Epilepsy in the Frontal Lobes: Neuropsychological Characteristics

ELSEVIER

Epilepsy in the Frontal Lobes: Neuropsychological Characteristics 1-3Dominic Upton and 2'3pamela J. Thompson

The disruption of cognitive functions by epileptic discharges arising from specific foci in the frontal regions have rarely been described, probably reflecting the previous difficulties in the collection of adequately described groups. We describe the neuropsychological consequences of frontal lobe epilepsy dependent on the epileptic focus in the frontal region. A group of 74 subjects with frontal lobe epilepsy (ELE) was assessed; 30 had a dorsolateral dysfunction (17 left, 13 right), 11 had mesial (7 left, 4 right), 10 had orbitofrontal (5 left, 5 right), 10 had motor/premotor (5 left, 5 right), and 13 had extensive (i.e., more than one frontal region, 8 left, 5 right) dysfunction. Comparisons were made between the groups on a battery of neuropsychological measures believed to be sensitive to frontal lobe dysfunction. The results indicated only 2 of 26 variables to be specifically impaired dependent on the location of epileptic foci in the frontal lobe (p < 0.05), an observation that emphasizes the difficulty in assessing functions in this region and the consequences that rapidly diffusing epileptic activity may have on cognitive function. We conclude that documentation of consistent deficits associated with frontal lobe epileptic foci will prove difficult. Key Words: Epilepsy--Neuropsychology--Frontal lobes--Cognitive systems.

Epileptic foci in the frontal lobes are believed to account for a sizable p r o p o r t i o n of all partial seizures (1) and there is increasing recognition of their behavioral correlates and physiological, biochemical, and anatomic characteristics (2). H o w e v e r , few researchers have explicitly studied the performance Received November 7, 1995; accepted February 1, 1996. From the 1Cardiff Institute for Higher Education, School of Human Sciences, Llandaff, Cardiff, 2Institute for Neurology, Queen Square, London, and 3National Society for Epilepsy, Chalfont St. Peter, Gerrards Cross, Bucks, U.K. Address correspondence and reprint requests to Dr. D. Upton at Cardiff Institute for Higher Education, School of Human Sciences, Llandaff, Cardiff CF5 6YB, U.K.

J. Epilepsy 1996;9:215-222 © 1996 by Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010

of subjects w i t h frontal lobe epilepsy (FLE) on neuropsychological measures. Although some characteristics are implied in certain reports (3-5), the cognitive consequences of FLE usually have not been the unique focus of s t u d y (5-7). Several reports have described certain characteristics of FLE, both in examination of single case studies (8) and, more recently, in large group studies (5,9). H o w e v e r , in these studies, FLE w a s v i e w e d from a general perspective w i t h o u t discrimination between foci in individual regions in the frontal lobes. This m a y limit the use of such studies: N u m e r o u s investigators have c o m m e n t e d on the diverse nature of the functions s u b s u m e d b y the individual frontal regions (10-13).

0896-6974/96/$15.00 PII S0896-6974(96)00016-3

D. UPTON AND P. J. THOMPSON The functions of the frontal region are not easy to characterize, however. Many investigations have been made of the possible functions and have produced a similarly large number of incongruous results (12). A possible explanation for this is the large number of functions controlled by the region and the possibility that the region cannot be viewed simply as a homogeneous region (14,15). Simply documenting the deficits associated with "frontal lobe lesions" may therefore have minimal value and the importance of documenting possible deficits associated with more discrete areas of dysfunction must be stressed. This lack of documentation of frontal lobe neuropsychological deficits is clearly evident with regard to epilepsy. No studies have documented the consequences of more discrete frontal lobe epileptic foci on neuropsychological performance (7), which may reflect the difficulty in diagnosis and categorization of frontal epileptic seizures. However, with recent increase in interest in frontal lobe seizures and their more easily recognized characteristics, it has become apparent that this area merits further investigation (5,16). We aimed to document the neuropsychological characteristics of a group of subjects with epilepsy with discretely localized foci in the frontal lobes.

Method Subjects Subjects were selected in a 30-rnonth period and consisted of all those attending a national center for epilepsy who had clearly defined cortical dysfunction limited to a unilateral frontal lobe. All subjects had epilepsy, with or without magnetic resonance imaging (MRI) identifiable lesions. Subjects were classified according to EEG monitoring, seizure history and behavior, and cortical imaging. Subjects with either electrophysiological or radiological evidence of dysfunction outside the frontal regions were excluded, as were those whose investigations showed conflicting localization. Similarly, those with a history of psychiatric disturbance or alcohol abuse were excluded. All subjects were righthanded or had been demonstrated to have left hemisphere dominance for language on sodium amytal testing. Seventy-four subjects with FLE were assessed (42 with left frontal and 32 with right frontal dysfunction). The subjects were then further subdivided 216 J EPILEPSY, VOL. 9, NO. 3, 1996

into groups dependent on the frontal region affected. This subdivision was based on cortical imaging, EEG monitoring, and seizure behavior. The groups shown in Table 1 are classified with regard to all the investigative data. The term "extensive" refers to subjects with dysfunction judged to extend over more than one region, although none extended beyond the frontal lobes (Table 1). There were no significant sex, age, educational, or occupational differences between the subject groups. Similarly, there was no significant difference in terms of basic epilepsy characteristics (e.g., duration of disorder, seizure type and frequency, number or type of medications prescribed, or etiology of disorder; Table 2). The lateralization differences were not significant between the localization groups (Chi-square = 2.16, df = 4, p = 0.71). In terms of background neuropsychological characteristics, there was no significant difference [all two-way analysis of variance (ANOVA) p > 0.05] between the groups in terms of Wechsler Adult Intelligence Scale-Revised (WAIS-R) Full scale I.Q. (F.S.I.Q), verbal I.Q. (V.I.Q.), Performance I.Q. (P.I.Q.) (abbreviated version) (17), or National Adult Reading Test (NART) I.Q. (18), nor was there any significant difference on tests of memory (Story recall, list and design learning, drawn from the Adult Memory and Information Processing Battery (AMIPB) (19), Recognition Memory Tasks (20), or tests of language functioning ]Token test of receptive function (21) and Graded Naming Test (22)].

Materials Several measures have been devised for the assessment of frontal dysfunction, yet none has proved entirely satisfactory (23,24). To overcome the limitations in the assessment of frontal lobe dysfunction, several different clinical measures believed to tap the variety of functions subsumed by the frontal lobes were used in the present study. These included measures of both executive skills and motor skills, both assumed to be dependent on frontal lobe integrity. Table 1. Areas of dysfunction according to EEG, MRL and seizure semiology. Area Dorsolateral Mesial Orbitofrontal Motor/premotor Extensive

Left frontal

Right frontal

17 7 5 5 8

13 4 5 5 5

EPILEPSY IN THE FRONTAL LOBES Table 2.

Basic demographic and epilepsy charactersitics of patient groups

Variable

Left Right frontal frontal

Sex

Male Female Age (yr) Mean SD Range Educational qualifications No formal qualifications GCSEs/"O"-levels "A"-levels/professional qualifications Degree Duration of epilepsy (yr) Mean SD Range Age at epilepsy onset (yr) Mean SD Range Drug regimen Monotherapy Polytherapy Etiology of epilepsy Head injury Dysplasia Tumor Vascular Unknown

19 23

19 13

28.5 8.76 16-61

29.41 6.90 17-53

32 3 7 2

19 8 2 3

18.94 8.02 3-40

15.57 6.98 2-26

9.3 7.09 1-40

11.10 9.72 3-47

5 27

1 31

8 12 5 3 14

8 14 8 2 1

Executive Skills

In the Modified Wisconsin Card Sorting Test (MWCST) (25), the number of perseverative errors, category errors, and categories achieved were recorded, together with the total time taken to complete the task. In the Twenty Questions Task (26), the subject is required to guess an animal the examiner has in mind, with the examiner responding only "Yes" or " N o . " The total number of questions asked is recorded, together with the first guess at the animal (considered an indication of impulsivity). The type of question asked is classified into one of three types: constraint seeking, in which half or more options are eliminated (thus an efficient question type: e.g., "Does it have four legs?"); pseudoconstraint, which appears similar to constraint but actually eliminates only one animal and thus inefficient question type (e.g., "Does it bark?"); and hypothesis scanning, in which the subject basically guesses (e.g., "Is it a dog?"). The mean score over two trials was recorded for all indexes of performance.

In the Verbal Fluency task (27), the subject is given 60 s to recall as m a n y words beginning with the letter S as possible. Subsequently, the subject is required to state as m a n y animals as possible in 60 s. In the Stroop Test (28), the subject is required to read a list of color names printed in different colors, and the time taken to complete the task is recorded. Subsequently, the subject reads the same list but states the color of the ink rather than the color name; again the time is recorded. The interference time is calculated (time taken to read ink colors minus time taken to read color names). In the Trail Making (29) task, the subject is first required to join a series of consecutive letters together (part A) and the time taken to complete the task is recorded. Subsequently, the subject is required to join alternate letters and numbers in sequence (part B). The "frontal lobe time" (time for part B--time for Part A) is calculated to reduce the importance of the motor component of the task (thus providing a measure of planning and flexibility). In addition, the number of errors m a d e in part B of the task is recorded. In the Cognitive Estimates task (30), the subject is required to estimate the answer to 10 questions which are in some w a y novel. Each question is given an error score: The greater the total score, the greater the impairment. In Cost Estimation (31), the subject is required to estimate the price of 10 c o m m o n objects. Each item is given an error score on the "bizarreness" of the response. The greater the score, the greater the impairment. In the Porteus Maze Test (32), the subject must complete a maze in the shortest possible route and time. Time taken to complete the test, along with errors (both wrong directions and pencil lifts), is recorded.

M o t o r s skills

In the Tapping Task (33), the subject is required to tap as quickly as possible, alternating between two metal plates. The number of alternations m a d e with both the dominant and n o n d o m i n a n t h a n d in 20 s is recorded. In the Bimanual H a n d Movements (34,35) task, the subject is required to alternate f i s t / p a l m as quickly as possible. The number of both alternations and perseverative errors in a 20-s period is recorded. In the Motor Sequences (36) task, the subject is J EPILEPSY, VOL. 9, NO. 3, 1996 217

D. UPTON AND P. J. THOMPSON

required to copy 10 three-item gesture sequences. The n u m b e r of correct sequences recalled is recorded. In the Gesture Span task (36), the subject is required to reproduce an ever-increasing sequence of h a n d span gestures. In the temporal order task, a series of four gestures is shown to the subject. Subsequently, the subject is shown the same gestures in r a n d o m order and is asked to recall the order of presentation. All subjects completed the test battery in two separate 1- to 2-h sessions. Data analyses were conducted with the Statistical Package for the Social Sciences PC version (Version 4-37). Analysis

A series of two-way ANOVAs was undertaken; the factors were lateralization (left or right) and area of cortical damage (extensive, orbitofrontal, mesial, m o t o r / p r e m o t o r , dorsolateral). WAIS-R F.S.I.Q. was treated as a covariate to reduce the importance of general intellectual ability. Post hoc analysis took the form of interaction contrasts with post hoc Scheff6 tests.

Results A n a l y s i s of the m o t o r skills tests (Table 3) showed only one significant result involving the frontal region. On the bimanual h a n d movements Table 3. Task Bimanual hand movements Left Right Bimanual hands--errors Left Right Gesture span Left Right Motor sequences Left Right Tapping: Nondominant hand Left Right Tapping: Dominant hand Left Right Temporal order for gesture Left Right

error measure, there was an interaction effect between lateralization and frontal area of dysfunction (F(4,62) -- 2.772; p -- 0.035). Post hoc multiple comparisons showed the extensive group (mean 0.97) in the right hemisphere to be less impaired than the extensive group in the left hemisphere (mean 4.05). Furthermore, in the right hemisphere, the m o t o r / p r e m o t o r group (mean 4.59) was more impaired than the extensive group (mean 0.97) and the dorsolateral group (mean 1.94). There were no significant differences between the groups in the left hemisphere. A main effect for lateralization was evident on two of the measures of motor skills. On the measure of bimanual h a n d movements (F(1,63) = 9.16, p = 0.004), the left hemisphere group (mean 25.62, SD 9.94) had fewer movements recorded than the right hemisphere group (mean 33.25, SD 13.95). However, on the measure of temporal order (F(1,63) = 5.33; p = 0.024), the left hemisphere group (mean 3.88, SD 2.24) was less impaired than the right hemisphere group (mean 2.91, SD 1.23). Neither of these measures showed either a significant main effect for frontal region or a significant interaction effect (Table 3). On the measures of executive skill only one variable showed a significant effect involving the frontal regions (Table 4). On the Twenty Questions task, there was no interaction effect for the first-guess measure, but there was a main effect for lateraliza-

Means and SD for motor skill tasks

Dorsolateral group

Orbitofrontal group

Mesial group

Motor/premotor group

Extensive group

25.59 (9.05) 38.08 (17.49)

29.29 (14.10) 33.00 (11.34)

25.20 (9.12) 34.20 (7.60)

22.60 (8.47) 21.80 (8.53)

24.75 (9.38) 31.40 (10.90)

2.15 (1.73) 1.56 (1.72)

1.44 (2.46) 2.50 (1.00)

4.00 (4.12) 2.14 (1.57)

1.86 (1.21) 5.17 (4.26)

4.11 (3.89) 6.58 (2.89)

2.88 (0.46) 3.05 (0.28)

2.57 (1.13) 3.00 (0.02)

2.80 (0.56) 2.40 (0.89)

2.80 (0.44) 2.80 (0.45)

2.63 (0.52) 3.00 (0.00)

4.53 (1.23) 6.39 (2.40)

3.57 (1.72) 4.75 (2.22)

4.40 (0.89) 4.80 (4.21)

4.80 (2.17) 5.20 (1.64)

4.38 (1.77) 3.60 (2.30)

59.12 (13.07) 67.23 (18.30)

51.86 (23.18) 58.50 (2.38)

63.00 (4.24) 65.00 (6.32)

63.20 (3.27) 57.80 (9.60)

64.25 (7.34) 57.40 (14.64)

71.12 (12.40) 76.31 (11.49)

69.00 (14.68) 67.25 (4.86)

74.00 (5.15) 70.00 (9.27)

74.51 (3.39) 69.00 (8.54)

73.38 (5.21) 63.20 (17.85)

3.47 (1.94) 2.85 (l.21)

5.00 (3.22) 2.75 (0.05)

4.20 (1.31) 3.40 (0.89)

4.80 (1.31) 3.00 (1.87)

3.00 (2.56) 2.60 (1.52)

218 J EPILEPSY, VOL. 9, NO. 3, 1996

EPILEPSY I1",ITHE FRONTAL LOBES

T a b l e 4. Task 20 Question: Constraint seeking Left Right 20 Questions: First guess Left Right 20 Questions: Hypothesis scanning Left Right 20 Questions: Pseudoconstraints Left Right 20 Questions: Total Left Right Cognitive estimates Left Right Cost estimation Left Right Fluency: Animals Left Right Fluency: S Left Right Porteus maze: Pencil lifts Left Right Porteus maze: Time Left right Porteus maze: Errors Left Right Stroop interference time Left Right Trail Making, part B: Errors Left Right Trail Making: Frontal lobe time Left Right MWCST: Categories Left Right MWCST: Category errors Left Right MWCST: Perseverative errors Left Right MWCST: Time Left Right

Means and SD for exective skill tasks

Dorsolateral group

Orbitofrontal group

Mesial group

Motor/premotor group

Extensive group

7.32 5.19

(2.15) (1.25)

6.50 4.63

(1.89) (1.47)

6.10 5.90

(2.45) (2.05)

6.60 5.80

(1.75) (1.83)

5.88 6.70

(1.39) (2.96)

6.05 4.69

(1.25) (1.72)

3.93 3.50

(3.00) (1.00)

5.70 5.14

(0.76) (2.26)

5.93 4.80

(2.21) (2.19)

6.67 6.50

(2.89) (3.43)

4.21 4.85

(2.47) (2.94)

6.64 4.00

(1.95) (1.59)

3.70 4.30

(2.00) (2.06)

7.00 4.90

(5.46) (1.34)

6.75 4.80

(2.11) (2.94)

1.91 0.54

(1.26) (0.31)

2.29 0.75

(1.79) (0.50)

2.50 1.00

(3.63) (1.37)

3.10 1.30

(1.00) (1.91)

1.81 1.20

(0.76) (0.34)

13.97 10.85

(3.86) (3.85)

16.00 9.50

(3.06) (2.01)

12.50 11.40

(2.27) (3.13)

16.90 12.40

(3.69) (3.45)

14.75 13.20

(2.50) (3.97)

9.24 4.62

(5.33) (2.96)

10.57 5.75

(5.99) (1.89)

7.00 3.60

(2.00) (2.88)

6.20 6.00

(2.95) (2.74)

8.88 8.60

(4.49) (2.61)

3.82 4.46

(1.47) (1.20)

4.72 4.00

(0.76) (0.82)

3.40 4.20

(0.89) (0.45)

4.20 4.80

(1.10) (0.45)

3.00 3.80

(0.03) (1.79)

15.24 17.92

(4.82) (6.37)

14.57 18.50

(3.45) (2.52)

16.00 13.80

(4.00) (2.59)

13.00 14.60

(1.87) (2.97)

14.50 16.00

(2.83) (4.85)

11.59 15.00

(3.18) (2.55)

8.85 15.00

(4.06) (4.69)

10.80 12.20

(2.28) (3.03)

10.81 11.40

(1.30) (2.88)

11.75 12.00

(3.85) (2.74)

1.53 1.08

(1.55) (0.95)

1.14 2.75

(1.22) (2.36)

0.20 1.20

(0.48) (2.68)

1.20 1.60

(0.47) (0.89)

1.00 1.40

(0.93) (1.67)

71.77 (33.15) 70.14 (20.98) 83.46 (46.49) 155.00 (66.58 0.88 0.69

(1.67) (0.75)

55.77 (30.56) 41.69 (32.79) 1.35 0.54

(1.54) (0.66)

30.41 (20.47) 16.46 (11.52)

0.86 0.75

(1.22) (0.96)

107.57(129.22) 73.25 (3.22) 1.57 2.25

46.00 (10.84) 85.00 (86.75) 0.60 0.40

(0.89) (0.89)

54.00 (22.25) 93.80 (59.94)

72.00 (18.25) 110.00 (41.38) 0.20 1.40

(0.45) (0.89)

95.40(108.14) 58.20 (20.28)

(2.15) (1.89)

0.80 (0.84) 6.20 (10.52)

1.80 2.00

(1.48) (2.35)

31.43 (47.05) 30.00 (6.00)

33.80 (19.73) 26.20 (18.11)

22.40 28.00

(7.37) (5.20)

65.00 (16.04) 102.00 (66.86) 0.63 0.20

(0.74) (0.45)

63.50 (24.39) 86.60 (53.53) 1.25 1.80

(1.28) (2.49)

19.38 (9.10) 24.60 (17.98)

5.59 5.46

(0.80) (0.78)

5.58 5.50

(0.79) (1.73)

5.80 5.60

(0.45) (0.89)

5.60 5.80

(0.55) (0.45)

5.00 6.00

(1.01) (0.00)

1.77 3.38

(0.83) (2.56)

1.75 4.75

(0.83) (0.96)

3.60 4.00

(3.05) (3.08)

4.00 4.80

(2.74) (4.44)

2.50 3.80

(0.93) (2.39)

2.35 3.23

(2.81) (2.98)

3.42 8.00

(4.89) (6.68)

1.80 5.20

(1.09) (2.95)

2.80 2.80

(2.28) (2.17)

3.50 2.80

(3.78) (2.63)

287.82 (104.52) 259.29 (84.92) 295.40 (42.07) 254.15 (70.89) 283.50 (40.77) 352.80 (122.51)

310.00 (171.11) 356.60 (136.45)

344.00 (230.84) 280.60 (149.22)

MWCST, Modified Wisconsin Card Sorting Test.

j EPILEPSY, VOL. 9, NO. 3, 1996

219

D. UPTON A N D P. J. THOMPSON

tion (F(1,73) -- 4.385, p -- 0.040) and for localization (F(4,73) = 3.169, p -- 0.019). With regard to the main effect for lateralization, the right frontal group (mean 5.30, SD 2.29) was more impaired (i.e., asked the question earlier) on the task than the left frontal group (mean 6.17, SD 2.40). With regard to the main effect for frontal region, the orbitofrontal group was the most impaired. When the groups were collapsed across lateralization and post hoc multiple comparisons (Scheff6 multiple range test, p = 0.05) were made, results suggested that the orbitofrontal group (mean 3.75, SD 2.04) was more impaired than the extensive group (mean 7.00, SD 3.20), the motor/ premotor group (mean 6.21, SD 1.63) and the mesial group (mean 5.70, SD 2.04), but not the dorsolateral group (mean 5.65, SD 1.52). Finally, indexes of performance drawn from the measures of executive skill showed a significant main effect for lateralization, with neither a main effect for frontal region or an interaction effect. First, on the cognitive estimates task (F(1,63) = 7.184, p -- 0.009), the left frontal group was more impaired (mean 8.76, SD 4.78) than the right frontal group (mean 5.43, SD 3.03). Similarly, fluency for words beginning with the letter S was more impaired (F(1,63) = 8.055, p = 0.006) in the left frontal group (mean = 10.98, SD 3.26) than in the right frontal lobe group (mean 13.53, SD 3.23). The right hemisphere group took longer (mean 99.69, SD 59.94) to complete the Porteus maze task (F(1,63) = 5.89, p = 0.018) than the left frontal group (mean 67.17, SD 25.48). Similarly, the right hemisphere group (mean 4.50, SD 2.73) was more impaired in terms of the number of category errors made on the MWCST (F(1,66) = 14.17, p < 0.001) than the left hemisphere group (mean 2.61, SD 1.92).

Discussion Our results can be considered slightly disappointing, inasmuch as only two significant results involving the frontal regions (i.e., bimanual hand movements and first guess in the Twenty Questions task) were demonstrated in 26 analyses. Several differences in terms of lateralization were demonstrated, but in the manner expected, given the results of a previous investigation (9). Overall, our results of this investigation suggested few differences between the frontal region subgroups. However, the lack of any observable deficits should not be dismissed as irrelevant, for in 220 J EPILEPSY, VOL. 9, NO. 3, 1996

themselves, they suggest several explanations that may be of significance in investigations of FLE. First, the inadequacy of many measures of frontal lobe function in providing quantitatively different results depending on qualitatively different deficits must be highlighted. Although different deficits may exist, the available measures may preclude their measurement. Several recent reports have suggested that even the most popular of neuropsychological measures believed to be sensitive to frontal d y s u n f u n c t i o n m a y have limited validity (22,38,39), which obviously may severely affect any investigation of frontal lobe dysfunction. Second, several epilepsy characteristics were not controlled for in the present study. Seizure frequency, type, and severity may all influence neuropsychological performance. Furthermore, age at onset is an important variable that should be considered in any neuropsychological investigation of FLE. Evidence suggests that there are discrete stages in frontal lobe development, and different cognitive skills may be disrupted depending on the stage at which damage occurs (40-42). However, in controlling for these factors, the number of subjects will be decreased, and analysis may thus prove problematic. Even in our study, although the original sample was relatively large, grouping of the sample according to frontal region and lateralization resulted in small numbers of subjects in the specific groups. Consequently, subtle deficits may not have been detected. Indeed, some of the results show wide variance in some of the interaction cells, which consequently may have obscured more moderate but nevertheless significant differences. Third, although great care was taken to ensure that the sample selected was a "pure" cohort of subjects with discrete frontal lobe epileptic foci, we cannot state with certainty that it was. The difficulty in the characterization of frontal lobe seizures and their rapid propagation (16) to other cortical regions ensures that the selection of subjects to form a homogeneous study sample will always prove problematic. A possible solution w o u l d be the adoption of more controlled single case studies in which the background epilepsy characteristics can be ensured and conclusions can be drawn with relative confidence. This may prove even more convincing if neuropsychological characteristics are defined preoperatively and the operative procedures are discrete and result in total cessation of seizures. Finally, the frontal region may be considered a homologue, or a system, and attempts at differentiating specific deficits associated with the different regions may prove difficult in an epilepsy sample.

EPILEPSY IN THE FRONTAL LOBES

Our findings suggest that a strict localization approach to frontal lobe function may not be possible in an epilepsy sample. Other evidence suggests that one brain region alone is insufficient for successful completion of many tasks, supporting a "systems" model of cortical organization (14,43-46). These frontal systems (whethc:~ conceptualized at the anatomic or cognitive level) may be disrupted by epileptic activity. This can occur in any frontal region and result in disruption of the neuronal pathways, impairing functions associated with all of them, which suggests that cognitive functions disrupted by FLE may be difficult to differentiate. It may be especially difficult to draw conclusions from large group studies and apply the conclusions to individuals. Although some researchers have suggested that several tests may be capable of distinguishing frontal lobe lesions (4), our findings suggest that this may be an overoptimistic viewpoint. To expect frontal dysfunction to be illuminated by one simple test may be unrealistic (14,47,48). It may be necessary for both clinicians and researchers not to rely on one simple test but to devise novel and appropriate methods of combining the results from several neuropsychological measures. This will have the benefit of reducing the reliance on single measures and ensuring that as many functions of the frontal cortex are assessed appropriately and, possibly, allowing greater neuropsychological discrimination between the frontal regions.

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