Disruption of Inhibitory Control of Memory Following Lesions to the Frontal and Temporal Lobes

SPECIAL ISSUE DISRUPTION OF INHIBITORY CONTROL OF MEMORY FOLLOWING LESIONS TO THE FRONTAL AND TEMPORAL LOBES Martin A. Conway1 and Aikaterina Fthenaki2 (1Department of Psychology, University of Durham, England; 2Department of Experimental Psychology, University of Bristol, England)

ABSTRACT A group of patients with lesions to the frontal lobes, a group with lesions to the temporal lobes, and groups of non-brain damaged controls took part in three experiments. The first experiment used directed forgetting (DF) by items, the second DF by lists, and the third retrieval induced forgetting (RIF). Frontal patients with right side lesions could not intentionally inhibit but all frontal patients showed normal RIF. Temporal patients with left side lesions had abnormal DF by lists and all the temporal patients had abnormal RIF. These findings are explained in terms of impairment to executive thought avoidance control processes in frontal patients and impaired knowledge access to long-term memory in temporal patients. Key words: memory executive control processes, recognition, recall, inhibition, retrieval, intention to inhibit, automatic inhibition, frontal and temporal patients, retrieval induced forgetting, directed forgetting, disexecutive syndrome

DISRUPTION

OF INHIBITORY CONTROL OF MEMORY FOLLOWING TO THE FRONTAL AND TEMPORAL LOBES

LESIONS

Recalling information from long-term memory very frequently entails selecting a specific target from a set of potential targets that compete for access to the retrieval process. For example, recalling sending an email to ‘X’ yesterday, an item from a meeting a week ago, a visit to a particular restaurant, even where one parked one’s car this morning, all require selection of a specific item from a range of potential candidate items (Bjork, 1989). A substantial body of evidence currently indicates that when a selection is made between competing items in long-term memory then strongly competing unselected items are inhibited (see Bjork, Bjork et al., 1998 for a review). One view is that this inhibition occurs automatically when a choice is made between competitors (see, for example, Anderson and Spellman, 1995 or Conway et al., 2000). However, the conditions that trigger inhibition may take different forms. For instance, an intention to forget (Bjork, 1989) or explicit and repeated attempts at forgetting (Anderson and Green, 2001) may under certain circumstances trigger inhibition (although the inhibitory process itself remains outside direct conscious control). In contrast, simply accessing an item from a set of items may automatically trigger inhibition without any intention to forget or suppress. An important point Cortex, (2003) 39, 667-686

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here is that when inhibition is triggered intentionally then executive control processes will modulate the triggering of the inhibitory process. When, however, inhibition is triggered automatically, in the absence of an intention to forget, then executive processes may have less of a mediating role. One implication of this is that patients with brain injuries to those networks that support executive processes in memory may have a reduced ability to generate the conditions that could trigger inhibition while still showing normal inhibition in tasks in which inhibition is triggered automatically. The purpose of the present study was to evaluate this conjecture in patients with predominantly frontal injuries compared to a group with predominantly temporal injuries. We reasoned that frontal patients with impaired executive processes would have difficulties in intentional inhibition whereas this might not be the case for temporal patients with intact executive processes. Although the frontal lobes have long been associated with executive control function and damage to these areas typically results in impaired reasoning abilities (Luria, 1966, McAndrews and Milner, 1991; Stuss and Benson, 1986; Shallice, 1988) recent research has shown that frontal networks also support processes critical to memory (see Wheeler et al., 1997). Petrides (2000), for example reviews the evidence that networks in regions of mid-dorsolateral prefrontal cortex mediate the monitoring of output from long-term memory while ventrolateral prefrontal networks appear to play a more direct role in memory retrieval itself. Indeed, these and other prefrontal sites have been identified as regions that mediate various aspects of working memory (Smith and Jonides, 1999), a memory system which, as Moscovitch (1992) pointed out, supports active construction, evaluation, modification, and general use of longterm memory. A good example of this can be found in the construction of autobiographical memories which is a dynamic and temporally extended process featuring the interplay of frontal and posterior networks (Conway and PleydellPearce, 2000; Conway et al., 2001) – a process which can become severely disrupted following brain injury to several different regions of both prefrontal and posterior cortex (see Conway and Fthenaki, 2000, for a review). In addition to this, and as Anderson and Green (2001) note, there are strong grounds for supposing that intentional inhibition, e.g. triggered by active thought avoidance, is mediated by regions of dorsolateral prefrontal cortex (DLPFC) possibly the same or closely associated networks as those implicated in monitoring output from long-term memory. Thus, injuries in the region of DLPFC, or (frontal) areas with input to DLPFC networks, would compromise the ability to use inhibition to manage memory retrieval. One of the consequences of such an impairment could be a reduced ability to discriminate between items in long-term memory leading to impoverished knowledge access. As is well known, patients with frontal lobe damage typically perform poorly in the production of items from categories in long-term memory and they also often have ‘clouded’ autobiographical memories that lack the usual amount of memory detail (Baddeley and Wilson, 1986). On the other hand the opposite may occur and a reduced ability to intentionally trigger inhibition during remembering could give rise to recall of task irrelevant or incongruent information and, possibly, this might contribute to the confabulations sometimes present in frontal patients. In

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general it seems possible that an underlying feature of ‘dysexecutive syndrome’ may be a disruption to inhibitory control processes which leads to a reduced ability to discriminate between items in long-term memory, items which nonetheless can still be accessed (see Moscovitch and Mello, 1998). A reduction in the ability to intentionally trigger inhibition appropriately i.e. to select for recall a target item and not a non-target item and so trigger inhibition of non-targets, will compromise memory performance. However, it may be the case that when the (intentional) selection of a specific item from a set of items is bypassed, perhaps by the presentation of highly specific cue, then inhibition will be triggered automatically and in this case memory performance may not be compromised. It is possible then that frontal lobe patients who are impaired in tasks that require intentional inhibition may nonetheless show less impairment in tasks in which inhibition is triggered automatically. In contrast to this hypothesized pattern of impaired and preserved triggering of inhibition in frontal lobe patients another patient group, those with temporal lobe lesions, may suffer from problems relating to knowledge access rather than in the selection of those items that can be accessed. We suggest that when a temporal lobe patient with mild anterograde and retrograde amnesia is able to access some recently acquired knowledge then inhibition of that knowledge can be intentionally triggered. If this is the case then the pattern of memory performance for inhibited items in temporal lobe patients should be the reverse of that seen in frontal lobe patients. In order to test these conjectures we conducted a series of memory inhibition experiments with groups of frontal patients, temporal patients, and matched controls. The first two experiments used a directed forgetting (DF) procedure in which items or lists are paired with a cue to forget or remember. Subsequent recall and recognition are tested for both to-be-remembered (TBR) and to-beforgotten (TBF) items. In non-brain damaged groups TBF items are typically recalled at a low level and are inhibited (see MacLeod, 1997 for a review). From the present perspective we expect F cues, an explicit instruction to intentionally forget what has just been learned, to have little effect on performance in the frontal group but to be normal in the temporal group (although this may be in the context of overall reduced recall). In a third experiment we used a retrieval induced forgetting procedure (Anderson and Spellman, 1995) that does not entail intentional forgetting but rather induces automatic inhibition between competing items in memory. It is expected that frontal patients will be less impaired on this task, i.e. they will show some inhibition. EXPERIMENT 1 In this first experiment, participants took part in a DF experiment using a standard item method (cf. Basden, et al., 1993). In this procedure each word is followed by an instruction to remember (R cue) or forget (F cue). This typically leads to a high level of performance for TBR items and a very low level for TBF items and this is the case in both recall and recognition (Basden, et al., 1993). These differences are thought to arise from reduced elaborative rehearsal

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of TBF items which occurs in response to the F cue. Of central interest here is whether a similar pattern will be present in the two patient groups. Given that frontal patients may have disrupted or reduced executive and attentional processes it is possible that they will not show the usual pattern. This may be because of their reduced ability to respond to the R and F cues and effectively control rehearsal at encoding. On the other hand as item-by-item DF does not necessarily involve inhibition, the reduced memory performance for F items is achieved by selective rehearsal, it may prove to be the case that frontal patients perform relatively normally on this task. The temporal lobe patients, who do not have such severely disrupted executive processes (see Table II ahead), should be able to respond to the R and F cues appropriately, control rehearsal, and so show the normal pattern in both recall and recognition. Method Design A 2 × 3 mixed factorial design was employed with Type of Instruction (R and F cues) as a within subjects factor and Group (Frontal lobe, Temporal lobe and Control group) as a between-subjects factor. Dependent variables were recall and recognition rates of TBR and TBF words. Order of presentation of words was unsystematic, i.e. the cards on which the TBR and TBF words were printed were thoroughly shuffled prior to presentation to each participant. The pairing of R and F cues with words was random within the constraint that there were an equal number of each type of cue. TABLE I

Patient Characteristics Brain Damage Frontal Group 1. P.S. 2. M.S. 3. T.N. 4. P.B. 5. L.D. 6. J.L. 7. B.W. 8. R.K. 9. E.K.

*AVM HI AVM HI HI HI HI HI HI

Temporal Group 1. M.P. EP 2. F.S. Astrocytoma 3. J.N. EP 4. M.H. EP 5. K.W. EP 6. R.S. EP 7. T.I. EP 8. G.S. EP 9. M.T. EP 10.C.P. EP

Location

Age at test

Education

Left Frontal Left Frontal Left frontal Left Frontal Right Frontal Right Frontal Right Frontal Right Frontal Right Frontal

48 35 51 44 54 23 21 35 30

11 12 11 11 11 12 11 11 11

Left Medial Temporal Left Medial Temporal Left Hippocampus Left Temporal Left Hippocampus Right Hippocampus Right Hippocampus/amygdala Right Hippocampus/amygdala Right Hippocampus/amygdala Right Temporal

39 26 30 50 29 36 37 36 45 26

12 11 12 11 11 12 13 11 11 11

* AVM, HI and EP, refer to Anterior Venous Malformation, Head Injury and Epilepsy.

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TABLE II

Performance on Neuropsychological Tests Frontal

Temporal

Control

93 101 96

98 105 101

114 114 115

WMS-R GMI VMI VIMI AMI DMI

90 90 86 91 90

89 90 91 98 88

115 119 99 98 119

BADS STROOP FAS

75 44 18

92 95 33

102 110 39

WAIS-R* VIQ PIQ FS

* Wechsler (198) Adult Intelligence Scale-Revised, Verbal IQ, Performance IQ, Full Scale IQ. Wechsler (1998) Memory Scale-Revised, General Memory Index, Verbal Memory Index, Visual Memory Index, Attention Index, Delayed Memory Index. Behavioural Assessment of the Dysexecutive Syndrome (Wilson, et al., 1996), Age Standardised Score. Stroop test: Mean umber of correct responses on the C-W condition. FAS Verbal Fluency test: Total number of words produced in 3 minutes.

Participants The sample of 29 male participants was composed of nine patients with unilateral frontal lobe lesions (four left and five right), ten patients with unilateral temporal lobe lesions (five left and five right) and ten control participants. The patients were identified by review of medical records and computed tomography (CT) or magnetic resonance (MRI) at the Frenchay Hospital in Bristol, England. Note that patients were selected because their records indicated only frontal or only temporal pathology. It is, however, possible that lesions in one or the other lobe went undetected. This is especially possible in the patients with closed head injuries who may have had undetected minor lesions in the temporal lobes with major, detected, lesions in the frontal lobes. We acknowledge that this is a potential problem although we also emphasise that the medical records did not document lesions in the temporal lobes for the head injured patients. Unfortunately specific details of lesion sites were not available in terms of Brodmann areas and the medical notes indicated only laterality of injury and general extension, which for all the frontal patients in Table I included prefrontal areas. The epileptic patients were part of an neurosurgical programme and had undergone WADA, a range of other tests, and neurosurgery. Their lesions sites were therefore well established and localised to regions shown in Table 1. None of the patients had a history of substance abuse or depression. Table 1 presents patient’s characteristics. The frontal lobe patients averaged 37.8 years of age (range 21-54 years) and 11.2 years of education (range 11-12 years). The mean age and educational level at examination for the temporal lobe group were 35.4 years (range 26-50 years) and 11.5 (range 11-13 years) respectively. Table II shows performance on standard neuropsychological tests and it can be see from this table that the frontal lobe patients scored within the normal range on

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standard tests of intelligence and memory (see Table II). The two patients groups did not differ reliably from each other on any of these tests but both were significantly poorer on all but the visual memory index of the WMS-R (see Table II). Thus, both patients groups suffered from depressed IQ and memory abilities relative to the control group but as their performance was within the normal range their IQ and memory performances although low were not pathological. This frontal group, however, exhibited impairment on the three neuropsychological tests that have been shown to be sensitive to frontal lobe injury. On the Behavioural Assessment of the Dysexecutive Syndrome (BADS) they had an impaired performance relative to both the control group [t (17) = 6.65, p < 0.05] and the temporal lobe group [t (17) = 4.3, p < 0.05]. On the Stroop test, the frontal lobe group were reliably poorer (mean 43.6) than the other two groups [t (17) = 8.7, p < 0.05; t (17) = 6.8, p < 0.05] and on the FAS Verbal Fluency test their recall performance (mean 18.0 words) was also impaired relative to the other groups [t (17) = 7.88, p < 0.05; t (17) = 5.3, p < 0.05]. The 10 healthy volunteers (all men) were recruited by an advertisement. They were matched with half of the frontal lobe patients and half of the temporal patients on the basis of age and education. Their average age was 42.0 years (range 26-54 years) and time in education was 11.3 years (range 11-13 years). Materials Thirty-two words were selected from Kucera and Francis (1967) according to the following criteria: they were semantically unrelated and they had approximately equal word frequency (43 per million). The words were randomly assigned to two lists of sixteen. One list was used as the target list in the study phase whilst the second list was unsystematically interspersed with the target list to provide new items in the 32-item recognition test. Each word was printed on a separate card in bold upper-case black letters on a white background. Separate cards with the instruction either to Remember or Forget were generated in the same manner as the cards containing the words. One study booklet was prepared including 8 cards with TBR words, 8 cards with TBF words, with the constraint that the same instruction could appear no more than twice consecutively. A 3minute paper and pencil arithmetic task was administered between the presentation phase and memory testing. The arithmetic task consisted of 30 multidigit addition, subtraction and multiplication problems. Procedure Participants were tested individually in a session lasting approximately 30 to 40 minutes. Each session had four phases: (a) study, (b) a filled interval, (c) free recall, and (d) recognition. Prior to the study phase participants read the following set of instructions: “This is a memory experiment. You will be shown a list of words, one word a time. Each word will be presented for two seconds in bold upper-case black letters on a white page and your task is to focus on this word. Following this, a voice on a tape recorder will tell you to turn the page. You will then see either an instruction to Remember or to Forget the previous

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TABLE III

Mean Free Recall of TBR and TBF items Group

TBR

TBF

LF (N = 4) RF (N = 5) Mean

0.37 0.20 0.29

0.15 0.40 0.28

LT (N = 5) RT (N = 5) Mean

0.47 0.65 0.56

0.15 0.20 0.18

CF (N = 5) CT (N = 5) Mean

0.67 0.82 0.75

0.15 0.12 0.14

L = Left Hemisphere, R = Right Hemisphere. F = Frontal, T = Temporal, C = Control.

word. If the Remember instruction is shown try to remember the word you just saw for a later test. If the Forget instruction is shown you need not remember that word. A voice on a tape recorder after 5 seconds will tell you to turn the page. This sequence will be repeated until all the words and their instructions have been presented”. After reading these instructions, participants were asked to summarise the instructions and questions were answered. The filled interval immediately followed the study phase, after which was the free recall test and then the recognition test. In the recall test participants were given a separate page with 16 blank lines and requested to write as many words as they could remember from the words they had seen in the study phase, regardless of which cue, R or F, the words had originally been paired with. The recall test was terminated by participants when they could not remember any more words or when a 5-minute interval had passed. In the recognition test participants were given five minutes to circle words they had seen in the study list again regardless of what cue they had been previously paired with. The studied and unstudied words appeared in the same random order on the test sheet for all subjects. Participants were debriefed at the end of the study. Results and Discussion The number of words correctly recalled from both the TBR and TBF words was calculated for each participant and this raw data was used in the analysis. Following standard practice, however, mean probabilities are shown in Table III. Note that Table III also shows the mean proportions in terms of laterality. The analyses were based on a standard analysis of DF data developed by and reported in Conway et al. (2000). These are structured around a set of planned comparisons (Keppel, 1991) within groups focused on the finding of high recall of TBR items with low recall of TBF items. Note that for all the F values reported here and in the subsequent experiments effect size and power were estimated by calculating omega squared from the formula 4-1 in Keppel (1991, p. 65). In general the significant values of F yielded omega squared values greater than .12, and effect sizes were therefore ‘medium’ to ‘large’ with all

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Martin A. Conway and Aikaterina Fthenaki TABLE IV

Mean Recognition of TBR and TBF Items by Patient Group and Laterality Condition

TBR

TBF

LF (N = 4) RF (N = 5) Mean LT (N = 4) RT (N = 5) Mean CF (N = 4) CT (N = 5) Mean

0.79 0.65 0.72 0.77 0.83 0.80 0.98 0.92 0.95

0.75 0.87 0.81 0.50 0.54 0.52 0.41 0.49 0.45

L = Left Hemisphere, R = Right Hemisphere. F = Frontal, T = Temporal, C = Control.

power values exceeding the critical .8 level (Cohen, 1988, 1992). These analyses demonstrate that even with small groups of participants and relatively short list lengths large effect sizes are present and power is high, a pattern previously reported for DF procedures (see Conway et al., 2001). Consider first the overall analyses of differences within groups (mean values shown in Table III). No reliable difference of TBR over TBF items was found in the frontal group, F < 1, but in the temporal and control groups this effect was significant, F (1, 9) = 10.96, MSe = 48.05, p < 0.01; F (1, 9) = 69.93, MSe = 47.9, p < 0.01. Analyses of the groups by laterality of pathology found that only the left frontal (LF) and the control group (CT) showed a significant difference in their recall performance of the TBR and the TBF items, LF: F (1, 3) = 13.36, MSe = 60.13, p < 0.05; CF: F (1, 4) = 15.47, MSe = 44.10, p < 0.05; CT: F (1, 4) = 196.00, MSe = 78.40, p < 0.01, while the temporal lobe groups differences were not reliable, t < 1, although the means were in the predicted direction. In contrast, the right frontal lobe group showed a reversed pattern with fewer items from the TBR list and more from the TBF list – an effect that was at significance F (1, 4) = 7.6, MSe = 47.3.40, p = 0.05. A similar pattern was observed in recognition memory performance and Table IV shows the mean hit rates. It can be seen from Table IV that both the temporal and control groups had a DF effect in recognition with TBR items better recognised than TBF items, F (1, 9) = 5.13, MSe = 39.2, p < 0.05 for the temporal group and F (1, 9) = 45.00, MSe = 80.00, p < 0.01 for the controls. Both these groups also had reliably lower TBF rates than the frontal group: t (17) = 2.95, p < 0.05 for the temporal group and t (17) = 2.95, p < 0.05 for the controls. For the frontal group there was no reliable difference in hit rates for TBR and TBF items and recognition of TBF items was abnormally high. This pattern was again most evident in patients with lesions in the right frontal lobe who recognised reliably more TBF items than the control group, [Tukey HSD: t (8) = 3.8, CD = 3.5, p < 0.05]. Finally, note that both intrusions in free recall and false positives in recognition were low (less than 10% for both patient groups and absent in the controls), and overall both these types of errors were more frequent in the temporal than the frontal group.

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In summary, the data show that the DF manipulation did not lead to enhanced recall and recognition of TBR items with impaired recall of TBF items for the frontal lobe group. In contrast, the temporal lobe group and the control group showed a robust directed forgetting effect in both recall and recognition. Additionally it was found that laterality of injury interacted with this and the right frontal group showed disrupted DF in recall and recognition. The left frontal patients showed a statistically reliable standard DF effect in recall and the expected pattern in recognition. Thus, the right frontal lobe group may have a particular difficulty carrying out the complex operations required to encode the TBR and TBF items effectively. Indeed, given that they recalled and recognised more TBF than TBR items (see Tables III and IV) it may even be the case that they suffer from some sort of “rebound” effect in which intentionally unattended items intrude, later, into awareness (cf. Wegner, 1994). EXPERIMENT 2 Experiment 2 examined the DF effect using the list method in the same groups of participants. In this procedure a list of words is studied for later recall and at the end of the study period either an F cue is given or participants are instructed to continue to remember (an R cue) the newly acquired list while learning a second list. In the within-subjects version of this there are then four lists: F list 1, F list 2, R list 1 and R list 2. Each is studied in pairs and then free recalled, e.g. study R list 1, present R cue, study R list 2, then free recall both R lists and, study F list 1, present F cue, then study F list 2, and again free recall of both F lists. The standard DF effect is seen in poor recall of F list 1 relative to R list 1 and F list 2 and is usually only found in free recall. (MacLeod, 1998). Directed forgetting with lists is considered to entail inhibition of F list 1, rather than reduced rehearsal (Bjork, 1989; Bjork et al., 1998; Conway, et al., 2000) and, therefore, is a more direct test of disrupted inhibitory processes in frontal patients. Method Design A 2 × 3 mixed factorial design was used with List Type (RememberRemember, Forget-Remember) as a within subjects factor and Group (Frontal lobe, Temporal lobe and Control group) as a between-subjects factor. The main dependent measure was recall rate although recognition rates were also collected. The participants were the same as those in Experiment 1 and the two experiments were separated by a minimum period of six weeks, but otherwise varied for each participant. Materials Twenty-four unrelated common words were selected from Friendly and Rubin (1986) according to the following criteria: all words had 4-6 letters, the

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average probability of their recall was high (above .65), and in the same list, no word started with the same letter (see Fthenaki, 2003, for the full list). The words were randomly assigned to four lists of six words for the study phase. (Note that list length was reduced in order to try to raise the overall level of memory performance in the patient groups). Two lists were allocated to the Remember- Remember condition while the other two were assigned to the Forget-Remember condition. Two study booklets were prepared with each word printed on a separate card in bold upper-case black letters on a white background. The first study booklet contained two sets of TBR words (six words in each set) while the other study booklet contained a set of TBF words (six words) and a set of TBR words (six words). The two booklets were rotated across participants to counterbalance presentation order. The twenty-four words from the study phase were intermixed with a further set of twenty-four new words from Rubin and Friendly (1986) to provide a series of forty-eight items in the recognition test. A new 3-minute paper and pencil arithmetic task was administered between the study phase and recall and recognition. Procedure The procedure was the same as that previously used with the following changes: After presentation of list 1 an R or F cue was presented. In the test phase a sheet with 24 blank lines was presented and participants wrote as many words as they could recall, from either R or F lists, one word to a line in order of recall. The recall test was terminated by participants when they could not remember any more words or when a 5-minute interval had passed. Free recall was followed by a recognition test including 24 old and 24 new words intermixed unsystematically. Participants were allowed 5 minutes to circle words they had seen in the study list regardless of whether they had been previously instructed to either remember or forget them. Results and Discussion The two critical differences to show a DF effect in the list procedure are: reliably greater recall of F list 2 and R list 1 compared to F list 1. For the frontal group neither the first comparison, t (8) = 1.6, SE = 0.624, p = 0.147, nor the second (t < 1) was significant. In fact recall of both lists by frontal patients in the F condition was reliably higher than recall of the corresponding lists from the R condition, t (8) = – 2.41, p < 0.05, again suggesting a rebound in which items targeted for inhibition are recalled to unexpectedly high levels (see Table V). For the temporal lobe group, the critical contrast between F list 1 and F list 2 approached significance, t (9) = – 2.18, p = 0.057, and the F list 1 and R list 1 comparison was significant, t (9) = – 2.75, p < 0.05. These findings indicate a slightly attenuated but otherwise normal DF effect. For the control groups a DF effect was observed: F list 1 versus F list 2, t (9) = – 7.65, p < 0.01, and F list 1 with R list 1, t (9) = – 4.88, p < 0.01. Table V also shows mean recall rates by laterality of injury. For the right frontal group neither of the critical comparisons were significant, t < 1,

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TABLE V

Mean Recall Rates for Groups by Laterality of Injury in Experiment 2 Condition

Frontal (N = 9) LF (N = 4) RF (N = 5) Temporal (N = 10) LT (N = 5) RT (N = 5) Control (N = 10) CF (N = 5) CT (N = 5)

R-R

F-R

List 1

List 2

List 1

List 2

0.16 0.16 0.16 0.50 0.36 0.63 0.33 0.30 0.36

0.18 0.20 0.16 0.10 0.03 0.16 0.26 0.23 0.30

0.33 0.20 0.43 0.18 0.16 0.20 0.08 0.06 0.10

0.40 0.50 0.33 0.40 0.05 0.30 0.51 0.40 0.63

indicating no DF effect and an abnormal pattern of remembering. For the left frontal group also, neither contrast was reliable although here the means were in the predicted direction and so, perhaps, indicate attenuated rather than abolished or seriously abnormal DF. For the left temporal group F list 1 versus F list 2 differed reliably, t = – 4.47, p < 0.05, but the comparison between F list 1 and R list 1 did not reach significance despite the means being in the expected direction. For the right temporal group only the F list 1 versus R list 1 contrast was significant, t = – 6.5, p < 0.01, and the means were again in the predicted direction. The pattern for the temporal groups indicates, then, attenuation rather than dissolution of the DF effect. In the two control groups (CF, CT, in Table V) strong DF effects were observed. The contrasts for F list 1 versus F list 2 and F list 1 versus R list 1 for CF and CT respectively were, t (4) = – 4.47, p < 0.05, t (4) = – 2.75, p = 0.052, and t (4) = – 8.55, p < 0.05, t (4) = – 4.0, p < 0.05. In the recognition tests nearly all of the differences in contrasts were abolished and, as is usually found, recognition overcame the effects of DF. The means are shown in Table VI and these are not decomposed by laterality as no reliable/interpretable differences were found. Intrusions and false positives were at a similar level to that of Experiment 1 and were distributed in the same way. In summary, the findings show that, again, frontal patients could not intentionally inhibit items designated as TBF. Temporal patients too had a reduced, but not abolished, ability to inhibit in the list directed forgetting procedure and this stands in contrast to the strong inhibition in item-by-item direct forgetting that this group showed in Experiment 1. There was also further TABLE VI

Mean Recognition Rates for DF by Lists Condition

Frontal (N = 9) Temporal (N = 10) Control (N = 10)

R-R

F-R

List 1

List 2

List 1

List 2

0.73 0.86 0.78

0.79 0.58 0.78

0.63 0.61 0.73

0.77 0.76 0.66

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indication that problems in intentional inhibition may be more strongly associated with lesions (both frontal and temporal) of the right compared to left cortical hemisphere. Although these indications were in the direction of the means rather than in reliable contrasts. EXPERIMENT 3 Experiment 3 investigated automatic inhibition that occurs in the retrieval induced forgetting procedure or RIF (Anderson and Spellman, 1995). In RIF participants study a list of category exemplars drawn from several different categories, e.g. Orange, Apple, Banana, Train, Bus, Car, etc. The study phase is followed by a retrieval practice phase in which a subset of items are recalled to category cues, e.g. Fruit-O_____?, for some of the categories. This manipulation causes inhibition of unpractised items from practised categories which is detected in the poor recall rates for these items relative to recall of items from unpractised categories and, of course, to practised items themselves (which show enhanced recall). In the example above recall of ‘Apple’ and ‘Banana’ would be attenuated relative to recall of ‘Train’, ‘Bus’, and ‘Car’, and recall of ‘Orange’ would be enhanced relative to items from an unpractised category. One of the central questions of the present study is whether or not frontal patients will also be impaired with this less intentionally initiated more automatic form of inhibition. Method Design The design of this experiment was the same as that of Anderson et al. (1994), Experiment 1. Three factors, Retrieval Practice Status, Category Composition, and (patient) Group were employed. Retrieval practice status was a within-subjects factor and had three levels: (a) Rp + items, which constituted the items that were practised three times in a category-plus-stem-recall practice test (e.g. Fruit-Or_____) during the retrieval practise phase; (b) Rp – items, which were the items from the same group as the Rp + items that were not practised during the retrieval practise phase, and (c) Nrp items, which were not members of a practised category. The Nrp category was divided into two subgroups for counterbalancing purposes (Nrpa and Nrpb), which were used as a baseline against which to compare the recall performance of Rp + and Rp – items. Category composition was also a within-subjects factor and had two levels: strong associates, i.e. highly typical exemplars (average rank order of 8 according to Battig and Montague, 1969); and weak associates, low typical (average rank order of 33). The only difference from the experimental design of Anderson et al. (1994) was the introduction of Group as a between-subjects factor. The same group of patients and controls took part and they were tested at least one month after taking part in Experiment 2. The dependent variable was the number of items of each type of item correctly recalled in a cued-recall test.

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Materials Six categories, two of which were fillers, with six exemplars from each category were selected from the 10 categories used by Anderson et al. (1994). Two of the categories contained strong exemplars (for category and exemplar selection see Anderson et al., 1994, Experiment 1) while the other two contained weak exemplars. Learning booklets contained 24 experimental and 12 filler items. Each page of the learning booklet included one category exemplar pair presented in bold upper-case black letters in the centre of a white background. The order of the exemplars within a booklet was unsystematic as was the order of the experimental stimuli within each block with the restrictions that (a) in the first block, the filler items appeared first, (b) in the last block, filler items appeared at the end, and (c) throughout the booklet no two categories appeared sequentially more than once. The retrieval practice booklets were constructed in the following manner: the category label was presented in bold upper-case letters in the centre of a white background with the first two letters of the exemplar followed by a solid line, e.g. Fruit Or_____. Order of retrieval practice items was random and preceded and followed by filler items. No two categories were tested sequentially and the average test position of each category was kept constant. The order of the categories and the exemplars that were practised or not was counterbalanced across participants in order to ensure that each item was included in each condition equally. Cued recall test booklets each contained one category cue presented separately at the top of a page. There were four pages that contained the experimental categories and the first page of the test booklet included one of the filler categories. The order of the experimental categories was random. The test booklets for the category-plus-stem cued-recall test contained every category exemplar pair with the constraints used in the construction of the retrieval practice booklets. Procedure Participants were tested individually in a test session lasting approximately 40-60 minutes. The memory study had four phases: (a) study, (b) retrieval practice, (c) filled interval, and (d) cued recall. In the study phase, participants were randomly allocated to one of the two random study orders and given a study booklet. The following instructions (from Anderson et al., 1994: Experiment 1) were given: “You are participating in an experiment on memory and reasoning. Your task will be to study category exemplar pairs and to relate each exemplar to its category. Each category and its exemplar will appear for 5 seconds in bold upper-case black letters on a white page. Following this, a voice on a tape recorder will tell you to turn the page. This sequence will be repeated until all pairs in the learning booklet had been presented”. After reading these instructions, participants were asked to summarise the instructions and raise any possible questions. The study phase then followed. After this the participants were allocated randomly to one of the four practice orders. Test booklets were then supplied and the following instruction was given: “Each page of this recall booklet contains one of the category labels that you studied in the previous phase along with a hint about the exemplar it was originally paired with. The

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hint consists of the first two letters. Your task is to recall the item you had seen rather than responding with any exemplar that fit the letter cues. You will be given 10 seconds to recall each cued exemplar and a tape-recorded voice will instruct you to turn pages” (Anderson et al., 1994). Comprehension of the retrieval practice instruction was checked and the practice phase then started. At end of the retrieval practice phase booklets were collected and participants then solved arithmetical problems for 20 minutes. The cued recall test booklets were then presented with the following instruction: “At the top of the page, you will see the name of one of the categories studied previously. Your task is to recall all exemplars of this category that you had studied at any time during the experiment. You will be given 30 seconds for each category”. Results and Discussion Cued-recall performance of the three groups in the different retrieval practice conditions is shown in Table VII. Consider first the pattern of findings for the strong associates. For the frontal group there was a strong main effect of retrieval practice, F (2, 16) = 22.1, MSe = 11.3, p < 0.001, and Rp + performance was reliably higher than Rp –, t = 6.6, p = 0.01, and Nrp, t = 4.0, p < 0.01, and Rp – was reliably lower than Nrp, t = 2.6, p < 0.05. Thus, frontal patients were found to show the normal pattern of increased recall for practised items with inhibition of strongly associated unpractised items. Temporal patients also showed a main effect of retrieval practice, F (2, 18) = 4.3, MSe = 1.37, p < 0.05, and although Rp + items were recalled to a significantly higher level than Rp – items, t = 2.8, p < 0.02, the difference between Rp + and Nrp was not reliable. The contrast between Rp – and Nrp items was, however, significant, t = 2.1, p < 0.05. The temporal group do not, then, show a reliable benefit from retrieval practice but do show some, albeit mild (see Table VII), inhibition of strongly associated unpractised items. Both control groups showed the expected pattern: For the frontal controls there was a main effect of retrieval practice, F (2, 8) = 26.9, MSe = 9.9, p < 0.001, and for the contrasts: Rp + versus Rp – t = 7.3, p < 0.001, Rp + versus Nrp t = 3.1, p < 0.02, and for Rp – versus Nrp t = 4.2, p < 0.01. For the temporal controls, F (2, 8) = 32.2, MSe = 8.6, p < 0.001, and for the contrasts: Rp + versus Rp – t = 7.9, p < 0.001, Rp + versus Nrp t = 3.1, p < 0.02, and for Rp – versus Nrp t = 4.9, p < 0.01. Overall, the pattern of findings show intact RIF for the frontal patients whose performance was similar to that of their control group and weakened RIF for the temporal group who also did not benefit from retrieval practice. TABLE VII

Mean Cued Recall in RIF for Frontal, Temporal and Controls Group

Frontal (N = 9) Temporal (N = 10) Control (N = 10)

Strong Items

Weak Items

Rp +

Rp –

Nrp

Rp +

Rp –

Nrp

0.85 0.56 1.00

0.11 0.30 0.10

0.40 0.50 0.60

0.62 0.50 0.70

0.29 0.13 0.23

0.29 0.30 0.40

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For the weak category associates (see Table VII) the frontal group showed a reliable main effect of retrieval practice, F (2, 16) = 3.9, MSe = 3.0, p < 0.05. Within this Rp + differed reliably from Rp –, t = 2.4, p < 0.03, and Nrp, t = 2.4, p < 0.03, but Rp – did not differ from Nrp. This indicates some benefit from retrieval practice with no inhibition of weakly associated unpractised items, in short the standard finding with weak associates. The temporal group showed a similar pattern, F (2, 18) = 8.3, MSe = 3.0, p < 0.01, Rp + versus Rp –, t = 4.1, p < 0.01, Rp + versus Nrp, t = 2.2, p < 0.05, and no significant difference between Rp – and Nrp. For the controls, the pattern for the frontal controls was, F (2, 8) = 26.0, MSe = 3.5, p < 0.01, Rp + versus Rp –, t = 7.0, p < 0.01, Rp + versus Nrp, t = 5.2, p < 0.01, and no significant difference between Rp – and Nrp, and the pattern for the temporal controls was, F (2, 18) = 13.5, MSe = 1.8, p < 0.01, Rp + versus Rp –, t = 5.2, p < 0.01, Rp + versus Nrp, t = 2.6, p < 0.05, and for Rp – versus Nrp, t = 2.6, p < 0.05. Unusually, then, the temporal controls showed some inhibition for weakly associated unpractised items and, possibly, this was because these items were processed as associated to the retrieval practice items on at least some occasions. Finally, an analysis with patient groups divided by cortical hemisphere of injury was undertaken and the main finding was that for the strong associates all groups showed a normal and reliable RIF effect with the exception of the left temporal groups whose means, Rp + 0.46, Rp – 0.33, and Nrp 0.53, did not differ reliably (t < 1.5 for all contrasts). Thus, in the temporal group only the patients with right temporal temporal lesions showed the normal patterns of increased recall for practised items and inhibition of unpractised strongly associated items. (Note that for weak items the patterns were the same as that reported for the groups not separated by hemisphere of injury). The main conclusion to be drawn from the data is that frontal lobe patients do not show disrupted inhibition in RIF in contrast to their performance on intentionally initiated DF tasks where severe impairment was observed, especially in patients with right side lesions. In contrast, left side temporal patients do not show the usual RIF patterns, although the means are in the predicted direction, and this suggests attenuated effects of practice and of inhibition. GENERAL DISCUSSION The findings of the three memory inhibition experiments reported here point particularly strongly to a simple conclusion: patients with frontal lobe injuries suffer impairments in intentionally initiating inhibitory memory processes. They do not, however, have similar impairments, or an impairment to the same extent, when inhibition is not intentional. Table VIII presents data from all three experiments in the form of inhibition indices, calculated as follows: the index for Experiment 1 was the percentage of TBR items minus TBF items in free recall (see Table III), in Experiment 2 it was the R minus the F items in the F-R free recall condition, (see Table V) and Experiment 3 it was the Npr cued recall rate minus the Rp- rate (Table VII). Mean values in Table VIII vary between zero and one with a score of zero

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Martin A. Conway and Aikaterina Fthenaki TABLE VIII

Inhibition Index across Experiments 1, 2, 3

Group Frontal Temporal Control

Experiment 1*

Experiment 2

Experiment 3

DF Items

DF Lists

RIF Strong

RIF Weak

0.01 0.38 0.61

0.07 0.22 0.43

0.29 0.20 0.50

0.00 0.17 0.17

*For Experiment 1, Inhbition = R items – F items, in Experiment 2 Inhibition = F group List 2 – F group List 1, and Experiment 3 Inhibition = Nrp items – Rp – items. In all cases a score of approximately .20 or higher indicates inhibition, with a score of 1 indicating total inhibition and a score of zero indicating no inhibition. Intermediate scores indicate degree of inhibition.

indicating no inhibition and a score of one total inhibition. Across the three experiments a score of approximately 0.20 indicates reliable levels of inhibition, i.e. differences of 20% and greater were found to be significant in all three experiments. Consider the performance of all three groups in Experiments 1 and 2. The frontal group are clearly severely impaired and show little or no inhibition in either experiment. The analyses reported earlier established that patients with right frontal lesions showed the greatest degree of impairment with a reliable and abnormal tendency to recall more TBF than TBR items in both experiments. In contrast, patients with left frontal lesions were found to have a more normal pattern of performance and their means were as predicted and the reverse of the right frontal group. A strong implication here is that networks in right frontal regions mediate willed attempts not to encode current information (Experiment 1) as well as to forget recently acquired knowledge (Experiment 2). Given that the predominant form of injury in this group was closed head injury 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 in this region. However, what remains curious is that this right frontal group recalled more TBF than TBR words and this was statistically reliable. A connection that can be made here is to the work of Wegner and colleagues on thought avoidance (see Wegner, 1994, for a review). In this work participants try to avoid thinking about certain thoughts specified by the experimenter and typically these thoughts then intrude during the early part of the thought avoidance period. After avoidance ceases a rebound effect is often observed during which the avoided thought once again persistently intrudes into consciousness - the person cannot now stop thinking about the avoided thought. One possible explanation for the performance of the right frontal patients reported here is that they cannot, to an abnormal extent, avoid thinking about items designated TBF and this is because the executive control needed to achieve effective avoidance is no longer available to them. What might such control entail? A possible explanation is provided by recent work and by a consideration of nature of DF in Experiment 1. In Experiment 1 DF was initiated by presentation of R and F cues during the study phase. The accepted account of DF in this procedure is that the F cue causes a reduction in rehearsal of an item and this attenuates integration in memory. More specifically it is thought that the F cues lead to a reduction in elaborative rehearsal and this

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impairs integration of F cued items with a representation of the entire list in long-term memory. If it is accepted that elaborative rehearsal is the usual or default mode of encoding during intentional learning then in order to prevent, attenuate, or disrupt this an intentional effort has to be made to actively avoid integrating list items, i.e. to avoid thinking about them. Similarly, in Experiment 2 in response to an F cue rehearsal of the recently acquired list has to cease, and when items from it come to mind, during second list learning , these have to be avoided and suppressed (cf. Anderson and Green, 2001, and Conway, 2001). Indeed, Conway et al. (2000) found that when a secondary task was performed while the 2nd list in the F-R condition was studied, subsequent DF was significantly weakened and, under certain conditions, abolished altogether and replaced by a rebound effect in which TBF items were better remembered than TBR items. Conway et al. argued that this attenuation of DF occurs because the secondary task reduces processing resources that would otherwise be available to executive control processes. The chief consequence of this is that executive processes cannot initiate effective (thought) avoidance under conditions of reduced processing resources and, therefore, paradoxically TBF items become integrated with the representation in memory. Moreover, because what reduced resources are available become targeted on TBF rather than TBR items this leads to better recall of the former relative to the latter – the rebound effect. We suggest that this is precisely what occurs in the right frontal patients in Experiments 1 and 2. Reduced processing resources in right frontal networks, the operations of which are attenuated by diffuse brain damage, prevents or disrupts thought avoidance and, consequently, inhibition is not triggered. The resources available are mainly used in the processing of TBF items (failed attempts at avoidance) rather than the encoding of TBR items. Ironically (see Wegner, 1994) this leads to the recall of more TBF than TBR items in both experiments. It can also be seen from Table VIII that the group of temporal patients showed a very different pattern of inhibition to that of the frontal patients. In Experiment 1 the temporal patients had a reliable DF effect, although this was not as strong as in the controls and was weakest in the left temporal patients (Table III). In Experiment 2 this pattern emerged even more strongly and right temporal patients showed a comparatively normal DF effect in contrast to left temporal patients who had a reversal of the DF effect (see Table IV), although this was not significant. (Note that, this difference is obscured in Table VIII where the data are averaged over hemispheres). Right temporal patients were then found to show a normal pattern of DF effects in the context of overall weak memory performance (compared to controls). Left temporal patients had attenuated but essentially normal DF when this arose from factors relating to the encoding of individual items (Experiment 1) but had an abnormal pattern when this entailed inhibiting an already acquired list (Experiment 2). It seems unlikely that this is due to any general differences in levels of retention as this group often, across conditions and experiments, recalled more than the frontal patients. We suggest that this group may have problems accessing knowledge in longterm memory and that proactive interference, even from successfully inhibited items, may dramatically reduce second list recall (see Table IV). By our earlier

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reasoning right temporal patients, on the other hand, have a mildly attenuated ability to avoid TBF items (and induce inhibition), but in general they are able to do this and so show the normal DF pattern. Experiments 1 and 2 indicate dissociations between the groups with right frontal patients showing no inhibition whereas left frontal patients were comparatively normal. In contrast, temporal patients showed the reverse pattern with left temporal patients showing no or abnormal inhibition in Experiment 2, whereas right temporal patients had normal inhibition. In Experiment 3 this pattern of dissociations was reversed. Frontal patients, left and right, had a normal pattern of inhibition and enhanced recall resulting from a RIF manipulation (Table VIII). Temporal patients, right and left, did not benefit from retrieval practice and showed only a marginal inhibitory effect (for strong associates) that was at significance. From this it can be concluded that patients with temporal lobe lesions have attenuated RIF. In intentional forgetting inhibition in left temporal patients is more severely disrupted than in patients with right side lesions where it may be attenuated rather than disrupted. In contrast, patients with right frontal lesions appear not to be able to intentionally initiate inhibition but patients with left frontal lesions although performing at a lower level nevertheless show a relatively normal pattern. Both left and right frontal patients have intact inhibition when this is not intentionally initiated. These striking dissociations between and within patient groups have several implications. Most compellingly they suggest that DF and RIF may involve different inhibitory processes or, alternatively, they may involve different ways of initiating inhibition. We believe that the latter is the case and that in both types of task the actual process of inhibition is the same and it is the way in which the process is triggered that differs. In DF inhibition is intentionally triggered and this involves active thought avoidance. The idea being that the frequency of active thought avoidance increases the likelihood of inhibition (see Anderson and Green, 2001). In DF by items, elaborative rehearsal is reduced by active avoidance of an item and it is this that triggers inhibition. In DF by lists, recall of F items during second list learning leads to avoidance of the entire list and, again, this triggers inhibition (see Conway et al., 2000). In RIF inhibition is triggered by selective attention processes that focus attention on a single item in a recently formed representation that includes competitor items. Crucially, however, this occurs automatically as a consequence of attentional focus and does not require any intentional thought, willed or otherwise, on the part of the rememberer. Patients with temporal lesions experience problems in focusing on knowledge in long-term memory and so do not show a strong RIF effect. Frontal patients may not suffer from this problem, they can focus on items in long-term memory and, therefore, trigger RIF. What these patients cannot do to normal levels of performance is trigger inhibition by actively avoiding thoughts and this is most severe in patients with right side frontal lesions. Finally consider the implications of this pattern of findings for hemispheric models of encoding and retrieval. In their original meta-analysis Nyberg et al. (1996) concluded that left PFC networks primarily mediated encoding whereas as right PFC was specialised for episodic retrieval processes. Subsequently, however, it emerged that in more complex retrieval tasks (more complex than

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recognition) left PFC networks become involved in post-access processes (Nolde et al., 1998; see too Conway et al., 2000, for evidence of strong left PFC involvement in constructing autobiographical memories). More recent work has focused on the various roles of different regions of PFC in the access of knowledge and in the evaluation of that knowledge (see for example, Fletcher et al., 1998; Henson et al., 1999; Rugg and Wilding, 2000). One current view is that right ventrolateral PFC mediates processing of retrieval cues prior to retrieval whereas, and in contrast, dorsolateral PFC mediates evaluation of knowledge accessed in long-term memory. In the present case the findings from the right frontal patients suggest that role of right PFC may be a more complex one than processing retrieval cues prior to retrieval, although it may include this too. In Experiment 1 right frontal patients could not selectively control rehearsal and this may reflect impaired processing in right ventrolateral PFC networks. Additionally, however, these patients could not intentionally trigger inhibition (Experiment 2) and this suggests that networks in the right PFC may also play a role in the intentional control of retrieval, as implied in the original Nyberg et al. (1996) model. In addition to this, left frontal patients although recalling to a lower level than controls nonetheless showed a relatively normal pattern and, consequently, it might be argued that these patients have generally attenuated rather than disrupted retrieval and encoding processes. Thus, preserved right PFC function appears critical for control of encoding and retrieval. Acknowledgements. The research reported in this paper was supported by the Department of Experimental Psychology, Centre for Learning and Memory, University of Bristol. Martin A. Conway was additionally supported by the Biotechnology and Biological Sciences Research Council, grant 7/S10578, and Katerina Fthenaki by a Greek government postgraduate training grant. REFERENCES ANDERSON MC, BJORK RA and BJORK EL. Remembering can cause forgetting: Retrieval dynamics in long-term memory. Journal of Experimental Psychology, Learning, Memory and Cognition, 20: 1063-1087, 1994. ANDERSON MC and GREEN C. Suppressing unwanted memories by executive control. Nature, 410: 366369. 2001. ANDERSON MC and SPELLMAN BA. On the status of inhibitory mechanisms in cognition: Memory retrieval as a model case. Psychological Review, 102: 68-100, 1995. BADDELEY AD and WILSON B. Amnesia, autobiographical memory, confabulation. In DC Rubin (Ed), Autobiographical Memory. Ch. 13., pp.225-252. Cambridge: Cambridge University Press, 1986. BASDEN BH, BASDEN DR and GARGANO GJ. Directed forgetting in implicit and explicit memory tests: A comparison of methods. Journal of Experimental Psychology: Learning, Memory and Cognition, 19: 255-268, 1993. BATTIG WF and MONATGUE WE. Category norms for verbal items in 56 categories: A replication and extension of the Connecticut norms. Journal of Experimental Psychology, 80: 1-46, (monongraph), 1969. BJORK RA. Retrieval inhibition as an adaptive mechanism in human memory. In: HL Roediger and FIM Craik. (Eds), Varieties of Memory and Consciousness: Essays in Honour of Endel Tulving. Ch. 16, pp. 309-330. Hillsdale: Lawrence Erlbaum Associates, 1989. COHEN J. Statistical power analysis for the behavioural sciences. New York: Academic Press, 1977. COHEN J. A power primer. Psychological Bulletin, 112: 155-159, 1992. CONWAY MA. Repression revisited. Nature, 410: 319-320, 2001. CONWAY MA, HARRIES K, NOYES L, RACSMA’NY M and FRANKISH CR. The disruption and dissolution of directed forgetting: Inhibitory control of memory. Journal of Memory and Language, 43: 409-430, 2000. FTHENAKI A. Memory impairments in frontal and temporal patients. Doctoral dissertation, University of

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Bristol, in preparation. 2003. HENSON RN, SHALLICE T and DOLAN RJ. Right prefrontal cortex and episodic memory retrieval: a functional MRI test of the monitoring hypothesis. Brain, 122: 1367-1381, 1999. KEPPEL G. Design and Analysis. A researcher’s handbook. Englewood Cliffs: Prentice Hall, 1991. KUCERA H and FRANCIS W. Computational analysis of present day American English. Providence: Brown University Press, 1967. LURIA AR. Higher Cortical Functions in Man. New York, Basic Books, 1966. MACLEOD CM. Directed forgetting. In JM Golding and CM MacLeod (Eds), Intentional forgetting: interdisciplinary approaches. Ch. 1, pp. 1-57. Mahwah: Lawrence Erlbaum Associates, 1998. MCANDREWS MP and MILNER B. The frontal cortex and memory for temporal order. Neuropsychologia, 29: 849-859, 1991. SHALLICE T. From neuropsychology to mental structure. New York: Cambridge University Press, 1988. SMITH EE and JONIDES J. Storage and executive processes in the frontal lobes. Science, 283: 1657-1661, 1999. STUSS DT and BENSON DF. The Frontal Lobes. New York: Raven Press, 1986. WECHSLER D. Wechsler Adult Intelligence Scale-Third Edition. Town: The Psychological Corporation, 1998. WECHSLER D. Wechsler Memory Scale-Third Edition. Town: The Psychological Corporation , 1998. WHEELER MA, STUSS DT and TULVING E. Towards a theory of episodic memory: The frontal lobes and autonoetic consciousness. Psychological Bulletin, 121: 351-354, 1997. WILSON BA, ALDERMAN N, BURGESS PW, EMSLIE H and EVANS JJ. Behavioural Assessment of the Dysexecutive Syndrome. Bury St Edmunds: Thames Valley Test Company, 1996. Martin A. Conway and Katerina Fthenaki, Department of Psychology, University of Durham, Science Laboratories, South Road, Durham, DH1 2LE, England. e-mail: [email protected]