Download Heightened Interference on Implicit, but Not Explicit, Tests of

BRAIN AND COGNITION
ARTICLE NO.
30, 44–58 (1996)
0004
Heightened Interference on Implicit, but Not Explicit, Tests
of Negative Transfer: Evidence from Patients with
Unilateral Temporal Lobe Lesions
and Normal Old People
GORDON WINOCUR
Rotman Research Institute, Baycrest Centre for Geriatric Care and Trent University,
Toronto, Ontario, Canada
MORRIS MOSCOVITCH
Erindale College, University of Toronto, Ontario, Canada and Rotman Research Institute,
Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
AND
JOSEPH BRUNI
Department of Neurology, Wellesley Hospital, Toronto, Ontario, Canada
The present research investigated alternative explanations of heightened interference in AB-AC learning in individuals with memory loss related to medial temporal
lobe dysfunction. In Experiment 1, patients with left or right temporal lobectomy
and control subjects were administered the standard AB-AC test. Relative to the
other groups, left temporal patients exhibited significant negative transfer that was
characterized by large numbers of response intrusion errors. In Experiment 2, groups
of community-dwelling old and young adults were administered the standard test
and an implicit version in which, during AC testing, subjects were instructed to
provide the first word that comes to mind in response to stimulus words. There
were no differences between groups on either version. Of particular interest was
that both groups made significantly more intrusion errors on the implicit test and
did not differ on this measure. It was concluded that exaggerated interference in
AB-AC learning, as reflected by response intrusion errors, is related to the use of
This research was supported by MRC Grant (MA-6694) to G.W. and M.M. and by a Research Associateship to MM from the Ontario Mental Health Foundation. We thank Lorna
Morris, Robin Green, Lee Smith, and Mary McCauley for their assistance. Address reprint
requests to Gordon Winocur, Baycare Centre for Geriatric Care, the Rotman Research Institute,
3560 Bathurst Street, Toronto M6A 2E1, Canada.
44
0278-2626/96 $18.00
Copyright  1996 by Academic Press, Inc.
All rights of reproduction in any form reserved.
HEIGHTENED INTERFERENCE
45
implicit memory processes rather than a failure of inhibitory mechanisms. Memoryimpaired individuals, who have a selective loss of explicit memory, are vulnerable
on this task because they rely excessively on implicit memory processes.  1996
Academic Press, Inc.
The present research addresses the issue of interference effects in memory
from both a structural and functional perspective. Over a period of years,
we conducted several studies on interference in brain-damaged and aging
populations using a variation of the A-B, A-C negative transfer paradigm
(Winocur, 1982; Winocur & Weiskrantz, 1976; Winocur & Kinsbourne,
1978; Winocur & Moscovitch 1983). In this paradigm, subjects are presented
with a list of semantically related pairs of words (e.g. soldier–battle) for
acquisition during the initial A-B phase of the experiment. After a 20- to
30-min filled interval, they are taught a second A-C list in which a new,
equally related response item, must be associated with the original stimulus
word (e.g. soldier–army). Because memory-disabled individuals can learn
the A-B list, this test provides an opportunity to assess interference effects
in various populations against a background of comparable baseline performance.
Our previous results showed that neurological patients with memory disorders and institutionalized old people were severely impaired in List 2 learning and, in the process, exhibited large numbers of intrusion errors from
List 1. These results provide evidence that susceptibility to interference is
a dominant feature of memory disorders in which there is some known damage or presumed impairment of particular brain regions.
At the functional level, there are two possible interpretations of the interference effects, one relating to a loss of inhibition and the other to a loss of
memory. According to the inhibition hypothesis, our impaired subjects were
unable to suppress previously correct, but currently inappropriate, responses.
The memory hypothesis is based on evidence that conscious recollection
is impaired but non-conscious implicit memory processes are preserved in
amnesia (Cohen & Squire, 1980; Moscovitch, Vriezen, & Goshen-Gottstein,
1993) and normal aging (Moscovitch, 1982; Howard, 1991). Because the
stimulus and response items in our AB-AC paradigm are related, the paradigm can be considered as an implicit conceptual repetition priming test in
which the stimulus items (A) can elicit the response items (B,C). As a result,
performance by our elderly and amnesic subjects on the AB-AC task may
have been driven more by preserved non-conscious implicit processes than
by explicit memory processes, which were impaired (Mayes, Pickering, &
Fairburn, 1987). By this view, it follows that heightened interference in amnesia and aging is linked to the pattern of lost and spared memory functions,
rather than to deficits in inhibition.
The brain region which has been most often implicated in both memory
function and the control of interference is the medial temporal lobe which
46
WINOCUR, MOSCOVITCH, AND BRUNI
includes the hippocampus. Severely amnesic patients, with lesions involving
the medial temporal lobe, were impaired on A-B, A-C learning (Winocur &
Weiskrantz, 1976) and on other tests with a strong interference component
(Warrington and Weiskrantz, 1974). Similar experiments conducted on animals with brain-lesions provide converging evidence that the hippocampal
formation is a critical structure in mediating performance on memory and
high interference tests (Douglas, 1967; Jarrard, 1975; Kimble, 1968; Winocur, 1979).
In this paper we report two experiments that address issues related to brain
mechanisms and cognitive processes that control interference in negative
transfer. In Experiment 1, we tested patients with unilateral temporal lobectomy to determine whether damage restricted to the medial temporal lobe
is sufficient to produce exaggerated interference effects, comparable to those
found in amnesic patients. Experiment 2 was concerned with the functional
question of whether these interference effects are produced by impaired inhibition or are related to increased reliance on implicit memory processes. To
answer this question, we devised an implicit version of the AB-AC test and
administered it to groups of normal young and old people. Greater interference on the implicit than on the explicit version of the test in all our subjects
would support the memory hypothesis.
EXPERIMENT 1
In Experiment 1, we evaluate the importance of the medial temporal lobe
in controlling interference by testing a group of patients with damage to this
region on A-B, A-C learning. All the patients had unilateral surgical excision
of the temporal lobe for control of epilepsy. Because A-B, A-C learning is
a verbal test, it was predicted that only patients with left temporal lobectomy
would be impaired.
Method
Subjects. Eight patients with left temporal lobectomy and 12 with right temporal lobectomy
participated in the study. The characteristics of the patients are presented in Table 1. Only
three patients were not strongly right-handed, as determined by Bryden’s (1977) questionnaire
(2 right-temporal, 1 left-temporal), but all had speech represented in the left hemisphere as
TABLE 1
Age of Temporal Lobe Patients and Their Scores on WAIS-R and WMS Tests
Group
n
Age
V1Q
P1Q
FS
MQ
Right temporal
Left temporal
12
8
29.7 (18–54)
30.9 (26–37)
93.3
94.0
89.8
98.9
92.2
94.6
109.6
90.0
Note. V1Q 5 Verbal IQ, P1Q 5 Performance IQ, FS 5 Full Scale IQ, MQ 5 Memory
Quotient.
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47
determined by the sodium amytal test. Each patient underwent an en bloc resection of the
temporal lobe that included large removal of the pes, parahippocampal gyrus, and the hippocampus. Depending on the patient, the resection extended 5.0 to 8.5 cm along the Sylvian
fissure from the anterior tip. For one patient in the right-temporal group, the excision extended
into the right inferior frontal gyrus. She was included in the study because her performance
resembled that of the other right-temporal patients.
The WAIS-R was administered to all patients. In five cases, absolute scores were not available but only the category (e.g., low normal). In such instances, we chose the middle of the
category range as the score. Testing in all patients was conducted between 2 months and 5
years postsurgery.
The control group consisted of nine normal young adults recruited from a subject pool of
non-university, community volunteers. Their average age of 29.6 years (range 20–40) was
not significantly different from that of the temporal lobectomy patients.
Materials. Two lists of 12 paired–associate words were prepared with the same stimulus
words but different response words. The lists were the same as those used in previous studies
involving normal old people (e.g., Winocur & Moscovitch, 1983) and brain-damaged populations (e.g., Winocur & Weiskrantz, 1976). Each word was printed in large black letters on a
blank 3 3 5″ index card. The two lists consisted of 12 triads of high frequency words drawn
from the A or AA categories of the Thorndike-Lorge (1944) word counts. Each pair of words
was closely linked on the basis of their common semantic characteristics (e.g., List 1: army–
soldier: List 2: army–battle). Three versions of each list were prepared with the pairs arranged
in different sequences to discourage rote order memorization.
Procedure. The procedure was similar to that followed by Winocur and Moscovitch (1983).
Subjects were given four study trials of List 1 with instructions to read aloud each pair and
try to associate the words. They were told that, after four presentations of the list, they will
be given the first word of each pair and asked to provide the second word. The pairs were
presented at the rate of one pair every 2 sec, with 60 sec elapsing between versions. These
periods were filled with conversation unrelated to the test. Recall of List 1 response words
was tested 60 sec after the fourth presentation. For the recall test, each stimulus word (A)
was presented for 10 sec, or until the person responded, after which the correct response
(B) was always provided. Following List 1 recall, the subject was offered coffee and engaged
in distracting conversation for approximately 20 min.
The 12 pairs of List 2 words were presented once only followed by a series of trials in
which subjects were to provide the new response words for the same stimuli as in List 1. No
advance information was provided about the types of words or their relationship to List 1.
During the study trial, the pairs were shown at a 2-sec rate, but in the test trials subjects had
10 sec to respond to each stimulus word (A), after which the correct response (C) was always
provided. Testing was terminated when an errorless list trial was achieved or when four trials
had been administered.
Results
On recall of list 1, the left temporal group made an average of 1.7 errors,
as compared to 0.3 errors by the right temporal group, and 0.2 errors by the
control group. It should be noted that of the total of 13 errors made by the left
temporal group, five were committed by one patient. The group difference,
although small in absolute terms, was statistically significant, F(2, 26) 5
5.96, p , .01.
The results for List 2 performance in Experiment 1 are presented in Table
2. Patients with left temporal lobectomy, however, were markedly impaired
on all aspects of negative transfer on List 2, whereas the performance of
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WINOCUR, MOSCOVITCH, AND BRUNI
TABLE 2
List 2 Performance as Measured by Mean Trials to Criterion and Mean Total Errors and
Errors Categorized as Omission, Response Intrusion from List 1, and Extra-List Intrusion in
Normal Control Subjects and in Patients with Unilateral Temporal-Lobe Lesions.
Group
n
Trials to
criterion
Total
errors
Omission
Response
intrusion
Extra-list
intrusion
Control
Right temporal
Left temporal
9
12
8
1.9
1.8
3.9
1.3
1.5
11.8
0.4
0.8
3.4
0.6
0.4
7.0
0.3
0.3
1.4
patients with right temporal lobectomy was indistinguishable from that of
normal control subjects. This impression was confirmed by separate one factor analyses of variance on the various measures of List 2 learning. Significant differences were obtained in the total number of errors F(2, 26) 5 43.97,
p , .0001; MS 5 308.65, and in trials to criterion F(2, 26) 5 22.85, p ,
.0001; MS 5 11.80. Of the eight left temporal patients, five failed to reach
criterion and the remainder required the maximum four trials. All the right
temporal lobectomy patients and normal control subjects reached criterion
with only one right temporal patient requiring the allotted four trials.
The errors were categorized into omission errors, response intrusions from
List 1, and extra-list intrusions. Significant differences were found in omission errors, F(2, 26) 5 3.75, p , .04; MS 5 22.24; response intrusions, F(2,
26) 5 23.05, p 5 .0001; MS 5 123.33; and extra-list intrusions, F(2, 26)
5 20.98, p , .0001; MS 5 59.04. It is noteworthy that the extra-list intrusion
errors were semantically related to the stimulus word. On all measures, the
left temporal patients performed worse than the other two groups (Scheffe
F test, p , .01 or greater), which did not differ significantly from each other.
The number and type of errors made by the left temporal group during
List 2 learning were unrelated to the group’s performance on List 1. If anything, there was a slight tendency for the five subjects who made zero or
one error on List 1 to make more response intrusion and extra-list intrusion
errors than the other three subjects.
Discussion
The present results clearly indicate that lesions of the left medial temporal
cortex produced severe deficits on all measures of negative transfer. Right
temporal lobe lesions produced no effect, indicating a striking functional
asymmetry between the left and right temporal lobes, as predicted, given the
verbal nature of our AB-AC task. This result is consistent with reports of
similar asymmetries following temporal lobectomy on a variety of other verbal memory tests (Milner, 1974). The present findings indicate that lesions
restricted to the left medial temporal lobe are sufficient to produce the type
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49
of heightened interference previously observed in amnesic patients and institutionalized old people. It is important to emphasize that the results do not
rule out the possibility that other brain regions, notably the frontal lobes,
may also be implicated in controlling interference (Luria, 1971; Shimamura,
in press).
Having established that left medial temporal lobe lesions produce increased interference, we turn to a consideration of the processes that may
have been disrupted. It was suggested in the Introduction that performance
by normal subjects on the AB-AC test reflects a form of conceptual repetition
priming in addition to conscious recollection of the learned associations. In
standard tests of conceptual priming, subjects study a list of items which they
later reproduce in response to a semantically related cue without conscious
reference to the study episode. In our task, having studied the associated
pairs in List 1, subjects then responded with a word that was conceptually
related to the stimulus item at test. Unlike normal subjects, patients with
impaired memory may have relied primarily on implicit processes in responding to the stimulus at test. When there were no competing responses,
as in List 1 learning, conceptual repetition priming may have been sufficient
to compensate for explicit memory loss and lead to normal performance in
our patients. When there were strong competing responses, as in List 2 learning, reliance on conceptual priming was detrimental to performance. Patients
often responded with the associated item that had been primed most strongly,
namely, the List 1 item which was presented four times as compared to the
List 2 item which had been presented only once. There may also have been
an effect of prior entry, which may have contributed to the lasting dominance
of List 1 over List 2 priming (Schacter, Moscovitch, Tulving, McLachlan, &
Freedman, 1986). In contrast, normal people, with intact medial temporal
lobes, could overcome the detrimental effects of priming by consciously recollecting the item they had previously studied rather than responding with
the first word that came to mind.
The data from Experiment 1 could also be interpreted in terms of an inhibitory hypothesis. According to such an hypothesis, the large number of List
1 intrusion errors made by left medial temporal patients resulted from a failure of inhibitory processes that normally suppress inappropriate responses.
By this view, it is immaterial whether responses are tied to implicit or explicit
memory. Rather, it emphasizes the role of a central inhibitory mechanism
in controlling response selection across all domains (Shimamura et al., 1991;
Moscovitch, 1992).
To test the alternative hypotheses, for Experiment 2 we devised a more
purely implicit version of A-B, A-C learning and administered it to normal
young and old adults. If the memory interpretation is correct, the performance of both groups should resemble that of patients with left medial temporal lobe lesions. That is, the number of intrusion errors they make in the
List 2 condition should increase and the number of List 2 responses decrease
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WINOCUR, MOSCOVITCH, AND BRUNI
in relation to performance on the nominally explicit version of the test. However, if the inhibition hypothesis is correct, the young subjects should perform normally but the older adults should show a disproportionate number
of intrusion errors (Winocur, 1982; Hasher & Zacks, 1988).
EXPERIMENT 2
For this experiment, we devised a version of A-B, A-C negative transfer
that was similar to Mayes et al.’s (1987) test in emphasizing the implicit
component. This was accomplished by converting a nominally explicit test
to a nominally implicit conceptual repetition priming test. In the implicit
version, the crucial change was introduced in the test phase of List 2. Subjects
were asked to produce the first word that came to mind in response to the
stimulus word rather than recollect the appropriate response word from List
2. We administered both the implicit and explicit versions of the test to
groups of normal young and old people whose memory was equivalent to
that of the control subjects in the previous study. The memory hypothesis,
in contrast to the inhibition hypothesis, predicts strong interference effects
only on the implicit version of the test, even in young people.
Method
Subjects. Forty-eight people, divided equally into young and old groups, participated in
Experiment 2. The young subjects, were undergraduates at Erindale College, University of
Toronto, and had an average age of 20.9 years and 14.5 years of education. The old adults,
part of a subject pool of senior volunteers, had an average age of 71.6 years and 15.8 years
of education. The mean scores of the elderly and young adult subjects on the Mill Hill Vocabulary Test were 17.0 and 14.4, respectively.
Materials. Three equivalent lists of related word pairs were constructed. Each list consisted
of 12 stimulus words each of which were paired with two associates (AB, AC). For each
stimulus word, the two associates were chosen such that they had approximately equal response
rates on word association norms (Postman & Keppel, 1970). Word pairs were moderately
highly associated in the word norms (e.g., eat–drink, food; music–sound, note). Within each
list, the associate with the higher response rate in the word pairs was the AB associate in half
the pairs and the AC associate in the other half. Assignment to one of the three lists, as well
as to the AB or AC portion of any single list, was random. The stimulus words of the other
two lists appeared at test and served to provide baseline measures.
With a couple of exceptions, both the stimulus and response words had a high frequency
(A, AA) of occurrence according to Thorndike and Lorge (1944).
Procedure. The young and old adults each were subdivided into groups of 12 and assigned
to either the explicit or the implicit test condition. Within each group, subjects studied one
of the three lists.
The study phase was identical for the explicit and implicit tests. Pairs of words were presented at a rate of one pair every 2 sec, with 60 sec elapsing between list presentations. Subjects
were told to read the words aloud and to attempt to remember them by associating the words
with one another. To achieve equivalent baselines of near-perfect List 1 learning, the procedure
was repeated twice for the young adults and three times for the old adults. The order of word
pairs varied across presentations. After the final presentation, the subjects were engaged in
distracting conversation for 1 min to prevent rehearsal. Memory for the AB pairs was then
51
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tested by presenting an index card with the stimulus word and subjects had 10 sec to respond.
The experimenter provided the correct response if the subject failed to produce any response
or responded incorrectly.
After a 20- to 30-min delay filled with irrelevant, non-verbal tasks, the AC word pairs were
presented once and the subjects were again told to try to remember them. Following a 1-min
delay filled with conversation, the test phase began.
In the explicit test, subjects were again shown each of the 12 stimulus words (A) on a card,
and they were asked to provide the new response word (C). In the implicit test, subjects were
shown a list of 96 words in one of two orders randomized across subjects. Each word was
presented separately on an index card, and subjects were asked to freely associate and supply
the first word that came to mind. They were encouraged to respond quickly. To reduce further
the possibility that subjects would intentionally retrieve the responses they had learned, they
were led to believe that this task was merely a distractor prior to the memory test. They were
told that information they supplied would serve as norms for another experiment.
Two orders of presentation of the 96 words were used. Of these words, 12 were targets,
24 were stimulus words from the other two lists, and the remainder were lures that were
unrelated to the targets. The subjects’ responses to the 24 stimulus words from the other lists
provided baseline response rates against which learning and priming could be compared.
Results
There were no differences between groups in list 1 (AB) learning. Nine
of the 12 old and 11/12 young subjects obtained perfect scores and the remainder made one error each.
To determine baserates for the implicit test, responses to stimulus items
from the two non-studied lists were scored as either B or C if they corresponded to the nominal response items on those lists. Baserates of B and C
responses to each of list were analyzed separately by ANOVA for each response in young and old subjects. Because no significant differences were
obtained in any of the tests, the values were collapsed across the three lists
to provide one baseline measure for each associate, B or C, for each age
group. The baseline rates are given in Table 3. As a correction for guessing,
these baserates were then subtracted from the number of correct responses
for each subject in each condition. These corrected values were then entered
into subsequent analyses.
TABLE 3
Mean Number of Correct (C) Responses (List 2) and Prior (List 1)
Intrusions (B) Corrected for Guessing on Explicit and Implicit
Versions of A-B, A-C Negative Transfer
Explicit
Implicit
Baserates
Group
C
(Correct)
B
(Intrusion)
C
(Correct)
B
(Intrusion)
C
B
Young
Old
9.83
9.00
1.58
2.08
4.33
4.83
3.83
2.92
1.61
1.00
1.40
1.13
Note. Baserates represent guessing rate in each condition.
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WINOCUR, MOSCOVITCH, AND BRUNI
As predicted by the memory hypothesis, List 1 intrusions in the test phase
of List 2, were much greater in the implicit than in the explicit version of
A-B, A-C learning (see Table 3). There were no noticeable differences between the performance of young and old subjects. These impressions were
confirmed by ANOVA with group (old vs. young) and test-version (explicit
vs. implicit) as between-subject factors and response-type (B vs C) as a
within-subject factor. There were significant main effects of test-version,
F(1, 44) 5 28.64, p , .0001; MS 5 65.01; response-type, F(1, 44) 5 27.17,
p , .0001; MS 5 236.25; and a significant interaction between test-version
by response-type, F(1, 44) 5 53.34, p , .0001; MS 5 463.76. The significant
interaction is due to a larger number of correct (C) responses on the explicit
than the implicit version and the greater number of intrusions (B) on the
implicit version.
Note that in the implicit tests significant priming effects above baseline
performance were obtained for both B and C responses in young and old
subjects on both lists. T-tests were conducted for each response type in each
age group. In all cases, t(11) . 2.45 p , .01.
Discussion
When subjects were instructed to produce the first word that came to mind,
significant priming effects for List 1 and List 2 responses were observed in
the test phase of List 2. These results indicate that when the negative transfer
task is modified to emphasize implicit processes, it becomes an effective
test of conceptual repetition priming. Under such circumstances, interference
effects in old and young people were increased over and above those observed in the standard version of the test. This confirms similar results obtained by Mayes et al. (1987) and provides clear support for the memory
hypothesis.
Our demonstration of increased interference effects in an implicit test of
memory, in comparison to its explicit counterpart, appears to conflict with
Graf and Schacter’s (1987) report of effects in the opposite direction. Although there are numerous differences between their study and ours that may
account for the discrepancy, two in particular should be emphasized. One
relates to the degree of association between the word pairs—ours were
highly related, whereas theirs were randomly associated. Another crucial difference is that theirs was a repetition priming test in which the first three
letters of the response word served as a perceptual cue to complete the word.
In our test, the stimulus word served as a semantic cue for the primed response. Taken together, these points suggest that because the words were
unrelated in Graf and Schacter’s test, the weight of the priming effect falls
on the perceptual features of the response item rather than on the semantic
association between the common stimulus word and the two competing responses. In our test, however, the stimulus word is highly related to both
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53
competing responses, increasing the likelihood of interference effects. This
is especially the case given that no perceptual cues were provided to direct
the response.
Our finding of heightened interference in the implicit version of the negative transfer test supports the hypothesis that on the standard version of the
test, the implicit component contributes substantially to the interference effect. Normal people show little interference because of their ability to use
explicit memory processes to differentiate between competing responses.
When these explicit memory processes are impaired, as they are in people
with memory disorders, performance reflects the greater contribution of the
implicit component and leads to heightened interference. As our results
show, comparable interference effects can be obtained in people with intact
memory when they are directed to rely on the implicit component in the
negative transfer test. These results are not consistent with the inhibitory
hypothesis, which does not predict differences in interference between explicit and implicit versions of the AB-AC test.
It is worth noting that the performance of the old people was statistically
indistinguishable from that of the young people on both the explicit and
implicit versions of the test. These results are consistent with our earlier
report that high-functioning, community-dwelling old people performed well
on the negative transfer test (Winocur & Moscovitch, 1983). If response
disinhibition were the cause of interference effects, elderly subjects, whose
inhibitory processes are believed to be deficient (Hasher & Zacks, 1988),
would have shown more intrusions than young subjects on both versions.
Interestingly, the performance of the community old people contrasts with
that of some institutionalized elderly people who, despite normal intelligence, show heightened interference effects and severe memory impairment
related to medial temporal lobe dysfunction (Winocur, 1982; Winocur &
Moscovitch, 1983).
GENERAL DISCUSSION
The principal finding of the first experiment was that left temporal lobectomy that involves large removal of the hippocampus greatly exacerbates
interference in a verbal, negative transfer test. The second experiment
showed that comparable interference effects can be obtained in normal people on an implicit version of the negative transfer test. The latter result suggests that the increased interference that patients with medial temporal/hippocampal lesions experience on verbal memory tests is related to impaired
explicit memory and greater reliance on implicit memory processes. The
hypothesis that memory loss, rather than impaired inhibition, is the primary
cause of interference effects following medial temporal/hippocampal lesions
is consistent with other evidence from the human and animal literatures,
which we now review briefly.
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WINOCUR, MOSCOVITCH, AND BRUNI
Increased interference effects have been widely associated with damage
to the hippocampus, a critical structure in the medial temporal lobe. In humans, these effects are expressed in various forms, such as, intrusion errors
in list learning, difficulties in reversal learning, deficits on verbal and nonverbal versions of the Brown-Peterson test, and susceptibility to distractors
on recognition memory tests. Studies involving animals have also provided
numerous examples of interference effects in a variety of paradigms (see
Winocur, 1982; Smith, 1989).
In both the human and animal literatures, these interference effects have
often been attributed to a loss of behavioural inhibition (Douglas 1967; Gray
1982; Kimble, 1968). The hypothesis that a loss of inhibition is fundamental
to the hippocampal deficit has been challenged by evidence that behaviour
is normal in some tasks that require inhibition of inappropriate responses.
In both human and animal studies, the primary problem seems to involve
poor memory for the appropriate cue-response association rather than inhibition of the inappropriate response. When the appropriate salient retrieval cues
are reinstated to serve as an aid to memory, there are numerous examples to
indicate that interference is reduced or eliminated. In the animal literature,
a paradigmatic example of a task that requires response inhibition is passive
avoidance learning in a runway situation. In the standard test, rats learn to
approach a goal box at the end of the runway for reward. When shock is
later introduced in the goal box, normal rats readily learn to suppress the
approach response. In contrast, rats with hippocampal lesions continue to
approach the goal box. To test the idea that it is their poor memory for
response consequences, rather than response inhibition per se, that accounts
for their abnormal behavior, Winocur and Black (1975) provided rats with
a reminder by reinstating the goal box cues prior to test. This reminder was
sufficient to induce normal performance in hippocampal rats. If increased
interference were caused by a damage to a hippocampal-inhibitory mechanism, the lesioned animals should have continued to emit inappropriate responses even in the presence of reminder cues.
Similarly, our research with memory-impaired humans has shown that
providing salient contextual cues on various tasks can reduce interference
effects and improve the level of performance in amnesics and institutionalized old people with poor memory. For example, interference on the A-B, AC task was substantially reduced when contextual environmental cues were
provided to remind subjects that one list is distinguishable from the other
(Winocur & Moscovitch, 1983; Winocur & Kinsbourne, 1978; Kinsbourne &
Winocur, 1980, see also Mayes, 1988).
These results suggest that an important function of the hippocampus is to
create distinctive memories that do not interfere with each other, as can happen with (implicit) memories mediated by non-hippocampal structures. The
idea that the hippocampus is necessary for reducing interference in learning
and memory has been incorporated into recent connectionist neural network
HEIGHTENED INTERFERENCE
55
models. A number of investigators have shown that catastrophic interference
results if sequential learning is dependent on only a single, connectionist
network that allows for cross-talk, i.e., extensive cross-referencing due to
multiple, common associations (McCloskey & Cohen, 1989; Ratcliffe,
1990). McClelland, McNaughton, and O’Reilly, (1995), however, have
shown that this type of interference can be minimized by introducing a second network that forms distinctive independent memory representations
whose information can be incorporated slowly into old, stored knowledge
in the first network. McClelland et al. likened the second network to the
hippocampus, which can form distinctive memories that are consolidated
over time into cortex and stored as knowledge. It is not necessary to agree
with McClelland et al.’s equating of memory with knowledge to appreciate
that their model captures an important aspect of hippocampal function and
its contribution to memory formation.
It is important to emphasize that the memory interpretation does not rule
out inhibition as part of the process of reducing interference. According to
our view, inhibition of inappropriate responses may be initiated only when
the relevant explicit memory has been recovered. The essential point is that
an inhibitory mechanism is not necessarily compromised in individuals with
medial temporal lobe damage. Rather, failure of inhibition is secondary to
their loss of explicit memory.
Although the focus of this paper is on the medial temporal lobe/hippocampal region, other brain structures have been implicated in reducing interference. Among these structures, the frontal lobes figure most prominently (Luria, 1971; Moscovitch, 1982). Evidence that frontal-lobe damage is
associated with perseveration (Mishkin, 1964; Milner, 1964) as well as with
distraction by irrelevant stimuli suggests that the frontal lobes are fundamentally involved in the inhibitory control of behaviour (Shimamura, Janowsky, & Squire, 1991; Stuss & Benson, 1986).
The effects of frontal lobe lesions on AB-AC learning have been examined
in two published studies. Shimamura et al. (1995) reported a deficit in List
2 learning in a group of patients with unilateral frontal lobe lesions (four
left, two right). The deficits in these patients were milder than in our lefttemporal lobe patients, even though, on average, their patients were 35 years
older than ours. In addition, response intrusions accounted for only 25% of
the frontal lobe patients’ errors, as opposed to over 60% of the left temporal
patients errors.
In a second study, Van der Linden, Bruyer, Roland, and Schil (1993) examined A-B, A-C learning in patients with aneurysm of the anterior communicating artery (ACoA). Such patients frequently sustain damage to the ventromedial frontal cortex as well as to structures in the basal forebrain and
striatum. Although Van der Linden et al.’s patients showed heightened interference effects on A-C learning, there were no significant correlations between performance on negative transfer and performance on standard tests
56
WINOCUR, MOSCOVITCH, AND BRUNI
of frontal function (e.g., WCST, verbal fluency and Stroop). A possible interpretation of their results is that non-frontal structures are critical for AB-AC
learning, whereas frontal-lobe involvement is minimal.
An alternative interpretation is that the ventro-medial regions of the frontal
lobes may be involved in AB-AC learning and that other frontal-lobe regions
mediate performance on standard tests. Unpublished data from our laboratory on two patients with confirmed lesions in the ventro-medial frontal cortex argue against this interpretation. Both patients scored normally on all
aspects of AB-AC learning, despite poor performance on WCST and verbal
fluency.
In addition to these patients, we have tested nine patients with unilateral
and three with bilateral frontal lesions on the AB-AC test. The bilateral patients exhibited severe memory loss and poor List 2 learning. In contrast,
the unilateral patients had minimal memory loss and, with one exception,
experienced little difficulty with the task.
Taken together, the evidence suggests some frontal lobe involvement in
AB-AC learning. It would appear that unilateral right or left lesions produce
a milder deficit and one involving fewer response intrusions than that seen
following left medial temporal lobe lesions. The most severe deficits in List
2 learning tend to occur in patients with bilateral lesions and are frequently
accompanied by global memory loss. Loss of inhibition in frontal-lobe patients may well be a factor in producing heightened interference on the ABAC task. However, the available evidence suggests that the effect of inhibition is small relative to that associated with memory loss following left medial temporal lobe damage.
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