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Functional Magnetic Resonance Imaging and Working Memory inAdolescents with Gestational Cocaine Exposure

HALLAM HURT, MD, JOAN M. GIANNETTA, MARC KORCZYKOWSKI, MA, ANGELA HOANG, KATHY Z. TANG, LAURA BETANCOURT, PHD,NANCY L. BRODSKY, PHD, DAVID M. SHERA, SCD, MARTHA J. FARAH, PHD, AND JOHN A. DETRE, MD

bjective To assess the effect of gestational cocaine exposure on the prefrontal cortex (PFC) with functional magneticesonance imaging (fMRI).

tudy design Using an n-back task, we obtained fMRI with a 3T Siemens scanner on 49 adolescents, 25 who were exposedo cocaine and 24 who were not exposed. The primary outcome was PFC activation during task performance. Five functionallyerived regions of interest (ROI) were defined; in addition, 2 a priori anatomical ROIs were generated for Brodmann regions0 and 46.

esults Of the 49 adolescents who underwent imaging, data from 17 who were exposed to cocaine and 17 who were notxposed were in the final analysis. Groups had similar performance on the n-back task (P > .4), with both showing a fewerumber of correct responses on the 2-back than the 1-back (P < .001), indicating increased demands on working memory withreater task difficulty. In functionally derived ROIs, imaging results showed increased activation for both groups in the 2-backersus the 1-back condition. In anatomical ROIs, both groups showed greater activation in the 2-back versus the 1-backondition, with activation in the non-exposed group proportionally greater for the left prefrontal region (P � .05).

onclusion In this sample of adolescents, participants who were exposed to cocaine and participants who were not exposedere similar in performance on an executive function task and in fMRI activation patterns during task performance.J Pediatr 2008;152:371-7)

he growing pre-clinical and clinical literature suggest that gestational cocaine exposuremay affect developing monaminergic (dopamine, serotonin, and noradrenaline) sys-tems that are widely distributed throughout the brain.1,2 These findings, in turn, have

iven rise to concern about injury to the prefrontal cortex in exposed children, with resultantffects on executive functioning, a diverse set of skills such as planning, problem solving,ognitive control, working memory, and reward processing.3 In this regard, investigationsssessing neurobehavioral outcomes and executive function in children with gestational co-aine exposure have found effects ranging from none, to minimal, to impaired recognitionemory, to altered task persistence, to self-regulatory deficits.4-13 There have been several

fforts to anchor such clinical findings with neuroanatomical bases;14-16 however, no consis-ent patterns have been identified. We investigate the neural bases of injury through exami-ation of patterns of brain activation by using functional magnetic resonance imaging (fMRI)uring a task of executive function—in this case, non-spatial working memory as assessed bysing an n-back task.17

Although our earlier behavioral assessments have failed to find an effect of cocainexposure with both spatial and non-spatial working memory tasks,18 behavioral equiva-ence does not imply neural equivalence. Specifically, 2 groups may achieve the sameehavioral performance by using different neural systems, with 1 group’s performanceesulting from compensatory processing mechanisms that differ from the normal brainrocessing involved in the task.19 We therefore undertook an fMRI study to assess the

ocation and degree of neural activation underlying working memory performance inhildren with and without cocaine exposure. We hypothesized that exposed and non-

NOVA Analysis of varianceMRI Functional magnetic resonance imaging

DLPFC Dorsolateral prefrontal cortexROI Region of interest

From the Department of Neonatology, TheChildren’s Hospital of Philadelphia, Philadel-phia, Pennsylvania (H.H., J.G., N.B.); Depart-ment of Neurology and Neuroradiology,Center for Functional Neuroimaging, Hos-pital of the University of Pennsylvania, Phil-adelphia, Pennsylvania (M.K., A.H., K.T.,J.D.); Center for Cognitive Neuroscience,University of Pennsylvania, Philadelphia,Pennsylvania (L.B., M.F.); and Departmentof Biostatistics and Epidemiology, The Chil-dren’s Hospital of Philadelphia, Philadelphia,Pennsylvania (D.S.).

Supported by grants from the NationalInstitutes of Health/National Institute onDrug Abuse (R01-DA14129), National In-stitutes of Health/National Center for Re-search Resources (M01-RR00240), andNational Institute of Child Health and Hu-man Development (MRDDRC-HD26979,R21-DA01586, and R01-HD043078).

Submitted for publication Dec 13, 2006;last revision received May 25, 2007; ac-cepted Aug 9, 2007.

Reprint requests: Hallam Hurt, MD, De-partment of Neonatology, The Children’sHospital of Philadelphia, 3535 Market St,Room 1509, Philadelphia, PA 19104. E-mail:hurt@email.chop.edu.

0022-3476/$ - see front matter

Copyright © 2008 Mosby Inc. All rightsreserved.

ES Socioeconomic status BOLD Blood oxygenation level dependent

10.1016/j.jpeds.2007.08.006

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xposed groups would perform similarly on behavioral tasks,ut differ in activation patterns. Specifically, we hypothesizedhat the exposed group would exhibit less robust activation innticipated areas of activation or would exhibit compensatoryctivation in areas not activated in the non-exposed group.

METHODS

articipantsParticipants were selected from a cohort of exposed and

on-exposed subjects who have been observed since theirirth (1989-1992). Full details of enrollment have been re-orted earlier.20 All participants were born at a single inner-ity hospital to mothers of low socioeconomic status (SES).xposed children’s mothers admitted to cocaine use in at leasttrimesters of pregnancy. The mothers of non-exposed, or

ontrol, participants denied cocaine use, and both mothersnd children had urine samples that were negative for cocaineetabolites at delivery. Mothers were excluded when they did

ot speak English, had a major psychiatric disorder, or usedubstances other than cigarettes, marijuana, or alcohol duringregnancy. Infants were excluded when they were �34 weeksestational age, had an Apgar score �5 at 5 minutes of age,r had fetal alcohol syndrome or any syndrome known to bessociated with developmental delay. Some exposed subjectsere also exposed to cigarettes, alcohol, and/or marijuana.ne control subject was exposed to cigarettes.

Subjects selected for fMRI met these criteria: they wereight-handed, had no metal appliances, and were taking noedications. Because of concerns for possible confounding

ffects of sex and IQ, we further selected exposed and non-xposed children by sex and group quartiles of 4-year Wech-ler Preschool and Primary Scale of Intelligence-Revisedcores. The protocol was approved by The Children’s Hos-ital of Philadelphia Institutional Review Board. Informedonsent was obtained from participants’ caregivers. All par-icipants gave assent.

asksAll tasks were implemented in E-Prime software ver-

ion 1.1 (Psychology Software Tools, Pittsburgh, PA), withubjects required to monitor a visually presented randomequence of letters and press a button every time a target letteras displayed on the screen. Non-target letters were all other

etters viewed by subjects for which no button press wasequired. For the x-detection task, the target letter was an “x.”he 1-back task required that the button be pressed when any

etter was repeated, one after another, with the repeated lettereing the target. The 2-back task required that the subjectress a button when any letter was repeated with exactly 1ntervening letter. For the 2-back task, the repeated letter waslso the target. For example, in the 2-back task, for theequence “J-M-J,” the subject would press the button whenhe second “J,” the target, was presented.

The 1-back and 2-back tasks were administered twice

o each subject, 2 runs of 1-back alternating with the x-de- t

72 Hurt et al

ection task followed by 2 runs of 2-back alternating with the- detection task. Thus, subjects were scanned during 4 fMRIuns. The 1-back task was used in runs 1 and 2. The 2-backask was used in runs 3 and 4. Each run consisted of 10 blocksf alternating x-detection and n-back tasks, with each blockonsisting of 20 trials. Within each run, there were a total of0 target and 70 non-target trials for each task (x-detection,-back, or 2-back). The order of task presentation (1-backefore 2-back) provided baseline behavioral measurements sohat working memory, as operationalized by the 2-back, coulde singled out as the cognitive process of interest. For allasks, letters were presented on the screen individually withnterstimulus intervals equal to 1500 ms and stimuli presen-ations equal to 500 ms.

maging ProceduresProject personnel accompanied subjects to the Center

or Advanced Magnetic Resonance Imaging Spectroscopy athe Hospital of the University of Pennsylvania. An initial visitntroduced the subject to the MRI environment with a sim-lator without time constraints. The study was conducted on3T Siemens Trio whole body MRI scanner with a product

olume head coil. Visual stimuli for the task were back-rojected onto a Mylar screen with an LCD projector withomputer control. Responses were recorded with a fiberopticutton box (FORP; Current Designs, Philadelphia, PA).

The imaging protocol consisted of a 1-minute 3-axisocalizer, a 5-minute inversion recovery prepped 3-dimen-ional T1-weighted anatomical scan with 1 mm isotropicesolution used for spatial normalization, and 2-dimensionalulti-slice gradient-echo echoplanar imaging with relaxation

ime of 3 seconds, echo time of 30 msec, 3 mm isotropicesolution, and prospective motion correction (Siemens PACE)or detecting blood oxygenation level dependent (BOLD) con-rast fMRI. Twelve seconds of “dummy” scans preceded thenset of the n-back tasks to allow magnetization to reach ateady state.

ata AnalysisGroup baseline characteristics were compared with �2,

, or Mann-Whitney U test, as appropriate. Three behavioralcores were analyzed: 1) the number of correct responses tohe target condition (hits), 2) the number of correct responseso the non-target condition (correct rejections), and 3) totalorrect, the sum of hits and correct rejections. Three separateroup (exposed versus non-exposed) by gender by age analysesf variance with repeated measures (RM-ANOVA) for taskere conducted, 1 for each of the 3 behavioral scores.

Functional data were analyzed on Linux workstationssing VoxBo (www.voxbo.org). Preprocessing included slice-iming correction, rigid body realignment to the subject’s firstunctional volume,21 and spatial smoothing with a 3D Gauss-an filter (9 mm kernel, 3 � 3 � 3 voxels). A modified generalinear model21 with a 1/f estimate of intrinsic autocorrela-

ion22 was applied voxelwise to each individual’s fMRI data.

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ime series data were filtered in the frequency domain toemove the highest frequencies and lowest frequencies, up tout not including the fundamental task frequency. Data wereonvolved with an empirically derived estimate of hemody-amic response,23 and scan effect covariates were included toemove scan-to-scan variation.

The fMRI data for 1-back and 2-back runs were ana-yzed both separately and in combination, and within-subjectonditions included the x-detection (x), 1-back (1b), and-back (2b) tasks. Beta maps were constructed for theseontrasts: (1b)-(x), (2b)-(x), and (2b)-(1b). Individual dataere spatially normalized with Statistical Parametric Map-ing 2 (www.fil.ion.ucl.ac.uk/spm) to a standard Montrealeurologic Institute (MNI) template,24 and group maps were

enerated for those contrasts by using a random effects modelomparing mean statistical parametric maps across subjects toero with a t test for each voxel. Discrimination scores for the-back and 2-back tasks were also included as a covariate inhe group analyses to remove variation caused by task perfor-ance. Discrimination scores were calculated with the equa-

ion:

�Hits ⁄ Total possible hits�� �Incorrect rejections ⁄ Total possible rejections�.

Group analyses were thresholded by cluster-constrainedermutation analysis,25 with 2000 sign permutations of thendividual maps to generate a null hypothesis distribution forluster-corrected thresholds (cluster size � 30, P � .05).

A priori anatomical regions of interest (ROIs) wereenerated for Brodmann regions 10 and 46 with the Wakeorest University PickAtlas26 in Talairach space (Figure 1),n the basis of the work of Casey et al.17 Functionally derived

igure 1. ROI masks. 1. A priori anatomical ROIs for Brodmann regions0 and 46. A, Surface renderings of Brodmann regions 10 and 46. B,utaway rendering of Brodmann regions 10 and 46. 2. Functional ROIs

or cingulate, right DLPFC, left DLPFC, right parietal, and left parietal.unctional ROIs were derived from the beta map of the non-exposedohort during the 2-back condition, at a significant threshold of t � 4.16,lpha � 0.05. A, Functional ROI surface rendering. B, Functional ROIutaway rendering.

OIs were also defined for cingulate, left and right dorsolat- i

unctional Magnetic Resonance Imaging and Working Memory in Adoles

ral prefrontal cortex (DLPFC), and left and right parietalegion on the basis of the work of Owen et al.27 Areas wereetermined by using the beta map from the (2b)-(x) conditionn non-exposed subjects, the contrast of which provided thereatest amount of activation. The proportion of positiveoxels within each ROI at zero threshold was determined for1b)-(x) and (2b)-(x) by using beta values.28 The fractionalOI activation for the (2b)-(1b) condition was determined by

he difference between the (2b)-(x) and (1b)-(x) conditionetween exposed and non-exposed groups.

RESULTSForty-nine subjects, 25 exposed and 24 non-exposed,

nderwent imaging. Nine subjects (5 exposed, 4 non-ex-osed) were excluded because of motion artifact, data logssues, or scanner technical difficulties. Six additional subjects3 exposed and 3 non-exposed) underwent imaging success-ully in only 3 of the 4 runs and were excluded from analyses.he 34 remaining subjects underwent imaging successfully in

ll 4 runs, with their results forming the basis for analyses.Groups were similar, except exposed subjects were older

t the time of testing and were more likely to be exposed toaternal cigarette, marijuana, and alcohol use during preg-

ancy (Table). The median days of exposure to cocaine for thexposed group was 117 days, which constitutes a high level ofxposure and is consistent with the high rate of maternal urineest results that were positive (81%) for cocaine at delivery,lso a marker for heavy maternal use.29 The 34 subjects whonderwent imaging successfully were compared on the char-cteristics shown in the Table with the 15 excluded subjectsnd the remaining 71 cohort subjects who did not undergomaging. Groups were similar in all characteristics (P � .08),xcept subjects who did not undergo imaging had lower fullcale IQ scores than did the group of 34 subjects who under-ent imaging successfully and the 15 subjects who underwent

igure 2. Number of correct responses to target condition in runs 1 to 4n exposed and non-exposed groups. By repeated measures ANOVA, P �69 for group across runs; P � .001 for runs 1 and 2 versus runs 3 and 4;

� .001 for run 3 versus runs 1, 2, and 4.

maging but were excluded (P � .013).

cents with Gestational Cocaine Exposure 373

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ask PerformanceFor the x-detection task, performance was similar across

ll 4 runs in both groups (data not shown). The number oforrect responses to the target condition (hits), the non-targetondition (correct rejections), and the sum of hits and correctejections did not differ between the exposed and non-ex-osed groups, male subjects and female subjects, or across ageP � .27) with RM-ANOVA (data not shown). In compar-ng the performance on the 4 n-back runs for both groups,

igure 3. Areas of activation for functional ROIs (left to right): 1-backinus x-detection; 2-back minus x-detection; and 2-back minus 1-back.� 17 for non-exposed subjects (top), n � 17 for exposed subjects

bottom). t � 4.16.

able. Subject characteristics

Ex

hild characteristics at time of fMRINFemale genderAge at testing, years 14.7 � 0.African American raceaternal characteristics at child’s birthUrine positive for cocaine at delivery 13/Days of cocaine use in pregnancy 11Marijuana use in pregnancy 10/Cigarette use in pregnancyAlcohol use in pregnancy 10/

hild characteristics at birthBirth weight �10th percentileHead circumference �10th percentileApgar, 5 minutesCranial ultrasound scanning abnormality

hild examinations during childhoodAny neurolgical abnormality at 6.5 years¶ 3/�1 neurological abnormality at 6.5 years¶ 1/Full scale IQ at 4 years 84.1 � 15

N (%).Mean � SD.Range.Median.Subjects examined by a developmental pediatrician.

owever, the number of correct responses to the target con- d

74 Hurt et al

ition decreased between runs 1 and 2 (1-back): run 1 (ex-osed [Exp]): (mean (�) SD [ ] � range) 26.8 � 5.3 [18];on-exposed [Non-E]: 28.1 � 2.8 [8]) and run 2 (Exp: 27.4 �.2 [7]; Non-E: 28.4 � 2.5 [9]) and runs 3 and 4 (2-back):Exp: 18.8 � 5.9 [19]; Non-E: 18 � 5.9 [24]) and run 4 (Exp:2.5 � 6.9 [21]; Non-E: 21.8 � 5.6 [19]; P � .001; Figure 2).dditionally, the number of correct responses to the target

ondition increased between runs 3 and 4 (P � .001). Theseesults demonstrate the increased working memory demandshat are associated with runs 3 and 4 (2-back), with a moreronounced effect observed for run 3. The improved perfor-ance between runs 3 and 4 is possibly related to a practice

ffect. The decrease in target response accuracy in the 2-backondition across exposed and non-exposed subjects indicateshat both groups were challenged by the increasing complex-ty of the 2-back task.

In a post hoc analysis, we reviewed the behavioral datao identify any subjects who did not achieve at least 50% totalorrect on the x-detection and n-back tasks, to avoid thenclusion of outliers. With this approach, no subject meetinghese performance criteria was identified from either thexposed or non-exposed group. Thus, on an executive func-ion task assessing working memory, exposed subjects per-ormed as well as non-exposed subjects.

magingThere was an increase in activation from the (1-b)-

x) to the (2b)-(x) condition (Figure 3)in the functionally

ed Non-exposed P value

177)* 9 (53) 13.2-15.9)‡ 13.8 � 0.8 (12.9-15.3) .0018) 17 (100) .48

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erived ROIs for all regions defined (cingulate, left and

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ight DLPFC, left and right parietal) in both exposed andon-exposed groups. The ROI percent activation was greater

n the non-exposed group in all regions. For the (2b)-(1b)ontrast, the ROI percent activation in cingulate, left DLPFC,nd right DLPFC showed greater volumes of activation for theon-exposed group compared with the exposed group. How-ver, in both right and left parietal ROIs, the exposed groupemonstrated a greater ROI percent activation than the non-xposed group. These differences did not reach a statisticalignificance.

In the a priori anatomical ROIs, Brodmann’s regions 10nd 46, a comparison of the average percent ROI activationor non-exposed versus exposed groups showed that, althoughoth groups increased activation from the (1-b)-(x) to the2-b)-(x), the level of activation in the non-exposed group wasroportionally greater. A 1-tailed t test for the (2b)-(1b)ondition between the non-exposed group and exposed groupn the left hemisphere yielded a borderline significant value of

� .05.Although it is difficult to assess the clinical significance

f the differences seen in activation, especially lacking aignificant group performance difference, we can neverthelessse the estimated proportions activated in both functional andnatomical ROI to compute approximate post hoc observedffect sizes. For each area of interest, we computed task1-back versus 2-back) effect size for each group (cocaine-xposed and non-exposed) and then computed the differencen group effect sizes. For example, in the cingulate, the 2-backersus 1-back effect size was 0.9 SDs for the non-exposedroup and 0.66 SDs for the exposed group, both large effectizes. The group difference in effect size was 0.25 (a smallffect). Results for the right and left DLPFC, parietal area,nd Brodmann’s areas were similar, reflecting a large changen activation from the 1-back to the 2-back within bothroups, which is relatively easy to detect, but a smaller dif-erence in the groups.

DISCUSSIONIn this study, cocaine exposed and non-exposed inner-

ity adolescents performed similarly on a non-spatial workingemory task and demonstrated similar activation patterns

uring fMRI. We did not find differences in the behavioralesults between exposed and non-exposed participants duringdministration of a non-spatial working memory task. Theask was an appropriate one in that there was the predictedncrease in difficulty when subjects first encountered the-back task after having performed the more simple x-detec-ion and 1-back tasks. During the 2-back task, the correctesponses to both targets (that is, subjects were less likely toorrectly identify the target and perform the button press) andon-targets (that is, subjects were more likely to press theutton in the absence of the 2-back target) decreased. Whenuns 1 and 2 (1-back task) were compared with runs 3 and 42-back task), we found significant decreases in total correctesponses (Figure 2) by both exposed and non-exposed par-

icipants. p

unctional Magnetic Resonance Imaging and Working Memory in Adoles

Thus, for this working memory task, performance byxposed and non-exposed participants was similar. This oc-urred despite evidence of heavy gestational exposure: a me-ian level of 117 days of cocaine exposure, and 81% ofaternal urine sample test results were positive at delivery. In

n investigation suggesting worse neurodevelopmental out-ome with the heavy exposure, heavily exposed subjects wereefined as having prenatal exposure for only 61 days.

Whether the similar behavioral performance was asso-iated with similar or dissimilar patterns of brain activationas examined with fMRI. A particular point of interest, in

ight of subjects’ similar performance on the behavioral task,as whether tasks were accomplished by using compensatoryeural mechanisms, as would be evidenced through differentctivation patterns. Map-wise comparisons of both exposednd non-exposed subjects confirmed activation patterns inxpected regions of cingulate, DLPFC, and parietal lobe,27

emonstrating the validity and reliability of the n-back task aspplied to our population. Group statistical maps in both ex-osed and non-exposed groups showed greater activation withncreased task complexity, particularly in bilateral DLPFC re-ions. The most robust activation occurred in expected direc-ions during the 2-back condition, which requires the greatestorking memory demands, as evidenced by performance re-

ults. Our results are consistent with earlier literature onunctional activation during n-back tasks.17,30-32 In particular,asey,17 reporting on a small healthy control sample of 9- to1-year-old children with the n-back working memory task,bserved activation of inferior and middle frontal gyri (Brod-ann’s 46 and 10). In that sample of young subjects, activa-

ion patterns also increased in expected directions with greaterask complexity and also correlated with behavioral perfor-ance. Thus, the imaging and behavioral performance results

f the present study are consistent with Casey et al, in whichctivation increased and response accuracy significantly de-reased across subjects with increasing task complexity.

Earlier studies indicate that increasing the numbersback” correspondingly increases the degree of activation.herefore, decreasing performance in response to increasedorking memory load produces an increase in brain activa-

ion.31,33 However, the work of Callicott et al indicates thatertain load-sensitive loci within the working memory net-ork demonstrate capacity-limited response. The beta map

or the non-exposed group for the 2-back minus 1-backondition demonstrates a greater degree of activation than thexposed group, despite analogous behavioral performanceFigure 3). This would suggest that the exposed cohort ex-eriences a memory capacity breach at a lower difficulty levelhan the non-exposed cohort. This effect is seen particularlyn the prefrontal cortex, which is analogous to the results ofalicott et al.31 Although a similar pattern of reduced acti-

ation with normal behavioral performance is seen in patientsith schizophrenia,33 various other patterns also have beenocumented in developmental disorders. For example, adultsith autism spectrum disorder who have similar behavioral

erformance as control subjects show increased brain activa-

cents with Gestational Cocaine Exposure 375

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ion in tests of executive function.34 Further, medication naïvedolescents with attention deficit hyperactivity disorderhowed reduced brain activation independent of task perfor-ance during an initiation and error detection task, findings

elt to confirm a relationship between behavioral impulsivitynd neural abnormalities.35

Our results are also consistent with studies that examinehe relationship between frontal lobe mediated informationaintenance and manipulation with time, central to the n-

ack working memory task. D’Esposito et al36 contend thathe DLPFC is necessary for working memory and both main-enance and manipulation tasks activate ventral and DLPFCegions. To further explore the relationship between infor-ation maintenance and manipulation in the broader con-

ext of central executive processing in normal subjects,agland et al32 used an n-back task to define the brain

egions that activate in distinct maintenance or manipulationonditions. During a 1-back minus 0-back task designed tosolate information maintenance, they observed inferior pari-tal and DLPFC activation. During a 2-back minus 0-backask designed to assess the cumulative effect of maintenancend manipulation, they reported activation in inferior parietalegions and dorsal and ventrolateral PFC regions. During a-back minus 1-back “manipulation only” task designed toemove the maintenance demands across conditions, broaderLPFC and anterior cingulate activations were observed.he results of both studies, with the exception of observed

ctivations in ventrolateral PFC, are consistent with thisnvestigation. We found increasing DLPFC activation withask difficulty, and the emergence of anterior cingulate acti-ation in the 2-back minus x detection condition, suggestingsimilar role for these regions in working memory function inur cohort.

Thus, although our study shows anticipated patterns ofctivation, there are no differences between exposed and non-xposed participants. Possible explanations for our null resultsre several. It may be that differences do exist, but that theumber of subjects was too small (although our study is a

arge study by typical fMRI standards) to detect such differ-nces. It may well be that investigations with a larger numberf subjects will detect differences between exposed and non-xposed groups. Another possibility is that an enriched envi-onment for exposed subjects placed out of the home couldmeliorate effects of cocaine exposure; in our sample, how-ver, there was no difference in out-of-home placement in thegroups. Is it possible that some of our non-exposed partic-

pants were, in fact, exposed to cocaine? This is possible, butoubtful because we had negative history from mothers, neg-tive urine test samples for both mothers and babies, and aaternal profile (cocaine-using mothers were older, had less

renatal care, had more sexually transmitted diseases, andere more likely to be polysubstance users) of cocaine-usingothers that differed from non-using mothers.20 Perhaps theore compelling question is why, given our exposed subjects’

reater exposure not only to cocaine but also alcohol, ciga-

ettes, and marijuana, did we not detect differences between

FC

76 Hurt et al

xposed and non-exposed groups? It may be that fMRI,ependent on the BOLD signal from blood flow, simply isot sensitive enough to detect changes that do exist, or thatecently described cerebral blood flow differences in our sam-le between exposed and non-exposed groups influenced re-ults.37 However, perhaps any effects of gestational exposureresent early on have been remediated through the matura-ional processes that normally occur during childhood anddolescence,38 or there may be characteristics unique to ourample that are responsible for null results. Finally, gestationalocaine exposure simply may be less injurious than predicted.n this regard, there are a number of studies of global intel-ectual functioning in exposed children at young ages showinghese children are not severely and irreparably damaged asuggested by some early reports.39 In our sample, as describedere, so far we have not found consistent differences betweenxposed and non-exposed in executive function.10,18,40 Inome investigations in older subjects, however, differences inxecutive functions such as attention and arousal have beeneported. Thus, the full impact of effects of gestational co-aine exposure, if any, remains to be determined.

In conclusion, with a working memory task in thisample of low socioeconomic status subjects, exposed andon-exposed groups had similar task performance and brainctivation patterns. These data provide a basis for futurenvestigations that may explore subject groups of differingES, IQ, and ethnicity.

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