~ ) Pergamon

Neuropsycholooia, Vol. 33, No. 3, pp. 341-352, 1995 Copynght© 1995 Elsevier Science Ltd

Printed m Great Britain. All rights reserved 0028-3932/95 $9 50+0.00

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THE ROLE OF PREFRONTAL REGIONS IN THE STROOP TASK

PERE VENDRELL,*t CARME JUNQUI~,t JESIOS PUJOL,:~ M. ANGELES JURADO,~- JOAN MOLET§ and JORDAN GRAFMANll

tDepartment of Psychiatry and Psychobiology, University of Barcelona, Spain; :~Centre Diagn6stic Pebralbes, Barcelona, Spain; §Neurosurgery Service, Sta. Creu i St Pau Hospital, Spain; and tlCognitive Neuroscience

Unit, Medical Neurological Branch, NICDS, Bethesda, Maryland, U.S.A.

(Received 22 July 1994; accepted 3 October 1994)

A b s t r a c t - - T h e Stroop is a classical paradigm that presumably involves the inhibition of automatic responses and is frequently used to assess the frontal lobe functions. We investigated the effect of discrete prefrontal lesions in a Stroop task. A sample of 32 patients with frontal lesions were matched with normal controls by sex, age and years of education. Significant differences between patients and controls were found for errors but not for reaction time. Regression analysis showed that the region most related to errors was the right prefrontal lateral cortex. Left lobectomies did not impair the Stroop performance. Our results favour the role of the right prefrontal cortex in sustained attention, and disagree with the conception of the left prefrontal cortex having a role in the inhibition of verbal automatic responses.

Key Words: prefrontal; Stroop; attention.

INTRODUCTION

Protection against interference from both inside and outside the organism has been described as one of the most important functions of the prefrontal cortex in the organization of behaviour. The inability to maintain consistent directed attention over time because of vulnerability to interference is a basic deficit in monkeys with frontal lobe damage [7, 8]. The Stroop test directly assesses the issue of interference in humans and widely resembles the go/no-go tasks used in the investigation with monkeys [22]. In this test, reaction time in a colour-naming task is increased by the interference due to the presentation of incongruent semantic information in the target stimulus, for example, when the subject is asked to name the colour of the letters (say red) that form the word GREEN on a monitor screen [12].

Abnormality in Stroop test performance has frequently been used to indicate frontal dysfunctions in patients without clear focal frontal lesions. For example, it has been used to demonstrate frontal involvement in Parkinson's [4] and Huntington's diseases [-3] and also in patients with psychiatric illness: schizophrenia [5] and obsessive-compulsive disorder [-13]. The use of the Stroop as a frontal lobe test is mainly based on the findings of Perret [18], who, in 1974 suggested a left frontal location for the functions involved in the resolution of such interference. However, there are several contradictory data. For example, the

*Address for correspondence: Departament de Psiquiatria i Psicoblologla, Universitat de Barcelona, Adolf Florensa S/N, 08028 Barcelona, Catalonia, Spain.

341

342 P VENDRELL et al.

performance ofleukotomized patients with orbitofrontal lesions was similar to controls [22]. In addition, recent PET studies with normal subjects concluded that the right anterior cingulate plays a role in the attentional aspects of the Stroop task [2, 17].

Although localization of the function of inhibition within the frontal cortex is accepted, there is no information about the concrete location of lesions capable of producing impairment of this function.

We investigated the effects of focal prefrontal lesions on Stroop performance in a series of patients, analyzing six functional regions in resonance images. The aim of the study was to determine the lesions responsible for the impairment in this task.

METHOD Subjects

Patients were selected from clinical and neuroradiological data bases according to the presence of selective frontal lobe lesions, and they were invited to participate in the study. All consecutive patients who agree to participate in a neuropsychological and neuroimaging protocol (prospective magnetic resonance imaging) were included. The sample consisted of 32 patients; 25 had unilateral lesions, 15 in the right hemisphere, 10 in the left, and seven had bilateral lesions. The etiologies were traumatic brain injury in 13, cerebral tumours in 13 (five with astrocytoma grade I-II, four with astrocytoma grade III-IV, two with oligodendroglioma, two with meningioma), five were vascular (three haemorrhages and two strokes), and one patient suffered an abscess (see Table 1 ). All the patients with tumours and haemorrhages, the patient with the cerebral abscess, and seven of the traumatic patients were studied after surgical treatment. Time post onset or surgery ranged from 2 to 112 months with a mean 28.91 + 30 76 months. Nineteen were male and 13 female. Mean age was 40.53 + 13.51 years, and mean education 9.53 + 3.02 years.

We selected a sample of 32 matched controls. Matching criteria were sex, age ( + 5 years) and years of education ( + 3 years). Mean age was 40.41 + 14.89 years, and education mean 10.06 + 3.67. Controls were unpaid volunteers without neurologic or psychiatric antecedents.

Neuroimagm9 study

We performed a specific MRI protocol designed to facilitate the location of lesions. A superconducting MRI magnet was used at a field strength of 1.5 Tesla (Signa system, General Electric, Milwaukee, WI). On sagittal view, anatomical references for transversal and coronal projections were established. For coronal projections we used an inversion-recovery sequence (TR/TE/TI=1800/20/650msec) to delimitate tissue lost and for transversal projections we included spin-echo T2 weighted images (TR/TE = 2500/90 msec) to dehmltate the extent of tissue damaged. A field of view of 24 cm, and a slice thickness of 5 mm with interslice gap of 2.5 mm were used in every pulse sequence. The inversion-recovery sequence was acquired in a 256 x 192 matrix and the spin-echo sequence in a 256 x 256 matrix.

MRI measurements were performed by a single investigator who was blind to the neuropsychologlcal data. The presence or absence of lesion in the selected areas was determined using the templates proposed by Damasio and Damasio [6]. We superimposed over the MRI slice a transparent template that contained anatomical cells representing neural areas of interest. Each of those cells was limited by a linear boundary and had a letter and number code on the basis of which it can be anatomically identified. We considered a region damaged when a minimum one-quarter of the area appeared to be involved in the inversion/recovery sequence. In Table l we can see the distribution of patient's lesions in six regions of interest: anterior cingulate gyrus (Brodmann's area 24), prefrontal mesial (Brodmann's areas 8, 9, 10); opercular lateral (Brodmann's areas 44, 45), prefrontal lateral (Brodmann's areas 8, 9, 46), orbital anterior (Brodmann's area 10) and orbital posterior (Brodmann's areas I l, 12, 13, 47).

Stroop test

The test consisted of eight sets of six stimuli each. In four sets the subject was required to name the colour of dots (naming task without interference). In the other four sets the task consisted in naming the colour of the ink of the letters forming the name of a different colour, for example the word RED printed in green ink (naming with interference). The sets with and without interference were presented alternately. The colours used were red, green, yellow and blue. Each stimulus was presented in the centre ofa colour monitor screen. The subject was required to name the presented colours as quickly as possible. The reaction time was recorded for correct responses. Reaction times were measured by a peripheral unit connected to a microcomputer that executed the program. The measure of reaction time consisted in the time between the stimulus presentation and the activation of a vocal relay by the subject's verbal response. By pressing a key, the examiner registered the correct, incorrect or invalid value after each subject response. Invalid responses were considered when the vocal relay was activated as a consequence of

PREFRONTAL REGIONS IN THE STROOP TASK

Table 1. Localization of patients' lesions, etiology and surgical treatment

343

SS E

Right Left Me&al Lateral Orbital Medial Lateral Orbital

S AC PF OP PF AN PO AC PF OP PF AN PO

1 1 3 2 1 1 + + 3 3 1 4 1 0 5 2 1 + + + 6 3 3 + 7 1 0 8 1 3 9 1 3 + + +

10 3 0 + 11 1 0 12 1 0 13 3 0 + 14 1 1 + + + + 15 2 1 + + + + 16 1 3 + + + 17 1 3 + + + + 18 2 1 + + + + 19 2 1 + + + + 20 2 2 + 2l 1 0 22 2 1 + + + + 23 2 2 + + 24 2 1 25 2 1 26 2 2 + + + 27 2 1 + + + 28 2 1 + + + 29 2 2 30 4 1 31 1 0 32 3 0

+ + + + + ÷ + + + +

+ + + + + ÷ + + + +

÷

+

+ + + + + +

+ +

+ + +

+ +

+ +

+ +

+ + + + +

+ + + + +

+ + + +

+ +

+ + + + + + + + +

+ + + + +

+

+ + + + +

A C = A n t e n o r cingulate; AN=Anter ior ; E = E t i o l o g y ( l = h e a d injury, 2=tumour , 3=vascular, 4 = abscess), OP = Opercular; PO = Posterior; PF = Prefrontal; S = Surgical treatment (0 = none, 1 = lobec- tomy, 2 = tumour removal, 3 = haematoma evacuation); SS = Subjects.

extraneous noise (e.g. cough). When the response was qualified as non-valid, the program automatically located this stimulus at the end of the respective set, and it was presented again. The stimuli remained on the screen until there was a response. The time that elapsed between the response by the subject and the presentation of the next stimulus was 1.5 sec. A set of six stimuli was presented for practice.

To avoid possible extreme values, we used the me&an of reaction time. For the Stroop effect, we computed the Stroop reaction time (difference in reaction time for colour naming with interference minus reaction time for colour naming without interference) and the number of errors.

RESULTS

To identify the frontal regions related to the Stroop performance, we carried out a multiple regression analysis using the stepwise method. We used reaction time in naming colours, Stroop reaction time, and Stroop errors as dependent variables and the presence (1) or absence (0) of lesions in the selected regions as predictor variables. To explain reaction time for naming only one region entered in the equation, the right anterior cingulate (R = 0.36; F = 4.50: P = 0.042). The same region, entered to explain the Stroop reaction time (R = 0.37:

344 P. VENDRELL et al.

F = 4.79; P = 0.037). For the Stroop errors, entered the lateral prefrontal cortex (R =0.43; F = 6.93; P=0.013).

Since the right prefrontal lateral area examined is relatively large we performed a "post- hoc" analysis of regression that included Brodmann's areas 8, 9, and 46 of the coronal cuts, and we found that the area most related to errors was Brodmann's area 9 (R = 0.42; F = 6.12; P=0.019).

Comparisons between groups' performance in naming reaction time, the Stroop reaction time, and number of errors were carried out using parametrical analysis (Student t-test) for the overall sample and non-parametrical analysis (Mann-Whitney test) for the subgroups. This distinction was made according to the size of the groups and the significant difference of variances.

When we compared the performance of patients according to the presence or absence of lesions in the areas identified by the regression analysis, we obtained congruent results. Patients with lesions in the right anterior cingulate (n= 13) performed more slowly than patients without these lesions (n = 19) in naming reaction time (Z= -2.01, P = 0.044) and in Stroop reaction time (Z= - 1.98, P = 0.048). Similarly, patients with lesions in right lateral region (n= 12) made more errors than patients without such lesions (n=20), (Z= -2.27, P=0.023).

Table 2 summarizes comparisons between patients and their matched normal controls. In the overall sample, significant differences between patients and controls were obtained for errors. Patients with right lateral lesions differed from their controls in naming reaction time and Stroop errors and patients with right anterior cingulate lesions performed more slowly in naming.

Taking as a criterion for abnormal performance more than two errors (the highest value in the control group was two errors) or a Stroop reaction time longer than 458 msg (the mean plus two standard deviations of the control group), nine patients were impaired. Among those, six had right frontal lesions, one left and two bilateral. It is interesting to note that, according to this criterion, the five patients with left lobectomies performed the task normally (see Figs 1 and 2 and Table 3).

DISCUSSION

We found that only one region in the right hemisphere, the prefrontal lateral, was consistently related to Stroop effect. This finding is in disagreement with the results expected on the basis of previous lesional data.

Since the prefrontal cortex is anatomically and functionally heterogeneous, it is not surprising that the prefrontal lesions did not systematically cause an impairment in the ability to solve conflictive responses. The Stroop test cannot thus be considered globally as a frontal lobe test since 71% of our patients with prefrontal lobe lesions performed normally.

Perret [18-1 hypothesized that cerebral lesions in the left hemisphere would entail low performance in the Stroop because of the verbal aspect of the test and frontal lesions would lead to impaired performance as a consequence of the inability to suppress habitual responses. His results corroborate the hypothesis since he found that the left frontal group performed worse than the control group and the other lesional groups. Our left lobeetomized cases and those of Richer et al. [21] indicate that the left frontal lobe does not have a relevant role in the inhibition of reading. In our series, five patients with left lobectomies performed the Stroop task accurately and speedily. This contradictory result may be due to the sample

PREFRONTAL REGIONS IN THE STROOP TASK

Table 2. Comparison between groups of patients and their respective matched controls in the Stroop task

345

Overall sample Patients (n = 32) Controls (n = 32)

Mean _ S.D. Mean _+ S.D. t P

Naming RT (msec) 693.33 4- 162.59 659.51 _+ 188.02 0.77 0.444 Stroop RT (msec) 245.87+__ 181.03 231.80+ 112.69 0.37 0.711 Stroop errors 1.91 +2.56 0.84+0.85 2.23 0.032

Right lateral lesions Patients (n = 12) Controls (n = 12)

Mean + S.D. Mean + S.D. Z P

Naming RT (msec) 758.81 +__ 178.82 611.10+96.64 -2.14 0.033 Stroop RT (msec) 307.83+249.83 247.85+99.41 -0.12 0.908 Stroop errors 3.17+3.46 1.00+0.85 -2.26 0.023

Right anterior cingulate lesions Patients (n= 13) Controls (n= 13)

Mean + S.D. Mean + S.D. Z

Naming RT (msec) 763.23 _ 174.11 621.96+ 104.45 -2.18 0.029 Stroop RT (msec) 325,79+240.02 282.25+ 112.23 -0.13 0.898 Stroop errors 2.85 + 3.36 1.23 + 0.93 - 1.65 0.100

Naming RT = reaction time for naming coloured dots. Stroop RT = increase in reaction time for naming (Stroop effect). Stroop errors = number of errors (Stroop effect). t = t-value (Student t-test separate variance estimate). Z= Z-value corrected for ties (Mann-Whitney U test). P = 2-tailed probability.

Table 3. Performance of patients with left lobectomies

Patient 2 Patient 3 Patient 24 Patient 25 Patient 30

Naming RT 690 msec 444 msec 662 msec 764 msec 494 msec Stroop RT 309 msec 145 msec 287 msec 128 msec 177 msec Errors 2 1 1 0 1

Naming RT = reaction time for naming coloured dots. Stroop RT =increase in reaction time for naming (Stroop effect). Errors = number of errors (Stroop effect).

studied. Perret [18] tested patients before undergoing brain surgery; in this condi t ion a

compress ive effect of the t u m o u r or the white mat ter dysfunction may produce general

slowness. Compress ive effects in our sample were not present because the patients were

examined several mon ths after tumora l resection or h a e m a t o m a evacuat ion.

The slowing in the S t roop test has been described in several dysfunctions involving the white mat ter , subcort ical vascular patients with leuko-araiosis [9], no rmal elderly subjects

with leuko-araiosis [24], and in pat ients with mult iple sclerosis [20]. Kar t sounis et al. [10]

studied pre- and pos topera t ive ly psychiatr ic patients subjected to stereotaxic subcaudate

t r ac to tomy which involves the dest ruct ion of bifrontal pathways located beneath and in front

of the head of the caudate nucleus. In the postsurgical study performed 2 weeks after the

346 P. VENDRELL et al

operation their patients performed the Stroop test worse in both errors and Stroop reaction time but in a second analysis performed 6 months after the operation the patients achieved near normal values. The authors interpreted that the Stroop impairment could be dependent of the severity of cerebral oedema. Vilkki et al. [23] reported normal performance for the Stroop test administered to a series of 43 patients with frontal lesions due to rupture of intracranial aneurism examined 1 year after surgery. Normal values in the Stroop test were also found by Stuss [22] in patients with leukotomies performed several years before. Leimkuhler and Mesulam [11] reported reversible deficits in a go/no-go task after surgical excision of a meningioma involving the medial aspects of the frontal lobes.

White matter but not individual cortical lesions affects the Stroop reaction time probably because the accurate performance of the Stroop task requires the integrated action of several cortical areas. Thus, a single cortical lesion may not affect performance to the same extent as white matter lesions which disrupt connections between two or more cortical regions. Subcortical and white matter lesions are more frequently encountered causes of the frontal lobe syndrome than lesions which involve prefrontal cortex directly. Assuming that the physiological function of the frontal lobe is to integrate network for combined action, the emergence of the frontal lobe dysfunctions should come as no surprise in the cases where there is a disruption of the internetwork coordination [15].

Functional neuroimaging studies point to a role of the right anterior cingulate in the solution of the Stroop conflict. In a PET study, Pardo et al. [17], found that when normal subjects were required to respond to ink colour in which a conflicting colour name was present there was a strong activation of the anterior cingulate. Bench et al. [2], in a similar investigation, failed to find the activation of the right cingulate in the first experiment but confirmed the results about the anterior cingulate in the second. However, they claimed that the activation of the anterior cingulate was found in several PET experiments involving a great variety of tasks, for example in naming congruent colours. In our study, lesions in the anterior cingulate cortex did not produce selective changes in the Stroop effect, but increased the reaction time for naming in the non-interferent condition. This result agrees with the involvement of anterior cingulate in several cognitive processes I-2].

The absence of significant differences between patients with right anterior cingulate lesions and their matched controls for the Stroop effect (reaction time and errors) allows us to consider that focal lesions promote compensatory effects and force the participation of other cerebral areas. The anterior cingulate is a large structure with heterogeneous functions [ 1,2, 16]. Moreover, multiple foci of activation have been seen in this region during the performance of different tasks requiring different aspects of attention [2]. It is likely that following a lesion to the anterior cingulate there is a degree of recovery of function which involves recruitment of other (possibly contiguous) areas within the unilateral or bilateral cingulate.

Our data favour the suggestion that reaction time and errors must be considered separately in the Stroop tasks. In general, errors and reaction time in the Stroop tasks are not differentiated; errors are corrected and the patients are then told to go on as rapidly as possible. Using this procedure, the number of errors indirectly increases the total performance time. In our test the errors did not penalize the total performance in reaction time because the reaction time was not registered when the response was wrong; thus this method is capable of separating speed of response from errors.

The increase in errors is the most consistent finding in our study; the whole sample of frontal patients differed from controls and the right hemisphere lesions were responsible for

PREFRONTAL REGIONS IN THE STROOP TASK 347

Fig 1 (a~(c)

348 P VENDRELL et al.

Fig. 1 (d) and (e).

Fig. 1. MRI coronal cuts of patient No. 3. Despite the extensive lobectomy involving almost all the prefrontal cortex the Stroop performance is normal.

t~

p~

tm~

m~

©

Z

©

Z p~

©

©

350 P VENDRELL et al

Fig. 2 (d) and (e).

Fig. 2. MR! of patient No. 2 who suffered a bifrontal orbital concussion and a decompresslve left prefrontal lobectomy. His Stroop performance is also unimpaired.

PREFRONTAL REGIONS IN THE STROOP TASK 351

this difference. The right prefrontal lateral region appeared to be the most important region for maintaining the correct performance. We interpreted this finding within the model of the right hemisphere dominance for attention [14, 15]. According to Posner and Dehaene [19], the anterior attentional system (frontal) has an executive function: attention to action. The prefrontal cortex appears to play a role in avoiding distractions. Errors may reflect a deficit in the ability to maintain tasks requiring effort, as a consequence, lateral prefrontal lesions favour the easiest, most automatic response, i.e. reading.

In summary, our results do not support the hypothesis that the Stroop is a test of verbal inhibition that implies the normal functioning of the left prefrontal cortex. The right lateral prefrontal cortex seems to be involved in the attentional component of the task, which allows the task to be performed correctly over a period of time.

Acknowledgement--This work is supported by the grant DGICYT PM91-0161.

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