Epilepsia, 45(9):1124–1133, 2004 Blackwell Publishing, Inc. C 2004 International League Against Epilepsy
A Dissociation between Implicit and Explicit Verbal Memory in Left Temporal Lobe Epilepsy ∗ Nicole Del Vecchio, †Joyce Liporace, †Maromi Nei, †Michael Sperling, and †Joseph Tracy ∗ Drexel University, and †Department of Neurology, Thomas Jefferson University/Jefferson Medical College, Philadelphia, Pennsylvania, U.S.A.
Summary: Purpose: Temporal lobe epilepsy patients are well known to present deficits on explicit verbal memory procedures (e.g., recall, recognition). The integrity of implicit memory procedures in these patients is not established. Previous studies in this area used implicit memory measures contaminated by the effects of explicit memory. Methods: We examined the integrity of verbal implicit and explicit memory in left temporal lobe epilepsy (LTLE) patients and hypothesized that a clear dissociation in performance would be found with a relative preservation of implicit memory. TLE patients (n = 15) and age- and education-matched healthy normal patients (n = 15) were shown a 40-word study list, followed by a test phase requiring completion of word stems based on the study words or new/unseen words. Experimental conditions involved instructions to provide either the old (study) words or novel/nonlist words when completing the stem. Measures of au-
tomaticity and recollection provided uncontaminated indices of implicit and explicit memory, respectively. Results: The data showed a significant difference (p < 0.001) between the patients (Recollection, 0.12; SD, 0.18) and controls (0.50, SD, 0.15) on the measure of explicit memory. In contrast, the patients (Automaticity, 0.51; SD, 0.11) and controls (0.45, SD, 0.18) performed similarly on the implicit memory measure, with patient scores clearly at normative levels based on other Process Dissociation Procedure data. Conclusions: The data demonstrate the integrity of implicit memory in LTLE patients. Finding a dissociation between the two forms of verbal memory in LTLE patients provides evidence that they rely on different neuroanatomic systems. Key Words: Implicit memory—Explicit memory—Episodic memory—Epilepsy—Medial temporal lobe.
Explicit and implicit memory processes have been identified as two separate, qualitatively different informationprocessing systems controlled by different neural circuits (1) (see also 2,3). Explicit memory is a conceptually driven system that relies on the intention to learn. It is typically measured by what are referred to as direct tests of memory, which are designed to measure one’s conscious recollection of past events (i.e., recall, cued recall, recognition) (4–6). In contrast, implicit memory involves nonconscious memory for past experiences that indirectly influence an individual’s future behavior. It is considered a data-driven system, unintentional and automatic in its implementation, and is typically measured by indirect tests (7). Word-stem completion, word-fragment completion, word-association generation, and category-exemplar generation tasks, in addition to repetition priming tasks, have been used (1,8). The anatomic structures subserving explicit memory are well established. Individuals with medial temporal
lobe abnormalities such as epilepsy patients are known to perform poorly on direct tests of explicit memory, as this area (left hippocampal and parahippocampal gyri) and other regions (anterior prefrontal) are strongly implicated in this skill (9–15). Evidence is accumulating to suggest that the prefrontal cortex is specifically involved in retrieval effort, with the medial temporal lobe system, in contrast, mediating the experience of conscious recollection (11). Patients with left temporal lobe epilepsy (TLE) show evidence of mesial temporal lobe hippocampal atrophy, as measured through magnetic resonance imaging (MRI) volumetry (16–20). Their deficits in explicit memory are well documented (21–25). Temporal lobe lesion patients and others demonstrating impairment in explicit recollection often perform at normative levels on measures of implicit memory (25– 29). The neuroanatomic basis of implicit memory is less clearly worked out than that of explicit memory, and the neuroanatomy differs depending on the type of implicit memory procedure. Conceptual priming, which is based on a performance benefit from strictly the semantic aspects of a prior stimulus, appears associated with the inferior and superior temporal lobe regions (13), with reductions
Accepted May 16, 2004. Address correspondence and reprint requests to Dr. J.I. Tracy at Department of Neurology, Thomas Jefferson University/Jefferson Medical College, 900 Walnut Street, Suite 206, Philadelphia, PA 19107, U.S.A. E-mail:
[email protected]
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IMPLICIT AND EXPLICIT MEMORY IN TLE PATIENTS also observed in left prefrontal cortex (30,31). Others have observed activation associated with left inferior frontal gyrus, left middle gyrus, and left inferior temporal gyrus on conceptual memory tasks (32). In contrast, perceptual memory processes are those in which the physical attributes of the stimulus are used for performance enhancement or memory benefit. These processes appear mediated by the same sensory regions that are recruited during the original encoding or at the point of retrieval. For instance, strong evidence from visually based lexical and repetition priming studies indicates that occipitotemporal cortex (e.g., extrastriate cortex) and the insula mediate this process in important ways (8,12,33,34). With perceptual priming, the involved areas will depend on the nature of the stimulus, with occipital cortex mediating visual stimuli and superior temporal regions used for auditory stimuli (32). The major studies to date of implicit memory in epilepsy have been hampered by problems with the influence of implicit on explicit memory and vice versa (29,35–37). These studies did much to establish the cognitive differences and potentially separate neuroanatomic bases for conceptual and perceptual effects during language tasks and demonstrated the importance of “study” and “test” compatibility to enhance performance. The studies, however, did not quantify automatic versus intentional effects on memory, and the implicit and explicit memory tests were implemented by separate tasks. Last, the studies counterbalanced the order of the direct and indirect tests, making it possible for implicit memory processes to be influenced by explicit memory under certain experimental conditions. In contrast to these studies, others have implicated temporal lobe structures in implicit memory performance. For instance in a later study, Zaidel et al. (25) measured neuronal density in hippocampal subfields (CA1, CA2, CA3) and found associations between CA1 integrity and implicit verbal memory performance in both left and right temporal lobectomy patients. Some studies in motor skill learning have suggested that the hippocampus is involved in implicit memory when evaluated through tasks such as motor sequence learning (38). The Zaidel et al. study, however, did not control for contamination effects, as explicit recall immediately followed the study session and preceded the implicit memory task of word-stem completion. All these studies suffered from the unintended influences of explicit memory, as no direct control was exerted for involuntary recollection strategies. Several studies have provided strong evidence of contamination effects on implicit memory tests by explicit memory strategies, and conversely, the contamination on explicit memory by implicit memory strategies (10,33,39). Schacter (33) identified two possible reasons for explicit memory influences on priming tasks. One, individuals may become aware of being tested, and thus change their behavior accordingly,
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or, two, they may make use of an unintentional retrieval strategy when calling to mind a study-list word. Both activities have been associated with hippocampal activity (40), and such influences may reflect an involuntary, conscious recollection strategy. Schacter (33) (p. 298) reviewed the extant neuroimaging literature on contamination effects in explicit and implicit memory and concluded that, “The finding of hippocampal activity in the absence of anterior prefrontal activation during priming . . .,” likely indicated the operation of involuntary conscious recollection and thus contamination from explicit memory procedures. Above and beyond methodologic issues, theoretical models differ regarding the role of the hippocampus in implicit memory. For instance, explicit learning models posit that the medial temporal lobe is necessary for long-term storage of facts that will need to be consciously accessible at the time of later use (40,41), suggesting that conscious awareness at both learning and re-expression is necessary for the hippocampus to be recruited (42). By this model, no role would be available for the hippocampus to play in implicit memory. A different memory model (43), referred to as relational memory, argues that the hippocampus is crucial to associative learning processes and will be invoked whenever such stimulus–stimulus or stimulus–response connections are required. The essence of the relational model is that the hippocampus is crucial not to item storage per se but to the binding of items, defining, and then storing the relation (association) between them (44,45). Other models of hippocampal functioning are still viable, including its role in responding to novel stimuli, and its special role in navigational memory. In a review of the literature, Cohen et al. (44) argued persuasively that extant evidence favors the relational model. By this account, the hippocampus can be involved in either explicit or implicit memory as long as associative learning is present. A strategy to overcome potential contamination effects was proposed by Jacoby (46). His process dissociation procedure (PDP) separates conscious, intentional processes from unconscious, automatic processes by setting explicit and implicit memory in opposition to each other. By the PDP procedure, after standard presentation of a word list, two experimental conditions are administered in a word-stem completion format. Under the inclusion condition, the subject is instructed to complete the stem with a previously studied word. Success during this condition requires the joint contribution of explicit and implicit memory processes. Under the exclusion condition, the subject is instructed to complete the stem with a novel word, not with one from the study list. Here, conscious and unconscious processes are opposed, and the degree to which the subject cannot refrain from using a study word is taken as evidence of a deficit in explicit memory and the force of implicit memory processes. This single-task strategy also overcomes limitations and criticisms stemming from the use of separate tasks because of differences in Epilepsia, Vol. 45, No. 9, 2004
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difficulty and task-order effects. The PDP method differs from the aforementioned studies in its use of a single task to measure both memory processes, each uninfluenced by the other. The method provides a way to quantify automatic and intentional forms of memory and places them in opposition to each other. The goal of the present study was to determine in an uncontaminated fashion whether implicit memory processes are intact and independent from explicit forms of memory in individuals with left TLE. These issues were addressed through use of the PDP (46) with verbal material. This procedure uses a single task, containing both direct and indirect tests of memory, to quantify both explicit and implicit memory. The PDP procedure has shown great utility with amnestic patients in dissociating implicit from explicit memory and demonstrating the relative integrity of implicit memory processes (47,48). Our hypothesis, which emerges from the literature, is that the left temporal lobe abnormalities of the epilepsy patients will impair explicit verbal memory, while leaving implicit memory relatively intact because of the latter’s implementation by extra–temporal lobe structures.
TABLE 1. Group characteristics LTLE group No. Age (yr) Sex Handedness Ethnicity Education Age at onset Medication/ Dosage (mg)
Males Females Right Left White Black Latino 18 yr Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9
METHODS Participants Participants (n = 30) were between the ages of 18 and 50 years. The groups consisted of 15 TLE (mean age, 37 years; SD, 10.2) diagnosed with intractable left TLE and 15 normal controls (mean age, 35 years; SD, 11.3; see Table 1). The TLE patients were candidates for left hemisphere epilepsy surgery, admitted to an inpatient Comprehensive Epilepsy Center at Thomas Jefferson University (TJU) Hospital, and were taking anticonvulsant medication (AEDs). Patients were included in this study, provided they had met the following inclusion criteria: unilateral left hippocampal sclerosis as identified through MRI and surface EEG recordings consistent with unilateral left-sided temporal lobe seizure onset. TLE patients and normal controls were excluded from the study on any of the following grounds: medical illness with central nervous system impact other than epilepsy; head trauma; prior or current alcohol or illicit drug abuse; and psychiatric diagnosis or hospitalization for a Diagnostic and Statistical Manual of Mental Disorders, IV (DSM-IV) psychiatric disorder (n.b., epilepsy patients with depression were permitted, and Beck Depression Inventory scores were collected). Three patients were formally diagnosed with Dysthymic Disorder and taking a serotonin reuptake inhibitor. TLE patients were excluded from this study if they had a fullscale IQ below 79. The TLE and normal controls groups were matched for age. A trend was noted toward a difference in education [t(28) = 2.1; p < 0.09]. All partici-
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Case 10 Case 11 Case 12 Case 13 Case 14 Case 15 Intelligence measures BDI
VIQ PIQ FSIQ
15 37 (SD, 10.2) 7 (47%) 8 (53%) 11 (73%) 4 (27%) 12 (80%) 2 (13%) 1 (7%) 13.0 (SD, 1.69) 7 (M, 7.86; SD, 5.9) 8 (M, 34.25; SD, 10.2) Trileptal, 1,200 Zonegran, 100 Keppra, 500 Carbatrol, 1,000 Carbatrol, 900 Topamax, 100 Lamictal, 200 Carbatrol, 200 Keppra, 2,000 Dilantin, 200 Neurontin, 900 Tegretol XR, 400 Phenobarbital, 324 Keppra, 1,000 Klonopin, 3 Dilantin, 300 Keppra, 1000 Zonegran, 400 Topamax, 900 Keppra, 2000 Dilantin, 400 Topamax, 400 Trileptal, 1500 Tegretol XR, 400 Zonegran 100 92 (SD, 13.0) 101 (SD, 11.0) 96 (SD, 12.0) 13.3 (10.0)
Control group 15 35 (SD, 11.3) 5 (33%) 10 (67%) 12 (80%) 3 (20%) 15 (100%) 0 0 15.6 (SD, 3.09)
Topamax, topiramate; Zonegran, zonisamide; Tegretol, carbamazepine; Trileptal, oxcarbazepine; Dilantin, phenytoin; Keppra, levetiracetam; Klonopin, clonazepam; Neurontin, gabapentin; Carbatrol, carbamazepine; Lamictal, lamotrigine; VIQ, verbal IQ; PIQ, performance IQ; FSIQ, full-scale IQ; BDI, Beck Depression Inventory.
pants provided written informed consent and were paid for participation. The study was approved by the Thomas Jefferson University Institutional Review Board for Research with Human Subjects. Materials The words used in this experiment comprised a pool of 141 five-letter nouns of low, medium, and high frequency (49), originally used by Jacoby et al. (50). The task was constructed with the same parameters as Jacoby et al. used (50). The 80 selected words were divided into two sets of words that corresponded to 40 study words and 40 novel words. Each of the two sets was presented under two test conditions: inclusion and exclusion
IMPLICIT AND EXPLICIT MEMORY IN TLE PATIENTS (explained later). Each set of words had an equal distribution of word frequency in the English language (49) and of response pool size (the number of possible five-letter word completions for the stems). To avoid primacy and recency effects, five buffer items were placed at the beginning and end of the list, and these were not included in the analyses. The resulting study list was composed of 50 words (40 study items and 10 buffer items). Procedure The experimental procedure replicated the experimental procedure and design of Jacoby et al. (50). During the learning phase, words were presented one word at a time on a Macintosh computer by using customizable experimental laboratory software (Superlab Pro; Version 1.74, Cedrus Corporation, San Pedro, CA, U.S.A.). The character size of the stimuli was ∼3 × 5 cm, and all were presented in lower case. Words were presented in white letters on a black background in the center of the screen and appeared for 1.5 s, followed by 0.5 s of blank screen. Participants were instructed to read the words aloud and to remember them for a later memory test. In the test phase of the experiment, immediately after the study phase, word stems consisting of the initial three letters of a five-letter word followed by two dashes were presented one stem at a time on the computer screen. The test list consisted of 80 three-letter word stems corresponding to the 40 study words and 40 novel/new words. Word stems were presented in lower-case letters in the center of the computer screen. Each of the three-letter word stems had at least one other word with the same first three letters, but only one of the completions would appear in this experiment (i.e., mer —; mercy, merge, merit, and merry). For each word type (i.e., study list words, the novel/unseen words), half of the stems were chosen randomly to be in the inclusion test condition, and the other half were randomly assigned to the exclusion condition with the number of low-, medium-, and high-frequency words counterbalanced across the two conditions. Last, the order of presentation for the inclusion (40 trials) and exclusion (40 trials) was randomized, allowing a good intermixture of the trials in one large list (80 trials) of word stems. During this test phase, each word stem was preceded by the presentation of either the prompt OLD or the prompt NEW, centered two lines above the word stems in capital letters. The prompt remained on the screen with the word stem until the participant responded or until 15 s had elapsed. The instructions used those of Jacoby et al. (50). Participants were told to use the word stems first as cues for recall of words presented in the previous study list; however, they also were told that recall of a previously identified presented word would not always be possible because some of the stems could be completed only with a novel word. The OLD prompt cued the participant to
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use a recalled word from the study list, whereas the NEW prompt cued the participant to use a novel word as a completion. For the NEW condition, participants were explicitly told not to use a study-list word. Participants also were told that if they could not come up with a novel word for the NEW prompt, they should complete the stems with the first five-letter word that came to mind. After the participant’s response, a key-press removed the word stem from the screen, and a second key-press started the next trial. If participants were unable to provide a response, they were told to attempt a suitable completion for the word stem, given the allotted time (15 s) to do so, and then the next trial was initiated. Participants could not change their response if they realized they responded with an OLD word in the exclusion condition. Each of the successful wordstem completions had to be five letters long, and no plurals or proper names were scored as correct. A graphic depiction of the PDP procedure and the joint contribution that explicit (recollection) or implicit (automatic) memory processes make to various task responses is provided in Fig. 1. Variable construction and statistical analyses Recollection (explicit memory) and automaticity (implicit memory) were calculated for the inclusion and exclusion conditions by using the equations developed by Jacoby (51) (see Appendix A). An independent sample t test was used to compare the epilepsy and control groups on the probability scores for each condition and the Recollection and Automaticity scores. An analysis of variance on Accuracy for the inclusion and exclusion conditions was conducted with Test Condition (inclusion, exclusion) and experimental group (epilepsy patients, normal controls) as the independent variables, with the interaction included in the model. The probability of responding with an OLD word in the inclusion condition is the probability of recollection plus the probability of a word coming automatically to mind. A probability score was calculated after taking the total number of study words given by the participant and then dividing that number by the total possible study-word completions (i.e., 20). In contrast, an OLD word is produced during the exclusion condition when it automatically comes to mind and one is unable to recollect that it was presented earlier. The probability measure for the exclusion condition was calculated in an identical manner. Recollection was estimated by subtracting the probability of completing a stem with a study word in the exclusion condition (i.e., ×/20) from that of completing a stem with a study word during the inclusion condition (i.e., ×/20). A high inclusion score and low exclusion score is associated with a higher probability of recollection. Automaticity was estimated by dividing the number of study list words delivered in the exclusion condition by the failure of recollection (1 minus Recollection). Thus the Epilepsia, Vol. 45, No. 9, 2004
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FIG. 1. Graphic depiction of the process distribution procedure and joint contribution of explicit (recollection) or implicit (automatic) memory processes.
probability of an OLD word originating from an automatic basis of responding is the probability of responding with a study-list word during the exclusion condition divided by the failure of recollection (n.b., memory performance uncontaminated by explicit memory). Last, the probability of correctly solving the 20 novel stems with the NEW prompt during the exclusion condition provided a measure of base-rate word-stem completion skill. RESULTS Proportion of stems completed with OLD words The table presented in Fig. 2 displays the group mean percentage of stems completed with study words (OLD words) in the inclusion and exclusion conditions, along with estimates of recollection and automaticity. Figure 2 also provides a graphic display of this information. Analysis of variance (ANOVA) was run on the proportion of stems completed, using test condition (inclusion or exclusion), study group (patients or controls), and their interaction as terms in the model. The ANOVA revealed a significant Group × Test condition interaction [F(1, 56) = 34.1; p < 0.000], with the epilepsy patients showing a significantly (p < 0.01) reduced proportion completed under the exclusion condition. The t test revealed that the probability of completing stems with studied (OLD) words during the inclusion condition was higher for the controls (M = 0.73) compared with the epilepsy patients (M = 0.57), t (28) = 3.29, p = 0.003. This suggests that when implicit and explicit mechanisms converge, the memory of controls is Epilepsia, Vol. 45, No. 9, 2004
superior to that of the epilepsy patients. The probability of incorrectly completing a stem with a study word during the exclusion condition was higher in the epilepsy group (M = 0.45) compared with the control group (M = 0.22), t (28) = 5.08; p = 0.000. This suggests that implicit memory was intact in the epilepsy group, as words from the study list (OLD words) were expressed successfully, although inappropriately, during the exclusion condition. It is important to note that the error rates used to determine implicit memory may vary as a function of response productivity. That is, individuals skilled at wordstem completion may by chance produce study words during the exclusion condition. Thus baseline rates of performance must be taken into account when examining implicit memory. An independent t test revealed that the groups did not differ statistically in terms of base-rate productivity [controls: mean, 0.75 (SD, 0.16); epilepsy patients: 0.64 [SD, 15)]. A trend in this direction was noted (Controls, M = 0.75; epilepsy patients, M = .64; t (28) = 1.93; p = 0.06). As a precaution, we reevaluated these ANOVAs by using base rate as a covariate. The results were the same with the Group × Test condition interaction significant [F(1, 55) = 35.5; p < 0.000] and the effect for base rate not significant. Measures of recollection and automaticity Estimates of recollection and automaticity were then calculated by using the PDP formulas developed by Jacoby et al. (51), as described in Appendix A. An independent samples t test was performed on the estimates of recollection, revealing a significant effect of group: t (28) = 6.25, p = 0.000 (see Fig. 2B). These findings demonstrate that the probability of conscious and explicit recollection
IMPLICIT AND EXPLICIT MEMORY IN TLE PATIENTS A
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.8 .7 .6 .5 .4 Inclusion
Mean
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FIG. 2. A: Graphic depiction with means data on probability of completing a stem with an “OLD” Word during each test condition. B: Graphic depiction with means data for the estimates of recollection and automaticity.
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was greater for normal controls (M = 0.50) compared with the epilepsy group (M = 0.12). Estimates of automaticity did not reveal a significant difference between the groups, suggesting that implicit memory was equivalent (see Fig. 2B). As precaution, we reevaluated the findings for implicit memory (automaticity) by using base rate as a covariate in an ANOVA that included group as a between-subject factor. This analysis showed the groups did not differ in terms of implicit memory performance (automaticity) even after accounting for potential differences in baseline word-stem performance.
Because of the high comorbidity between depression and epilepsy and the known effect of depression on effortful processes such as explicit retrieval, we examined the relation of our recollection and automaticity variables to depression (Beck Depression Inventory Scores). Neither of these variables was related to depression. DISCUSSION Our goal was to compare implicit and explicit memory in LTLE by using a measure that controls for contamination effects in either form of memory. The results from
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this study corroborate the previous literature on intentional (explicit) influences of memory in LTLE by showing that these patients clearly perform poorly on tasks that tap explicit memory (21–25,52–55). In contrast, performance on our measure of implicit memory, free of contamination from explicit memory effects, was intact and comparable to that of normal controls. Thus despite differences in methodology used, this study leads to the same conclusion as other studies examining implicit memory in these patients (29,35–37). Specifically, the probability of completing stems during the inclusion condition was higher for normal controls, suggesting that when both memory processes converge, the performance of controls is superior. The probability of incorrectly completing a stem with a previously seen word during the exclusion condition was higher for the epilepsy group, suggesting that implicit memory is intact. These findings are reiterated in the measure of conscious recollection, which used relative rates of responding with previously seen words under the different conditions. These data clearly demonstrate higher levels of explicit, intentional memory for normal subjects compared with the patients. The measure of automaticity, which assesses the probability of responding with a study word during the exclusion condition after taking into account the level of conscious recollection, was equivalent in the two groups. This demonstrated that implicit memory was intact in both the healthy controls and the epilepsy patients. Thus our data demonstrate a dissociation between the two forms of memory in epilepsy patients. The data support models indicating that implicit and explicit memory are subserved by separate neural systems (1,12). An explicit learning model, in particular, is compatible with our data because it supports the notion that the hippocampus is important to memory that requires intention and conscious recollection, but is unimportant to memory productions that are implicit and automatic. In terms of the relational memory model, our results do not provide as clear a picture of support. If one sees associative learning present [i.e., the target words with their source (the previously seen list)], then, indeed, explicit memory should be impaired in LTLE patients. However, implicit memory in this situation also should have been impaired. Conversely, if one does not see associative learning present, then the task should not have required the hippocampus, and therefore LTLE should not have disturbed either explicit or implicit memory processes. Explicit memory, because it was disrupted in our patients, appears reliant on mesial temporal structures. On this basis, implicit memory can be said to be nonmesial temporal in nature because of its relative integrity (34). Our data do not specify the nonmesial temporal regions implementing implicit memory; however, they do strongly suggest that these regions are unaltered and unaffected by LTLE. Epilepsia, Vol. 45, No. 9, 2004
When comparing the performance of our epilepsy patients with the pattern of results collected in previous studies using the same inclusion and exclusion measures (50,51,56), we can see that, indeed, our epilepsy patients have reduced explicit memory. Their explicit memory scores were impaired at a level comparable to that in other samples in which experimental manipulations of attention (e.g., divided attention) or individual differences (age) have compromised operation of explicit memory procedures. Perhaps most impressive is that our epilepsy patients also demonstrated levels of implicit memory that were comparable to the levels of implicit memory observed for the normal controls in Jacoby’s studies (56) [mean for divided attention group, 0.46; mean for aged group, 0.46 (51); divided attention, 0.47; aged, 0.46 (50)]. This provides convincing evidence that the patients’ performance on implicit memory was at normative levels and not a product of sampling bias or other study-specific methodologic factors. Our study’s results take into account guessing (false positives during the explicit memory condition) and general word-stem completion skill by measuring base-rate levels of performance. We reexamined the status of implicit memory after accounting for base-rate performance, and the results did not change (i.e., we again found equivalence between the groups). Through other analyses, the potential confounding effects of depression were ruled out in our sample of LTLE patients. We must acknowledge, however, certain limitations arising from our methods and experimental design. For instance, we cannot determine whether conceptual and perceptual cues triggered the automaticity responses evident in our sample, as means of furthering our understanding of the exact nature of the implicit memory system at work in our patients. The possibility exists that the neural system implementing implicit memory is altered in LTLE and that we are observing a duplicate neural system in right temporal cortex or a reorganized system. If such compensation had occurred, then temporal lobe structures may, indeed, be capable of implicit memory. Unfortunately, we did not include right temporal lobe patients in our study to test this possibility. Finally, the PDP procedure has been subject to criticism. For instance, some have questioned the independence assumption (n.b., that automatic and controlled processing operate independently). For instance, Jacoby and Shrout (57) noted that some words may be more familiar and thus easily recollected, providing an avenue by which explicit recollection can be influenced by both voluntary and involuntary automatic influences. As a solution, Jacoby (50) proposed intermixing direct-retrieval instructions with generate–recognize instructions, such as asking the subject always to exclude a word during the exclusion condition if the word appears familiar. We should note that in our study, the frequency-of-occurrence in the English language (49) was counterbalanced across
IMPLICIT AND EXPLICIT MEMORY IN TLE PATIENTS experimental conditions with a mixture of low, moderate, and high frequency, which should have the effect of reducing the role of familiarity in biasing the results. An additional criticism involves the complexity of the PDP exclusion-condition instructions (e.g., subjects may give an old word without realizing it) (58). Other limitations arise from the nature of epilepsy samples. Heterogeneity related to the unique pathophysiology (e.g., tumor, stroke, dysplasia) of the patients’ seizures is a potential contributor to the results, perhaps worsening their explicit memory performance or enhancing their implicit memory performance in unknown ways. The role of specific hippocampal pathologies and extent of effects (e.g., hippocampus, parahippocampus, rhinal cortex) could cause explicit memory failure for very different reasons. Based on our data, we have no access to these individual differences. It also is possible that individual variation in the integrity of temporal cortex and its potential excitatory or inhibitory effects on other neural circuits caused unforeseen and undiscernible disruptions of explicit memory or preservations of implicit memory. Future studies can control for such effects by obtaining a more tightly homogeneous LTLE group. In addition, our data, as noted earlier, in no way address right temporomesial structures and their role in implicit memory, verbal or nonverbal. We should highlight that our patients had exclusive left-temporomesial lesions and were tested before surgery. Thus, it is not clear whether the findings would hold for postsurgical patients. Last, whereas the epilepsy and control groups were matched on important variables such as gender and age, group differences potentially remain in areas such as IQ, as the neurocognitive characteristics of the controls was not well defined (n.b., normal controls were all healthy, well-functioning working adults, and thus no reason exists to suspect that their IQs were in a range below Average or Low Average). The epilepsy patients as a whole demonstrated an average fullscale IQ (i.e., M, 94; SD, 11.0). Nevertheless, future research should address neuropsychological functioning in both groups to eliminate more reliably such rival factors. CONCLUSION This study adds to the growing literature suggesting that explicit memory and implicit memory can be dissociated on both behavioral and neuroanatomic grounds by virtue of the fact that epilepsy patients with known abnormalities in medial temporal lobe structures showed a dissociation on these two memory processes. This dissociation supports the notion that the neural systems implementing these two forms of memory are distinct. In particular, the observed difference in explicit memory was expected and supported by the literature in TLE, based on the well-demonstrated association between explicit memory and mesial temporal lobe integrity. The
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equivalence of the groups on implicit memory adds to the very limited literature on implicit memory in epilepsy, and does so by using a reliable implicit memory measure uncontaminated by the effects of explicit memory. Clearly, continued work with lesion models in humans (i.e., temporal lobe epilepsy patients), can be of theoretical importance to neuroanatomic models of implicit verbal memory. Our study provides evidence that implicit memory is intact in these patients and unaltered by the pathophysiology of their temporal lobe seizures. Although this study cannot specify the neural structures involved in implicit memory, it is clear from this study that they must not be left mesial temporal in nature. A follow-up study with functional MRI will allow us to determine the exact structures involved in the intact implicit memory of these epilepsy patients. APPENDIX A: Process Dissociation Procedure (PDP) Formulas Equation 1 (Probability of OLD Words, Inclusion Condition) • •
Inclusion test score = Number of OLD words from previous list The probability of responding with a previously seen word in the inclusion condition is the probability of recollection plus the probability of a word coming automatically to mind, when a failure of recollection occurs [A (1-R)].
Equation 2 (Probability of OLD Words, Exclusion Condition) • •
Exclusion test score = Number of OLD words from previous list An old word will be produced during the exclusion condition when it automatically comes to mind, and one is unable to recollect that it was presented earlier Equation 3
• •
Recollection = Inclusion test score – Exclusion test score The probability of recollection is the probability of responding with an old word during the inclusion condition minus the probability of responding with an old word during the exclusion condition Equation 4
• •
Automaticity = Exclusion test score (1 – R) The probability of an old word originating from an automatic basis of responding is the probability of responding with an old word during the exclusion condition divided by the failure of recollection Epilepsia, Vol. 45, No. 9, 2004
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