Download Retrograde Amnesia

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Retrograde Amnesia: Forgetting Back
David C. Riccio,1 Paula M. Millin, and Pascale Gisquet-Verrier
Department of Psychology, Kent State University, Kent, Ohio (D.C.R., P.M.M.), and
Laboratoire de Neurobiologie, Université Paris-Sud, Paris, France (P.G.-V.)
Abstract
Recently, the field of animal
memory research has seen a resurgence of interest in the
mechanisms underlying retrograde amnesia (RA) and in the
use of RA as a technique for
studying memory processes. A
recent report from a major
neuroscience lab, which demonstrated RA for an old reactivated memory, revitalized the
debate regarding the widely
accepted memory-consolidation
theory of RA. Here, we discuss
a number of the characteristics
of RA and consider the findings
that led to the development of
the memory-consolidation hypothesis, as well as those suggesting an alternative retrievaldeficit explanation.
Keywords
memory; retrograde amnesia;
consolidation; retrieval deficits
In August of 1997, Princess Diana of Wales and two other people
were killed in a car accident in
Paris. The task of piecing together
the events leading up to the deadly
crash might be less difficult if
Trevor Rees-Jones, the sole survivor of the accident, were able to recall the critical events preceding it.
Rees-Jones’s case is but one wellknown instance of retrograde amnesia (RA), or memory loss for
events occurring prior to a traumatic insult.
RETROGRADE AMNESIA:
CHARACTERISTICS
AND ISSUES
As is typical of RA cases, ReesJones’s memory is intact for all but a
short period before his concussion.
In some extreme cases, RA can extend backward to include events that
occurred hours or days prior to the
trauma, but more commonly, only
those memories most contiguous to
the insult are left inaccessible. The
increased sparing of memories as
they become older is often referred
to as the temporal gradient of RA.
Although concussive brain injury
is a common cause of retrograde
memory loss in human beings, a
diverse inventory of afflictions that
injure the brain can produce RA, including seizure, encephalitis, stroke,
aneurysm, and chronic alcohol
abuse (Kapur, 1999). In animals,
RA can be induced experimentally
by treatments such as electroconvulsive shock (ECS) to the brain,
disruption of basal body temperature, selected brain lesions, and
inhibition of protein synthesis, all
of which disrupt normal brain activity.
Case studies of humans have
provided valuable heuristic hypotheses in memory research, but
as is true with case studies in general, contaminating factors can
pose interpretive difficulties. For
example, might emotionally charged
memories be better retained than
nonaffective memories, and if so,
how would this be reflected in RA
gradients? Furthermore, although
RA appears to extend back for
Copyright © 2003 American Psychological Society
41
years in some cases of brain injury,
evaluating the exact temporal nature of the memory impairment is
difficult. Considerable care and effort have gone into the development of questionnaires that test
memory for recent versus remote
“salient” public events, but even
these assessments may be influenced by education and socioeconomic factors (see Kopelman, 2002).
Indeed, an interpretation of the RA
gradient in many case studies is
confounded by the possibility that
older memories are less susceptible
to amnesia because they have been
rehearsed or repeated more than
newer ones.
It is important, then, that the
time-dependent characteristic of
RA has been observed not only in
human case studies, but also in
highly controlled animal experiments. In a classic experiment by
Duncan (1949), rats were trained to
traverse a gridded runway to avoid
a mild shock to the feet and, depending on the experimental
group to which they were assigned, received ECS to induce
brain seizure at one of several delays following each training trial.
Duncan found that when ECS followed training by a minute or less,
memory for the runway task was
severely impaired; however, as the
delay of ECS increased, the memory loss diminished. Thus, controlled laboratory experimentation
confirmed that susceptibility to
amnesia was inversely related to
the age of the memory.
The temporal gradient of RA
seen in clinical cases as well as in
laboratory research poses a fundamental question: Why is RA characterized by differential memory
loss that varies inversely as a function of the age of the memory? That
new memories are more vulnerable
to amnesia than older memories is
especially surprising given that in
everyday life it is typically older
memories that people have trouble
recalling.
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VOLUME 12, NUMBER 2, APRIL 2003
RETROGRADE AMNESIA AND
CONSOLIDATION THEORY
Because RA is relatively simple to
induce experimentally, and because
of its potential for elucidating memory processes, it became a widely
employed paradigm for investigating the nature of memory storage
and retrieval. The temporal gradient
of RA provided part of the impetus
for the prominent memory-consolidation theory espoused cogently in a
seminal article by McGaugh (1966).
This model built on the earlier physiological speculation of Hebb (1949),
who proposed that the neural circuits activated by a learning episode
continue to “reverberate” for some
period following the experience,
strengthening the neuronal connections necessary for a permanent
memory. According to consolidation theory, the temporal gradient of
RA indicates that memories continue to be processed (or consolidated) for some time following initial learning. If this process is
somehow disrupted, for example,
by a concussive head injury, the
memory fails to be stored, leading to
RA. If enough time passes following
initial acquisition, however, the process of consolidation is thought to be
complete, making the consolidated
memory more or less permanent and
impervious to future disruption.
The popularity of consolidation
theory grew as major laboratories
replicated and extended Duncan’s
findings using a variety of amnestic agents, species, learning tasks,
and intervals between acquisition
and amnestic insult. It seemed that
the consolidation model was an
open-and-shut case.
FINDINGS PROBLEMATIC
FOR CONSOLIDATION
Recent years, however, have
seen a shift away from the tradi-
tional consolidation (storage-disruption) model of RA toward interpretations that focus on retrieval
deficits. Several lines of evidence
have led to this shift. First, there is
a delayed onset in the development of RA, such that memory performance remains intact at short
intervals after the amnestic insult.
In other words, there is a window
of time following the amnestic
insult (minutes to hours) during
which the critical information remains available for recall; forgetting does not occur until some time
later. This finding, initially reported in rats receiving ECS (e.g.,
Miller & Springer, 1971), has a parallel in the observation that rugby
players sustaining momentary concussive head injuries could recall
relevant information immediately,
but became amnestic for the events
an hour or so later (Lynch & Yarnell,
1973). The slow onset of RA can be
accommodated by a consolidation
model that distinguishes between
short-term memory (which remains intact) and the establishment
of long-term memory (which is impaired), although this two-process
view seems strained when the onset of RA is delayed for many hours,
as has been reported.
A second set of findings poses a
more central problem for consolidation. If amnesia treatments prevent storage of long-term memory,
then recovery from RA should not
occur. Indeed, under controlled
laboratory conditions with animals, spontaneous recovery of forgotten memories is a rare exception. Spontaneous “shrinkage” of
amnesia has been reported in humans, but interpretation of this
finding is complicated by the possibility that the patients acquired
the missing information from conversations or other sources but believed they were remembering the
events.
More problematic for the consolidation theory is the phenomenon
of induced recovery. A number of
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laboratory studies have shown that
certain experimental manipulations can reverse or at least partially alleviate RA. In one early and
extensive study by Miller and
Springer (1972), rats were trained
to avoid a compartment associated
with shock. When ECS occurred
shortly after this fear training, subjects readily reentered the chamber, an indication of RA. Substantial recovery from the ECS-induced
RA for the fear response was produced by administering a brief
shock to the foot (the aversive stimulus used in training) as a reminder. The shock was presented
in an apparatus very different from
that used during training. Control
animals receiving only the reminder treatment with no prior
training demonstrated little evidence of fear when tested. This
finding indicates that recovery
from amnesia in the experimental
rats was not attributable to new
learning from the reminder.
Moreover, at least partial reversibility of RA has subsequently been
demonstrated in a number of studies. In addition to presentation of
the reminder shock, effective reminder treatments have included
brief exposure to other components of the training situation.
Even reexposure to the agent used
to induce amnesia can produce
memory recovery. One example of
this seemingly paradoxical outcome is provided in a study that
used whole-body cooling to induce
RA in rats. Animals that were recooled prior to testing showed
much less RA than nonrecooled
control rats (Hinderliter, Webster,
& Riccio, 1975). A similar effect has
been reported for other amnestic
agents.
It is possible, of course, to render the evidence of recovery irrelevant by defining RA as a permanent failure of memory. However,
such a theoretically based definition would seem to beg the question of what the characteristics of
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CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE
amnesia are. At the same time, failures to alleviate RA have been reported, and these cases cannot always be dismissed by retrieval
theorists as due to inadequate reminder cues.
In 1968, a now classic study by
Misanin, Miller, and Lewis provided additional evidence that is
problematic for consolidation.
These authors noted that the age
and activity status of a memory are
generally confounded in that older
memories are typically less active
than newer memories. To unconfound these two variables, Misanin
et al. conditioned rats to associate a
tone with a shock to the foot, and
then 24 hr later reactivated the fear
memory by briefly exposing the
rats to the tone. When this reactivation was followed by ECS, substantial RA for the fear memory was
later observed. Control rats that
had received the same conditioning but whose fear memory had
not been reactivated prior to ECS
showed no RA. Because the memories were the same age in the two
groups, the results indicate that the
activity level of a memory is a critical factor in RA.
This demonstration cast doubt
on the view that only new information is susceptible to RA. If RA
were caused by a disruption of
memory storage, as proposed by
consolidation theorists, then how
could an “old,” presumably well
consolidated (and permanently
stored) memory be rendered amnesic? Because the traditional consolidation view did not include a provision for reconsolidation of a
previously stored memory, other
mechanisms seemed to be implicated.
Several other studies using different techniques were able to replicate the work of Misanin and his
colleagues. Differences as well as
similarities between RA for new
and old (reactivated) memory were
observed (Mactutus, Ferek, George,
& Riccio, 1982). However, the phe-
nomenon of RA for old memory
apparently ran counter to the zeitgeist, because with only a few sporadic exceptions (e.g., Sara, 2000),
the research topic remained in a
state of limbo for nearly 30 years.
A NEW LOOK AT AN
OLD ISSUE
In 2000, the zeitgeist shifted
abruptly with the publication of
several articles that caught the attention of investigators in the neuroscience community. A report by
Nader, Schafe, and LeDoux (2000)
had particular impact. Extending
earlier work from LeDoux’s lab,
which had demonstrated that injection of anisomycin, a protein synthesis inhibitor, into a specific area
of the brain (the amygdala) produced RA for new learning, Nader
et al. found that this treatment also
produced amnesia for memory that
was 1 day or even 2 weeks old. As
was the case in earlier studies
(Mactutus et al., 1982; Misanin et
al., 1968), RA was obtained only if
the old (fear) memory was reactivated by brief exposure to the cue
that had signaled the aversive
event (shock) during training.
Moreover, the memory loss was
time dependent, decreasing as the
interval between memory reactivation and amnestic treatment increased.
This initial study by Nader et al.
was important in at least two very
different ways. First, by using a
highly analytic technique, it implicated a specific area of the brain in
producing amnesia for an earlier
established fear memory. Second,
the report captured the interest and
attention of neuroscientists in a
way that the earlier research by
Misanin and others quite obviously
had not. In the eyes of many investigators, perhaps this finding from
a major neuroscience lab “legitimized” the phenomenon of recon-
Copyright © 2003 American Psychological Society
solidation and made it worthy of
study.
Another finding that contributed to the emerging new zeitgeist
was reported that same year. In
rats, damage to an area of the brain
known as the hippocampus following reactivation of a response acquired 30 days earlier was shown
to produce RA (Land, Bunsey, &
Riccio, 2000). Although this brain
structure has been considered a
sort of holding ground for memory
of events that over time become
stored elsewhere (perhaps in neocortex), Land’s finding suggests
that reprocessing the memory requires the hippocampus.
AN ALTERNATIVE
TO CONSOLIDATION
If this array of findings—delayed
onset of RA, recovery of memory,
and RA for old memory—has been
problematic for a storage-disruption interpretation, can RA be explained in terms of other processes? The basic phenomenon of
temporally graded RA, which fits
so readily with a consolidation
view, seems to be inconsistent with
a retrieval model. However, if retrieval is conceptualized as involving a corresponding relationship
between the conditions at encoding
and at retrieval, as much evidence
suggests, then a resolution may be
found.
One retrieval-based approach is
predicated on the concept of statedependent memory. According to
this view, memory for an event is
disrupted when the internal state
of the organism at the time of retrieval differs substantially from
the internal state of the organism at
the time of encoding. For example,
information a person learns while
under the influence of a drug may
be more difficult to recall when the
drug is no longer present. This notion can be extended to RA by as-
44
suming that information continues
to be processed for some time following a learning event and that an
amnestic treatment induces an unusual state, or internal context
(much like a drug). Thus, a memory processed during an amnestic
state would be difficult to retrieve
later during a nonaltered state. In
short, whereas the consolidation
view posits that RA occurs because
the long-term memory trace fails to
become established, the proposed
retrieval view implies that memory
loss occurs because the information
becomes embedded in a context
that is typically not present later
(Hinderliter et al., 1975).
From this perspective, the temporal gradient of RA reflects the
fact that with increased delays, less
of the information is associated
with the amnestic state and thus retrieval is largely intact (i.e., there is
less state dependency). Moreover,
because the internal state produced
by ECS and other amnestic agents
dissipates slowly, the onset of RA
should be delayed. As long as the
amnesic state lingers, retrieval of
the memory remains intact. RA for
old (reactivated) memory represents not the disruption of reconsolidation but the reencoding of
reactivated information in association with the current internal context (Millin, Moody, & Riccio,
2001).
A counterintuitive finding has
provided additional support for a
modified state-dependent interpretation of RA. As already mentioned, among the cues that can
facilitate recovery from RA is reexposure to the amnestic agent itself
(e.g., Hinderliter et al., 1975). Reinstating the amnestic state restores
critical cues that allow for retrieval
of the memory. Less obviously accounted for is recovery of memory
by reminder treatments involving
components of training (e.g., foot-
VOLUME 12, NUMBER 2, APRIL 2003
shock), although in many cases it
seems likely that the effects of the
reminder and the amnestic event
are both stressful, and thus the internal contexts they produce are
similar, facilitating retrieval.
CONCLUSIONS
The phenomenon of RA provides
a salient example of how assumptions determine the types of questions investigators ask. For example, because many of the more
molecular neuroscientists seem to
assume that the amnestic treatment
eradicates memory, they seldom include a strong test of the reversibility of RA in their experimental designs. The retrieval model described
here has been heuristically useful
but will almost surely prove inadequate. Characterizing and quantifying in more detail both the similarities and the differences between RA
for new and old information, determining the neurophysiological disruptions that are necessary and sufficient to produce these amnesias,
and exploring the possible therapeutic value of inducing amnesia
for old (reactivated) traumatic
memories are among the interesting
issues on the horizon.
Recommended Reading
McGaugh, J.L. (2000). Memory—a
century of consolidation. Science,
287, 248–251.
Riccio, D.C., Moody, E.W., & Millin,
P.M. (2003). Reconsolidation reconsidered. Integrative Physiological &
Behavioral Science, 37, 245–253.
Riccio, D.C., & Richardson, R. (1984).
The status of memory following
experimentally induced amnesias:
Gone, but not forgotten. Physiological Psychology, 12, 59–72.
Spear, N.E., & Riccio, D.C. (1994).
Memory: Phenomena and principles.
Needham Heights, MA: Allyn &
Bacon.
Published by Blackwell Publishing Inc.
Acknowledgments—Preparation of this
manuscript was supported in part by National Institute of Mental Health Grant
MH37535 to D.C.R.
Note
1. Address correspondence to
David C. Riccio, Department of Psychology, Kent State University, Kent,
OH 44242-0001; e-mail: driccio@
kent.edu.
References
Duncan, C.P. (1949). The retroactive effect of electroshock on learning. Journal of Comparative
and Physiological Psychology, 42, 32–44.
Hebb, D.O. (1949). The organization of behavior.
New York: Wiley.
Hinderliter, C.F., Webster, T., & Riccio, D.C.
(1975). Amnesia induced by hypothermia as a
function of treatment-test interval and recooling in rats. Animal Learning and Behavior, 3 ,
257–263.
Kapur, N. (1999). Syndromes of retrograde amnesia: A conceptual and empirical synthesis. Psychological Bulletin, 125, 800–825.
Kopelman, M.D. (2002). Disorders of memory.
Brain, 125, 2152–2190.
Land, C.L., Bunsey, M., & Riccio, D.C. (2000).
Anomalous properties of hippocampal lesioninduced retrograde amnesia. Psychobiology, 28,
476–485.
Lynch, S., & Yarnell, P.R. (1973). Retrograde amnesia and delayed forgetting after concussion.
American Journal of Psychology, 86, 643–645.
Mactutus, C.F., Ferek, J.M., George, C.A., & Riccio,
D.C. (1982). Hypothermia-induced amnesia
for newly acquired and old reactivated memories: Commonalities and distinctions. Physiological Psychology, 10, 79–95.
McGaugh, J.L. (1966). Time-dependent processes
in memory storage. Science, 153, 1351–1358.
Miller, R.R., & Springer, A.D. (1971). Temporal
course of amnesia in rats after electroconvulsive shock. Physiology and Behavior, 6, 229–233.
Miller, R.R., & Springer, A.D. (1972). Induced recovery of memory in rats following electroconvulsive shock. Physiology and Behavior, 8,
645–651.
Millin, P.M., Moody, E.W., & Riccio, D.C. (2001).
Interpretations of retrograde amnesia: Old
problems redux. Nature Reviews Neuroscience,
2, 68–70.
Misanin, J.R., Miller, R.R., & Lewis, D.J. (1968).
Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace. Science, 160, 554–555.
Nader, K., Schafe, G.E., & LeDoux, J.E. (2000). Fear
memories require protein synthesis in the
amygdala for reconsolidation after retrieval.
Nature, 406, 722–726.
Sara, S.J. (2000). Retrieval and reconsolidation: Toward a neurobiology of remembering. Learning and Memory, 7, 73–84.