Impulsivity and risk-taking behavior in focal frontal lobe lesions
D. Floden a,b, M.P. Alexander a,c,d,e,f, C.S. Kubu g, D. Katz h,i, D.T. Stuss a,b,!
a Rotman Research Institute, Baycrest, Toronto, Ont., Canadab Departments of Psychology and/or Medicine, University of Toronto, Toronto, Ont., Canada
c Harvard Medical School, Boston, MA, United Statesd Behavioral Neurology Unit, Beth Israel Deaconess Medical Center, Department of Neurology, Boston, MA, United States
e Youville Hospital, Cambridge, MA, United Statesf Memory Disorders Research Center, Boston University, Boston, MA, United States
g The Cleveland Clinic, Department of Psychiatry and Psychology, Section of Neuropsychology, Cleveland, OH, United Statesh Department of Neurology, Boston University School of Medicine, Boston, MA, United States
i Brain Injury Program, HealthSouth Braintree Rehabilitation Hospital, Braintree, MA, United States
Received 26 January 2007; received in revised form 24 July 2007; accepted 25 July 2007Available online 3 August 2007
Impaired behavioral regulation, such as impulsivity (IMP)and risk-taking behavior (RTB), is commonly observed afterinjury to the frontal lobes. Attempts to objectively evaluate thesebehaviors are complicated by the interrelated character of thesebehaviors. The operational definitions of IMP and RTB are notstraightforward, and it is sometimes unclear if a particular behav-ior represents ‘impulsivity’ or ‘risk-taking’ or both (i.e., a spurof the moment leap from a cliff into an unfamiliar lake). Forpatients with brain injury who exhibit poor behavioral control,
it may be important to distinguish between IMP, which mayhave one set of potential causes (i.e., stimulus-bound responses,poor response inhibition, etc.) and RTB, which may have anotherset of potential causes (i.e., poor computation of risk, bluntedconcern about risk, etc.). Single case studies of patients withfrontal lobe damage have provided striking descriptions of bothbehavioral types (Eslinger & Damasio, 1985; Shallice, Burgess,Schon, & Baxter, 1989).
Systematic investigations of IMP and RTB in frontallobe patients have employed gambling paradigms (Bechara,Damasio, Damasio, & Anderson, 1994; Miller, 1992; Rogerset al., 1999). In particular, the Iowa Gambling Task (Becharaet al., 1994) is sensitive to the behavioral problems that frontalpatients may exhibit in their everyday lives. This task does not,however, permit unambiguous behavioral separation of IMP andRTB (although some excellent modeling work has been done tofractionate the contributing mechanisms post hoc; Busemeyer
214 D. Floden et al. / Neuropsychologia 46 (2008) 213–223
& Stout, 2002). Other gambling tasks designed to separate thesebehavioral influences have not produced consistent results infrontal lobe patients. Results of one study suggested increasedIMP (Miller, 1992) whereas work with a related paradigm sug-gested increased RTB (Clark, Manes, Antoun, Sahakian, &Robbins, 2003; Manes et al., 2002; Mavaddat, Kirkpatrick,Rogers, & Sahakian, 2000; Rogers et al., 1999). The con-flicting data may be due to procedural differences in thesetwo tasks: skilled processing (Miller, 1992) or probabilisticdecision-making (Rogers et al., 1999); inverse (Miller, 1992)or independent (Rogers et al., 1999) relations between rewardvalues and probabilities. Substantial differences in lesion distri-butions and in methodologies for analyzing and reporting lesionsite also exist between studies. With these issues unresolved, therelative contribution of impulsivity and risk-taking to behav-ioral problems in patients with frontal lobe damage remainsunclear.
To address these questions, we developed a gambling taskwhich represents a compromise between the techniques used inother studies. The current procedure removed all elements ofskilled performance and carried an explicit, consistent, inverserelationship between success probability and reward values(high probability-low reward, and vice versa). The conflictbetween reward size and probability of obtaining that rewardensures that preference for high reward values reflects actualrisk-taking; preferences for large rewards where there is ahigh probability of obtaining them would reflect an adaptivedecision-making process rather than true risk-taking. More-over, previous decision-making research has demonstrated thatdecision options phrased in terms of possible gains promoterisk-aversive responding whereas options phrased in terms ofpossible losses result in risk-seeking response tendencies—aphenomenon referred to as the Framing Effect (Kahneman &Tversky, 1984). To maximize our ability to detect risk-takingand minimize additional influences on decisions, the task didnot involve losses.
This study had three main objectives. The first was to deter-mine whether patients with frontal lobe lesions were more likelythan control subjects to exhibit IMP or RTB. To best addressthis question within the context of prior work, we designed agambling task to separate IMP, which we defined as a failureto suppress an immediate reaction to a stimulus (i.e., a lackof control over behavior), from RTB, which we defined as apreference for responses associated with a low probability ofobtaining a large reward (i.e., a type of poorly calibrated con-trol over behavior). The underlying assumption is that RTBis a strategic response which is selected whereas IMP reflectsreduced control over behavior and is evoked. We recognize thatIMP, in particular, is a complex construct and many differenttypes of impulsivity may exist. As a check on the ecologicalvalidity of our impulsivity measure, subjects also completedthe Barratt Impulsiveness Scale (Patton, Stanford, & Barratt,1995).
The second objective, closely allied with the first, was toexamine whether specific lesion locations in our small samplewere associated with IMP or RTB. We identified individual sub-jects with excessive IMP or RTB and compared their lesion
locations to identify critical lesion sites. We anticipated thatRTB would be more frequent with lesions encroaching on ven-tral frontal regions that constitute part of the reward circuitry(Rolls, 2000). IMP, on the other hand, was hypothesized tobe related to more dorsal and medial regions of the frontallobes that play a role in attentional and motor control (Floden& Stuss, 2006; Ullsperger, 2006). The third objective wasto characterize response patterns that might provide insightsinto the processes underlying IMP or RTB. Specifically, weinvestigated how subjects modified their behavior followingpositive or negative outcomes. Positive and negative feedbackare crucial elements in acquiring and altering stimulus-rewardassociations. In fact, people tend to use feedback to guidebehavior even in contexts that do not require stimulus-rewardlearning (i.e., the Gambler’s Fallacy). There is growing evi-dence that some patients with frontal lobe damage fail to makeuse of this feedback (Bechara et al., 1994; Fellows & Farah,2005a).
We also evaluated how the timing of reward opportunitiesmay influence performance on this task. Our task manipulationwas based on the Common Difference Effect (Loewenstein &Prelec, 1992) from formal decision-making theory. Researchin both humans and non-human animals has demonstrated thatimposing a delay between reinforcement opportunities biasesdecisions towards larger rewards. This is best illustrated by con-trasting two decisions: given a choice between one dollar todayand two dollars tomorrow, most people will chose the smallbut immediate reward. However, if a time constant is addedto both options, one dollar in 50 days or two dollars in 51days, preferences switch and most people will choose the largerdelayed reward. This effect is observed in decision contextsinvolving choice between two delayed options (in contrast tosimple temporal discounting contexts involving choice betweenan immediate and a delayed option) but has not, to our knowl-edge, been investigated in the decision contexts similar to thecurrent type of gambling task involving serial presentation ofmultiple options. We manipulated the intertrial interval to eval-uate the influence of delayed reinforcement opportunities onperformance in the patient and control groups. Our procedureis idiosyncratic in that we use probabilistic options rather thansurety of rewards. The probabilistic nature of the choices meansthat, in effect, choice of any gamble is a selection of rewarddelay. Extending the intertrial adds a temporal constant to eachchoice, although it does not change the expected value of eachchoice.
2. Methods
The Research Ethics Board of Baycrest Centre for Geriatric Care and Uni-versity of Toronto approved the study. All participants gave written consent inaccordance with the Declaration of Helsinki.
2.1. Subjects
Eleven patients with chronic focal frontal lobe damage, six brain-damagedcontrols with cortical lesions outside the frontal lobes, and 11 age- and education-matched neurologically normal control subjects participated in the study (seeTable 1). Exclusion criteria included history of neurological or psychological
D. Floden et al. / Neuropsychologia 46 (2008) 213–223 215
a Pre-injury and post-injury total scores on the Barratt Impulsiveness Scale, 11th ed.
disorder unrelated to lesion, estimated premorbid IQ < 90, history of alcoholor drug abuse, and impaired and uncorrected hearing or vision. All patientswere in the chronic stage of recovery (4+ months post-event). Lesion location(documented from structural scans obtained for clinical purposes), etiology,chronicity, and size are displayed in Table 2. Focal lesions in patients diagnosedwith epilepsy were a result of surgical intervention for treatment of seizures.All frontal patients diagnosed with epilepsy had late onset seizures (in adult-hood). Of the nonfrontal patients diagnosed with epilepsy, two patients had earlyonset while three had late onset of seizures. All patients surgically treated forseizures, as well as two patients with frontal tumour resections and two patientswith frontal lesions due to cerebrovascular events, were on standard dosages ofanticonvulsant medications. One patient with epilepsy was taking medicationthought to produce significant drug-related cognitive impairments (i.e., Topi-max), although this was a patient with nonfrontal damage. All patients whounderwent tumour resection had non-invasive/infiltrating masses and did notundergo chemotherapy or radiation treatment. A mixture of etiologies ensuredlesion representation in all frontal regions. Prior work has demonstrated thatetiology is less relevant for cognitive performance than lesion location (Burgess& Shallice, 1996; Stuss et al., 1994; Stuss, Floden, Alexander, Levine, & Katz,2001). Two frontal patients had minor lesion extension into nonfrontal areas.Lesions were depicted on a standard anatomical template (Stuss et al., 2002)
based on cytoarchitecture (Petrides & Pandya, 1994) and coded for the presenceor absence of a lesion in each of seven lateralized frontal regions (see Table 2).
2.2. Baseline neuropsychological measures
All subjects completed a battery of clinically validated neuropsychologicaltests to establish baseline cognitive function. Tests assessed naming (BostonNaming Test; Kaplan, Goodglass, & Weintraub, 1983), comprehension (TokenTest; Benton, Hamsher, & Sivan, 1994), visuospatial perception (Judgmentof Line Orientation; Benton, Sivan, Hamsher, Varney, & Spreen, 1983), ver-bal attention span [Weschler Memory Scale-Revised (WMS-R) Digit Span;Wechsler, 1997], working memory (Consonant Trigrams; Brown, 1958; Peterson& Peterson, 1959), verbal fluency (phonemic and semantic; Benton et al., 1994),associative learning (WMS-R Verbal Paired Associates I and II; Wechsler,1997), and executive function (Trail Making Test, Army Individual Test Battery,1944; Wisconsin Card Sorting Test, Heaton, 1981), as well as questionnaires ofdepression symptoms (Beck Depression Inventory, Beck & Beck, 1972), absent-mindedness (Cognitive Failures Questionnaire, Broadbent, Cooper, Fitzgerald,& Parkes, 1982), and diurnal rhythms (Morningness–Eveningness Question-naire, Horne & Ostberg, 1976).
Table 2Lesion characteristics
Subject no. Sex Hand Pol Orb IM AC SM DL VL NF Etiology Chronicity (months) Lesion sizea
Frontal Nonfrontal
Frontal500b M R B R B R R R R 0 Ruptured aneurysm 51 6.47504c,d M R 0 0 0 0 0 L L 0 Sx, low grade glioma 72 2.08505c,d M L L L L 0 0 0 0 0 Sx, late onset seizures 20 1.66507b,d M R 0 0 0 R R R 0 0 Sx, late onset seizures 34 1.19509c,d F R 0 0 0 0 0 L L 0 Sx, benign meningioma 32 1.44517b M Amb 0 0 0 B B B 0 0 Sx, falx meningioma 33 9.09523 F R R R R R R R R R CVA 48 12.67 0.22525c,d M R 0 L 0 0 0 0 L 0 Trauma 8 0.91527 M R R 0 R 0 R 0 0 0 Trauma 10 2.05529c F R B B R 0 0 0 L 0 Trauma 24 1.42531c,d M R B B R 0 0 0 0 R Trauma 20 1.31 0.21
Nonfrontal511 M R 0 0 0 0 0 0 0 L Sx, late onset seizures 49 3.37513b M R 0 0 0 0 0 0 0 L Sx, early onset seizures 34 3.95516 M R 0 0 0 0 0 0 0 L Sx, early onset seizures >19 2.61521b F R 0 0 0 0 0 0 0 R Sx, late onset seizures 19 0.51532b F R 0 0 0 0 0 0 0 L CVA 10 NA537 F R 0 0 0 0 0 0 0 R Sx, late onset seizures 38 2.93
a Lesion volume expressed as percentage of whole brain.b Impulsive.c Risk-taking.d Reduced response to negative outcomes.
216 D. Floden et al. / Neuropsychologia 46 (2008) 213–223
2.3. Barratt Impulsiveness Scale
All subjects completed the Barratt Impulsiveness Scale-11 (BIS-11; Pattonet al., 1995), a self-report measure of real-world impulsive behaviors. Others(Berlin, Rolls, & Kischka, 2004) have found that patients with orbital frontallesions report more impulsivity on BIS-11. The questionnaire contains sub-scales for attentional, planning, and motor aspects of IMP. Our definition ofimpulsivity is most similar to the behaviors reflected in the motor or non-planning subscales. To assess changes from premorbid status, patients alsoreported the incidence of the same behaviors before any neurological event (Pre-BIS).
2.4. Gambling task
2.4.1. Trial eventsFive cards (4 cm " 6 cm) were presented on a touch screen, face-down in
a horizontal array (see Fig. 1). There were two Order conditions (Add andSubtract). In the Add condition, the screen was initially blank and one card wasadded to the display every 2 s, in a left-to-right order. In the Subtract condition,all five cards were initially present and the right-most card disappeared every2 s. Subjects were informed that one of the five cards displayed the word ‘WIN’on its face whereas the other four cards were blank. Subjects were instructedthat they could touch the screen at any time to stop the adding or removingprocess and “turn over” the cards present. If the WIN card was among the cardspresent at the response, the subject earned points. If the WIN card was absent atthe response, no points were awarded. Thus, outcome information was availableimmediately after each response.
The position of the WIN card was random on each trial, meaning that themore cards on the screen, the higher the probability that the WIN card was
present. However, the point value of the WIN card was inversely related tothe number of cards on the screen (i.e., more cards/higher probability = fewerpoints). The random nature of the WIN card location on each trial, the indepen-dence of each trial from every other, and the probability/reward contingencieswere explicitly described to each subject. The likelihood of finding the WINcard and its associated value were displayed on the screen at all times dur-ing the trial to minimize memory demands. These values are indicated inFig. 1. Subjects were instructed to try to win as many points as possi-ble. Given the complexity of the task, instructions were repeated/paraphrasedas needed to ensure that all subjects understood the nature of thetask.
Subjects initially completed five practice trials of each presentation condition(Add and Subtract) to ensure comprehension for the task. Subjects then com-pleted 20 Add trials and 20 Subtract trials (block order counterbalanced acrosssubjects) with a 2 s delay between response/reward delivery and the beginningof the next trial (Fast ITI). To evaluate the Common Difference Effect, Add andSubtract blocks were repeated (order reversed) with a 10 s delay between trials(Slow ITI). This procedure is somewhat idiosyncratic in that we use multipleprobabilistic options rather than surety of two rewards to evaluate the CommonDifference Effect. The probabilistic nature of the choices means that, in effect,choice of any gamble other than a sure thing is actually a selection of delay toreward. For example, choosing the first card means that, on average, one will haveto make this choice 5 times (or minimum of 10 s given a 2 s intertrial interval) toobtain a reward, whereas choosing the third card means that, on average, one willonly have to make this choice 3 times (or minimum of 18 s given a 2 s ITI plus 2card presentations at a 2 s rate) to obtain a reward. Extending the intertrial adds atemporal constant to each choice, although it does not change the expected valueof each choice. This is the crux of the Common Difference Effect manipulation.Note that the timing of card presentation (2 s interstimulus interval) did notchange.
Fig. 1. Gambling task displays and contingencies. A schematic diagram of successive screen displays during the gambling task. In the Add condition, presentationorder moves from top to bottom. In the Subtract condition, presentation order moves from bottom to top. Each display is present for 2 s or until the subject makesa response and the trial is terminated. Each trial is then followed by a blank screen for the intertrial interval (2 s in the Fast ITI condition and 10 s in the Slow ITIcondition). Reward contingencies are shown adjacent to each display, Pwin = the probability of finding the WIN card, WIN = point value for the WIN card. Note that,as the probability of finding the win card increases, the point value decreases.
D. Floden et al. / Neuropsychologia 46 (2008) 213–223 217
2.4.2. Statistical analysisRTB and IMP were dissociated through comparison of Add and Subtract
performance. A risk-taking subject will respond on the basis of few cards inan attempt to gain a large reward (despite the low probability of obtaining thatreward). This means a risk-taker will respond quickly in the Add conditionbut wait for some cards to be removed in the Subtract condition. In contrast, animpulsive subject will show disinhibited, rapid responses, regardless of stimuluspresentation order. This means they will respond with few cards present in theAdd condition but many cards present in the Subtract condition. Therefore,the difference between the number of cards present at response for the twoconditions (Subtract and Add) should be small for risk-taking subjects and largefor impulsive subjects.
Impulsivity was operationally defined as use of significantly fewer cardsin the Add compared with the Subtract condition (to reflect large differencesaccording to a Wilcoxon signed-rank test). Risk-taking was operationally definedas use of fewer than three cards on average in both presentation conditions (highrewards with an average probability of success less than .6). Performance pat-terns were evaluated for each subject and coded for presence or absence ofimpulsivity and risk-taking. As noted in Section 1, these patterns were mutuallyexclusive given that risk-taking reflected a performance strategy whereas impul-sivity represented the absence of strategy. Chi-square analysis was employed toidentify group differences in the proportion of subjects exhibiting each perfor-mance pattern.
A trial-by-trial analysis examined performance change in response to nega-tive and positive outcomes. If no reward is obtained on a trial (negative outcome),an adaptive strategy would be to respond on the basis of more cards on thenext trial, thereby improving the odds of obtaining a reward. Conversely, ifa reward is obtained on a trial (positive outcome), a subject might chose torespond on the basis of fewer cards on the next trial, in an attempt to obtain alarger reward. Subjects with behavior change less than 1.5S.D. from the controlmean were considered to show reduced or ‘low’ responses to negative or positiveoutcomes.
2.4.3. Lesion analysisWe grouped patients on the basis of performance and used chi-square to
examine the relationship between lesion location and performance pattern. Thisapproach differs from the typical procedure of dividing patients into mutuallyexclusive groups based on gross lesion location and then comparing performancepatterns across groups. Such groupings are, to a greater or lesser degree, artifi-cial in that lesions rarely respect these divisions, either invading or undercuttingother cortical territories. At best, large samples can reveal group differences butdo not allow identification of critical areas within the larger region. At worst,such groupings can obscure meaningful effects when they contain heterogeneouspatients. Our approach is therefore to use a priori criteria for identifying partic-ular behavior patterns in individual patients and only then investigate whethermeaningful relationships exist with lesion location. Others have adopted similarbehavior-based strategies to identify brain-behavior relationships in a range ofcognitive domains, including decision-making (Bechara et al., 1994), amnesia(von Cramon, Hebel, & Schuri, 1985), alexia (Cohen et al., 2003), and unilateralneglect (Hillis et al., 2005). However, care must be taken in using this techniquewith small sample sizes and conclusions based on few cases must be viewed aspreliminary.
3. Results
3.1. Baseline neuropsychological measures
Neuropsychological test performance was highly similaracross groups, demonstrating the excellent recovery in thepresent patient sample. Only the Paired Associates I WMS-R subtest showed a group difference (F(2, 25) = 8.4, p < .005),where the nonfrontal group performed significantly worse thaneither frontal patients or controls (all t(15) > 2.8, p < .05). Thisis consistent with associative memory deficits frequently notedin mesial temporal lobe dysfunction secondary to temporal lobe
epilepsy and/or anterior temporal lobe resection. Group perfor-mance for all tests is shown in Table 3.
3.2. Barratt Impulsiveness Scale
Self-reported impulsivity did not differ across groups (seeTable 1) although there was a trend for frontal lobe patientsto report more cognitive impulsivity after the injury (t(10) = 2,p = .07). The frontal group also showed a weak relationshipbetween cognitive impulsivity and increased absentmindednesson the Cognitive Failures Questionnaire (r(10) = .58, p = .06).Patients with larger frontal lobe lesions also reported more post-injury motor impulsivity (r(10) = .76, p < .01).
3.3. Gambling task
Fig. 2 displays the number of cards used during the Addand Subtract conditions for each a priori defined performancepattern (RTB, IMP) as well as for subjects whose performancewas neither risky nor impulsive.
3.3.1. ImpulsivityThree frontal subjects (500, 507, 517), three nonfrontal
subjects (513, 521, 532), and seven control subjects showedimpulsive responding in at least one of the ITI conditions (FastITI or Slow ITI). There was no group difference in the proportionof impulsive subjects (!2 = 1.64, p = .4).
3.3.2. Risk-takingRTB was specific to frontal lobe damage; six frontal lobe
patients (504, 505, 509, 525, 529, 531) demonstrated risky per-formance in at least one ITI condition while NO nonfrontalor control subjects were classified as risk-taking (!2 = 8.3,p < .005). All six risk-taking patients had either left ventrolat-eral or left orbitofrontal damage whereas patients who werenot risk-taking did not have damage to this region (!2 = 11.0,p < .001; see Fig. 3). Within the frontal lobe group, RTB cor-related negatively with lesion size (point bi-serial r(10) = #.64,p < .05), indicating that risky performance was not an artifact oflarge lesions. RTB was not related to any other lesion char-acteristic (chronicity r(10) = #.16, p = .64; etiology, !2 = .45,p = .52).
3.3.3. Response to negative and positive outcomesOn average, all subject groups responded on the basis of
more cards on trials following a negative outcome (non-win tri-als); frontal subjects used an average of .47 additional cards(S.D. = .32), nonfrontal subjects used an average of .81 addi-tional cards (S.D. = .49), and controls used an additional .79cards (S.D. = .40). Six frontal subjects (504, 505, 507, 509, 525,531), two control subjects, and no nonfrontal subjects were clas-sified as low responders (less than 1.5S.D. from the control meanor an average increase of less than .19 cards).
Five of the six frontal lobe patients identified as low respon-ders had also been identified as risk-taking, suggesting thatrisk-taking may be related to reduced behavioral correctionafter negative outcomes. Just as with risk-taking, then, there
218 D. Floden et al. / Neuropsychologia 46 (2008) 213–223
a Value reflects total number correct.b Required non-parametric comparison.
was a significant relationship between left orbital or left ven-trolateral lesions and reduced response to nonreward (!2 = 4.4,p < .05), and a negative correlation between low response to non-reward and lesion size (r(10) = #.65, p < .05), indicating thatthis also was not an effect of large lesions. There was no rela-tion of low response to nonreward to other lesion characteristics(chronicity, r(10) = #.06, p = .86; etiology, !2 = .62, p = .23).However, response to nonreward did correlate with education(r(27) = .58, p < .001) such that low responders were also lesseducated.
Responses to positive outcomes, or reward on the previoustrial, were likewise in the expected direction. Frontal subjectsresponded with an average of .29 fewer cards (S.D. = .21), non-frontal subjects used .37 fewer cards (S.D. = .23), and controlsused .48 fewer cards (S.D. = .24) following a successful trial.However, there was no observed relationship between responseto reward (positive outcomes) and lesion location or RTB, indi-cating that RTB was more associated with processing of negativeoutcomes.
3.3.4. Delayed reward opportunitiesThere was a significant effect of ITI condition (F(1, 25) = 5.9,
p < .05, MSE = .594) which did not interact with presentationcondition (Add, Subtract), or group (all F < 1). Fig. 4 shows thegeneral trend to use fewer cards (i.e., prefer larger reward values)when reinforcement was delayed (Slow ITI), consistent with theCommon Difference Effect.
4. Discussion
This study used a novel gambling task to dissociate IMP andRTB. In our sample, IMP was NOT exacerbated in patientswith frontal lobe damage. RTB, on the other hand, was exag-gerated following frontal lobe damage in some patients. Severalstudies using the Cambridge Gambling Task have also reportedincreased risk-taking (rather than impulsivity) in patients withfrontal lobe damage (Clark et al., 2003; Manes et al., 2002;Mavaddat et al., 2000). Both the current procedure and the Cam-bridge Gambling Task emphasize probabilistic decision-making
Joseph DeSouza
D. Floden et al. / Neuropsychologia 46 (2008) 213–223 219
Fig. 2. Performance-based groups. Average cards employed for the Add and Subtract conditions for risk-taking and impulsive subjects, as well as for subjects whoseperformance did not meet a priori criteria for either category. Consistent with those criteria, risk-taking subjects used fewer than 3 cards on both conditions whereasimpulsive subjects showed large differences between Add and Subtract performance. Sample size is denoted for each group. Error bars represent the standard errorof the mean.
with explicit reward contingencies. In contrast, Miller (1992)used a skilled problem-solving task without explicit rewardcontingencies and found increased impulsivity rather than risk-taking. Together, this suggests that probabilistic decision tasksencourage RTB, not impulsivity, in patients with frontal lobedamage.
Risk-taking was not a general consequence of frontal lobedamage; it occurred only in patients with ventrolateral andorbitofrontal lesions. Others have reported poor probabilisticdecision-making after lesions to the ventral surface (Mavaddatet al., 2000; Sanfey, Hastie, Colvin, & Grafman, 2003). Many
studies using the Iowa Gambling Task (i.e., Bechara et al., 1994;Fellows & Farah, 2005a) have also reported poor decision-making in patients with ventromedial lesions. Discrepancies inventral lesion location across studies may be largely termino-logical rather than anatomical. Surface depictions of the Iowapatients’ lesion appear almost discretely orbital and medial, butthe projections on coronal slices reveal extensive undercutting ofthe ventrolateral region we have identified here. However, not allstudies in patients with well-defined frontal lesion locations haveidentified RTB in patients with orbital and ventral lesions. Maneset al. (2002) found RTB was greater only in patients with large
Fig. 3. Lesion location comparison for frontal patients. Left hemisphere is to the right, according to radiological convention. Lesion density is indicated by colourbar on the right. (A) Patients showing risky performance show maximal overlap in the inferior regions of the left frontal lobe (green arrows). (B) Patients who do notuse a risk-taking strategy do not have lesions in these areas.
220 D. Floden et al. / Neuropsychologia 46 (2008) 213–223
Fig. 4. Delayed reward opportunities. Average number of cards used by eachgroup in the Add and Subtract conditions in the Fast and Slow ITI conditions.Consistent with the Common Difference Effect, there was a significant effectof ITI such that subjects used fewer cards during the Slow ITI condition whenreward opportunities were delayed relative to the Fast ITI. Note, however, thatthe small nonfrontal group did not show this tendency in the Add condition.Error bars represent standard error.
lesions whereas Rogers et al. (1999) found that patients withventromedial lesions were risk-averse rather than risk-taking.The reason for these conflicting findings is unclear althoughseveral lesion and demographic variables have been proposed tocontribute to decision-making patterns.
For example, lesion laterality and gender may play a role indecision-making performance. The effect of laterality is a dif-ficult question to address in patient studies given the relativerarity of unilateral lesions in ventral areas. Left-sided lesionswere most relevant in the present study, although the small sam-ple size prevents strong conclusions regarding lateralization.Fellows and Farah (2005a) also found that left-sided lesionswere most associated with RTB. Others have argued that rightlesions are critical for observing impairment on gambling tasks(Clark et al., 2003; Tranel, Bechara, & Denburg, 2002). Tranel,Damasio, Denburg, and Bechara (2005) have recently suggestedthat laterality alone does not determine performance but rather,that laterality interacts with gender. In a series of directed com-parisons, they demonstrated that decision-making deficits seemto occur more frequently after left-sided lesions in men and right-sided lesions in women. They propose that this is consistent withsex differences in approach to problem-solving. We looked forsimilar effects in our small sample of risk-taking patients butdid not find a consistent interaction of gender and lesion loca-tion. Nonetheless, this is a very intriguing idea that deservesfurther study in an effort to understand the possible contributionof lesion laterality.
Risk-taking was also associated with a reduced behavioralreaction to negative outcomes. That is, orbital and ventrolat-eral patients who showed RTB did not alter their performanceto the same degree as non-risk-taking subjects on trials follow-ing nonreward. Similar observations have been made in reversallearning studies where patients (Fellows & Farah, 2003) or non-human primates (Rolls, 2000) with lesions to ventral frontal
regions fail to alter established stimulus-reward associations inthe face of repeated negative feedback. Convergent functionalneuroimaging studies (Elliott, Frith, & Dolan, 1997; Paulus,Feinstein, Tapert, & Liu, 2004) have repeatedly demonstratedthat orbitofrontal cortex is active during flexible modification ofstimulus-reward associations. It may be that RTB in our patientsmay be one manifestation of impaired reversal learning.
Alternatively, RTB may be a consequence of a general impair-ment in setting stimulus-response criteria and flexibly modifyingthat criteria based on experience or feedback. Our prior work hasdemonstrated that left ventrolateral lesions (Petrides & Pandyaareas 44/45) impair contingent criterion setting and subsequentresponse bias on multi-dimensional choice reaction time tests(Stuss, Binns, Murphy, & Alexander, 2002), sustained attentiontests (Alexander, Stuss, Shallice, Picton, & Gillingham, 2005),and recognition memory tests (Alexander, Stuss, & Fansabedian,2003). Similarly, an event-related fMRI and EEG study reportedleft ventral frontal activation only on error trials when reactiontime on the subsequent trial slowed (Garavan, Ross, Murphy,Roche, & Stein, 2002). This is consistent with our suggestionthat this region calibrates response selection as behavior unfolds.
The reversal learning and criterion setting accounts are notnecessarily mutually exclusive and could account for com-plementary aspects of impaired adaptive decision-making orproblem-solving. Our findings may represent separable frontalsystems defined by unique patterns of cortico-cortical (Petrides& Pandya, 2002) and cortico-striatal (Alexander, DeLong, &Strick, 1986) connectivity. One system involves the ventrome-dial and medial orbital surfaces that have major connectionswith limbic system: hypothalamus, amygdala, and ventral (lim-bic) striatum. Lesions in this region may disrupt the drive statesor emotional responses to reward value that motivate behaviorand underlie reversal learning (Rolls, 2000). Another systeminvolves the ventrolateral and lateral orbital surfaces that havebidirectional connections with parietal and temporal associationcortex and discrete, topographically distinct cortical-striatal net-works. Based on the connectivity of this region, lesions herecould disrupt the attention-dependent capacity to establish andmodify response criteria based on feedback. Thus, differencesin placement within limbic or cognitive networks yield discreteexpectations about performance deficits following lesions toventrolateral versus ventromedial portions of the orbital surface.Functional imaging work has suggested similar conclusions withanatomical specificity for these processes consistent with the twolesion locations identified in the present study (Elliott, Dolan, &Frith, 2000; O’Doherty, Critchley, Deichmann, & Dolan, 2003).
All subjects, regardless of strategy and despite knowledgethat each trial was independent, showed a tendency to reducerisk following a nonreward trial and increase risk following arewarded trial. From the viewpoint of formal decision-makingtheory, this could be interpreted as a demonstration of suscep-tibility to the Gambler’s Fallacy, which is the mistaken beliefthat outcomes across random events are actually related. Thepatients who altered their performance less could therefore beseen as more rational decision makers. Similar observationshave been made in a recent study of ‘investment’ decisions inpatients with frontal lobe damage (Shiv, Loewenstein, Bechara,
D. Floden et al. / Neuropsychologia 46 (2008) 213–223 221
Damasio, & Damasio, 2005). These authors gave participantsthe option to ‘invest’ or pass on coin tosses and found that con-trol subjects were significantly more risk-averse following a losscompared to target patients with damage to orbital frontal lobeor other regions involved in emotional processing (i.e., amyg-dala, somatosensory cortex). These studies suggest that bluntedreaction to negative outcomes or failure to use negative feed-back to guide behavior is a beneficial factor when decisions areunrelated. In contrast, in contexts where trials are related andone must use feedback to learn to avoid options that were oncebeneficial, frontal lobe patients appear irrational.
There is some evidence that patients with focal frontallobe damage show normal susceptibility to other ‘irrational’decision-making tendencies that reflect the subjective value ofrewards. In the present study, we manipulated the delay betweenreward opportunities and found that frontal lobe lesions neitherincreased nor decreased susceptibility to the Common Dif-ference Effect (Loewenstein & Prelec, 1992) such that whenresponse options are equally delayed, the size of the reward hasmore influence over decision-making. This effect was apparentdespite the atypical structure of our task relative to traditionalCommon Difference Effect procedures. Likewise, Fellows andFarah (2005b) have demonstrated that frontal lobe patientsand control subjects show a similar tendency to undervaluedelayed rewards relative to immediate rewards, an effect knownas temporal discounting. Steeper discounting slopes have beenidentified in some studies of Attention Deficit Hyperactivity Dis-order (Barkley, Edwards, Laneri, Fletcher, & Metevia, 2001) anddrug abuse (Bickel & Marsch, 2001; Coffey, Gudleski, Saladin,& Brady, 2003; Dom, D’haene, Hulstijn, & Sabbe, 2006). Itmay be that more widespread neurochemical abnormalities arenecessary to disrupt these types of decision-making processes.
4.1. Clinical relevance for impulsivity
Our task evoked performance consistent with our definitionof IMP but, contrary to our hypothesis, it was equally prevalent inall subject groups. This result differs from Miller’s (1992) find-ing of increased IMP following frontal lobe lesions. In Miller’stask, decisions were based on problem-solving skill on visualor verbal puzzles. Patients with frontal injury show deficientstrategy use on a variety of tasks (Burgess & Shallice, 1996;Stuss et al., 1994). With failure to adopt a successful strat-egy, frontal subjects may ‘default’ to a stimulus-bound tactic,thereby appearing impulsive in comparison with control sub-jects. In the current task (and the Cambridge Gambling Task),strategy gains nothing because success is probabilistic; there isno winning strategy. Performance in control subjects and frontalpatients would not be differentially influenced by use of behav-ioral strategies. Our work and others (Clark et al., 2003; Maneset al., 2002; Mavaddat et al., 2000) reinforce the fact that somedegree of impulsive behavior is normal. Probabilistic decisions(as in the current study and the Cambridge Gambling Task;Rogers et al., 1999) may evoke IMP in normal subjects and, assuch, the selective problems in frontal lobe patients are only seenin situations where normal controls use behavioral strategies thatwould prevent disinhibited responses.
The chronicity of the lesions may also be a factor. IMP is oftennoted during the acute phase of recovery from frontal lobe dam-age. In Miller’s study (Miller, 1992), approximately a third ofthe sample was tested in the subacute (2–3 weeks post-surgery)stage of recovery. In contrast, the patients included in the workwith the Cambridge Gambling Task (Clark et al., 2003; Manes etal., 2002) and the current sample were tested during the chronic(>4 months) stage of recovery. IMP may resolve over time, atleast in well-recovered individuals. This has been demonstratedin Utilization Behavior, a disinhibition syndrome that may reflectIMP (Lhermitte, 1983). To our knowledge, no work has focusedon the evolution or recovery of IMP.
The lack of significant group differences in self-reported IMPon a real-world behavior questionnaire suggests that our sam-ple of patients is not excessively impulsive in other contexts.One might argue that failure to report IMP in daily life sim-ply reflects reduced insight. While this is always a possibility,particularly in patients with frontal lobe damage, we are hesi-tant to assume that this is overwhelmingly the case in the presentsample. Disturbed awareness correlates with the severity of cog-nitive dysfunction (Wagner & Cushman, 1994) and the presentsample showed no significant differences from controls on base-line neuropsychological testing. Case studies (i.e., Eslinger &Damasio, 1985) of patients with intact cognitive function whononetheless lack awareness into severe behavior disturbancestypically have had large bilateral frontal lesions and have beentoo behaviorally impaired – not cognitively impaired – to returnto work. In our patient group, six subjects with frontal lobedamage had returned to their previous employment and twoothers had resumed working, albeit in a different or modifiedcapacity. Others (Berlin et al., 2004) have found that patientswith orbital frontal lesions report more impulsivity on the samequestionnaire used here. Subtle differences in lesion size, pre-cise frontal location, or chronicity may underlie different results,however the presence of IMP appears to predict a poor functionaloutcome despite good “cognitive” recovery. In addition, theonly significant trend in the patient responses was for increasedmotor impulsivity in patients with larger lesions, whereas lackof insight might be expected to be greater in patients withlarger lesions. Regardless, we consider IMP to be a multifacetedconstruct and it is possible that our operational definition ofIMP would be unrelated to fully insightful responses on theBIS-11.
4.2. Summary and implications
This study explored the neural bases of impulsivity andrisk-taking behavior. Contrary to clinical descriptions, we didnot find evidence of impulsivity in a group of well-recoveredpatients with frontal lobe damage. Rather, poor decision-makingin some patients appeared to be a function of impaired reward-related processing as patients with left orbital and ventrolaterallesions engaged in risk-taking behavior and showed bluntedreaction to negative outcomes. This may be due to poor cali-bration of stimulus-response criteria, failure to reverse learnedreward associations, or some combination of these mechanismsdepending upon precise lesion location. Our data also suggest
222 D. Floden et al. / Neuropsychologia 46 (2008) 213–223
that behavior tends to become more risky when reinforcementopportunities are delayed.
These preliminary findings have important implications forunderstanding and managing behavior problems. First, theyhighlight the fact that impaired decision-making may arise fromdissociable sources and suggest that the location of damageor dysfunction may provide clues to the underlying mecha-nisms. For example, in the presence of ventral lesions, behavioralinterventions might target knowledge of behavioral contingen-cies and training of response-reward associations. Our findingsalso suggest that delaying response opportunities may exacer-bate, rather than prevent, poor decision-making. As a clearerpicture emerges of the neural and cognitive mechanisms under-lying these behaviors, behavioral and pharmacological treatmentshould translate into increased independence and quality of lifefor patients with frontal injuries.
Acknowledgements
This work was supported by a Rotman Group Grant (# MGC14974), Operating Grant (DTS # MT 12853), and DoctoralResearch Award (DF) from the Canadian Institutes of HealthResearch. D.T. Stuss was funded by the Reva James Leeds Chairin Neuroscience and Research Leadership. M.P. Alexander wassupported by the NICHHD, R01-HD046442-02. We are verygrateful to anonymous reviewers for helpful comments and sug-gestions and to D. Derksen, S. Gillingham, and C. Gojmerac fortesting participants. D.F. is now at the Cleveland Clinic, Centerfor Neurological Restoration and Department of Psychiatry andPsychology, Cleveland, OH.
References
Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organizationof functionally segregated circuits linking basal ganglia and cortex. AnnualReview of Neuroscience, 9, 357–381.
Alexander, M. P., Stuss, D. T., & Fansabedian, N. (2003). California VerbalLearning Test: Performance by patients with focal frontal and non-frontallesions. Brain, 126, 1493–1503.
Alexander, M. P., Stuss, D. T., Shallice, T., Picton, T. W., & Gillingham, S.(2005). Impaired concentration due to frontal lobe damage from two distinctlesion sites. Neurology, 65, 572–579.
Army Individual Test Battery. (1944). Manual of directions and scoring. Wash-ington: War Department, Adjutant General’s Office.
Barkley, R. A., Edwards, G., Laneri, M., Fletcher, K., & Metevia, L. (2001).Executive functioning, temporal discounting, and sense of time in adoles-cents with attention deficit hyperactivity disorder (ADHD) and oppositionaldefiant disorder (ODD). Journal of Abnormal Child Psychology, 29,541–556.
Bechara, A., Damasio, A. R., Damasio, H., & Anderson, S. W. (1994). Insensi-tivity to future consequences following damage to human prefrontal cortex.Cognition, 50, 7–15.
Beck, A. T., & Beck, R. W. (1972). Screening depressed patients in familypractice. Postgraduate Medicine, 52, 81–85.
Benton, A. L., Hamsher, K. S., & Sivan, A. B. (1994). Multilingual aphasiaexamination (3rd ed.). Iowa City: University of Iowa.
Benton, A. L., Sivan, A. B., Hamsher, K. S., Varney, N. R., & Spreen, O. (1983).Judgment of line orientations. Lutz: Psychological Assessment Resources,Inc..
Berlin, H. A., Rolls, E. T., & Kischka, U. (2004). Impulsivity, time perception,emotion and reinforcement sensitivity in patients with orbitofrontal cortexlesions. Brain, 127, 1108–1126.
Bickel, W. K., & Marsch, L. A. (2001). Toward a behavioral economic under-standing of drug dependence: Delay discounting processes. Addiction, 96,73–86.
Broadbent, D. E., Cooper, P. F., Fitzgerald, P., & Parkes, K. R. (1982). TheCognitive Failures Questionnaire (CFQ) and its correlates. British Journalof Clinical Psychology, 21, 1–16.
Brown, J. (1958). Some tests of the decay theory of immediate memory. Quar-terly Journal of Experimental Psychology, 10, 12–21.
Burgess, P. W., & Shallice, T. (1996). Response suppression, initiationand strategy use following frontal lobe lesions. Neuropsychologia, 34,263–273.
Busemeyer, J. R., & Stout, J. C. (2002). A contribution of cognitive decisionmodels to clinical assessment: Decomposing performance on the Becharagambling task. Psychological Assessment, 14, 253–262.
Clark, L., Manes, F., Antoun, N., Sahakian, B. J., & Robbins, T. W. (2003).The contributions of lesion laterality and lesion volume to decision mak-ing impairment following frontal lobe damage. Neuropsychologia, 41,1474–1483.
Coffey, S. F., Gudleski, G. D., Saladin, M. E., & Brady, K. T. (2003). Impulsivityand rapid discounting of delayed hypothetical rewards in cocaine-dependentindividuals. Experimental and Clinical Psychopharmacology, 11, 18–25.
Cohen, L., Martinaud, O., Lemer, C., Lehericy, S., Samson, Y., Obadia, M.,et al. (2003). Visual word recognition in the left and right hemispheres:Anatomical and functional correlates of peripheral alexias. Cerebral Cortex,13, 1313–1333.
Dom, G., D’haene, P., Hulstijn, W., & Sabbe, B. (2006). Impulsivity in abstinentearly- and late-onset alcoholics: Differences in self-report measures and adiscounting task. Addiction, 101, 50–59.
Elliott, R., Dolan, R. J., & Frith, C. D. (2000). Dissociable neural responses inhuman reward systems. Journal of Neuroscience, 20, 6159–6165.
Elliott, R., Frith, C. D., & Dolan, R. J. (1997). Differential neural response topositive and negative feedback in planning and guessing tasks. Neuropsy-chologia, 35, 1395–1404.
Eslinger, P. J., & Damasio, A. R. (1985). Severe disturbance of higher cog-nition after bilateral frontal lobe ablation: Patient EVR. Neurology, 35,1731–1741.
Fellows, L. K., & Farah, M. J. (2003). Ventromedial frontal cortex mediatesaffective shifting in humans: Evidence from a reversal learning paradigm.Brain, 126, 1830–1837.
Fellows, L. K., & Farah, M. J. (2005a). Different underlying impairments in deci-sion making following ventromedial and dorsolateral frontal lobe damagein humans. Cerebral Cortex, 15, 58–63.
Fellows, L. K., & Farah, M. J. (2005b). Dissociable elements of human foresight:a role for the ventromedial frontal lobes in framing the future, but not indiscounting future rewards. Neuropsychologia, 43, 1214–1221.
Floden, D., & Stuss, D. T. (2006). Inhibitory control is slowed in patients withright superior medial frontal damage. Journal of Cognitive Neuroscience,18, 1843–1849.
Garavan, H., Ross, T. J., Murphy, K., Roche, R. A. P., & Stein, E. A. (2002). Dis-sociable executive functions in the dynamic control of behavior: Inhibition,error detection, and correction. Neuroimage, 17, 1820–1829.
Heaton, R. (1981). A manual for the Wisconsin Card Sorting Test. Odessa:Psychological Assessment Resources.
Hillis, A. E., Newhart, M., Heidler, J., Barker, P. B., Herskovits, E. H., &Degaonkar, M. (2005). Anatomy of spatial attention: Insights from perfusionimaging and hemispatial neglect in acute stroke. Journal of Neuroscience,25, 3161–3167.
Horne, J. A., & Ostberg, O. (1976). A self-assessment questionnaire to deter-mine morningness–eveningness in human circadian rhythms. InternationalJournal of Chronobiology, 4, 97–110.
Kahneman, D., & Tversky, A. (1984). Choices, values, and frames. AmericalPsychologist, 39, 341–350.
Kaplan, E., Goodglass, H., & Weintraub, S. (1983). Boston Naming Test.Philadelphia: Lea & Febiger.
Lhermitte, F. (1983). “Utilization behavior” and its relation to lesions of thefrontal lobes. Brain, 106, 237–255.
Loewenstein, G., & Prelec, D. (1992). Anomalies in intertemporal choice: Evi-dence and an interpretation. Quarterly Journal of Economics, 107, 573–597.
D. Floden et al. / Neuropsychologia 46 (2008) 213–223 223
Manes, F., Sahakian, B., Clark, L., Rogers, R., Antoun, N., Aitken, M., etal. (2002). Decision making processes following damage to the prefrontalcortex. Brain, 125, 624–639.
Mavaddat, N., Kirkpatrick, P. J., Rogers, R. D., & Sahakian, B. J. (2000). Deficitsin decision making in patients with aneurysms of the anterior communicatingartery. Brain, 123, 2109–2117.
Miller, L. (1992). Impulsivity, risk-taking, and the ability to synthesize frag-mented information after frontal lobectomy. Neuropsychologia, 30, 69–79.
O’Doherty, J., Critchley, H., Deichmann, R., & Dolan, R. J. (2003). Dissociatingvalence of outcome from behavioral control in human orbital and ventralprefrontal cortices. Journal of Neuroscience, 23, 7931–7939.
Patton, J. H., Stanford, M. S., & Barratt, E. S. (1995). Factor structure of theBarratt Impulsiveness Scale. Journal of Clinical Psychology, 51, 768–774.
Paulus, M. P., Feinstein, J. S., Tapert, S. F., & Liu, T. T. (2004). Trend detectionvia temporal difference model predicts inferior prefrontal cortex activa-tion during acquisition of advantageous action selection. Neuroimage, 21,733–743.
Peterson, L. R., & Peterson, M. J. (1959). Short-term retention of individualverbal items. Journal of Experimental Psychology, 58, 193–198.
Petrides, M., & Pandya, D. M. (2002). Association pathways of the prefrontalcortex and functional observations. In D. T. Stuss & R. T. Knight (Eds.),Principles of frontal lobe function (pp. 31–50). New York: Oxford UniversityPress.
Petrides, M., & Pandya, D. N. (1994). Comparative architectonic analysis of thehuman and the macaque frontal cortex. In F. Boller & J. Grafman (Eds.),Handbook of neuropsychology (pp. 17–58). Amsterdam: Elsevier.
Rogers, R. D., Everitt, B. J., Baldacchino, A., Blackshaw, A. J., Swainson, R.,Wynne, K., et al. (1999). Dissociable deficits in the decision making cog-nition of chronic amphetamine abusers, opiate abusers, patients with focaldamage to prefrontal cortex, and tryptophan-depleted normal volunteers:Evidence for monoaminergic mechanisms. Neuropsychopharmacology, 20,322–339.
Rolls, E. T. (2000). The orbitofrontal cortex and reward. Cerebral Cortex, 10,284–294.
Sanfey, A. G., Hastie, R., Colvin, M. K., & Grafman, J. (2003). Phineas gauged:Decision-making and the human prefrontal cortex. Neuropsychologia, 41,1218–1229.
Shallice, T., Burgess, P. W., Schon, F., & Baxter, D. M. (1989). The origins ofutilization behavior. Brain, 112, 1587–1598.
Shiv, B., Loewenstein, G., Bechara, A., Damasio, H., & Damasio, A. R. (2005).Investment behavior and the negative side of emotion. Psychological Sci-ence, 16, 435–439.
Stuss, D. T., Alexander, M. P., Floden, D., Binns, M. A., Levine, B., McIntosh,A. R., et al. (2002). Fractionation and localization of distinct frontal lobeprocesses: Evidence from focal lesions in humans. In D. T. Stuss & R. T.Knight (Eds.), Principles of frontal lobe function (pp. 392–407). New York:Oxford University Press.
Stuss, D. T., Alexander, M. P., Palumbo, C. L., Buckle, L., Sayer, L., &Pogue, J. (1994). Organizational strategies of patients with unilateral orbilateral frontal lobe injury in word list learning tasks. Neuropsychology, 8,355–373.
Stuss, D. T., Binns, M. A., Murphy, K. J., & Alexander, M. P. (2002). Dissocia-tions within the anterior attentional system: Effects of task complexity andirrelevant information on reaction time speed and accuracy. Neuropsychol-ogy, 16, 500–513.
Stuss, D. T., Floden, D., Alexander, M. P., Levine, B., & Katz, D. (2001). Stroopperformance in focal lesion patients: Dissociation of processes and frontallobe lesion location. Neuropsychologia, 39, 771–786.
Tranel, D., Bechara, A., & Denburg, N. L. (2002). Asymmetric functional rolesof right and left ventromedial prefrontal cortices in social conduct, decisionmaking and emotional processing. Cortex, 38, 589–612.
Tranel, D., Damasio, H., Denburg, N. L., & Bechara, A. (2005). Does genderplay a role in functional asymmetry of ventromedial prefrontal cortex? Brain,128, 2872–2881.
Ullsperger, M. (2006). Performance monitoring in neurological andpsychiatric patients. International Journal of Psychophysiology, 59,59–69.
von Cramon, D. Y., Hebel, N., & Schuri, U. (1985). A contribution to theanatomical basis of thalamic amnesia. Brain, 108, 993–1008.
Wagner, M. T., & Cushman, L. A. (1994). Neuroanatomic and neuropsycholog-ical predictors of unawareness of cognitive deficit in vascular populations.Archives of Clinical Neuropsychology, 9, 57–69.
Wechsler, D. (1997). Wechsler Memory Scale: Revised. Toronto: The Psycho-logical Corporation, Harcourt, Brace, & Jovanovich, Inc..
