .048], with H�A (post hoc LSDleast significant difference] test p � .005) and ALC (p � .048)howing greater differences than CTL.

Median correct RTs for the Stroop Match-to-Sample task wereubjected to a repeated-measures ANOVA with congruent–in-ongruent, match–nonmatch, and single–pair stimulation asithin-subject factors and group as the between-subjects factor.he Stroop target effect was significant, with RTs to incongruentrials longer than to congruent trials [F (1,72) � 154.93, p �0001]. The cue–target match effect was significant with RTs fastero match trials than to nonmatch trials [F (1,72) � 146.21, p �0001]. The interaction between the Stroop and match conditionas also significant [F (1,72) � 16.32, p � .0001]. Here, the Stroopffect was greater in match than in nonmatch trials for all study

roups, independent of mean RT (see Figure 3, Table 3).

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The single versus paired target stimulation effect was notsignificant [F (1,72) � .65], but the target stimulation � matchinteraction was [F (1,72) � 4.66, p � .034], with paired targetseliciting shorter RTs in match (facilitation) and longer RTs innonmatch (inhibition) trials than single targets (Figure 4). More-over, there was a significant group effect [F (3,72) � 3.43, p �

Figure 1. Diagrammatic explanation of the Match-to-Sample task (left) and Stroop Match-to-Sampletask (right). A color sample (XXXX) was presented150 msec/300 msec before target presentation. Inthe Match-to-Sample task, targets were 4 Xs in color.In the Stroop Match-to-Sample task, target stimuliwere color words written in an ink congruent orincongruent to the words’ meaning. In both tasks,the ink of the target stimulus was either the same(match) or different (nonmatch) to the samples’color.

Figure 2. Match-to-Sample task: mean reaction times (in milliseconds) totargets that did or did not match the preceding color cue for each studygroup: control subjects (CTL), alcoholics (ALC), subjects with human immu-nodeficiency virus (HIV) infection, and subjects with both HIV infection and

alcoholism (H�A). Error bars represent SEM.

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022], with ALC (LSD test, p � .043) and H�A (p � .003) havingignificantly longer RTs than CTL, and significant interactionetween group and Stroop effect [F (3,72) � 3.18, p � .029].nteractions between group and target stimulation (single–pair)F (3,72) � 2.48, p � .068] and group and match [F (3,72) � 2.52,

� .064] differences showed statistical trends.Because of the significant Stroop � match interaction, we

alculated Stroop difference scores (incongruent minus congru-nt trials) for match and nonmatch trials separately. Reactionime differences between congruent and incongruent targettimuli (i.e., Stroop effect) approached significance between thetudy groups in the cue–target match condition [F (3,72) � 2.35,� .079] and differed significantly in the nonmatch condition

F (3,72) � 4.71, p � .005]. In the Stroop nonmatch condition,hen attention was misdirected by an incorrect color cue, postoc comparison of means indicated that H�A showed signifi-antly (LSD, p � .002, p � .003) greater Stroop effects than CTLnd HIV, and ALC showed a trend in the impaired direction (LSD,� .057, p � .087) (see Figure 5).We then used the Match-to-Sample task as a reference

ondition to investigate whether the Stroop � match interaction

igure 3. Stroop Match-to-Sample task: mean reaction times (in millisec-nds) to congruent and or incongruent targets that did or did not match thereceding color cue for each study group: control subjects (CTL), alcoholics

ALC), subjects with human immunodeficiency virus (HIV) infection, andubjects with both HIV infection and alcoholism (H�A). Data were pooledver single and paired conditions. Error bars represent SEM.

able 3. Condition Reaction Time Means for the Four Groups

CTL ALC

ongruent 934.21 (61.14) 1168.26 (111.76)

ncongruent 1073.47 (85.78) 1388.1 (123.96)

aired Difference 139.26 (31.87) 219.83 (28.93)

Test t � �4.37 t � �7.56p � .0001 p � .0001

ongruent % Errors .38 (.08) .55 (.12)

ncongruent % Errors .60 (.10) .76 (.13)

ilcoxon Test Z � �1.87 Z � �1.70p � .06 p � .09

Values in parentheses are SE. CTL, control subjects; ALC, alcoholics; HIV,

IV infection and alcoholism; ANOVA, analysis of variance; MANOVA, multivariat

(higher Stroop difference scores in the match than in thenonmatch condition) was driven by congruent or by incongruentword types. We found a significant match � congruency inter-action [F (1,72) � 18.39, p � .0001] but not a match � incongru-ency interaction [F (1,72) � .008, p � .93], suggesting that theStroop difference scores between congruent and incongruentword types were most likely driven by response facilitation inmatch but not nonmatch trials.

Alcoholic and H�A patients showed prolonged RTs comparedwith CTL that may indicate nonspecific, motoric slowing. Furtheranalysis revealed significant correlations between overall RT andStroop performance in match trials (ALC: rho � .53, p � .03; H�A:rho � .65, p � .002) but not in nonmatch trials (ALC: rho � .15, p

HIV H � A MANOVA/ANOVA

1088.10 (57.13) 1240.87 (81.08) F�2.753p�.049

1296.64 (82.42) 1530.98 (101.59) F�3.810p�.014

208.54 (33.18) 290.11 (37.45) F�3.537p�.019

t � �6.28 t � �7.74p � .0001 p � .0001

.82 (.18) 1.65 (.46) F�4.452p�.006

1.28 (.20) 2.05 (.46) F�5.672p�.002

Z � �2.99 Z � �1.61 F � .550p � �.003 p � .10 p � .65

ts with human immunodeficiency virus infection; H � A, patients with both

Figure 4. Stroop Match-to-Sample task: mean reaction times (in millisec-onds) to single or paired targets that did or did not match the precedingcolor cue for each study group: control subjects (CTL), subjects with humanimmunodeficiency virus (HIV) infection, alcoholics (ALC), and subjects withboth HIV infection and alcoholism (H�A). Data were pooled over congruentand incongruent Stroop conditions. Error bars represent SEM.

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.5; H�A: rho � .19, p � .4). Moreover, there was a correlationetween the HIV-related marker CD4 and Stroop–match perfor-ance (rho � .36, p � .01) but not Stroop–nonmatch performance

rho � �.003, p � .492) in the HIV and H�A groups. Lifetimelcohol consumption correlated positively with Stroop–nonmatchrho � .331, p � .002) and modestly with Stroop–match perfor-ance (rho � .185, p � .056) pooled over all groups.Although groups differed significantly in education, which

ight affect reading and word processing in Stroop, there was noignificant correlation between education and Stroop perfor-ance (pooled over match–nonmatch and single–pair condi-

ions), Stroop match, and Stroop nonmatch within any groupp � .05 for all groups and conditions). Using education as aovariate did not significantly change our main results. In aultivariate analysis of covariance, the group effect for total

troop [F (3,72) � 2.54, p � .06] showed a trend and was notignificant for the Stroop match condition [F (3,72) � 1.45, p �23], but the group effect in the nonmatch condition remainedignificant [F (3,72) � 4.81, p � .004].

Error rates for the Match-to-Sample task revealed a significantroup effect [F (3,72) � 3.86, p � .013], with H�A committingore errors than the other three groups. For the

troop Match-to-Sample task, however, an ANOVA for repeatedeasures (congruent–incongruent, match–nonmatch, single–air) revealed significant effects for Stroop [F (1,72) � 14.5, p �

0001] (more errors in incongruent than congruent trials) andatch conditions [F (1,72) � 7.08, p � .01] (higher number of

rrors in match than in nonmatch trials). Similar to the RT results,e found a significant Stroop � match interaction [F (1,72) �.89, p � .006], with number of errors highest in match–ncongruent trials. There was a significant main effect for groupF (3,72) � 5.56, p � .002]. Again, post hoc LSD test revealed that�A committed significantly more errors than the other threeroups. Number of errors and overall RTs were significantlyorrelated in all four groups (CTL: rho � .51, p � .03; ALC: rho

.67, p � .002; HIV: rho � .62, p � .005; H�A: rho � .46, p �05).

For further analysis of the Stroop � match interaction, weested whether shorter RTs in match congruent trials might haveeen caused by an increased error rate on congruent word typesi.e., augmented facilitation) and used Pearson’s correlation foratch and nonmatch conditions separately. There was a positive

igure 5. Stroop Match-to-Sample task: reaction time differences (in milli-econds) between incongruent and congruent targets (Stroop effect) that

atched (left) or did not match (right) the preceding color cue for eachtudy group: control subjects (CTL), alcoholics (ALC), subjects with humanmmunodeficiency virus (HIV) infection, and subjects with both HIV infec-ion and alcoholism (H�A). Error bars represent SEM.

orrelation between RTs and errors for match (r � .40, p � .0001,

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n � 76) and for nonmatch (r � .42, p � .0001, n � 76)conditions, suggesting that there was no speed–accuracy tradeoff(Salo et al 2001).

Discussion

In this study, we used a combined computerized Stroop andMatch-to-Sample task to test concurrently the role of attentionalcontrol on sensory and executive functions in patients withalcoholism, HIV, and their comorbidity. Performance on Stroopdiffered substantially as a function of color priming and cuevalidity. Patients with HIV did not differ from control subjects inStroop performance when the cue color misdirected attention(Stroop–nonmatch), but alcoholic subjects showed greater inter-ference than control subjects, with further exacerbation resultingfrom the combined diseases. By contrast, the groups did notdiffer when the cue color correctly predicted the target’s color(Stroop–match). Because the HIV groups were matched on viralload and CD4 counts and the alcohol groups were matched onlifetime alcohol use, the comorbid effect likely reflects a com-pounding of adverse factors rather than greater severity of eitherdisease alone.

The Effect of Sensory Control Processes on StroopIn general, our results showed Stroop effects in all groups

(i.e., shorter RTs to congruent than incongruent target stimuli).Interference effects can be minimized by directing attention tothe color attribute of the Stroop stimulus while suppressingattention to the competing word attribute (Hinkin et al 1999).This mechanism was manipulated by priming the color channelwith a color cue in the Stroop Match-to-Sample task. As hypoth-esized, color cues that correctly predicted the color of targetstimuli (match) elicited significantly shorter RTs than when thecue misdirected attention (nonmatch). The difference in RTbetween match and nonmatch conditions can be interpreted asan index of costs and benefits of attentional allocation (Posner1980). The significant Stroop � match interaction effect, withgreater interference in match than in nonmatch trials, demon-strates the facilitating and inhibitory effects of attentional alloca-tion on Stroop performance (Banich et al 2000; Salo et al 2002).Similarly, error analysis revealed a Stroop � match interaction,with greater Stroop difference in the number of errors in matchthan in nonmatch trials.

On first consideration, our results seem counterintuitive becauseone would expect more interference in nonmatch trials than inmatch trials. For example, Vivas et al (2003) reported that visuospa-tial attentional processing affected Stroop interference and foundless interference at cued than uncued locations. Furthermore, ourresult cannot be explained by ceiling effects on RTs in the nonmatchcondition compared with the match condition leading potentially tosmaller differences between incongruent and congruent trials forinvalidly cued trials (e.g., H�A had enhanced RTs and showedgreater [not less] Stroop conflict in the nonmatch condition than HIVor CTL). Alternatively, the conflict hypothesis suggests that incon-gruent trials preceded by incongruent trials will be processed fasterthan those preceded by congruent trials because of the cognitivecontrol mechanism involved in incongruent processing (Kerns et al2004). Applying the conflict hypothesis to the Stroop Match-to-Sample task implies that adjustments happen within each trial andnot between two trials. The common idea is that activation ofattentional control (by either a prior incongruent trial or an invalidcue) facilitates processing of consecutive conflicting information(i.e., incongruent trials). The conflict hypothesis assumes activation

of the same attentional control mechanism, whereas in our task two

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ifferent mechanisms are activated that are both part of the samettentional network (i.e., a parietal mechanism for reorienting ofttention [Thiel et al 2004] and a frontal mechanism for conflictrocessing [Banich et al 2000]). Attentional control mechanisms ofhe type served by parietal systems activated to disengage from thencorrectly cued color may actually have facilitated processing ofncongruent targets. In match trials, the source of conflict was solelyrom incongruent targets and drew on attentional control mecha-isms of the type served by frontal systems activated to monitoresponse conflict (Carter 2000; Pardo et al 1990) and to exertxecutive control (MacDonald et al 2000). Furthermore, valid cuenformation elicited facilitation effects on response selection. Thisue–Stroop context then results in greater RT differences betweenongruent and incongruent Stroop target conditions.

troop Performance in Alcohol Abuse, HIV, and CombinedisorderAs predicted for the Stroop Match-to-Sample task, patients

ith HIV alone performed comparably to control subjects,hereas patients with alcoholism alone showed mild delaysith further exacerbation resulting from the combined effectf HIV plus alcoholism. This finding is consistent with fMRItudies (Chang et al 2001; Ernst et al 2002) reporting that HIVatients showed similar behavioral performance to controlubjects but different brain activation patterns. Althoughlowing of psychomotor speed and information processing iscommon neuropsychological finding in HIV patients, in our

tudy both groups with HIV patients were relatively early inhe course of illness (moderate CD4 values and high Karnof-ky scores), and most were receiving HAART therapy. Byontrast, the impaired performance in ALC and in H�Andicates compromise of selective attentional control mecha-isms in alcoholism (Polo et al 2003).

When match and nonmatch trials were analyzed separatelyn the Stroop Match-to-Sample task, H�A patients did notiffer from control subjects in match trials but showed greatertroop conflict than control subjects in nonmatch trials. Thus,�A profited from valid match, whereas with invalid non-atch trials interference was enhanced compared with control

ubjects and HIV patients. Alcoholics demonstrated a slightlyreater interference than control subjects in Stroop nonmatchut not in Stroop match, suggesting a deficit in disengagingttention from the incorrectly cued color; however, HIVatients did not differ from control subjects and may be ableo compensate for invalid cueing on interference effects byngaging additional attentional control mechanisms imping-ng on brain reserves (Chang et al 2001; Ernst et al 2002).oreover, the correlation between CD4 and Stroop match

rials suggests that enhanced Stroop conflict in HIV possiblyesults from compromised executive control, whereas theensory attentional control mechanisms are unaffected.

In light of generalized slowing in the patient groups, it cane questioned whether the effects of alcohol dependence andts comorbidity with HIV are specific to the frontoparietalelective attention network or involve a more global deficitnd reduced cognitive resources. Because overall RT andtroop nonmatch performance were not correlated in any ofhe study groups, enhanced Stroop interference in alcohol andIV–alcohol comorbidity indicates a specific effect on parietalontrol over sensory information processing that seems to bectivated when disengaging attention (Corbetta et al 1993;osner and Petersen 1990). We speculate that the exaggerated

troop effect in the H�A group may reflect compromise of the

attentional cortico-cortical network, including frontal cortex,anterior cingulate gyrus, and posterior parietal regions. Struc-tural disruption of frontal and parietal cortical sites andconnections between cortices relevant to processes of selec-tive attention occur in both long-term alcohol abuse and HIVinfection (Kril et al 1997; Noel et al 2001; Winsauer et al 2002;for review see Pfefferbaum et al 2002).

Attentional Control of Sensory Functions in Alcohol Abuse,HIV, and Combined Disorder

In the Match-to-Sample task, ALC and H�A groups showedlonger RTs than control subjects. As expected, all subjects re-sponded faster to match than to nonmatch trials, but H�A hadgreater match–nonmatch differences than control subjects. Thisresult also suggests a difficulty in disengaging attention from theincorrectly cued color (Vivas et al 2003). Again, patients with HIValone performed at normal levels on the task, indicating intactattentional top-down control on color attribute selection (Giesbre-cht et al 2003).

To analyze whether visual bottom-up processing contributes tothe Stroop effect, we presented single and paired targets in theStroop Match-to-Sample task. Compared with other groups, H�Atended to have prolonged RTs to paired relative to single targets,indicating an inhibitory influence of processing redundant visualinformation. This effect was not observed in the simpleMatch-to-Sample task. We speculate that in H�A, processes respon-sible for engaging and disengaging attention are particularly dimin-ished and affect conflict processing. In tasks with high attentionalload, like the Stroop Match-to-Sample task, paired targets enhancethis deficit in attentional control. Thus, redundant visual informationseems to alter interference processing, presumably by compro-mised attentional control on stimulus attribute selection. Our find-ings that cueing (match–nonmatch) and to a less extent redundantvisual information (single–paired stimulation) influence Stroop per-formance support the concept of crosstalk between the two pro-cessing channels at a sensory attentional processing level, beforeresponse mechanisms are engaged (Kornblum 1994; Kornblum andLee 1995; Kornblum et al 1990). These sensory attentional andresponse selection processes are differentially affected by alcohol-ism and HIV, with compromised attentional control in alcoholismbut not in HIV and exaggeration of the compromise when thedisorders are combined.

We conclude that these performance patterns in alcoholic sub-jects and subjects with both HIV and alcoholism implicate degrada-tion of frontally and posterior parietally based brain functions ordisruption of the connections linking cortices in the selectiveattention network that underlie sensory and executive controlprocesses. Further, despite absence of observed attentional deficitsin HIV alone, the significant adverse effects of alcoholism incombination with HIV indicate a latent liability and heightenedvulnerability to agents that affect central nervous system functioning(c.f., Sullivan 2003) in ostensibly unaffected HIV individuals.

This research was supported by grants from the NationalInstitute on Alcohol and Alcoholism (AA05965, AA10723,AA12388, AA12999). We thank Anne O’Reilly, Ph.D., AnjaliDeshmukh, M.D., Stephanie Sassoon, Ph.D., Andrea Spadoni,B.A., Julia Sandler, B.A., and Marya Schulte, B.A., for help withrecruiting study participants and assistance in data collection;and Carol Kemper, M.D., Stanley Deresinski, M.D., and JuliaBuss, R.N., for recruitment and screening of the HIV and H�A

patients.

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