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CHAPTER 10
Memory consolidation, retrograde amnesia, and the
temporal lobe
Toshikatsu ~ u j i i ' . ~
Morris
,
~ o s c o v i t c and
h ~ ~Lynn
~
ade el^.*
' ~ e c t i o nof Neuropsychology, Division of Disability Science, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku,
of Psychology, Erindale College, University of Toronto, Mississauga, ON L5L IC6, Canada,
Sendai 980-8575, Japan. 2~epartment
3 ~ o t m a nResearch Institute, Baycrest Centrefor Geriatric Care, Bathurst Street, Toronto, ON M6A 2EI, Canada, and 4~epartment
of
Psychology and Neural system, Memory and Aging Division. University of Arizona. Tucson, AZ 85721, USA
Introduction
Memory consolidation refers to the idea that neurophysiological processes occurring after the initial
registration of information contribute to the permanent storage of memory (Miiller and Pilzecker,
1900; Burnham, 1903; Glickman, 1961; Squire
and Alvarez, 1995; Nadel and Moscovitch, 1997).
This idea has been supported by the phenomenon
of temporally graded (or temporally limited) retrograde amnesia, in which information acquired recently is more affected than information acquired
longer ago. It is an important, yet open issue at
present, how memory consolidation occurs in the
brain (Murre, 1997).
Retrograde amnesia (RA), the inability to retrieve information acquired prior to the onset of
brain damage, is sometimes extensive enough to
cover a patient's whole lifetime, or sometimes temporally limited. Typically, RA is caused by damage
to the medial temporal lobe, the diencephalon,
and the basal forebrain (Markowitsch, 1995;
O'Connor et al., 1995; Tranel and Damasio, 1995,
Yamadori et al., 1996). As far as the temporal lobe
is concerned, however, RA results from damage
not only to medial temporal regions, but also to
other regions in the temporal lobe with or without
damage to the medial temporal region. To gain a
better understanding of memory consolidation
processes and RA after damage to the temporal
lobe, we will review studies on amnesia after temporal lobe lesions in terms of lesion profile and the
naturelextent of RA.
In this chapter, we first review data on RA after
damage to the temporal lobe in humans (see Conway and Aikatomi, this volume; and Kapur (in
press) for reviews of RA following damage to other
structures). Then, we review the relevant literature
from the study of memory consolidation in animal
models. Finally, we propose a possible model of
memory consolidation based on the data available
to date.
Retrograde amnesia after damage to the temporal
lobe in humans
We examine data from patients with damage primarily in the temporal lobe, focusing on: (1) the
types of memory impaired in RA; (2) the extent of
impaired memory in RA; and (3) the relationship
between the naturelextent of RA and the lesion
profile. We imposed the following restrictions on
*Corresponding author. E-mail: [email protected]
223
our review. First, since patients with unilateral
temporal lobe lesion typically do not show severe
amnesia, we included only patients with bilateral
damage to the temporal lobes. Second, we only included patients whose structural damage was confirmed by CT, MRI, or autopsy. Third, we restricted our review to patients who developed
amnesia with acute or subacute onset, because assessment of the extent of RA is difficult when the
onset of amnesia is unknown, as it often is in degenerative disorders and Korsakoffs syndrome. Finally, we included only those cases which have appeared in the past 20 years, with the exception of
case HM, whose resected areas were recently confirmed by MRI (Corkin et al., 1997).
Conventionally, memory contents have been
fractionated into subtypes, such as episodic, semantic, and non-declarative memory, and more recently, finer distinctions, such as autobiographical
episodes, and autobiographical (personal) semantics have been proposed. Although these distinctions may be useful, the relationship or dependency
between these memory subtypes remains a controversial issue. In descriptions of the nature of RA
in this paper, we refer mainly to the following types
of memory: autobiographical episodes which contain experiential information acquired in a specific
temporal and spatial context, autobiographical semantics which includes personal facts about one's
life, and public knowledge including knowledge of
public events and that of personalities. We deal
concisely with general semantics in the text: general semantics acquired during adult life to the onset
of amnesia (for example, one's professional terms
and new vocabulary) and more basic general semantics acquired during childhood (knowledge
about the world, knowledge of one's own language,
and knowledge about objects, etc.). We will not
deal with procedural memory or priming.
Data are classified basically in terms of lesion
profile. We identified five subtypes with bilateral
damage: to the hippocampus proper (group 1); to
the hippocampal formation without bilateral involvement of other cortex (group 2); to the hippocampal complex without bilateral involvement of
other cortex (group 3); to the hippocampal complex and additional bilateral cortical lesion (group
4); and to the temporal lobes with preservation of
at least one hippocampal complex (group 5). The
hippocampal formation includes the hippocampus
proper (CA fields), the dentate gyrus, and the subicular complex. The hippocampal complex includes the hippocampal formation, and the entorhinal cortex, the perirhinal cortex, and
parahippocampal gyrus.
The relevant studies are summarized in Tables
1-5.
Retrograde amnesia for autobiographical episodes
Fig. 1 shows the estimated extent of RA for autobiographical episodes after various lesion subtypes
(some cases are not included in the figure because
of uncertainty of the extent of RA). If the extent of
RA is noted in the article, it was employed as the
estimated extent of RA; if extent of RA was not
noted clearly, we estimated it using the autobiographical incident schedule (Kopelman et al.,
1990). If a patient had impaired autobiographical
episodes in early adult life and preserved autobiographical episodes in childhood, we assumed 18
years as the preserved duration of autobiographical episodes.
In group 1 (Table l), in two cases whose lesions
were confirmed by autopsy, damage limited to the
hippocampus proper (CA 1 field) caused no or minimal RA for autobiographical episodes (Zola-Morgan et al., 1986; Rempel-Clower et al. 1996). Another case (Kartsounis et al., 1995) showed RA
for autobiographical episodes and autobiographical semantics extending back to his youth,
although the lesion was not confirmed by autopsy,
but specified by MRI. Later studies showed involvement of regions outside the hippocampal
complex, in particular the right thalamus (Kapur
et al., 1999). Most recently, Kapur and Brooks
(1999) reported two cases with RA extending from
about 2 to 10 years. In earlier studies, two cases
with lesion limited to the hippocampus proper confirmed by autopsy were reported (Cummings et
TABLE 1
Retrograde amnesia after damage to bilateral hippocampus propera
Authors (published year)
Age at onset
(years)
RA (autobiographical memory)
Zola-Morgan et al. (1986)
Kartsounis et al. (1995)
52
67
Rempel-Clower et al. (1996) case G D
(see also MacKinnon and Squire,
1989)
Kapur and Brooks (1999) case BE
43
Intact PE and F F
Intact AE (Crovitz)
Impaired AE and AS extending back to Impaired PE for at least 30 years, impaired F F for at least 20 years
his youth (AMI, Crovitz)
Difficult to judge (PE, FF) because of
Intact AE (Crovitz)
poor motivation
Kapur and Brooks (1999) case LC
36
45
RA (public knowledge)
Impaired AE for 2 years, normal AS
(AM11
Impaired AE for a few years
AA
MQ
FIQ VIQ PIQ
Yes
Yes
91
Nd
111
Nd
Nd
99
Nd
111
Yes
85
92
Nd
Nd
Yes
82
128
120
133
Impaired PE for 7 years, probably im- Yes
paired FP for 7 years
Nd
Nd
Nd
Nd
F1
Oc
Pa
Impaired FP for about 10 years
Etiology
Lesion profile
(lesion specification methods)
HP
Zola-Morgan et al. (1986)
Ischemia (autopsy)
Kartsounis et al. (1995)
Ischemic attack with seizure (MRI)
Rempel-Clower et al. (1996) case G D Ischemia (autopsy)
(see also MacKinnon and Squire,
1989)
Kapur and Brooks (1999) case BE
Encephalitis (MRI)
Kapur and Brooks (1999) case LC
Encephalitis (MRI)
R
L
R
H F HC Am T P
FG IT
MT ST
Fv
Others
*
*
*
L
*
R
*
L
*
P
(*I
Abbreviations used inTables 1-5: RA, retrograde amnesia; AA, anterograde amnesia; MQ, memory quotient of the Wechsler Memory Scale (or -Revised); FIQ, full IQ of
the Wechsler Intelligence Scale (or -Revised); VIQ, verbal IQ; PIQ, performance IQ; AE. autobiographical episodes; AS, autobiographical semantics; PE, public events; FF,
famous faces test; FP, famous people test including the Dead or Alive test (Kapur et al., 1989); FN, famous names test; AMI, Autobiographical Memory Interview (Kopelman et al., 1990), Crovitz, Galton-Crovitz method (Crovitz and Schifmann, 1974); Nd, not described; R, right hemisphere; L, left hemisphere; HP, hippocampus proper;
HF, hippocampal formation; HC, hippocampal complex; Am, amygdala; TP, temporal pole; FG, fusiform gyrus; IT, inferior temporal gyrus; MT, middle temporal gyrus;
ST, superior temporal gyrus; Fv, ventromedial frontal region; F1, lateral frontal region; Oc, occipital lobe; Pa, parietal lobe; BFB, basal forebrain; p, partial damage; (*),
probable damage.
a
0\
9
TABLE2
Retrograde amnesia after damage to bilateral hippocampal formationa
\
Authors (published year)
Age at onset
(years)
RA (autobiographical memory)
RA (public knowledge)
Impaired AE for whole life, preserved AS
Schnider et al. (1995)
55
Oxbury et al. (1997)
28
Impaired AE for 10-15 years (on the AMI,
impaired AE and relatively preserved AS
for early adult life)
Impaired AE and borderline AS for early
adult life (AMI)
No detectable impairment (AMI, Crovitz)
Impaired AE and borderline AS for early
adult life (AMI)
Borderline AE and impaired AS for early
adult life (AMI)
Impaired AE for whole life (AMI, Crovitz),
preserved AS (AMI)
Impaired AE and AS for 10 years (on the
AMI, poorly elaborated AE for whole life
and good AS for early adult life)
Eslinger (1998) case PD
40
Hirano and Noguchi (1998)
54
Fujii et al. (1999)
51
~d
99
93
Yes
Nd
91
89
96
Nd
Yes
Nd
117
106
129
Impaired PE and F F for at most 10 years
Nd
Yes
Yes
69
56
98
Nd
117 Nd
Nd
Nd
2.
Nd
Yes
68
91
Nd
Nd
$
Impaired PE for 10 years
Yes
52
94
96
92
Impaired PE and FP for 10 years
Mild 93
89
84
96
s%
Operated for epilepsy and seizure (onset, 13
years; operation 18 years) (Autopsy)
Reed and Squire (1998) case LJ Unknown (MRI)
Eslinger (1998) case MR
Status epilepticus (MRI)
Eslinger (1998) case PD
Encephalitis (MRI)
Hirano and Noguchi (1998)
Encephalitis (MRI)
Fujii et al. (1999)
Encephalitis (MRI)
H F HC Am T P
*
*
*
*
*
I.
-
*
R
L
R
L
R
L
*
*
*
*
*
*
*
*
*
*
*
*
*
.
4
HP
Oxbury et al. (1997)
-
~d
(lesion specification methods)
*
2.
Yes
Lesion profile
Warrington and Duchen (1992) Operated for epilepsy (onset, 25 years; opera- R
tion 54 years) (autopsy)
L
Schnider et al. (1995)
Systemic lupus erythematosus (MRI)
R
r--. -
0
Impaired PE for at least 30 years, impaired
F F for at least 15 years
Impaired FP for 10-15 years
Etiology
" See Table 1 for list of abbreviations.
MQ FIQ VIQ PIQ
3
Warrington and Duchen (1992) 54
Reed and Squire (1998) case LJ 51
Eslinger (1998) case MR
40
AA
*
*
*
*
*
*
FG
IT
MT ST
Fv
F1
Oc
Pa
Others
2
$
a
h
TABLE 3
Retrograde amnesia after damage to bilateral hippocampal complexa
Authors (published year)
Age at onset
(years)
RA (autobiographical memory)
RA (public knowledge)
AA
MQ FIQ VIQ PIQ
Warrington and McCarthy
(1988), McCarthy and Warrington (1992)
~ o n e d et
a al. (1994) case 2
53
Impaired AE at least encompassing entire
adult life, relatively preserved AS
Impaired PE for at least 15 years, Impaired
F F for at least 25 years
Yes
Nd
Nd
128
110
55
Impaired for 5 years (no information about
impaired memory type)
Impaired AE for 25 years (Crovitz)
Yes
70
97
105
87
Impaired PE and F F for 15 years
Yes
89
109 Nd
Nd
Impaired AE for 35 years (Crovitz)
Impaired PE and FF for 25 years
Yes
67
113 Nd
Nd
Impaired AE for whole life (AMI), moderately impaired AS (AMI)
Impaired PE for at least 30 years
Mild 104 94
Rempel-Clower et al. (1996)
54
case LM (see also Beatty et
a]., 1987; MacKinnon and
Squire, 1989)
Rempel-Clower et al. (1996)
64
case WH (see also Salmon et
al. 1988; MacKinnon and
Squire, 1989)
46
Kapur et al. (1996) case SP
Warrington and McCarthy
(1 988), McCarthy and Warrington (1992)
Yoneda et al. (1994) case 2
Rempel-Clower et al. (1996)
case LM
Rempel-Clower et al. (1996)
case WH
Kapur et al. (1996) case SP
Etiology
Lesion profile
(lesion specification methods)
HP
H F HC Am TP
Encephalitis (CT)
R
L
*
*
*
*
+
*
Encephalitis (MRI)
R
L
R
*
*
*
*
*
*
*
*
*
T
*
Epilepsy andlor ischemia (autopsy)
L
Unknown (probable ischemia) (autopsy)
Severe traumatic brain injury (MRI)
" See Table 1 for list of abbreviations.
R
L
R
L
*
*
P
P
*
*
*
FG
IT
MT ST
*
+
*
*
*
*
*
*
*
*
*
P
P
*
*
P
P
Fv
F1
Oc
92
Pa
98
Others
N
N
TABLE4
Retrograde amnesia after damage to bilateral hippocampal complex and additional bilateral cortical lesionsa
Authors (published year)
Age at onset
(years)
Scovile and Milner (1957), Cor- 27
kin (1984), Corkin et al.
(1997)
Cermak and O'Connor (1983), 50
O'Connor et al. (1995)
Damasio et al. (1985a)
55
Tulving et al. (1988), Tulving et 30
al. (1991)
O'Connor et al. (1992)
18
37
Yoneda et al. (1994) case 1
66
Schnider et al. (1994)
Reed and Squire (1998) case EP 70
Reed and Squire (1998) case GT 54
RA (autobiographical memory)
RA (public knowledge)
AA
MQ FIQ VIQ PIQ
Impaired AE for 11 years
Impaired PE and FP
Yes
67
Impaired AE for whole life, AS relatively
preserved
Impaired AE for whole life, AS relatively
preserved
Impaired AE for whole life
Impairment PE and FP for at least 40 years Yes
90
Impaired F F for whole life
Yes
62
Impaired F F
Yes
80
Impaired AE for whole life (Test like AMI, Impaired PE for 5 years
Crovitz), relatively preserved AS (Test like
AMI)
Impaired for 10 years (no information about impaired memory type)
Impaired PE and FP for whole life
Impaired AE for whole life (Interview)
Impairment of AE and AS extending back to Impaired PE and F F for at least 40 years
early adult life (AMI, Crovitz)
Impaired AE (AMI, Crovitz), impaired AS Impaired PE and F F for at least 40 years
for whole life (AMI)
Etiology
Lesion profile
(lesion specification methods)
HP H F HC Am TP FG IT
Scovile and Milner (1957). Cor- Operated for epilepsy (onset, 16 years;
kin (1984), Corkin et al.
operation 27 years) (MRI)
(1997)
Cermak and O'Connor (1983), Encephalitis (CT)
O'Connor et al. (1995)
Encephalitis (CT)
Damasio et al. (1985a,b)
Tulving et al. (1988),Tulving et Severe traumatic brain injury
al. (1991)
O'Connor et al. (1992)
Encephalitis (MRI)
Yoneda et al. (1994) case 1
Schnider et al. (1994)
Encephalitis (MRI)
Infarct (MRI)
R
L
R
*
*
*
*
*
*
(*)
*
*
*
*
*
L * * * * *
R P j l j l
L *
(*I
R
*
*
*
*
L
R *
* jl *
L
*
*
*
*
R
*
*
I.
*
*
*
*
MT ST Fv
(*I
*
(
*
*
(*I *
*
)
*
*
*
*
*
*
*
*
FI
*
*
*
(
*
*
(*I *
*
*
*
*
*
*
Yes
Yes
Yes
72
Nd
61
Yes
150
Oc Pa
Others
B. insula, Basal ganglia,
L. BFB
*
*
Mild 84
*
(*)
**
*
B.insula, anterior cingulate, BFB
L. insula
*
Reed and Squire (1998) case EP Encephalitis (MRI)
Reed and Squire (1998) case GT Encephalitis (MRI)
" See Table 1 for list of abbreviations.
B. insula, cingulate
I
(1)
(2)
(3)
Group
(4)
(5)
Fig. 1. Estimated extent of retrograde amnesia (impaired years) for autobiographical episodes in five subgroups classified by lesion profile. Preserved years is number of years since birth over which memory was normal. Broken line shows an uncertainty of the duration.
al., 1984; Duyckaerts et al., 1985). They appeared
to show temporally limited RA with severe anterograde amnesia, but the precise extent and nature
of RA could not be judged from the descriptions.
In group 2 (Table 2), the extent of RA for autobiographical episodes varied considerably, ranging from no RA (Reed and Squire, 1998) to R A
covering the patient's whole life (Warrington and
Duchen, 1992; Hirano and Noguchi, 1998).The remaining five cases showed RA for 10-22 years. We
do not include two studies in which lesions were
confirmed by autopsy (Woods et al., 1982; Victor
and Agamanolis, 1990), because we could not
judge either the extent of RA or which types of
memory were impaired.
In group 3 (Table 3), the extent of RA was described as 5,25,35, over 35 years, and the patient's
whole life (Warrington and McCarthy, 1988;Yoneda et al., 1994; Kapur et al., 1996; Rempel-Clower
et al., 1996).
In group 4 (Table 4), the extent of RA was more
extensive than in groups 2 and 3. Five out of eight
cases had RA covering their whole life period.
Group 5 (Table 5) consists of many cases reported as isolated or focal RA, i.e. severe retrograde amnesia in combination with relatively mild
or absent anterograde amnesia (see Kapur, 1993,
in press; De Renzi et al., 1997; Fujii et al., 1999).
Estimated RA was extensive in most of the cases,
and sometimes encompassed the patient's whole
W
0
Retrograde amnesia after damage to bilateral temporal lobe lesion with preservation of at least one hippocampal complexa
Authors (published year)
Age at onset RA (autobiographical memory)
(years)
Kapur et al. (1992)
Impaired AE for whole life (Interview,
Crovitz), somewhat impaired AS
Impaired AE for whole life (AMI), less
impaired AS
Impaired AE for early adult life (AMI,
Crovitz), normal AS
Impaired AE for whole life (AMI), Norma1 AS (AMI)
Impaired AE for at least 20-30 years
(AMI, Crovitz), less severely impaired
AS (AMI)
Impaired AE for early adult life (AMI,
Crovitz), impaired AS for whole life
(AM11
Probably impaired AE (difficult to check
because of confabulation), good AS
Impaired AE for whole life except for
early childhood
Impaired AE in childhood and borderline
in early adult life, impaired AS for
whole life (AMI)
Markowitsch et al. (1993)
Kapur et al. (1994)
Kapur et al. (1996) case GR
Calabrese et al. (1996)
Kroll et al. (1997) case AA
Kroll et al. (1997) case BB
Carlesimo et al. (1998)
Eslinger (1998), Eslinger et al.
(1996) case EK
Kapur et al. (1992)
RA (public knowledge)
AA
Impaired PE and FP for whole life
Mild
Impaired F F for 30 years, impaired FN
Mild
Moderately impaired PE and impaired FP Mild
for at least 20 years
Impaired PE, FF, and FN for whole life Mild
Impaired F F for at least 35 years
Mild
Impaired PE and F F for whole life
Mild
Moderately impaired PE and FF for whole Mild
life
Impaired PE for about 10 years
Mild
Impaired PE and FN for at least 30 years, Poor verbal
memory
good for F F
Etiology
Lesion profile
(lesion specification methods)
HP H F HC Am TP FG IT
Severe traumatic brain injury (MRI)
R
P
Severe traumatic brain injury (MRI)
Kapur et al. (1994)
Radiation necrosis (MRI)
Kapur et al. (1996) case GR
Severe traumatic brain injury (MRI)
Calabrese et al. (1996)
Encephalitis (MRI)
Kroll et al. (1997) case AA
Severe traumatic brain injury (MRI)
Kroll et al. (1997) case BB
Severe traumatic brain injury (MRI)
R
L
R
L
R
L
R
L
R
L
R
L
P
P
P
P
P
P
P
P
P
P
P
*
P
MT ST Fv F1
*
*
*
(*I *
(*I
*
*
*
*
* *
(*I *
*
(*)
*
*
*
L
Markowitsch et al. (1993)
MQ FIQ VIQ PIQ
*
*
*
Others
*
*
*
*
+
*
*
*
*
*
*
*
(*I
*
* *
*
*
*
*
*
*
*
*
*
*
*
*
Oc Pa
+
(*)
+
*
L. fornix, anterior perforated substance
Metizory consoliclation,retrogrude un~nesicz,and tlze temporal lobc
C/7. 10
life. The extent of RA for autobiographical episodes in group 5 is somewhat shorter than those in
group 4, but may be related to the mean age of onset, which is younger in group 5 than in group 4.
The same is true of RA for public knowledge,
which will be described later.
Retrograde amnesia for autobiographical semantics
It is difficult to determine the extent of RA for autobiographical semantics because many of the reports provide insufficient descriptions of this kind
of memory. However, in reports that refer to both
autobiographical episodes and autobiographical
semantics, autobiographical semantics tends to be
less impaired than autobiographical episodes (16
out of 22 cases). This tendency does not seem to be
related to lesion profile in any obvious way. Of the
remaining six cases, three showed impaired memory for both autobiographical episodes and autobiographical semantics over the same period. In the
remaining three cases, one showed impaired autobiographical semantics with borderline impairment of autobiographical episodes for early adult
life (case PD in Eslinger, 1998), another case
showed impaired autobiographical semantics for
the whole life period with preserved autobiographical episodes for childhood (case AA in Kroll et
al., 1997); and the last showed impaired autobiographical semantics for the whole life period with
borderline impairment of autobiographical episodes for early adult life (case EK in Eslinger,
1998).
McCarthy and Warrington (1992) pursued this
issue and found that their severely amnesic patient
was able to discriminate familiar acquaintances'
names from unknown names and to provide information about personal acquaintances when presented with their names. This report showed that,
at least in some cases after bilateral damage to the
hippocampal complex, autobiographical semantics
can be shown to be preserved if adequate tests are
used.
former groups showed RA for public knowledge
extending between 10 and 30 years. Two exceptional cases described by Zola-Morgan et al. (1986)
and by Reed and Squire (1998) showed either no
RA or at most a 10-year impairment of public
knowledge with no RA for autobiographical episodes. The cases in groups 4 and 5 tended to show
more extensive RA for public knowledge, ranging
from 5 years to the patient's whole lifetime.
Fig. 3 shows the relationship between the extent
of impaired autobiographical episodes and the extent of impaired public knowledge in the patients
in Tables 1-5 whose deficits were described for
both types of memories. RA for public knowledge
is not as extensive as for autobiographical episodes
Retrograde umnesia for public kno~vledge
(public events and personalities)
Fig. 2 shows the estimated extent of RA for public
knowledge after various lesion subtypes (some
cases are not included in the figure because of uncertainty of the extent of RA). Tests of personalities
include identification from their photographs,
identification from people's names, and occasionally, the Dead or Alive test (Kapur et al., 1989). In
some cases, the precise extent could not be judged
since memory was impaired over the entire period
that was sampled. On the whole, the extent of RA
for public knowledge is shorter for the cases in
groups 1-3 than for those in groups 4 and 5. The
(2)
(3)
Group
(4)
Fig. 2. Estimated extent of RA (impaired years) for public knowledge in five subgroups classified by lesion profile. Preserved years is
number of years since birth over which memory was normal. Broken line shows an uncertainty of the duration.
232
Impaired years of memory for autobiographical episodes
Fig. 3. Relationship between the extent of impaired autobiographical episodes and the extent of impaired public knowledge in amnesic
patients with temporal lobe lesions. The number in each circle designates the group we classified in terms of the lesion profile. Lines
with an arrow show the possible extent of RA. Open circles show cases whose memory for public knowledge was tested for both public
events and personalities. Dotted circles show the cases whose memory for public knowledge was tested only for personalities. Circles
with oblique lines show cases whose memory for public knowledge was tested only for public events.
in some cases and is the same as for autobiographical episodes in others. Cases with medial temporal
lobe lesions (groups 1-4) tended to show less extensive RA for public knowledge than for autobiographical episodes, while cases in group 5 appeared
to have the same extent of RA for both public
knowledge and autobiographical episodes.
Within the realm of public knowledge, the extent
of RA for public events and personalities is similar
in most of the cases in our review. However, the patient reported by McCarthy and Warrington
(1992) and Warrington and McCarthy (1988)
again showed a clear dissociation. Thus, the patient
showed evidence for well-preserved name vocabu-
lary and information about personalities despite
showing no evidence for knowledge of the events
associated with them. Within the domain of knowledge of personalities, one patient (Eslinger et al.,
1996) showed a dissociation in the ability to identify people from names and from photographs, with
the former impaired and the latter preserved. This
case can be thought of as a comprehension deficit
restricted to people's names rather than memory
impairment for personalities.
Though not the focus of this review, we note
briefly some studies of patients with lesions outside
the temporal lobe to underscore the point that
memory for autobiographical episodes and public
knowledge are dissociable one from the other. Dalla Barba et al. (1 990) described a patient with alcoholic Korsakoff syndrome who showed a severe
RA for autobiographical episodes with prominent
confabulation, but preserved knowledge of public
events and famous people. Hodges and McCarthy
(1993) described a patient with both anterograde
and retrograde amnesia after bilateral thalamic infarction. Their patient's knowledge of public
events, and especially of personalities, was surprisingly spared despite a grave deficit of autobiographical memory. Another case (Evans et al.,
1996) showed impaired memory for autobiographical episodes for the entire life though memory of
public events and famous faces was normal. This
case suffered from a rather rare etiology (vasculitis)
and showed marked bilateral atrophy of the frontal
lobe, the left parietal lobe, and the left temporal
pole. An amnesic patient described by Van der Linden et al. (1996) was able to identify famous personalities who became prominent during a period
when the patient had severe RA for autobiographical episodes. His amnesia was caused by bilateral
infarction in the territory of the posterior cerebral
artery resulting from transtentorial herniation.
Unfortunately, it is not clear whether the hippocampal complex is involved or not by descriptions
on CT findings, although his severe anterograde
amnesia suggests the involvement of the medial
temporal lobe or diencephalon bilaterally. Similarly, a patient with transient amnesia reported by
Venneri and Caffarra (1 998) showed a striking dissociation between a detailed knowledge of public
events and famous people and a severe impairment
of autobiographical information. During the attack, EEG showed bilateral frontotemporal slow
wave and SPECT showed hypoperfusion in the
right temporal and parietal lobes. Ross and Hodges
(1997) described a patient, following prolonged
cardiac arrest, whose amnesia was characterized
by severely impaired autobiographical memory
and knowledge of public events with well-preserved
knowledge of famous people. A CT scan was normal.
To sum up, amnesic patients after bilateral tem-
poral lobe lesion showed RA for public events
although the extent of it was shorter than that for
autobiographical episodes in some cases. Most of
the cases also showed RA for personalities, but
this form of memory was preserved in a thoroughly
examined case (Warrington and McCarthy, 1988;
McCarthy and Warrington, 1992). Some amnesic
cases with damage to regions other than the temporal lobe showed preserved memory for public
events and personalities, in contrast to what was
typically observed after temporal lobe lesion.
Retrograde amnesia for general semantics
Unlike the general semantic memory impairment
reported in some cases (Warrington, 1975; Yamadori et al., 1992; Hodges et al., 1994), most of the
patients do not show any apparent impairment of
language, object recognition, and intelligence
measured by WAIS-R (see Tables 1-5). Therefore,
basic semantic knowledge acquired during childhood is preserved. In many studies, however, it is
unclear whether general semantic knowledge acquired during adult life to the onset of amnesia is
preserved or not.
In this respect, Warrington and McCarthy
(1988) reported a postencephalitic patient who retained knowledge of words introduced into the lexicon during the retrograde period for both autobiographical episodes and public events. The
postencephalitic patient (Cermak and O'Connor,
1983) appeared to have intact knowledge about
physics and laser technology (his profession),
though he was amnesic for autobiographical episodes and public knowledge. In contrast, Beatty et
al. (1987) described a case (case LM in RempelClower et al., 1996) who showed impaired knowledge of terms commonly employed in his profession in the past 20 years. During this period, he
showed retrograde amnesia for both autobiographical episodes and public knowledge tapped by public events test and famous faces test as well as periodic grand ma1 seizures.
Preserved or impaired general semantics acquired during adult life to the onset of amnesia
has been demonstrated in patients with other lesions and etiologies. Verfaellie et al. (1995) reported an effect similar to the findings by Warrington and McCarthy (1988) in a group of seven nonKorsakoff amnesic patients with mixed etiologies,
although the severity and extent of their RA for autobiographical episodes and precise anatomical localization of their lesions were not given. Their patients performed normally (not significantly worse
than normal controls) on both recall and recognition tasks regarding memory for words that entered into the vocabulary in the past 25 years. In
contrast, Korsakoff amnesic patients in Verfaellie
et al. (1995) did show a temporally graded RA for
new words. The Korsakoff patient with severe autobiographical episodic impairment described by
Butters and Cermak (1986) also was unable to define professional terms once well known to him.
Preserved memory for autobiographical episodes
along with impairment in other types of memory after
bilateral damage to the temporal lobes
There have been five reports describing patients
who showed preserved autobiographical memory
with impaired semantic memory (De Renzi et al.,
1987; Grossi et al., 1988; Alexander, 1997; Yasuda
et al., 1997; Markowitsch et al., 1999). Among
these reports, cases described by De Renzi et al.
(1987) and by Yasuda, et al. (1997) are worth considering in some detail because these two patients
had bilateral anterior temporal lesions.
De Renzi et al. (1987) reported a postencephalitic patient who displayed a severe impairment of
semantic knowledge including knowledge of public
events and personalities as well as of more general
semantics, such as word meaning and object meaning, despite normal memory for autobiographical
episodes and autobiographical semantics. An
MRI scan showed a wide and irregular area of increased intensity extending over the inferior and
anterior part of the left temporal lobe, involving
the amygdala, the uncus, the hippocampal formation, the parahippocampal gyrus, the anterior part
of the fusiform gyrus, external capsule, and the in-
sular white matter. On the right there were minimal
signs of increased signal density in the white matter
of the inferior temporal lobe. Yasuda, et al. (1997)
described a similar patient following several surgeries and radiation therapy for a meningioma.
The patient showed severe impairment of memory
for public events, personalities, historical figures,
cultural items, knowledge of low frequency words
and technical terms relevant to her profession despite preserved memory for autobiographical episodes and autobiographical semantics. The T2
weighted MRI revealed lesions due to multiple surgeries in the anteroinferior temporal lobe and the
basal frontal lobe in the right hemisphere. Regarding the left hemisphere, the TI weighted MRI with
Gadolinium enhancement showed a lesion in the
anterior half of the middle temporal gyrus with relative sparing of the temporal pole and the posterior
inferior temporal region, although T2 weighted
MRI showed more extensive abnormal signal intensity. Both medial temporal lobe structures
seemed relatively undamaged.
Which lesions are criticalfor emergence of
retrograde amnesia for autobiographical episodes in
cases with preservation of at least one hippocampal
complex?
As shown in Table 5, bilateral damage to the medial temporal is not necessary for severe RA to occur.
If so, damage to which area other than the hippocampal complex is critical for RA in these cases?
Of the nine patients in Table 5, seven had unilateral
involvement of either hippocampal formation or
complex. Their lesions in the opposite hemisphere
were in the temporal pole (6/7), the fusiform gyrus
(2/7), the inferior temporal gyrus (2/7), the middle
temporal gyrus (2/7), the superior temporal gyrus
(1 / 7), ventromedial frontal region (3 / 7), and lateral frontal region (217). One is tempted to conclude
that the damage to the temporal polar region is important for RA in these cases. In the remaining
two cases, one (Markowitsch et al., 1993) had bilateral damage to the temporal pole as well as the
frontal lobe. The other postencephalitic patient
(Carlesimo et al., 1998) showed atypical lesions in
the bilateral white matter in the temporo-occipitoparietal lobes.
In two cases with preserved autobiographical
memory and impaired semantic memory (De
Renzi et al., 1987; Yasuda et al., 1997), it is of interest that their lesions spared both the hippocampal
complex and the temporal pole in either hemisphere.
A recent neuroimaging study using PET confirmed that the temporal pole as well as the hippocampal formation play an important role in retrieving autobiographical episodes (Maguire and
Mummery, 1999). In that study, enhanced activity
was observed for retrieval of autobiographical episodes (i.e. personally relevant, time-specific memories in their conceptualization) in the left hippocampus, medial prefrontal cortex, and temporal
pole. The observation that the temporal polar region is implicated in recovering autobiographical
memories is consistent with Markowitsch's (1995)
proposal that this region plays a central role in
this process by virtue of its rich anatomical connections to a network of memory structures. These include the amygdala and hippocampus in the medial
temporal lobes, the posterior neocortex, the thalamus, and the prefrontal cortex. Markowitsch places particular emphasis on the right temporal polar
region and its connection to the right frontal cortex
via the uncinate fasciculus (see also Levine et al.,
1998). Despite reports that some patients with extensive and dense RA have lesions in the right temporal pole or uncinate fasciculus, it is not yet certain whether the corollary is true: that right
temporal polar lesions produce dense RA. For example, unilateral surgical excisions for the relief of
temporal-lobe epilepsy almost always include the
temporal pole on the affected side, yet reports of
extensive RA in people with right temporal lobectomy are rare, though evidence of moderate remote
memory loss for faces (Warrington and James,
1967) and autobiographical episodes (Viskontas,
MacAndrews and Moscovitch (1999) cited in Moscovitch et al., 1999) has been reported. At the moment, the evidence for the centrality of the tempo-
ral polar region, and in particular the one on the
right, for recovery of autobiographical memory is
certainly provocative, but not conclusive.
Summary of the evidencefrom studies of humans
From the data we have reviewed, several points regarding RA after temporal lobe damage emerge.
(1) Damage to the hippocampus proper does not
necessarily cause RA for both autobiographical
episodes and public knowledge despite always giving rise to anterograde amnesia (Table 1). Firm
conclusions on this point, however, are unwarranted because only a few cases with such lesions
have been reported. In particular, the cases showing a lack of RA had damage restricted to just a
portion (CAI field) of the hippocampus proper. It
remains to be determined what effect damage including, but restricted to, all the CA fields would
have on memory for autobiographical episodes
and public knowledge. The few existing cases suffice to demonstrate that measurable anterograde
amnesia can occur in the absence of any RA, but
only as measured by current tests. The last proviso
is important since recent studies have shown that
when autobiographical memories are scored in
terms of the total number of details provided (Moscovitch and Melo, 1997; Moscovitch et al., 1999),
measurable, and quite extensive RA, is found even
in cases where patients score normally on more traditional tests such as the AM1 (Kopelman et al.,
1990) and the Crovitz test (Crovitz and Schiffman,
1974). Indeed, the results from those studies suggest that amnesic patients retain the gist and major
aspects of autobiographical episodes, but not a
richness of detail that characterizes these memories in normal people (Moscovitch et al., 1999).
(2) If the hippocampal formation or hippocampal complex are damaged bilaterally (Tables 2 and
3), RA for autobiographical episodes can extend
for 10-50 years. In many cases who have additional
bilateral lesions (Table 4), RA encompasses the patient's whole lifetime. Thus, the duration of RA for
autobiographical episodes appears to be related to
the extent of medial temporal lobe damage.
iMmmoy.c~oi7.solidrrtior~,
~.ctr.ogr.ucleut7zi7c~.sin,criirl the ttvripo/.~I
lobe
(3) Autobiographical semantics seem to be less
impaired than autobiographical episodes across
various lesion profiles when both types of memory
were evaluated (Tables 2-5).
(4) Bilateral lesions, including the hippocampal
formation or the hippocampal complex (Tables
24), result in RA for public knowledge. The extent
of RA for public knowledge also depends on the
extent of medial temporal lobe damage. It is not as
extensive as RA for autobiographical episodes in
many cases, but is parallel to that for autobiographical episodes in some. It is worth noting that
the relation between RA for autobiographical episodes and public knowledge is asymmetric; while
the former may be more severely impaired than
the latter, the reverse pattern is rarely reported
after damage to the medial temporal lobe (Fig. 3).
(5) Basic semantic knowledge (language, knowledge about objects, general intelligence, and the
like) acquired during childhood is unscathed in
temporal lobe amnesia (Table 1-5). At this time,
we cannot draw firm conclusions about the fate of
general semantics acquired during adulthood prior
to the onset of amnesia, because of inconsistent results and a dearth of relevant information.
(6) Extensive RA for autobiographical episodes
and for public knowledge can occur after bilateral
temporal lobe lesions even if the hippocampal
complex in either hemisphere is undamaged (Table
5). Anterograde amnesia is minimal in these cases.
The relation between RA for autobiographical episodes and public knowledge appears to be less
asymmetric than that in cases with bilateral medial
temporal lobe lesions (Fig. 3). In these cases, RA
appears to occur when lesions affect the temporal
polar region in one hemisphere in which the hippocampal complex is spared.
Animal studies of retrograde amnesia and memory
consolidation
Recognizing the inherent limitations of studies involving human subjects, a number of investigators
have examined retrograde amnesia and memory
consolidation in animal models, typically rodents,
C.71. I 0
but occasionally primates. In general, such studies
have three kinds of advantages: first, one can, in
principle, test subjects with lesions targeted at specific brain regions, although this is not quite as simple as it sounds; second, one can exert virtually
complete control over what is learned, and which
experiences experimental subjects have in the interim between learning and any retention test; finally,
one can carefully and systematically manipulate
the learning-retention interval. It is difficult, if not
impossible, to match these features in studies with
human subjects. On the other hand, there is a signal disadvantage in working with animals; namely,
it remains quite difficult to compare animal and human memory, feature by feature and type by type.
How, for example, can we characterize the difference between episodic and semantic memory in
rats, or monkeys? What in animals could possibly
count as autobiographical semantics?
Nonetheless, animal studies can contribute important insights, and in what follows, we briefly
discuss this literature and what it tells us about
memory consolidation. In particular, we focus on
several questions already brought to the fore in the
literature on humans: (1) which brain structures
are critical to memory formation, consolidation
and storage; (2) does the shape of the RA gradient
change as a function of the extent of damage in critical brain regions; (3) are there different RA gradients for different kinds of learned material? In a
recent review, Murray and Bussey (in press) have
carefully evaluated all of the studies investigating
the role of medial temporal lobe structures in consolidation in animals. Rather than repeat their effort, we will refer to it several times below.
Brain structures involved in memory
There is considerable support in the animal literature for the notion that there are multiple memory
systems, supported by distinct brain structures. Indeed, some of the earliest suggestions about multiple memory systems came from work with rats
(Hirsh, 1974; Nadel and O'Keefe, 1974) and monkeys (Gaffan, 1974). In parallel with the human lit-
Ch. 10 7: Fujii, M. Moscovitcll and L. Nude1
erature, much of the animal work has focused on
the hippocampus, and its neighbors in the temporal
lobe. Murray and Bussey (in press) considered the
central question of whether the group of structures
we have referred to as the hippocampal complex
are functionally equipotential with regard to consolidation. Murray and Bussey (in press) pointed
out that there is now considerable evidence against
this univocal view. For example, data demonstrating rather different roles for hippocampus and perirhinal cortex have been provided by Zola-Morgan
and Squire (1990) and Thornton et al. (1997), using
comparable tasks (object discrimination) and retention intervals. Murray and Bussey conclude, in
general, that different parts of the hippocampal
complex play crucial roles in the consolidation of
different kinds of memory. As we see below, there
is no single answer to the question of what structures are critical to consolidation: it depends upon
the nature of the memory being consolidated.
The shape of the RA gradienl
Given that there would appear to be multiple consolidation processes in different brain regions concerned with different kinds of memory, there cannot be a single answer to the question of the shape
of the RA gradient. As Murray and Bussey point
out, the gradient can be either graded or flat, depending on the kind of learning involved, and the
brain structures damaged.
Murray and Bussey tabulated 15 studies of retrograde amnesia after hippocampal complex lesions
since 1990. Of these, five studies employed maze
learning of one kind or another (Cho et al., 1993,
1995, 1996; Bolhuis et al., 1994), five utilized object
or scene discriminations (Salmon et al., 1985;
Zola-Morgan and Squire, 1990; Gaffan, 1993;
Wiig et al., 1996; Thornton et a]., 1997), three
used fear of both contexts and specific tone stimuli
(Kim and Fanselow, 1992; Maren et al., 1997;
Anagnostaras et al., 1999;), while the remaining
two used a socially acquired food preference (Winocur, 1990) and trace eyeblink conditioning
(Kim et al., 1995).
Of the five studies using spatial maze learning,
three employed lesions to the hippocampal formation, while four included groups with damage in
the entorhinal cortex. After hippocampal formation lesions, flat RA gradients were seen in 213
cases. After lesions restricted to the entorhinal cortex graded RA was observed in 414 cases.
In the studies using discrimination tasks, a more
complicated picture emerged. Gaffan (1993) employed a scene discrimination task (with clear spatial components) and relatively restricted fornix lesions, reporting a flat gradient. Several studies
using concurrent object discriminations and large
aspiration lesions, including several components
of the hippocampal complex, also reported flat
RA gradients (Salmon et al., 1985; Thornton et
al., 1997). However, two other studies using object
discriminations reported either graded RA (ZolaMorgan and Squire, 1990, who used extensive hippocampal complex lesions in monkeys; and Wiig
et al., 1996, who used fornix lesions in rats) or a
flat gradient (Wiig et al., 1996, in groups with perirhinal lesions).
In the three studies using context and tone fear
conditioning, the typical result has been an absence
of RA for tone conditioning, and graded RA for
context conditioning. The same pattern of graded
RA was reported in the two other studies utilizing
non-spatial tasks.
While there are no obvious generalizations that
capture this pattern of results, the following might
hold: when relatively complete lesions are placed
in the appropriate region for a given task, flat gradients will typically (but not always) be observed.
This seems to hold for spatial tasks and hippocampus proper lesions, and for object discrimination
tasks and perirhinal cortex lesions.
Additional considerations
Two very recent studies raise some critical questions (Land et al., 1998; Kubie et al., 1999). The
Land et al. study probed the traditional view of
graded RA by inserting a simple manipulation just
prior to testing rats for retention of a Y-maze sig-
naled avoidance task (this is a task typically assumed to not require an intact hippocampus for solution, given the use of a signal to indicate the correct arm on each trial). They reasoned as follows:
the traditional interpretation of graded RA is that
if one waits long enough before making a lesion in
the hippocampal formation, the memory no longer
depends upon the hippocampus, and that is why lesions are ineffective. In their situation, hippocampal lesions made 3 h after training severely impaired retention, while lesions made 30 days after
Y-maze training had little effect on performance,
indicating that the memory had survived. However,
if the animals received a 'reminder' of the experimental situation (rats were simply placed on the Ymaze and a cue light was turned on and off - no
training was allowed) just prior to the hippocampal
lesion 30 days after initial training, then severe
RA was observed. Somehow, the reminder activated the memory in such a way that hippocampal
lesions were now effective in inducing RA. This result cannot readily be accommodated within the
traditional model of consolidation. It is, however,
consistent with the view that the hippocampus remains important for retrieval of memories long
after the 'consolidation' period is complete.
Kubie et al. (1 999) tested rats in a dry version of
the Morris maze, and obtained a graded RA after
excitotoxic lesions to the hippocampus proper
(CA fields and dentate gyrus). However, more careful analysis of the data indicated that performance
in the animals lesioned after long retention intervals was not entirely normal. Their result is similar
to that reported by Cho et al. (1993), who also concluded that medial temporal lobe lesions after long
retention intervals yield animals who are not as severely impaired, but who are also not normal. Cho
et al. suggested that performance in animals receiving lesions after a long retention interval might
demonstrate shifts in behavioral strategy rather
than in the locus of the memory trace (i.e. from hippocampal formation to neocortex). Kubie et al. offer an intriguing explanation of their results. They
suggest that the hippocampal formation and cortex
are capable of forming two different kinds of spa-
tial representations, each of which can support performance on a previously learned maze. In their
view, the hippocampus is essential to the storage
of a true map-like representation, while the cortex
can store 'vector-field' representations that are impoverished compared to the hippocampal map,
but nonetheless sufficient to perform a previously
learned maze task. What is particularly appealing
about this notion is that it fits rather well the data
recently obtained in a human patient with extensive hippocampal damage (Rosenbaum et al.,
1999 cited in Moscovitch et al., 1999).This patient
demonstrated considerably preserved remote spatial memory, but was not normal when looked at
in careful detail. This finding parallels what has
been observed with remote autobiographical memory, as noted above: apparently normal performance has been shown to be deficient when more
precise tests measuring memory in finer detail are
employed.
In summary, the work with animals generally
confirms the impressions obtained in work with humans. Retrograde amnesia can cover very long
time periods, depending on the nature of the task
and the extent and location of the lesion. Damage
within the hippocampal complex, if sufficiently extensive, can yield flat RA gradients when spatial
tasks are used, or graded RA that upon closer examination reveals subtle defects even at retention
intervals where performance can appear normal
by some measures; damage in areas of neocortex
can yield flat gradients in other kinds of tasks.
Although results to date do not allow firm conclusions, they converge with the human data in suggesting that the standard model of memory consolidation has potentially serious shortcomings.
Models of memory consolidation and the temporal
lobe
In an excellent, extensive review of retrograde amnesia that includes neurological and psychological
causes, Kapur (in press) concludes by proposing
three main factors, each with multiple levels, that
determine the temporal extent, severity, and type
Ch. 10 7: Fujii, M. Moscovitch and L. Nadel
of retrograde amnesia. Those factors are the initial
strength of the experience, lesion characteristics,
and retention testing. Although we agree with Kapur's more parametric analysis that each of these
factors is important, we would like to take a more
theoretical approach in this last section and speculate about the neural mechanisms that can support
normal remote memory when they are intact and
give rise to the different types of retrograde amnesia when they are damaged. In light of the data we
reviewed, we evaluate two models, the standard
consolidation model and the multiple trace theory
(MTT), and propose that a modified version of the
latter can accommodate most of the available evidence.
The standard model
According to what we have termed the standard
model, memory consolidation begins when information, initially registered by the neocortex, is
bound into a cohesive memory trace by the hippocampus and related structures in the medial temporal lobes and diencephalon. In the early stage, the
hippocampus and related structures are needed
for the storage and retrieval of the memory trace,
but their contribution is diminished as the consolidation process proceeds, until the neocortex alone
can maintain the memory trace and mediate its retrieval. Long-term declarative memory results
from continuous, gradual strengthening of neural
connections in the neocortex that were formed initially (but very weakly) at encoding. Thus, the medial temporal lobes play a time-limited role in
memory until long-term consolidation is complete
and a permanent memory is established in the neocortex (Squire and Zola-Morgan, 1991; Squire,
1992; Alvarez and Squire, 1994; Squire and Alvarez, 1995).
Relatively brief RA for declarative memory supports this standard model of consolidation, by
showing that the hippocampal complex can play a
temporary role in memory storage and retrieval.
The data on humans singles out the hippocampus
proper for this role. Once damage extends beyond
the hippocampus proper, this model, however, has
considerable difficulty explaining the temporally
limited, yet extensive RA for declarative memory
that occurs even if damage is limited to the bilateral
hippocampal complex, unless it assumes that consolidation processes continue over many decades.
Furthermore, for the standard model to succeed,
it must posit that tight connections are formed
among memory fragments corresponding to perceptual aspects of the initial event, and coded by
distinct, geographically separate modality- and
category-specific association areas. From what we
know of the anatomy of these domain-specific regions, binding them into a cohesive network without recourse to regions outside these areas, such
as the hippocampal complex, is unlikely to occur.
Moreover, to contribute a true autobiographical
memory, the information in the network needs to
be constrained by specific temporal and spatial
contexts. Indeed, explaining the latter, context-specific retrieval of remote memories demands not
only that dispersed memory fragments be bound
together, but that contextual codes previously
formed within hippocampal regions somehow be
reconstructed outside this system. Finally, because
the standard model as articulated by Squire and
colleagues refers to 'declarative memory' as a
whole, it cannot explain dissociations within RA
among different types of 'declarative' memory after
damage to medial temporal lobe structures.
Nadel and Moscovitch (1997) proposed an alternative to the standard consolidation theory, which
they called the multiple-trace theory of memory
(MTT) (see also Moscovitch and Nadel, 1998; Nadel and Moscovitch, 1998; Moscovitch and Nadel,
1999). MTT focused on RA for autobiographical
episodes following hippocampal complex lesions.
Initially, the MTT was formulated to account for
the various temporal gradients and extent of RA
that had been reported for patients with such lesions. Little attempt was made to deal with cases
in which damage occurred to regions of the temporal lobe other than the hippocampal complex (but
see Moscovitch and Nadel (1999) for application
of MTT to semantic dementia, a degenerative dis-
order that spares the hippocampal complex, but
damages the lateral surface of the temporal lobes,
particularly the superior temporal gyrus). Nor was
MTT formulated to deal with RA for other types
of information, such as knowledge of public events
and personalities or of personal (autobiographical)
semantics, though it was suggested how MTT
could accommodate such evidence (Nadel and
Moscovitch, 1997, pp. 223-224). By and large, the
MTT accounts well for the additional evidence
gathered in this review, though some modifications
may be necessary to address the following three issues more fully.
(1) The different effects that subregions of the
hippocampal complex and other areas of the anterior temporal lobe have on RA. As we noted, iesions confined to the hippocampus proper, and restricted even to the CAI region, produce a
temporally limited RA as compared to the far
more temporally extensive RA once lesions include
other parts of the hippocampal complex.
(2) The dissociation between anterograde and
retrograde amnesia, particularly the dramatic effects observed following bilateral lesions to the
temporal pole in which extensive RA co-exists
with relatively mild AA.
(3) The differences in RA for autobiographical
episodes as compared to knowledge of public
events and personalities, and autobiographical semantics.
We first present the MTT as it was most recently
formulated and then consider what modifications,
if any, might be necessary in light of the evidence
gathered in this review.
The multiple trace theory
(1) According to MTT, the hippocampal complex
(and related diencephalic structures) rapidly and
obligatorily encodes all information that is attended or consciously apprehended (Moscovitch,
1995; Nadel and Moscovitch, 1997; Fukatsu et al.,
1998). The process entails the formation of a code
embodied in a sparse and distributed set of hippocampal complex neurons which bind neurons in
unimodal and heteromodal association areas that
represent the attended information (Teyler and
DiScenna, 1986; McLelland et al., 1995; Moscovitch, 1995; Squire and Alvarez, 1995; Nadel and
Moscovitch, 1997; Mesulam, 1998). These areas
are usually considered to be in posterior neocortex,
but can also include other regions, such as the
amygdala, in the medial temporal lobe, which contribute to emotional aspects of the conscious experience. We should be clear that the hippocampal
complex codes are not necessary for mediating the
conscious experience of the event while it is occurring, but are needed instead for the rapid creation
of memory traces of the experience and for later retrieval of those traces. We refer to this rapid binding process as short-term consolidation or cohesion
and believe it is hippocampally dependent, probably with little engagement of basal forebrain
structures (Fukatsu et al., 1998).
(2) These codes, which bind fragments of information that occurred more or less simultaneously
and in the same spatial context, are initially laid
down and stored in distributed ensembles of neurons in the hippocampal complex. They correspond to Conway's (1993, this volume) phenomenological records, each of which can be considered a
near sensory record of a 'scene' in a temporally extended episode event. During any single episode,
several such codes or phenomenological records
are created and stored.
(3) The entire ensemble of binding codes in the
hippocampal complex, and fragments of information in association areas, constitutes the memory
trace for a specific episode (e.g. dinner with X on
the last night of a conference in Arcachon).
(4) The binding codes in the hippocampus act as
a pointer or index to neurons in association cortex
(and elsewhere) that represent the attended information which forms the content of the memory
trace. It is via these codes that autobiographical
episodes are retrieved.
(5) After initial encoding, each reactivation of
these memory traces during retrieval may occur in
an altered neuronal and experiential context. Because the extended hippocampal encoding system
automatically creates codes binding information
that is attended, the reactivation of pre-existing
memory traces results in the creation of new codes
in the hippocampal complex which are also sparse
and distributed.
(6) In the course of time, autobiographical episodes will either have been lost, or if reactivation
occurs, will have benefited from the formation of
multiple traces in the hippocampal complex and
links between it and association areas. The older
the memory, the greater the number of codes in
the hippocampal complex and of links to association cortex.
In contrast to the standard model, MTT postulates no long-term consolidation process which
slowly strengthens neural connections in geographically separate modality- and category-specific association areas, with a resulting shift of storage
from the hippocampal complex to neocortex. Instead, this model proposes that the maintenance
and reconstruction of memory for autobiographical episodes involves the continued participation
of posterior association cortices and hippocampal
complex. Thus, remembering of autobiographical
episodes is achieved by means of activating via the
hippocampal complex many independent, geographically separate, but interconnected memory
traces in various brain regions.
Evaluation of MTT
This MTT is consistent with much of the evidence
in this review. The extent of RA and the shape of
the gradient varies according to the size of the lesion to the hippocampal complex. When lesions
are confined to the hippocampus proper, RA is
very short. As more regions of the hippocampal
complex are damaged, RA for autobiographical
episodes extends further in time, encompassing
the entire life in those cases where lesions cover
the entire complex. The temporal gradient, too,
would appear to be flatter with more extensive
damage, but the evidence is too poor to permit a
firm conclusion on this matter. In general, the
model also accounts for differences in RA among
different types of memory. According to our prediction, 'differences in the extent of RA would also
be determined by the complexity or richness of the
trace that is to be recovered. Because the full details
of an autobiographical episode are not likely to be
re-activated often, these details would be most vulnerable to disruption. On the other hand, the gist
of an episode, partial information about it, or facts
about one's personal life - those things that constitute personal semantic memory [autobiographical
semantics] - are more likely to be reactivated and
hence would be multiply represented. The same
would be true of semantic memory for public
events and personalities, as for personal semantic
memories, ... unless extremely detailed information
about semantic memory were required (Moscovitch and Melo, 1997)' (Nadel and Moscovitch,
1997, pp. 23-24). The relative preservation of autobiographical semantics and knowledge of public
events and personalities, in comparison to autobiographical episodes, is consistent with these predictions.
Despite the general agreement between the evidence reviewed in this chapter and the MTT, there
are some unexpected observations and some apparent discrepancies which need to be examined
more closely.
Efects of lesions to dzferent regions ofthe
hippocampal complex
As we noted earlier, lesions confined to the hippocampus proper, or restricted even to the CAI fields,
produce a very temporally limited RA with moderate AA. A possible interpretation of this finding is
that the hippocampus proper is crucial only for
short-term consolidation or cohesion, but not for
storage or retrieval, more in keeping with the role
assigned to it by the standard consolidation model
than by MTT. To reconcile MTT with this interpretation, the theory would have to be modified to
state that the hippocampus proper contributes to
the formation of the binding codes but that the codes themselves are mediated by neurons in other
parts of the hippocampal complex.
There are, however, alternative interpretations
of the effects of restricted, hippocampal lesions.
Except for a study by Reed and Squire (1998), the
evidence is based on tests of remote memory that
are not particularly sensitive to the richness of the
memory that is recovered. In most of those tests,
between 0 and 3 points are awarded for each episode that is recalled with the maximum allotted if
the time and place of the event is stated and some
detail is provided. In short, the tests may assess
one's memory of the gist of an event. Even Reed
and Squire, who evaluated the quality of the memory in terms of various categories, relied on the subjective impressions of the examiners. New tests
that emphasize the number of details that are recovered have shown that RA is extensive even in
amnesic people who displayed minimal RA when
assessed using more traditional tests (Moscovitch,
1997; Moscovitch et al., 1999). Until people with
lesions restricted to the hippocampus are submitted to tests that are scored in terms of total details,
one cannot discount the possibility that the hippocampus proper may be needed not only for cohesion, but also for storage and recovery of phenomenological records, the detailed near-sensory
content of memory for autobiographical episodes.
As predicted by MTT, memory for the gist of an
episode can survive such small lesions1
Correspondence between human and animal studies Because lesions confined to a single region
of hippocampal complex rarely occur in people,
our knowledge of the function each of these regions
depended, until recently, primarily on animal models and, to a lesser extent, on extrapolation from
studies in humans in which lesions to a particular
area were included in a larger area of damage.
More recently, functional neuroimaging techniques
have allowed investigators to focus on these small
regions of interest.
The difficulty in comparing animal with human
'
An intriguing possibility is that memory for gist, the abstracted
essence of an episode, may be encoded separately from the details. Whereas phenomenological records are encoded and
stored by the hippocampus, gist may be encoded and stored in
other regions of the complex (see below)
studies is that the categories used to investigate human memory, such as autobiographical episodes
and semantics, and knowledge of public events
and persons, have no natural counterpart in animals. Instead, animal studies deal with categories
related to specific domains of information such as
space, objects, and their interaction. Even so, studies of remote memory loss after lesions to various
medial temporal lobe subregions in animal models
are few in number. As we noted, the results could
be summarized as follows: complete lesions in an
area specialized for acquisition of domain-specific
information typically leads to extensive RA for
that information. The findings from animal studies,
however, do not always correspond exactly to those
suggested by the literature in humans when similar
tests are administered. Thus, hippocampal damage
in rats is associated with extensive RA for allocentric spatial memory. Humans with large lesions to
the hippocampus and adjacent cortex, however, retain remote allocentric spatial memories or cognitive maps of large-scale natural environments,
such as a neighborhood or a house (Rosenbaum et
al., 1999). Retrograde topographical amnesia in
humans is often associated, instead, with parahippocampal, parietal, or posterior cingulate lesions
(Aguirre and D'Esposito 1999, De Renzi, 1982).
While the recent work of Kubie et al. (1999) offers
a possible rapprochement, more work is needed to
determine if there has been some shift in the responsibility of different regions within the medial
temporal lobe with regard to the storage of longterm spatial information.
There is as yet no human counterpart to loss of
remote memory for objects following perirhinal
lesions in rats and monkeys. Although object agnosia is a possible candidate, it is a fundamentally
different disorder produced by lesions to inferotemporal, rather than perirhinal, cortex.
The imperfect correspondence between animal
and human studies of remote memory following lesions to subregions of the medial temporal lobe
stands in contrast to the excellent correspondence
in studies of anterograde memory. Probably the
main reasons for the discrepancy are that the study
knowledge, whether autobiographical or general.
Vargha-Khedem et al. (1997) demonstrated that
acquisition, maintenance, and retrieval of semantic
information is relatively spared in peoplc with neonatal lesions to the hippocampal formation despite
their severely impaired episodic memory. Nonetheless, other reports (Ostergaard, 1987; Broman et
al., 1997; DeLong and Heinz, 1997) suggest that
acquisition may not be as rapid or knowledge may
not be as detailed, especially for semantic knowledge acquired in adulthood.
Limitations of the MTT
MTT was not intended to be an all-encompassing
theory of memory. It was devised to address what
we believed were the shortcomings of traditional
consolidation theory, and to offer an alternative explanation of RA after medial temporal lobe lesions. As a theory of memory, and even of RA observed after damage to other structures, MTT is
incomplete. It needs to be supplemented by consideration of how the medial temporal lobes interact
with other structures, such as the prefrontal cortex,
which clearly play an important role in episodic
memory, self, and consciousness in humans and
possibly in non-human species. We noted briefly
what the nature of those interactions might be (see
Nadel and Moscovitch, 1997, 1998; Moscovitch
and Nadel, 1998) and we refer the interested reader
to more recent work on this topic (Moscovitch,
1992, 1995, 1999; Wheeler et al., 1997; Conway
and Fthenaki, this volume).
Even within its own frame of reference, the MTT
provides at best a sketchy account of the function
of the various components of the hippocampal
complex, with respect to episodic memory. A fuller
account will emerge when one can isolate these
components in humans, hopefully with the aid of
functional neuroimaging studies, and apply the lessons learned from animal models.
Summary
The evidence reviewed in this paper challenges tra-
ditional consolidation theory which states that the
hippocampal complex or medial temporal lobes
play a time-limited role in memory, being needed
for storage and recovery of memories only until
they are fully consolidated in other structures. The
review of the literature showed that bilateral lesions to the medial temporal lobes that include other regions in addition to the hippocampus produce
extensive RA, the severity and length of which increases as more regions are implicated, often leading to a RA that covers an individual's entire life.
In humans, RA is most severe for autobiographical
episodes, but is also substantial for knowledge of
public figures and events. When damage is limited
to the hippocampus proper in humans, the period
of RA is very short, though it may be shown to extend further if more sensitive tests were used. In animals, as in humans, RA can be extensive with temporal gradients of varying degree, but the type of
memory that is affected depends on the region of
the hippocampal complex that is damaged.
This evidence reviewed in this chapter is consistent with a multiple trace theory of memory. According to that theory, the episodic memory trace
consists of an ensemble of neurons in the hippocampal complex cohesively bound to neurons in
the neocortex (and elsewhere) which mediate a
consciously experienced event. Binding of the elements occurs during a short-term consolidation period typically lasting seconds or minutes, but no
more than a few days. The evidence suggests, but
is not conclusive, that the hippocampus proper
may be needed for short-term consolidation, after
which the trace depends on extra hippocampal
neurons in the hippocampal complex. There is no
need to postulate a long-term consolidation process that strengthens existing memory traces outside the hippocampal complex. Instead, as memory
traces are reactivated over time, multiple related
traces are formed in the hippocampal complex
and dispersed over wider areas of the system. Hippocampal complex neurons, however, remain an
integral part of the memory trace as long as it exists. As a result, damage to the hippocampal complex always produces a retrograde amnesia, but
more extensive lesions are required to eradicate
more remote memories. By virtue of its postulates,
MTT provides a good account of the pattern of
RA following temporal lobe damage. As such, it
can form the core of a more complete theory of
episodic memory that will take its hierarchical
structure and temporal sequencing into account.
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