Graham – Semantic dementia
Update
Comment
Semantic dementia:
a challenge to the
multiple-trace theory?
Kim S. Graham
I
n their recent reviews, Nadel and
Moscovitch1–3 challenged the ‘standard’
model of memory consolidation, in
which the hippocampal complex plays a
temporary role in the acquisition and
storage of recent episodic memories4–7.
Instead, Nadel and Moscovitch1 proposed a multiple-trace theory in which
‘consolidation processes last on the order
of decades, or indeed the entire lifetime’
(p. 221), on the basis that retrograde
amnesia in patients with damage to the
hippocampus and related structures is
often long-lasting, extending back in
time for as much as 25–40 years (although see Knowlton and Fanselow8 for
an alternative view). The main aim of this
commentary is to discuss whether neuropsychological data from patients with semantic dementia, who present with focal
atrophy to the inferolateral temporal
neocortex with sparing of the hippocampal complex9 are a challenge to Nadel
and Moscovitch’s multiple-trace theory.
The neuropsychology of semantic
dementia
Patients with semantic dementia, also
called progressive fluent aphasia10, present with problems in producing content words in spontaneous speech and,
as the disorder progresses, in word
comprehension11–16. Detailed neuropsychological studies of patients with
semantic dementia have documented
four main characteristics: (1) a loss of
verbal and non-verbal semantic knowledge about objects, facts, concepts,
people and the meanings of words;
(2) preservation of the phonological
and syntactic aspects of language; (3)
normal non-verbal problem-solving; and
(4) good visual-spatial and perceptual
abilities11–20. Neuroradiological investigations in patients with the syndrome
reveal focal atrophy of the inferolateral
temporal gyri of one or both temporal
lobes, with sparing (at least early in the
disease) of the hippocampi, parahippocampal gyri, and subiculum9,11,12,21–24.
Experimental investigations of longterm memory in semantic dementia have
found a neuropsychological profile
which, in some senses, is complementary
to that seen in amnesic patients. Two
studies, which used the Autobiographical Memory Interview25,26, documented better retrieval of autobiographical memories from the recent
time-period compared with childhood
and early adulthood in patients with
the disease21,27. This data initially suggested that patients with semantic dementia show a reverse temporal gradient on tests of autobiographical
memory, a double dissociation when
compared with data from amnesic patients21. Another, more detailed, study
of autobiographical memory in a single
case of semantic dementia (AM) revealed, however, that the preservation
of recent autobiographical memories is
typically more ‘step-like’ in nature, as
opposed to a genuine temporal gradient. AM was asked to produce detailed
and time-specific autobiographical
memories in response to 15 cue words
which were given in each of four time
periods which spanned the entire of his
life. AM produced significantly more
detailed and time-specific memories
for the most recent two years of his
life, while the majority of his autobiographical memories from the preceding 63 years lacked detail, were not
specific in time and were typically a superficial description of similar events
that had occurred at different times21.
Control subjects showed no significant
difference in performance across the
four time periods.
A similar, striking, ‘step-like’ effect
of time has also been demonstrated on
tests of semantic knowledge: patients
have been found to possess significantly
better factual information about current
celebrities17,27 and recent famous events28
than for people and events from the
more distant past. As for autobiographical memory, patients with semantic dementia show better performance in the
recent past for only a short period of
time, typically spanning the one or two
years prior to testing. Consistent with the
better recall of recent autobiographical
and semantic information on tests of remote memory in the syndrome are findings of preserved non-verbal recognition
memory and good re-learning of vocabulary (Refs 22,29 and Graham et al., unpublished data).
The multiple-trace model of memory
consolidation
In these studies, it has been proposed
that the experimental data from semantic dementia is strong support for
the standard model of memory consolidation, in which the hippocampal complex plays a time-limited role in the acquisition and storage of episodic and
semantic memory4,5,7,17,21,28,30,31. In their
1997 article, however, Nadel and
Moscovitch1 suggest a pertinent alternative explanation for the time-based
effects seen on autobiographical memory tests in the disorder: impaired
strategic retrieval caused by additional
frontal pathology.
According
to
Nadel
and
Moscovitch’s1–3 multiple-trace model,
repeated reinstatement of an event
(dependent upon the hippocampal
complex and neocortex) results in the
formation of multiple memory traces,
which comprise almost all the components of the event, within the hippocampal complex. While this process allows the consolidation of ‘factual’
information into our semantic system,
episodic memories remain dependent
upon continuing interactions between
the hippocampal complex and neocortex. In Nadel and Moscovitch1, the
authors proposed that older memories
are represented by more traces compared to recent memories and that the
number of memory traces is positively
correlated with ease of retrieval (i.e.
older episodic memories should be
easier to retrieve from the hippocampus than recent memories). Given this
point, neurologically normal subjects
(if tested appropriately) should show
better retrieval of older episodic memories compared to those from their more
recent past. With respect to the pattern
of retrograde amnesia typically seen in
amnesic patients, whereby older personal episodes are less affected than
more recent memories, Moscovitch and
Nadel3 suggest that lesion size is a critical factor: as older memories will, in
general, have more memory traces, the
representation of older memories will
comprise greater amounts of the
hippocampus than more recent memories. This proposal predicts that partial
hippocampal lesions will be more likely
to impair recent autobiographical memories compared to older memories and,
furthermore, size of hippocampal lesion
will be positively correlated with the
extent of retrograde amnesia.
Evidence from semantic dementia
Turning now to semantic dementia,
does the multiple-trace model explain
the pattern of remote memory impairment seen on tests of autobiographical
memory in the disease? Given that there
is accruing evidence that the hippocampus is relatively spared early in the
1364-6613/99/$ – see front matter © 1999 Elsevier Science. All rights reserved.
PII: S1364-6613(99)01284-X
Trends in Cognitive Sciences – Vol. 3, No. 3,
March 1999
Kim Graham is at
the MRC Cognition
and Brain Sciences
Unit, 15 Chaucer
Road, Cambridge,
UK CB2 2EF.
tel: +44 1223
355294 ext. 790
fax: +44 1223
359062
e-mail: Kim.Graham
@mrc-cbu.cam.ac.uk
85
Update
Graham – Semantic dementia
Comment
disease9, the multiple-trace model predicts that patients with semantic dementia should show a similar temporal
pattern of performance to control subjects on tests of autobiographical memory: better retrieval of older episodic
memories, which are represented by
more hippocampal traces, compared to
personal events from their more recent
past. Of course, given the progressive
deterioration of the temporal neocortex over the course of the disease, it is
likely that autobiographical memory,
which is reliant upon continuing interactions between the hippocampus and
neocortex, will be impaired in patients
with the disease. The multiple-trace
theory does not predict, however, that
this deficit will be affected by the age
of the memories, over and above that
expected for control subjects. Yet
patients with semantic dementia do
show a striking effect of time, whereby
very recent autobiographical and semantic memories are better preserved
than those from the more distant past.
To explain this result, Nadel and
Moscovitch1 proposed that malfunctioning, or inoperative, frontal processes could affect retrieval of remote
memories more than recent memories
writing that, ‘Indeed, because one can
envisage situations in which recovery
of remote memories requires more
strategic retrieval than recovery of recent memories (i.e. what one did yesterday versus last summer versus the
summer of one’s 14th year), it may be
possible to obtain a temporal gradient
opposite to that observed following
medial temporal lobe lesions. This prediction has recently been supported by
a study of subjects with semantic dementia, typically assumed to involve
frontal–temporal damage’ (p. 224).
While this is a valid proposal, it is
not clear that the striking reverse temporal ‘step-function’ seen in our patients
(for example, AM who showed preservation of autobiographical memories
for the last two years of his life) would
be a necessary consequence of this
type of damage. First, Nadel and
Moscovitch predict that patients with
semantic dementia should show a reverse temporal gradient in autobiographical memory. While this is true
for tests such as the Autobiographical
Memory Interview25, it is not evident
on tasks which measure the integrity
of autobiographical memory for the
whole of a patient’s life21. Second,
given ‘that the number of memory
traces’ favours better recall of older
memories and ‘impaired strategic retrieval’ assists recall of recent memories
in the multiple-trace theory, is it necessarily true that these two ‘opposing’
factors will interact to produce the
‘step-function’ seen in patients with semantic dementia?
Evidence from the frontal variant of
fronto–temporal dementia
Ignoring the theoretical issues concerning malfunctioning retrieval processes
for the moment, one piece of data which
would support Nadel and Moscovitch’s1–3
position would be documentation of a
reverse temporal gradient in patients
with the frontal variant of fronto–
temporal dementia. Hodges and Gurd32
described a 67-year-old man with a sixmonth history of personality change:
having previously been a placid, sociable and responsible man, he became
increasingly disorganised, unmotivated
and started to display poor judgement.
A CT scan at initial presentation revealed mild selective frontal atrophy
with enlargement of the anterior portion of the lateral ventricles bilaterally.
Contrary to Nadel and Moscovitch’s
theory, Hodges and Gurd’s patient
showed no evidence of a reverse temporal gradient on any tests of remote
memory (naming of famous faces, public events and autobiographical memory). The patient’s autobiographical
memories were, ‘rambling responses
that were lacking in specific detail and
were often not time-specific… All the
datable responses (six out of 10) came
from his early life (1930s and 1940s)’
(p. 825). It is clear from this description
of the patient’s performance on the
autobiographical memory test that, (1)
he was impaired compared to control
subjects; and (2) he showed the opposite temporal pattern to that seen in
semantic dementia, with most of his
memories coming from his early life
(1930s and 1940s). While one has to be
cautious in extrapolating from a single
case, in particular because Hodges and
Gurd’s patient showed evidence of a
mild anterograde amnesia which may
have been due to hippocampal damage, the result emphasises that patients with the frontal variant of
fronto–temporal dementia may not
show the same reverse temporal stepfunction that has been consistently
documented in semantic dementia.
Conclusion
While Nadel and Moscovitch1–3 are to
be congratulated for challenging the
validity of the standard model of memory consolidation and suggesting a
compelling alternative, it is not clear
whether the experimental data from
patients with semantic dementia are
consistent with the multiple-trace
theory. In particular, it is difficult to see
how the authors’ ‘strategic retrieval
hypothesis’ can account for the striking
step-function (the preservation of very
recent memories) seen on tests of autobiographical and semantic memory in
patients with the disease. Nor is there,
at least presently, any empirical evidence that patients with the frontal
variant of frontal–temporal dementia
will show a reverse temporal gradient
on tests of autobiographical memory32.
Nadel and Moscovitch1 write that, ‘we
will encourage investigators to reexamine the notion of long-term consolidation and to consider alternatives
that are more biologically and psychologically plausible’ (p. 225). Given that
86
Trends in Cognitive Sciences – Vol. 3, No. 3,
March 1999
the multiple trace theory has to invoke
two separate explanations to justify
the classic Ribot gradient and the
reverse temporal gradient seen in amnesia and semantic dementia respectively, while the standard model of
memory consolidation can account for
both patterns without additional neuropsychological deficits, the latter theory seems to provide (at least for the
present) a more parsimonious explication for neuropsychological deficits of
long-term memory.
Acknowledgements
I would like to thank Mike Page, Adrian Owen,
Jon Simons, Mieke Verfaellie and John Hodges
for comments on this article.
References
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2 Nadel, L. and Moscovitch, M. (1998) Hippocampal contributions to cortical plasticity
Neuropharmacology 37, 431–439
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8 Knowlton, B.J. and Fanselow, M.S. (1998) The
hippocampus,
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memory Curr. Opin. Neurobiol. 8, 293–296
9 Mummery, C.J. et al. (1999) Disrupted
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study J. Int. Neuropsychol. Soc. 2, 511–524
12 Breedin, S.D., Saffran, E.M. and Coslett, H.B.
(1994) Reversal of the concreteness effect in a
patient with semantic dementia Cognit.
Neuropsychol. 11, 617–660
13 Hodges, J.R., Graham, N. and Patterson, K.
(1995) Charting the progression in semantic
dementia: implications for the organisation
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14 Hodges, J.R. et al. (1992) Semantic dementia:
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Graham – Semantic dementia
Update
Comment
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15 Hodges, J.R., Patterson, K. and Tyler, L.K.
(1994) Loss of semantic memory: implications
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TraceLink model, in Neural Modelling in
32 Hodges, J.R. and Gurd, J. (1994) Remote
Brain Disorders (Reggia, J. et al., eds), Elsevier
memory and lexical retrieval in a case of
(in press)
frontal Pick’s disease Arch. Neurol. 51, 821–827
Cognit.
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16 Snowden, J.S., Goulding, P.J. and Neary, D.
(1989)
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Behav.
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17 Hodges, J.R. and Graham, K.S. (1998) A
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person knowledge in semantic dementia:
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semantic dementia:
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implications for the neural organisation of
long-term memory Neuropsychologia 36,
803–825
18 Snowden, J., Griffiths, H. and Neary, D. (1994)
Semantic
dementia:
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Cognit. Neuropsychol. 11, 265–288
19 Snowden, J., Griffiths, H. and Neary, D. (1995)
Autobiographical
experience
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meaning Memory 3, 225–246
20 Snowden, J.S., Neary, D. and Mann, D.M.A.
(1996) Fronto–temporal Lobar Degeneration:
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Aphasia,
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(1997)
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complex and the neocortex in long-term
memory storage: evidence from the study of
semantic dementia and Alzheimer’s disease
Neuropsychology 11, 77–89
22 Graham, K.S., Becker, J.T. and Hodges, J.R.
(1997)
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23 Harasty, J.A. et al. (1996) Quantification of
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24 Hodges, J.R., Garrard, P. and Patterson, K.
(1998) Semantic dementia, in Pick’s Disease
and Pick Complex (Kertesz, A. and Munoz,
D.G., eds), pp. 83–104, John Wiley & Co.
25 Kopelman, M.D., Wilson, B.A. and Baddeley,
A.D. (1990) The Autobiographical Memory
Interview, Thames Valley Test Company
26 Greene, J.D.W., Baddeley, A.D. and Hodges, J.R.
(1995) Autobiographical memory and executive
function in early dementia of Alzheimer type
Neuropsychologia 33, 1647–1670
27 Snowden, J.S., Griffiths, H.L. and Neary, D.
(1996) Semantic–episodic memory interactions
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28 Graham, K.S., Pratt, K.H. and Hodges, J.R.
(1998) A reverse temporal gradient for public
events in a single case of semantic dementia
Neurocase 4, 461–470
29 Graham,
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30 Murre, J.M.J. (1996) A model of amnesia and
consolidation of memory Hippocampus 6,
675–684
31 Graham, K.S., Murre, J.M.J. and Hodges, J.R.
Episodic memory in semantic dementia: a
computational
approach
based
on
the
W
e are indebted to Graham for raising the issue of semantic dementia and
its implications for multiple-trace theory [Graham, K.S. (1999) Semantic dementia: a challenge to the multipletrace theory of memory consolidation?
Trends Cognit. Sci. 3, 85–87]1. Investigating people with semantic dementia
to study hippocampal function and
episodic memory is an innovative departure from the typical strategy of
studying people with amnesia who
have lesions to the medial temporal
lobe and diencephalon. By capitalizing
on the observation that the medial
temporal lobes are spared in the early
to middle stages of semantic dementia,
one can evaluate their contribution to
episodic (and semantic) memory when
the lateral inferotemporal cortex, which
supports semantic memory, is damaged. In their investigations, Graham
and Hodges2 confirmed and extended
Snowden et al’s3 initial observations
that episodic and semantic memories
based on recent experiences are relatively spared in semantic dementia,
whereas remote memories are deteriorated or lost. Graham and Hodges2,4
concluded that these results provided
evidence for traditional consolidation
theory, which states that the medial
temporal lobes or hippocampal complex play only a time-limited role in
memory. By this view, once memories
are consolidated, they are retrieved directly from the neocortex and other
structures in which the memory or engram is represented. Because semantic
dementia results from neocortical degeneration, only these remote, consolidated memories would be lost. More
recent memories would be spared because they had not yet been consolidated and could still be recovered via
the medial temporal lobe structures
that are intact. We believe this interpretation is neither the only, nor the
best, available for data from these intriguing cases.
We recently offered an alternative
to traditional consolidation theory, the
multiple-trace theory5–7, which Graham1
believes fares less well than the traditional view in accounting for the
evidence from semantic dementia. In
order to respond to her criticisms, we
first would like to restate our theory
briefly because we believe that
Graham may have misinterpreted some
aspects of it. For example, Graham
quotes us out of context when she says
we proposed that ‘consolidation processes last on the order of decades, or
indeed the entire lifetime’ (p. 221).
That statement referred not to our theory but to what the traditional theory
would have to conclude based on reports of retrograde amnesia that lasts
decades or even a lifetime. Also, she
refers only to the hippocampus whereas
we explicitly stated that our theory
also includes the adjacent structures in
the medial temporal lobes, all of which
comprises what we called the hippocampal complex.
The multiple-trace theory
According to our theory, during consolidation the neural elements in neocortex and elsewhere mediating a particular conscious experience are bound
into a cohesive unit by the hippocampus and adjacent medial temporal lobe
structures (the hippocampal complex).
The resulting memory trace or engram
consists of a cohesive medial temporalneocortical ensemble. The medial temporal component, which may provide
the spatial context of the experience,
acts as a pointer or index to the neocortical elements needed to provide
the detailed content of the experience.
The medial temporal lobe units are an
integral part of the episodic memory
trace and are needed to recover it as
long as it exists. Over time, as an episodic memory is recovered, it is recoded
so that multiple, related memory traces
are formed and dispersed over wider
areas of the hippocampal complex. Because we believe that semantic memories can be acquired or retained without the medial temporal lobes (see
Ref. 8), we confined our model only to
episodic, autobiographical memories.
By virtue of the multiple-trace
aspect of the model, more extensive lesions to the hippocampal complex are
required to expunge more remote memories that are multiply-represented and
widely distributed. Because each of the
subregions of the hippocampal complex
has a distinct function, and because autobiographical, episodic memories are
multifaceted and rich in detail, it is likely
that each of these subregions is involved
in storing or recovering some aspect of a
remembered experience. Incomplete lesions to the complex will lead to a temporally-graded retrograde amnesia (RA).
Damage to all the subregions, or to those
1364-6613/99/$ – see front matter © 1999 Elsevier Science. All rights reserved.
PII: S1364-6613(99)01290-5
Trends in Cognitive Sciences – Vol. 3, No. 3,
March 1999
M. Moscovitch is at
the Department of
Psychology, University
of Toronto, Toronto,
Canada.
tel: +1 416 785 2500
ext. 3132
fax: +1 416 785 2862
e-mail: momos@
credit.erin.utoronto.ca
L. Nadel is at the
Department of
Psychology, University
of Arizona, AZ, USA.
tel: +1 502 621 7449
fax: +1 520 621 9306
e-mail: nadel@u.
arizona.edu
87