Directed forgetting in frontal patients’ episodic recall

Neuropsychologia 45 (2007) 1355–1362

Directed forgetting in frontal patients’ episodic recall Pilar Andr´es a,∗ , Martial Van der Linden b , Fabrice B.R. Parmentier a a

School of Psychology, University of Plymouth, Drake Circus, Plymouth PL4 8AA, United Kingdom b Cognitive Psychopathology Unit, University of Geneva, Switzerland

Received 25 May 2006; received in revised form 18 September 2006; accepted 19 September 2006 Available online 18 October 2006

Abstract The aim of this study was to examine the performance of a group of patients with lesions of the prefrontal cortex in directed forgetting in episodic memory, i.e. the capacity to actively forget irrelevant information. Four lists of 24 intermixed to-be-remembered (TBR) and to-be-forgotten (TBF) words were presented for retention. Restricted (TBR only) and unrestricted (TBR and TBF) recall were tested. The results showed that prefrontal patients presented with a general reduction in episodic memory but a normal ability to selectively recall the TBR items during restricted and unrestricted recall. These results are consistent with previous reports of intact directed forgetting in frontal patients and are discussed in terms of their implications for the current debate on the neural substrate of executive functions. © 2006 Elsevier Ltd. All rights reserved. Keywords: Memory; Executive functions; Directed forgetting; Inhibition; Prefrontal cortex

1. Introduction Human memory is limited, and so, being able to forget irrelevant information is a pivotal ability for efficient everyday life functioning. Research in cognitive neuroscience has shown that the prefrontal cortex is involved in this important 1 ‘filtering’ function (Knight, Staines, Swick, & Chao, 1999; Shimamura, 2000). However, remarkably few behavioral data have been obtained from humans with frontal damage when performing memory tasks requiring the suppression or forgetting of irrelevant information. Some studies have investigated the performance of patients with frontal lesions in the AB–AC paradigm (Shimamura, Jurica, Mangels, Gershberg, & Knight, 1995; Thompson-Schill et al., 2002), which measures the ability to suppress the interference from previously learned pairs of words. However, memory-based alternative explanations of the heightened interference observed in this paradigm have been suggested (Winocur, Moscovitch, & Bruni, 1996). Furthermore, neuropsychological studies show that the frontal cortex may not be sufficient or necessary for this process. In fact, patients with focal frontal lesions perform sometimes as well as control participants on this task (Gershberg & Shimamura, 1995, Experiment

∗

Corresponding author. Tel.: +44 1752 233157; fax: +44 1752 233176. E-mail address: [email protected] (P. Andr´es).

0028-3932/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2006.09.012

2; Thompson-Schill et al., 2002), whereas patients with temporal lesions may show significant deficits (Winocur et al., 1996). The present study focused on the role of the prefrontal cortex in the ability to intentionally suppress some information that was actively encoded and explicitly cued later as ‘to-be-forgotten’. This was investigated by Andr´es and Van der Linden (2002) using a working memory task for the first time. In that study, participants had to remember three letters (control condition) or two sets of three letters from which one was then to be forgotten (directed forgetting condition). The results showed that patients with focal frontal lesions suppressed the irrelevant information as efficiently as the controls despite a general reduction in working memory capacity. Andr´es and Van der Linden argued that the results were in favor of a distributed view of executive functions, according to which a cortical and subcortical network supports these processes. Such dissociation between deficient memory and intact ability to intentionally forget irrelevant information was also described by Schmitter-Edgecombe, Marks, Wright, and Ventura (2004) in patients with chronic severe closed-head injury, who typically also show damage to their frontal lobes (Mattson & Levin, 1990). Taken together, these findings suggest that residual memory deficits in patients with frontal lesions are unlikely to reflect inefficient suppression mechanisms. There are however reasons to further examine directed forgetting in patients with frontal lesions. First, restricted recall (asking participants to remember only the TBR items), which was the

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only type of recall assessed by Andr´es and Van der Linden (2002), may not necessarily evaluate inhibitory processes since correctly ‘tagging’ and segregating TBR from TBF items may suffice to perform successfully in that task. Second, it is possible that the cognitive operations involved in directed forgetting are more sensitive to frontal damage when tested with supraspan lists and in the longer term. This contention is supported by the work by Chao and Knight (1995, 1998) who showed that prefrontal patients and older adults are impaired by distractors (irrelevant sounds) on a task requiring the retention of environmental sounds, but more so at longer delays. Third, Conway and Fthenaki (2003) have reported a deficit in forgetting irrelevant items in patients with right frontal lesions, in contrast to other studies (Andr´es & Van der Linden, 2002; Schmitter-Edgecombe et al., 2004). There are also fundamental theoretical reasons to further investigate directed forgetting in patients with frontal lesions. Neuropsychological studies have demonstrated that the frontal lobes play an important role in episodic memory (see Wheeler, Stuss, & Tulving, 1997 for a review), even when recognition is evaluated (e.g., Bastin et al., in press). It has been suggested that these deficits may be linked to an inability to inhibit irrelevant information (e.g. Bjork, 1970; L¨ovden, 2003; Shimamura, 1995). Such link has however been difficult to confirm. For instance, Alexander, Stuss, and Fansabedian (2003) showed that the recall impairment exhibited by patients with frontal lesions is not due to intrusions, proactive interference or double recalls. Stuss et al. (1994) also showed normal intrusion rates in patients with focal frontal lesions (although right frontal patients exhibited more ‘double recalls’). Intact directed forgetting (Andr´es & Van der Linden, 2002; Schmitter-Edgecombe et al., 2004) in patients with frontal damage with reduced memory capacity would also speak against this link. Two directed forgetting paradigms are found in the literature. In the item-by-item paradigm, items are presented one by one and each item is followed by an instruction indicating whether it is TBR or TBF. In the list paradigm, items are presented into lists and an instruction to forget or to remember is presented after the encoding of each list. These two paradigms yield different patterns of findings (see Basden, Basden, & Gargano, 1993; McLeod, 1999). First, the item method consistently produces a directed forgetting effect (better memory for the TBR than for the TBF items) in recognition, whereas the list method does not. Second, the directed forgetting effect in recall is larger for the item method than for the list method. Third, when participants are asked to recognize whether an item was TBR or TBF (“tagging” test), only the item method produces reliable directed forgetting effects (McLeod, 1999). These differences can be summarized by saying that the item method produces greater and more reliable directed forgetting effects. Given its higher reliability and greater effect size, we used the item-based method of directed forgetting. Recent studies (Lehman, Srokowski, Hall, Renkey, & Cruz, 2003; PazCaballero, Menor, & Jimenez, 2004; Ullsperger, Mecklinger, & Muller, 2000; Zacks, Hasher, & Radvansky, 1996) suggest that the cognitive processes involved in forgetting items when using this method include: (1) an active suppression or inhibitory

mechanism that follows immediately the TBF instruction; (2) a tagging mechanism that will segregate the two types of items into two different memory sets; (3) differential rehearsal. Specific recall procedures can be used to measure the efficiency of these different mechanisms. First, restricted recall, where only TBR items have to be recalled, taps into the ability to segregate TBR from TBF items in memory (i.e., when participants are asked to recall only the TBR items, they focus on the TBR items, as long as they have been correctly ‘agged’). Second, unrestricted recall, where participants are unexpectedly requested to recall both TBR and TBF items, measures the actual proportions of TBR and TBF items in memory. The latter is used to measure the participant’s ability to suppress the TBF items (directed forgetting). In this study, we looked at the performance of a group of patients with lesions restricted to the frontal areas on a directedforgetting task where, contrary to earlier studies, both restricted and unrestricted recalls were evaluated. In the directed forgetting paradigm, participants were presented with both to-beremembered (TBR) and to-be-forgotten (TBF) items and asked to recall the TBR items (restricted recall) and later on to recall both the TBR and TBF items (unrestricted recall). Contrary to traditional views (e.g., Shallice, 1988), recent neuropsychological evidence suggests that executive processes are mediated by networks incorporating multiple cortical (posterior as well as prefrontal) and subcortical regions (Carpenter, Just, & Reichle, 2000; Collette, Van Der Linden, Delrue, & Salmon, 2002; Ericson, Ringo Ho, Colcombe, & Kramer, 2005; Heyder, Suchan, & Daum, 2004; Luna & Sweeney, 2004; Morris, 2004). There is also evidence suggesting that different prefrontal sub-regions seem support the same executive processes (Duncan & Owen, 2000). This emerging view (see Andr´es, 2003; Collette, Hogge, Salmon, & Van der Linden, 2006 for reviews) suggests that executive processes relate to brain connectivity, rather than to particular frontal areas. It also implies that executive processes could, potentially, prove more resistant to frontal damage than a fixed one-to-one mapping between structure and function. The current study should help to test this view. If executive control has a unique and privileged link with the frontal cortex, patients with lesions of this area should present a deficit in directed forgetting. If, on the contrary, executive control depends on a rather distributed neural network, these patients could present with normal performance on directed forgetting. 2. Methods 2.1. Participants The same 13 patients and 13 control participants who took part in our first directed forgetting study (Andr´es & Van der Linden, 2002) were included in the current investigation. Patients with frontal lesions were screened by neurologists in five French-speaking Belgian hospitals. The instructions concerning the selection criteria emphasized that a CT and/or MRI scan should confirm the presence of a prefrontal lesion. Only patients with lesions affecting the prefrontal cortex and strictly restricted to the frontal lobe were included in the study. Other restrictions were that participants had to be younger than 55 and could not present any antecedent of alcohol or drug abuse, or of any psychiatric disorder. Four patients had cerebral vascular accidents: two due to anterior communicating artery aneurysm (F3 and F10), one due to anterior cerebral artery aneurysm (F7) and one of unknown origin (F11). Seven patients had a traumatic

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Fig. 1. (A) Reconstruction of left frontal lesions based on CT scan and magnetic resonance scans. For each patient, the horizontal cuts, from left to right, go from most inferior to most superior. (B) Reconstruction of right and bilateral frontal lesions based on CT scan and magnetic resonance scans. For each patient, the horizontal cuts, from left to right, go from most inferior to most superior. brain injury: five due to motor vehicle accidents (F1, F4, F5, F6 and F14) and two due to falls (F2 and F8). Finally, two patients had been operated for excision of an astrocitoma (F12 and F15). Six patients had a left-sided lesion, four had a right-sided lesion and three had a bilateral lesion. The location of the lesions is presented in Fig. 1A and B. These figures illustrate the data from the patients’ last radiographic examination undertaken prior to testing. The affected regions were identified using the methodology of Damasio and Damasio (1989) with the help of an experienced neurologist working blind to the purpose of the study. As can be seen from Fig. 1A and 1B, the majority of our patients (11 out of 13) presented with a lesion affecting the dorsolateral frontal lobe, hypothesized to be particularly involved in executive control (see also Table 1 for specific location of lesions in our patients). Frontal patients were examined after a post-surgery period long enough to avoid the presence of a “mass effect” (see Vilkki, Virtanen, Surma-Aho, & Servo, 1996 for the importance of this factor) often observed when patients are examined in the acute period. The mean delay between the occurrence of the lesion and the neuropsychological evaluation was of 179.8 days (range = 39–467), the mean delay between the occurrence of the lesion and the latest radiographic examination was 99.9 days (range = 1–467) and the mean delay between the radiographic examination and testing was 84.18 days (range = 1–215). No patient was on anticonvulsant medication at the time of testing. Frontal patients were matched to control participants on the basis of their individual age, sex, and type and duration of education. The mean age and years of education were 33.2 (S.D. = 13.75) and 11.8 (S.D. = 2.9) respectively for the patients, and 32.8 (S.D. = 13.2) and 12.23 (S.D. = 0.8) for the control participants. All participants were males. A one way analysis of variance showed that the two groups were correctly matched in terms of age [F(1, 12) = 1.35; p = 0.268] and years of education [F(1, 12) = 3.26; p = 0.1]. All participants volunteered and gave their informed consent.

2.2. Materials, procedure and scoring A short battery of neuropsychological tests was used to assess general cognitive abilities: • The global cognitive profile was evaluated by means of the Mattis Dementia Rating Scale (DRS, Mattis, 1973). • Stroop test (two patients and two controls did not complete this test). The materials were adapted from the standardized Stroop test (Comalli, Wapner,

& Werner, 1962). Three white laminated A4 sheets of paper containing 100 stimuli each were used. Each sheet contained a different condition: word reading (WR), color naming (CN) and color incongruent (INC). Each stimulus was either a 5 mm × 15 mm rectangle or a color word (red, yellow, purple, green, blue and orange). In the WR condition 100 names of colors printed in black ink were presented and participants were asked to read the words aloud. In the CN condition, 100 colored rectangles were displayed and participants were required to name their color. In the INC condition, 100 words were written in an incongruent ink color (e.g. word ‘blue’ printed in red ink). Participants were asked to name the ink color and not the word. On each sheet, a first row of 10 stimuli was always used for practice. There were a total of 10 rows × 10 stimuli on each page, and participants were asked to process the stimuli across rows from left to right, and from the top row to the bottom row. Response times (RTs) were measured by the means of a stopwatch that was triggered by the experimenter when the participant read or named the first test stimulus and stopped when the participant read or named the last stimulus on the sheet. Errors were also counted, but as their occurrence was sparse (most participants produced no errors, with the maximum percent errors being 8% in one patient) and with no differences between groups, these data were not analyzed further. • Short-term memory was assessed using the digit span task where participants were presented with series of digits on cards presented at a rate of 1 s−1 . 2.2.1. Directed forgetting The task of Zacks et al. (1996) was adapted into French. The learning materials were 4 categorized word lists (24 words per list) in which some of the words from a particular category were associated with a remember cue and others with a forget cue. The 24 words from each list belonged to 6 different semantic categories (4 words per category). Each list included one category in which there were 0 TBR words and 4 TBF (0R-4F) words, one category with 1 TBR and 3 TBF (1R-3F) words, 2 categories with 2 TBR and 2 TBF (2R-2F) words, 1 category of 3 TBR and 1 TBF (3R-1F) words, and 1 category with 4 TBR and 0 TBF (4R-0F) words. This situation should create a particularly sensitive task environment for demonstrating some of the predicted group differences in directed forgetting. Specifically, given that the pre-experimental associative connections among members of a category are generally quite strong, it should be more difficult, relative to unrelated words, to suppress the TBF items from a category when other items from the same category have to be remembered. Words were presented on cards and each word was studied for 5 s before the card was turned over to present immediately either a TBR (green R for

X

F05

X

X X X X X

F04 F03

X X

X X X X X X

X X X

X

X

F02 F01

X X

X X X

X X X

X X

X

X

X

X X

X

X

X

X

X X X X

X X X X X X X X

X

X

X X X X

X

X X X X X

F1 F2 F3 F4 F5 F6 F7 F8 F10 F11 F12 F14 F15

F01

F02

F03

F04

F05

F06

F07

F08

F09

F10

F11

F12

F13

F14

Right Left

Regions Patien

Table 1 Identification of the lesion locations

Correspondence between Damasio and Damasio (1989) codes and Brodmann areas are: Median aspect, F01 anterior cingular gyrus (BA 24), F02 posterior cingular gyrus (BA 23, 31), F03 supplementary motor area (BA 6), F04 prefrontal area (BA 8–10), F05 rolandic region (BA 1–4). Lateral aspect, F06 frontal operculum (BA 44, 45), F07 prefrontal region (BA 8, 9, 46), F08 premotor region (6) and rolandic region (BA 1–4), F09 paraventricular, F10 supraventricular area. Orbital aspect, F11 anterior (BA 10), F12 posterior (BA 11, 12, 13, 47), F13 basal forebrain and F14 subventricular area.

X X X X

X

X X X X X X

X X

X

X

F06

F07

F08

X X X X

F09

X

F10

X

X X

X

X

F11

F12

F13

X

X X X X X

P. Andr´es et al. / Neuropsychologia 45 (2007) 1355–1362 F14

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‘rappeler’–‘recall’ in French) or TBF (red O for ‘oublier’–‘forget’ in French) cue for one second. Each list included fixed sets of 12 TBR words and 12 TBF words presented in random order. On the immediate restricted recall tests that followed each study list, participants had to recall as many TBR items as possible from the list without recalling the TBF items. After all four lists had been presented, the participants were given a list of 80 three-digit addition problems (e.g., 365 + 927 = ?), which they solved during the 5-min retention interval preceding the unrestricted recall test. In a final test, participants were asked to recall as many words from all of the study lists as possible, regardless of whether they had previously been designated as TBR or TBF items. Participants had unlimited time for both restricted and unrestricted recall. Although both groups were expected to show greater retention of TBR than TBF items on the delayed unrestricted test, the reduced ability of patients to suppress processing of TBF items should result in smaller TBR − TBF differences (directed forgetting effect) for this group. In other words, relative to each group’s performance on the TBR items, patients were expected to show better long-term retention of TBF items than controls.

3. Results 3.1. Neuropsychological functioning The mean overall score in the Dementia Rating Scale (DRS, Mattis, 1973) was significantly lower for frontal patients (M = 135; S.D. = 9.62) than for control participants (M = 141, S.D. = 2.6) [t(24) = 2.17; p < 0.05]. The analysis of the different subscales (Table 2) revealed significant differences in the Attention [t(24) = 2.51; p < 0.05] and Initiation subscales [t(24) = 2.85, p < 0.05]. This profile of performance is characteristic of that generally observed in other studies examining frontal patients (e.g. Shimamura, Janowsky, & Squire, 1991). Frontal patients also showed a reduction in shortterm memory (digit span task) compared to control participants [t(24) = 2.21, p < 0.05]. Finally, on the Stroop test, the patients were slower than the controls in all conditions [F(1, 20) = 5.1451; p < 0.05], and RTs differed between conditions [F(2, 40) = 119.94; p < 0.0001], with the slowest responses in the INC condition and the fastest in the CR condition, but there was no interaction between group and condition [F(2, 40) = 1.485; p = 0.239]. This absence of interaction was supported by equivalent interference indices, calculated using the formula (interference time − naming time)/(interference time + naming time); [t(20) = 1.50, p > 0.15]. Table 2 Neuropsychological examination for each scale and subscale Frontal

Control

Mattis DRS Attention Initiation Construction Concepts Memory

36.4 (0.9) 33.2 (4.8) 6 (0) 35.5 (5.1) 24 (1.5)

36.9 (0.3)* 36.4 (1.7)* 6 (0) 36.8 (1.9) 24.9 (0.6)

Stroop test Word reading Color naming Incongruent

50.6 (12.5) 80.9 (23.6) 124.1 (45.4)

39.5 (5.3) 59.6 (9.6) 98.5 (18)

Digit span Standard deviations in parenthesis. * p < 0.05.

5.3 (1.4)

6.8 (2.2)*

P. Andr´es et al. / Neuropsychologia 45 (2007) 1355–1362 Table 3 Average number of to-be-remembered (TBR) and to-be-forgotten (TBF) items recalled during restricted and unrestricted recall in the directed forgetting paradigm by frontal patients and control participants Restricted recall

Patients Controls

Unrestricted recall

TBR

TBF

TBR

TBF

27.8 (8.2) 33.2 (5.2)

2.9 (1.9) 4.1 (2.4)

14.3 (8.3) 22.7 (6.5)

6.4 (4.4) 10.3 (5.8)

Standard deviations in parenthesis.

3.2. Directed forgetting 3.2.1. Episodic memory We first compared the two groups of participants in terms of the total number of TBR items recalled (max = 48; see Table 3) to compare episodic recall levels. A 2 (group) × 2 (type of recall, restricted versus unrestricted) repeated measures ANOVA showed a significant effect of group [F(1, 24) = 6.69, p < 0.05] indicating that patients with prefrontal lesions recalled globally fewer items than controls and a significant effect of type of recall [F(1, 24) = 165.49, p < 0.0001] indicating that participants remembered more TBR items in the restricted recall test than during the unrestricted recall test. This was expected given that restricted recall immediately followed the presentation of the words whereas unrestricted recall was delayed by 5 min. Finally, there was no significant interaction between group and type of recall [F (1, 24) = 2.57, p = 0.12]. 3.2.2. Intrusion rate The proportion of TBF items out of the total number of items recalled in the restricted recall test was calculated in order to evaluate the participants’ ability to selectively recall the TBR items. This intrusion rate (see Table 4) was equivalent in both groups, F(1, 24) < 1; p = 0.422. In other words, patients were as capable as controls of selectively recalling the TBR items in the restricted recall condition. 3.2.3. Directed forgetting In order to evaluate the ability to inhibit irrelevant items while controlling differences in episodic memory between patients and control participants, the proportion of TBF and TBR items was Table 4 Proportion of to-be-remembered (TBR) and to-be-forgotten (TBF) items recalled during restricted and unrestricted recall in the directed forgetting paradigm by frontal patients and control participants TBR

TBF

Intrusion rate/DF effect

Restricted Patients Controls

0.91 (0.05) 0.89 (0.06)

0.09 (0.05) 0.11 (0.06)

0.82 (0.01) 0.78 (0.01)

Unrestricted Patients Controls

0.70 (0.12) 0.71 (0.10)

0.30 (.12) 0.29 (0.10)

0.40 (0.30)*** 0.41 (0.20)***

Intrusion rates relate to the restricted recall test and the directed forgetting effect (DF; *** p < 0.0001) relates to the unrestricted recall test. Standard deviations in parenthesis.

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calculated out of the total number of items recalled (see Table 4) in the unrestricted recall test. We observed a significant directed forgetting effect (difference between TBR and TBF recall) in both groups. Importantly, this effect was equivalent between groups, F(1, 24) < 1; p = 0.859. Moreover, this effect was still equivalent after entering recall of TBR items during restricted recall as a covariate to control for any possible inflation of TBR recall at unrestricted recall due to retrieval practice effects F(1, 23) < 1, p = 0.993. We also compared TBF recall during restricted and unrestricted recall phases and showed that both groups recalled significantly more TBF items in the unrestricted recall than in the restricted recall phases (frontals: t(12) = 2.51; p < 0.05; controls: t(12) = 3.8; p < 0.005). In order to unmask possible hidden individual deficits in directed forgetting, we also analyzed the individual performance of our patients. Within this single-case approach, we considered a patient performance as ‘impaired’ when it was beyond the interval defined by the mean proportion of TBF items recalled by the control group + 2.5 standard deviations and above the worse performance in the control group. The analysis showed normal performance in all the patients of the study. The lack of specificity of the lesion location (only one patient presented with a purely dorsolateral lesion) in our sample did not allow us to look at the effect of this variable on directed forgetting. It is worth noting however that the only patient with a lesion restricted to the left dorsolateral prefrontal cortex (F15) did not show any particular or exacerbated deficit. Finally, following previous reports of higher sensitivity to interference associated with right frontal lesions (e.g. Conway & Fthenaki, 2003), we compared performance between patients exhibiting right or bilateral lesions and patients presenting left frontal lesions.1 Frontal patients with a lesion involving the right hemisphere (M = 34.8; S.D. = 11.45) showed a greater proportion of TBF items than patients with left frontal lesions (M = 25.9; S.D. = 8.14), although not surprisingly given the small sample sizes compared, this difference did not reach statistical significance (U = 10; p > 0.05). 4. Discussion The purpose of the present study was to examine the ability of frontal patients to intentionally suppress irrelevant information in episodic memory. This ability involves different cognitive processes including suppression ones. We paid special attention to two methodological factors: the clinical state of our sample (patients were examined long enough after the occurrence of the lesion to avoid possible consequences of mass effects), and the selectivity of the brain damage (only patients with radiological evidence of lesions limited to the frontal lobes were included in the sample). Our results showed that, compared to controls, patients with prefrontal lesions present with a reduced performance in immediate and delayed episodic recall, which are consistent with 1

We thank Shlomo Bentin for suggesting this analysis.

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previous reports (see Wheeler et al., 1997 for a review) and provide additional support to the theoretical models suggesting an important role of the prefrontal cortex in episodic recall (Tulving, 2002; Wheeler et al., 1997). The results also show equivalent intrusion rates in prefrontal patients and control participants in the restricted recall phase. In other words, when asked to recall only the TBR items, prefrontal patients did not produce proportionally more intrusions than control participants. This may indicate that the patients successfully suppressed the TBF words from their memory or, as the restricted recall test depends on the ability to discriminate TBR from TBF items using a ‘tagging or labeling’ mechanism, that they performed this tagging as efficiently as the control participants. Moreover, we observed that the two groups of participants recalled significantly more TBF items in the unrestricted recall than in the restricted recall. This shows that at least part of the TBF items were present in memory but simply not outputted during the restricted recall condition. Other researchers (e.g. Jetter, Poser, Freeman, & Markowitsch, 1986; Stuss et al., 1994) have reported similar findings after frontal lesions. It is worth noting here that intrusions and confabulations in general are most common in the acute stage following the frontal injury, when patients are often still confused. Intrusions and confabulations then decrease with time, as patients stabilize (Kapur & Coughlan, 1980). As mentioned in our introduction, all our patients were seen well after the acute period. More critically, we observed significant and equivalent directed forgetting effects in patients and controls in the unrestricted recall condition, indicating that the ability to suppress the TBF items in memory was also relatively efficient in both groups. The present study also showed normal inhibitory abilities in frontal patients when evaluated with the Stroop test (Stroop, 1935). The findings from the current study are consistent with the findings from our previous studies (Andr´es & Van der Linden, 2001, 2002) looking at directed forgetting and executive functions in general, where normal executive performance was observed in the same group of patients. An issue that deserves some attention is the size of the lesions of our patients. When selecting patients with lesions restricted to the frontal lobe, lesions may be relatively small, as was the case with some of our patients (see Fig. 1A and B). This may make the detection of performance deficits more difficult, particularly under the hypothesis that different sub-regions may support the same executive functions measured by a behavioral test (Duncan & Owen, 2000). The comparison between the findings from the current study and that by Conway and Fthenaki (2003) is interesting in this respect. In their item-based directed forgetting experiment, Conway and Fthenaki found normal directed forgetting in patients with left frontal lesions, a finding that is consistent with our findings. However, these authors also reported a ‘reversed’ pattern of directed forgetting, i.e., higher recall level of TBF items than of TBR items in their patients with right frontal lesions relative to controls. This is in sharp contrast with our finding of a large and significant directed forgetting effect in our patients. It is difficult to ascertain why patients in our study and that of Schmitter-Edgecombe et al. (2004) showed

normal directed forgetting effects while Conway and Fthenaki’s patients did not, particularly since the latter neuroanatomical details about the lesions were not reported. Based on Conway and Fthenaki’s discussion (‘it seems likely that lesions would be widespread and diffuse, rather than focal, and this may have given rise to a general lowering of performance by networks’ p. 682), we can however speculate that the lesions of Conway and Fthenaki’s patients were more extensive than the lesions of our patients. Such explanation would be consistent with the findings from a neuroimaging study by Reber et al. (2002) showing increased neural activity in right midfrontal and parietal cortex during forget trials. Furthermore, Conway and Fthenaki’s patients were assessed while still possibly in an acute period (while our patients were tested well after the acute period). As we mentioned in the introduction, there are several processes at play in directed forgetting. Recent studies have shown that differential encoding and selective rehearsal of the TBR items are clearly necessary to perform the task (Basden & Basden, 1996; McLeod, 1999) when the item method is used, particularly when recall is restricted to the TBR items. There is however also evidence that suppression mechanisms are required. Using the item method, Paz-Caballero et al. (2004) showed that the electrophysiological variations occurring early after the TBR or TBF instruction (in the 100–300 ms epoch) were the best predictors of the directed forgetting effect (the difference in recall between TBR and TBF items). Within this time window, ERP differences only appeared in participants with great directed forgetting effects, and consisted of an enhanced positive activity elicited by the TBF instruction at frontal and prefrontal areas (100–200 ms) and a larger positivity associated with the TBR instruction at parietal area (200–300 ms). PazCaballero et al. interpreted these findings as suggesting that the processing of each item is kept on stand-by until the instruction is provided (also see McLeod, 1999). Then, if the TBR instruction appears, it reactivates the processing of the item by reinforcing its encoding, which mainly involves the parietal area. If the TBF instruction appears, it triggers an executive process aiming at suppressing such processing, which involves frontal and prefrontal areas. Paz-Caballero et al. also suggested that the early frontal and prefrontal activity triggered by the TBF instruction act to stop or to prevent the activity of the parietal area engaged in a more elaborate processing of the items (see also Zacks et al., 1996; Ullsperger et al., 2000). It could be argued that our sample of patients may not represent accurately the entirety of patients with frontal lesions due to the reduced number of participants (which is a consequence of the rarity of patients with lesions restricted to the frontal cortex). However, explaining equivalent directed forgetting in our study by a lack of statistical power is unsatisfactory for three reasons. First, significant differences between our patients and control participants were observed for several measures (e.g. Mattis Dementia Rating Scale, short-term memory recall and episodic recall). Insufficient statistical power should have masked such differences. Second, if the frontal cortex is necessary and sufficient to perform executive processing, a unique lesion of that area should affect executive control. Despite that the majority of our patients presented lesions in Brodmann areas 24, 9 and 46

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(see Table 1), which are hypothesized to play a crucial role in executive control (e.g. D’Esposito & Grossman, 1996), none of them exhibited significant deficits when analyzed on a singlecase approach. Third, the effect of directed forgetting was ‘very large’ (d > 2) (Cohen, 1988). One potential limitation of the measurement of directed forgetting in the present study may be that performance on the unrestricted recall task could be influenced by practicing recall in the earlier restricted recall task.2 This earlier recall of TBR words may have boosted memory for these words in the unrestricted test and inhibited memory for the remaining list items (most of which were TBF words), in line with studies of retrieval practice effects (e.g., Anderson, Bjork, & Bjork, 1994; Anderson & Spellman, 1995; Ba¨uml, Zellner, & Vilimek, 2005). Both effects may have inflated our measure of directed forgetting. The critical issue, however, is whether this effect may have been larger in one of the two groups of participants. Only one study compared frontal patients and control participants with regard to the strengthening of practiced items and the retrieval induced inhibition of the remaining list items (Conway & Fthenaki, 2003). In that study, both groups showed equivalent effects. It remains nevertheless possible that their conclusion may not apply to our paradigm, and so it is worth considering the possible implications of a potential retrieval practice effect. A weaker retrieval practice effect in the patients would have decreased the directed forgetting measure, meaning that the genuine ability of the patients to suppress TBF words would have had to be greater than that of the controls in order to result in the equivalent overall directed forgetting measures observed between our groups. Such outcome is arguably unlikely. More problematic however is the mirror situation in which frontal patients would exhibit a stronger retrieval practice effect. In that case, our measure of their directed forgetting ability would have been inflated relative to that of the control participants, thereby masking a deficit of our patients in successfully suppressing TBF words. The present study does not offer a definitive test of these potential effects. However, it is worth noting that our measures of directed forgetting remain similar in our groups when controlling for the proportion of TBR words recalled in the restricted test. Further research will be necessary to address this issue directly. From a theoretical perspective, the dissociation between episodic recall and executive control observed in patients with lesions limited to the frontal areas is important for the current debate on the neural substrate of executive functions. The emerging view (see Andr´es, 2003; Collette et al., 2006 for reviews) suggests that executive control is mediated by dynamic and flexible networks that can be characterized using functional integration and connectivity analyses. This view is compatible with the clinical observation of executive dysfunction associated with a wide range of pathologies, but also compatible with evidence that recovery of executive function can occur after brain injury, perhaps due to functional reorganization within executive networks (Elliott, 2003). This is also consistent with the fact that the patients included in the present study were investigated in

2

We thank an anonymous reviewer for flagging up this issue.

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a stable clinical state, when some reorganization of cognitive functions is likely to have started. In sum, patients with focal frontal lesions showed an overall lower performance in episodic recall and intact filtering mechanisms in a directed forgetting paradigm designed to evaluate how well participants prevent no-longer information from being retrieved. The results from the current study give support to previous research on directed forgetting in patients with frontal lesions (Andr´es & Van der Linden, 2002; Schmitter-Edgecombe et al., 2004). These results are important as little experimental evidence concerning behavioral measures of intentional suppression in memory in patients with focal frontal lesions is yet available. Further research is needed before firm conclusions can be reached regarding the role of the prefrontal cortex in directed forgetting, however. Indeed, it is possible that behavioral methods alone are not sensitive enough to capture inhibitory deficits in patients with focal frontal damage, particularly when they are studied in the chronic state. Future studies combining behavioral, electrophysiological and imaging methods in patients with frontal lesions when performing directed forgetting tasks (or any other inhibitory paradigm in memory) may shed further light on this issue. Acknowledgements The work reported in this paper was supported by the Spanish Foreign Office (C.G.R.I. in Belgium) and by the Camille Hela Foundation (University of Li`ege) in the form of a project grant to the first author. Thanks are due to Cecilia Bra˜nas, Bruno Kachsten, Bernard Sadzot and Eric Salmon for their neurological expertise and to Marie-Anne Van der Kaa and Eric Vincent for their help with the recruitment of patients. We are also grateful to Kirsten Burghardt, Michael Verde, Sabine Windmann, Shlomo Bentin and two anonymous reviewers for their useful comments on an early version of this article. References Alexander, M., Stuss, D. T., & Fansabedian, N. (2003). California verbal learning test: Performance by patients with focal frontal and non-frontal lesions. Brain, 126, 1493–1503. Anderson, M. C., Bjork, R. A., & Bjork, E. L. (1994). Remembering can cause forgetting: Retrieval dynamics in long-term memory. Journal of Experimental Psychology: Learning, Memory, Cognition, 20, 1063–1087. Anderson, M. C., & Spellman, B. A. (1995). On the status of inhibitory mechanisms in cognition: Memory retrieval as a model case. Psychological Review, 102, 68–100. Andr´es, P. (2003). Frontal cortex and the central executive of working memory: Time to revise our view. Cortex, 39, 871–895. Andr´es, P., & Van der Linden, M. (2001). Supervisory attentional system in patients with focal frontal lesions. Journal of Clinical and Experimental Neuropsychology, 23, 225–239. Andr´es, P., & Van der Linden, M. (2002). Are central executive functions working in patients with focal frontal lesions? Neuropsychologia, 40, 835–845. Basden, B. H., & Basden, D. R. (1996). Directed forgetting: Further comparisons of the item and list methods. Memory, 4, 633–653. Basden, B. H., Basden, D. R., & Gargano, G. J. (1993). Directed forgetting in implicit and explicit memory tests: A comparison of methods. Journal of Experimental Psychology: Learning, Memory and Cognition, 19, 603–616.

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