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The Journal of Neuroscience, March 1, 1998, 18(5):1841-1847
Successful Verbal Encoding into Episodic Memory Engages the
Posterior Hippocampus: A Parametrically Analyzed Functional Magnetic
Resonance Imaging Study
Guillén
Fernández1, 2,
Helga
Weyerts1,
Michael
Schrader-Bölsche1,
Indira
Tendolkar1,
Henderikus G. O. M.
Smid1,
Claus
Tempelmann1, 3,
Hermann
Hinrichs1,
Henning
Scheich3,
Christian E.
Elger2,
George R.
Mangun4, and
Hans-Jochen
Heinze1
1 Department of Clinical Neurophysiology,
University of Magdeburg, 39120 Magdeburg, Germany,
2 Department of Epileptology, University of Bonn,
53105 Bonn, Germany, 3 Federal Institute for
Neurobiology, 39008 Magdeburg, Germany, and
4 Center for Neuroscience and Department of
Psychology, University of California, Davis, California 95616
 |
ABSTRACT |
The medial temporal lobe (MTL) is essential for episodic memory
encoding, as evidenced by memory deficits in patients with MTL damage.
However, previous functional neuroimaging studies have either failed to
show MTL activation during encoding or they did not differentiate
between two MTL related processes: novelty assessment and episodic
memory encoding. Furthermore, there is evidence that the MTL can be
subdivided into subcomponents serving different memory processes, but
the extent of this functional subdivision remains unknown. The aim of
the present functional magnetic resonance imaging (fMRI) study was to
investigate the role of the MTL in episodic encoding and to determine
whether this function might be restricted to anatomical subdivisions of the MTL. Thirteen healthy volunteers performed a word list learning paradigm with free recall after distraction. Functional images acquired
during encoding were analyzed separately for each participant by a
voxel-wise correlation (Kendall's tau) between the time series of the
T2*-signal intensity and the number of subsequently recalled words
encoded during each particular scan. Of the 13 participants, 11 showed
voxel clusters with statistically significant, positive correlations in
the posterior part of the hippocampus. Across participants, an ANOVA on
the number of voxels with significant, positive correlations within
individually defined volumes of interest confirmed a statistically
significant difference in activation for anterior versus posterior
regions of the hippocampus. However, no differences between left and
right hippocampal activation were revealed. Thus, these findings
demonstrate that successful encoding into episodic memory engages
neural circuits in the posterior part of the hippocampus.
Key words:
episodic memory; declarative memory; encoding; memory
formation; hippocampus; medial temporal lobe; functional neuroimaging; fMRI; parametrical analysis; Alzheimer's disease
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INTRODUCTION |
Episodic memory, which is accessible
to conscious recollection and concerned with unique personal
experiences, is dependent on the integrity of the medial temporal lobe
(MTL) (Tulving, 1972 ; Squire and Zola-Morgan, 1991). However, it is not
clear to what extent the MTL can be divided into subcomponents
subserving different memory processes (Eichenbaum et al., 1994;
Zola-Morgan et al., 1994). At the very least, the hippocampus is
required for episodic memory, because lesions confined to the
hippocampus are sufficient to induce anterograde and temporally limited
retrograde amnesia (Zola-Morgan et al., 1986; Victor and Agamanolis,
1990; Rempel-Clower et al., 1996). Furthermore, as revealed by
intrahippocampal electrical stimulation, the MTL is involved in both
episodic memory encoding and retrieval (Halgren et al., 1985).
Nevertheless, several functional brain imaging studies failed to reveal
encoding-related MTL activations (Petersen et al., 1988; Frith et al.,
1991; Démonet et al., 1992; Grasby et al., 1993a, 1994; Kapur et
al., 1994, 1996; Raichle et al., 1994; Shallice et al., 1994; Tulving
et al., 1994a; Fletcher et al., 1995; Nyberg et al., 1996a).
In contrast, studies comparing brain activity during processing of
novel versus familiar items have demonstrated MTL activations, and
these activations were interpreted as encoding-related, assuming that
familiar items need less encoding than novel items (Tulving et al.,
1994b; 1996; Grady et al., 1995; Haxby et al., 1996; Stern et al.,
1996; Dolan and Fletcher, 1997; Gabrieli et al., 1997). However, from
these studies it is difficult to disentangle memory encoding from
novelty assessment, a process that computes novelty and familiarity for
incoming information. Novelty assessment either influences encoding
success or represents an early stage of memory encoding, but it does
not represent the whole process of episodic memory encoding (Metcalfe,
1993; Tulving and Kroll, 1995; Tulving et al., 1996). Because the MTL
is involved in episodic memory processing as well as novelty assessment
(Squire and Zola-Morgan, 1991; Knight, 1996; Tulving et al., 1996), it
is reasonable to assume that reported MTL activations could be based on
either or both of these two processes.
Most imaging studies of memory have relied on subtraction methods, but
a few studies have used parametric designs (Grasby et al., 1993b, 1994;
Nyberg et al., 1996b). In parametric studies of memory, correlations
between the number of items retrieved and the signal intensity of each
voxel across a time series and/or across subjects were calculated to
identify activated brain regions. Positron emission tomography (PET)
scans showed positive correlations between MTL blood flow and the
number of retrieved items (Grasby et al., 1993b; Nyberg et al.,
1996b).The scans in these studies were acquired during a recognition
task or across study and free recall tasks. Thus, no separate analysis
of encoding-related activity was performed. However, parametric
analyses require no control task and show the direct relationship
between specific tasks and the brain regions that are involved.
Therefore, they are also well suited to investigate encoding-related
processes.
The aim of the present functional magnetic resonance imaging (fMRI)
study was to identify MTL structures that are involved in episodic
memory encoding, using a word list learning paradigm with free recall
after distraction. The higher spatial and temporal resolution of fMRI
allows the analysis of single subject data, the investigation of
encoding separately from retrieval, and a topographical analysis within
the MTL.
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MATERIALS AND METHODS |
Participants. Thirteen healthy volunteers (9 females,
4 males) participated in the study. Each gave written informed consent. The study was approved by the Ethics Committee of the Otto-von-Guericke University, Magdeburg. All were right-handed and had normal vision; German was their first language. The mean age was 25 years (range, 18-41 years).
Stimulus material. A total of 300 German nouns were selected
from the CELEX Lexical Database (word frequency: mean ± SD,
47 ± 8/1 million) (Baayen et al., 1993). Words contained 3-10
letters (5.85 ± 1.53), and 50% of the words had an abstract
meaning. The pool of words was partitioned pseudorandomly into 20 study
lists of 15 words each, under the constraints that the word lengths and
the ratio of abstract/concrete meanings were balanced between the lists
and that within one list neither semantic nor phonological similarities
occurred. The order of the lists and of the words within and across
lists was counterbalanced across participants.
Procedure. Participants laid in a supine position in the MRI
scanner with their head stabilized by an individually molded vacuum
cushion. The stimuli were projected upside down onto a mirror located
at the end of the scanner bore. The participants wore prism glasses so
they saw the projection upright, in central vision, and without optical
distortion. The experiment consisted of 20 blocks. Each block included
three tasks: the encoding task, the distraction task, and the recall
task (Fig. 1A). During
encoding, words of each study list (15 words) were presented
sequentially in upper case (white on a black background). The words
subtended maximum horizontal and vertical visual angles of ~3.0 and
0.6°, respectively. Words were presented for durations of 500 msec
each, with an interstimulus interval of 2.5 sec, during which a
fixation asterisk was displayed. To avoid associative processing, the
participants were required to memorize each presented word separately
using a rote mnemonic strategy. They were explicitly instructed to
avoid elaborate strategies like making rows, sentences, stories,
pictures, or to connect the words in any other way. Furthermore, the
participants were advised to avoid any speech movement during the
encoding task. After the presentation of each study list, a distraction task was presented for 15 sec to prevent ongoing rehearsal. In this
task, pairs of signs (! # or ! ! or # #) were displayed on the screen
for 150 msec each with an interstimulus interval of 850 msec.
Participants were required to give a same-different response, with
equal emphasis on speed and accuracy. They responded with their right
hand, pressing one button of a computer mouse when the two signs were
different and the other button when the two signs were identical. The
distraction task was followed by the presentation of three question
marks for 45 sec, which indicated the recall task. During recall, the
participants were instructed to say aloud the previously presented
study words in any order. Responses were recorded by a tape recorder
for later analyses.
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Figure 1.
A, Depiction of one experimental
block. Encoding task with the sequential presentation of
15 words per list (duration of each presentation, 500 msec;
interstimulus interval, 2500 msec). Each set of MRI scans was acquired
during the presentation of five words (15 sec).
Distraction task: a 15 sec same/different decision task
(duration of each presentation, 150 msec; interstimulus interval, 850 msec). Free recall task for 45 sec. This sequence was
performed for a total of 20 blocks in each participant.
B, One example of changing hemodynamic response pattern
by shifting the assignment between word list and each particular scan
by zero, one, or two words, respectively, for 0, 3, or 6 sec. Brain
regions showing a significant, positive correlation between their fMRI
signals and the number of successfully encoded words. Colored
voxels exceeded the statistical threshold (<0.05) and were
overlaid on structural images. The left side of each
scan is the right side of the brain.
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Image acquisition. All participants were scanned in a Bruker
Biospec 30/60 system (field strength: 3.0 Tesla; Bruker Analytik GmbH,
Rheinstetten, Germany) with a birdcage head-coil and an asymmetric
gradient system (30 mT/m). Functional MR images were acquired
continuously during the whole experiment. The functional images were
collected using a FLASH gradient echo sequence with 40 phase encoding
steps, repetition time (TR) = ~375 msec, echo time (TE) = 37.65 msec,
and a flip angle of 12°. The gradient rise time was 2500 µsec. The
field of view of 16 cm and the in-plane matrix of 64 × 64 pixels
led to a pixel size of 2.5 × 2.5 mm. Structural scans in a
parasagittal plane covering the hippocampus were used to select seven
8-mm-thick contiguous coronal sections for the functional images that
covered the hippocampus in a plane perpendicular to its long axis. The
synchronous acquisition of this set of seven functional images lasted
15 sec. Additionally, in all experiments in-plane anatomical scans were
obtained using a FLASH sequence with TE = 19 msec, TR = 300 msec, and a flip angle of 60° in the functional measurement
planes.
Image analysis. The fMRI protocol yielded time series of
data points at each voxel. From these time series, the data acquired during the encoding task were extracted for further analysis. This
encoding-related data set consisted of 60 data points per voxel (three
images per list for 20 study lists). Each list contained 15 words;
hence, each data point represents the mean signal during the encoding
of five words. We used the correlation between the time series of
T2*-signal intensity and the number of subsequently recalled words (0 to 5 of 5) to characterize the response of each voxel. To consider the
physiological delay in the hemodynamic response, the word lists
assigned to each scan must be shifted by several seconds (Malonek and
Grinvald, 1996). Because the exact hemodynamic response latency is
unknown for the human MTL, it was impossible to select an a priori
shift value. Therefore, it was necessary to make a data-derived
optimization to find the maximal phase delay by analyzing all data sets
without a shift as well as with shifts of one and two words. A shift by
one or two words, a delay of 3 or 6 sec, respectively, would be well in
line with the peak latency of the hemodynamic response as directly revealed by optical imaging in the visual cortex of monkeys (Malonek and Grinvald, 1996). It was also necessary to decide whether the shifts
in each participant should be one or two words, and whether this should
be different for each subject. This decision was made by counting the
number of significant voxels in each entire imaging set, and the shift
that led to the largest number of active voxels was chosen for further
analysis. This procedure led to a shift by one word in five
participants and by two words in eight participants. As shown in Figure
1B, these shifts led to an improvement of the signal-to-noise ratio but not to a general change in the pattern of
results.
The imaging data were analyzed off-line using the software package
KHOROS 2.1 (Khoral Research, Albuquerque, NM) with the extension KHORFU
(Gaschler et al., 1996) and a motion correction program (Hinrichs et
al., 1994). To analyze the data, the following steps were performed for
each subject separately. (1) To remove trend effects of the signal
intensity, the best fitting polynomial of first, second, or third order
was subtracted from the time series of each voxel. (2) A motion
correction algorithm was applied to all scans (Hinrichs et al., 1994).
The mean distance for corrective shifts was 0.2 mm in the
x-, y-, and z-axes. (3) Afterward, the functional images were carefully inspected visually for further artifacts using a sequential animation tool. This inspection led to the
removal of three single images in the data of three different participants. (4) By using the Kendall's tau procedure (Kendall, 1970), a correlation matrix between the time series of each voxel and
the subsequent recall performance was calculated. (5) Each voxel in the
functional map whose correlation exceeded the 95% level of
significance (p < 0.05) was coded. (6) The
resulting matrices were processed with a median filter with the spatial width of two voxels to emphasize spatially coherent patterns of activation and then overlaid on the corresponding anatomical scan. (7)
The anatomical localization of significant voxels was determined using
the brain atlases of Duvernoy (1991) and Jackson and Duncan (1996) as
references.
Volumes of interest (VOIs). To analyze the interhemispheric
and anterior versus posterior differences of significant MTL
activations across subjects, four individually adjusted VOIs were
defined according to anatomical landmarks within the MTL (Amaral and
Insausti, 1990; Duvernoy, 1991; Jackson and Duncan, 1996). These were
the left anterior MTL, right anterior MTL, left posterior MTL, and right posterior MTL. The VOIs were rectangular in shape and had the
same size within each participant and similar sizes between participants. The VOIs enclosed the hippocampus and the parahippocampal gyrus, including the entorhinal, perirhinal, and parahippocampal cortices (Amaral and Insausti, 1990). The slice that included the head
of the hippocampus was defined as the anterior border, and the slice
with the crus fornix defined the posterior border. The division between
the anterior and posterior VOIs was located halfway between these two
borders. The VOI definitions were performed on the anatomical scans
without overlaid functional maps. Finally, the number of
median-filtered voxels with a significant, positive correlation was
automatically counted within each VOI and analyzed with a repeated
measure two-way ANOVA with the factors left versus right and anterior
versus posterior.
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RESULTS |
Behavioral data
The mean rate of correctly recalled words was 35.1% (range, 24.7 to 44.3%). On average, 1.75 words per scan were subsequently recalled
(SD = 1.21). The mean number of scans with zero, one, two, three,
four, or five subsequently recalled words showed a wide (kurtosis,
 0.70) and slightly left-shifted distribution (skewness, 0.24). As
intended, this yielded a fairly balanced and widely distributed basis
for the correlation between the recall rate and the T2*-signal
intensity. The distraction task was performed with high accuracy
(correct responses: mean = 88.4% correct; range, 80.1-94.2%)
and will not be discussed further.
Imaging data
In 11 of the 13 participants, clusters of voxels with significant,
positive correlations (p < 0.05) between the
number of subsequently recalled words and the T2*-signal intensity
during the encoding task were detected within the posterior MTL and the hippocampus (Fig. 2). These hippocampal
activations were more pronounced (larger number of active voxels) on
the left side of six and the right side of five participants. In
addition to these hippocampal activations, clusters of voxels with
significant, positive correlations were found in the cerebellar
hemispheres in eight participants, in the right precentral gyrus
(Brodmann's area 4) in five, in the left precentral gyrus (Brodmann's
area 4) in two, and in the posterior part of the left superior temporal gyrus and posterior transverse temporal gyrus (Brodmann's area 22/42)
in five of the 13 participants. These extratemporal activations frequently appeared in parallel within subjects: eight participants exhibited combinations of these activations, whereas five participants exhibited none of these extratemporal activations.
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Figure 2.
Brain regions showing a significant, positive
correlation between their fMRI signals and the number of successfully
encoded words. Colored voxels exceeded the statistical
threshold (<0.05) and were overlaid on structural images. In the
top row the red bar depicts the
approximate location of structural and functional images in the column
below. The bottom three rows depict adjacent slices from
three subjects (A-C), with one row corresponding
to one individual. The left side of each scan is the
right side of the brain. The arrows indicate voxels with
significant, positive correlations in the posterior part of the
hippocampus.
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VOI statistics
The mean number of voxels with significant, positive correlations
in each VOI are depicted in Table 1. The
two-way ANOVA (left/right × anterior/posterior) revealed a
significant main effect of anterior versus posterior
(F(1,12) = 7.05; p = 0.024). Therefore, as also indicated by the mean values, the encoding-related enhancement of neural activity was significantly more pronounced in the
posterior part of the hippocampus, and no inter-hemispheric differences
were reliable across participants. The voxels with a significant
positive correlation within the anterior VOIs were in the most
posterior slice and thus were interpreted as being related to the
larger activations within the posterior hippocampus. Additionally, some
small clusters of voxels (approximately two to three connected voxels)
without consistent localization across participants were counted in the
anterior VOIs. These activations do not exceed the general background
level of activity; thus, they most likely reflect noise or statistical
type I errors.
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Table 1.
Mean number of voxels with significant, positive
correlation (p < 0.05) within individually
defined volumes of interest
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DISCUSSION |
To identify MTL structures engaged in verbal encoding into
episodic memory we performed a parametrically analyzed fMRI study. The
main result was that 11 of the 13 participants showed clusters of
voxels with significant, positive correlations between the number of
successfully encoded words and the T2*-signal intensity in the
posterior part of the hippocampus. Across participants, there were no
differences between left and right hippocampal activations.
The finding that the encoding-related activity occurred in the
posterior hippocampus has some parallels with the findings of Gabrieli
et al. (1997), who found posterior parahippocampal activation for
encoding of novel pictures, and Stern et al. (1996), who found a
posterior hippocampal and parahippocampal activation also during
encoding of novel pictures. As already mentioned, from these studies it
is difficult to differentiate activity related to episodic encoding
from that related to novelty assessment. Because we presented common
words that are frequently encountered during life and just once during
the experiment, our findings cannot be interpreted as a correlate of
novelty assessment. Furthermore, our activations were certainly in the
posterior MTL; however, in contrast to the activations in novel versus
familiar paradigms, the activations revealed here were almost confined
to the hippocampus. This localization of encoding-related activity is
in agreement with findings in amnesic patients with hippocampal lesions
(Zola-Morgan et al., 1986; Victor and Agamanolis, 1990; Rempel-Clower
et al., 1996). To our knowledge, there is no lesion study in humans
that compares the impact of anterior versus posterior hippocampal
lesions, although one study showed that anterior hippocampal volume
reductions in chronic alcoholics were not correlated with episodic
memory impairments, indicating that episodic memory is not critically dependent on the anterior hippocampus (Sullivan et al., 1995). Studies
conducted in rodents have also shown that the posterior part of the
hippocampus exerts more control on spatial memory than does the
anterior part (Moser et al., 1993; Laurent-Demir and Jaffard, 1997).
Our results are in line with these findings, because they demonstrate
that the posterior hippocampus is activated during episodic memory
encoding in healthy humans.
Because memory deficits of patients with left-sided hippocampal lesions
mostly affect memory for verbal material and right-sided lesions affect
memory for material that cannot be readily verbalized (Hermann et al.,
1997), one might have expected a stronger activation within the left
than the right hippocampus. Such neuropsychological findings are
usually obtained by tests using auditorily presented words. Therefore,
our visual presentation could have led to additional visuospatial
encoding processes (Helmstaedter et al., 1995). However, the large
differences in memory performance between patients with bilateral and
unilateral hippocampal lesions seem to indicate that episodic memory
processes generally involve both MTLs (Zola-Morgan et al., 1986; Victor
and Agamanolis, 1990; Rempel-Clower et al., 1996; Baxendale, 1997;
Hermann et al., 1997; Oxbury et al., 1997). Our results extend this
notion by demonstrating that episodic memory encoding engages both
hippocampi in healthy subjects. However, it is possible that
neuroimaging methods based on hemodynamic measurements do not have
enough sensitivity to assess small asymmetries that are evident with
more direct measures such as intrahippocampal electrical recordings
(Elger et al., 1997).
In the present study, the encoding success was indexed by the
subsequent free recall. The comparison of brain activity during encoding of subsequently retrieved and unretrieved items is a well
established method to assess encoding-related activity as measured by
event-related potentials (ERPs) (for review, see Rugg, 1995). We did
not separately acquire the T2*-signal resulting from single-word
processing, and therefore we did not separate brain activity for each
subsequently recalled and unrecalled word. However, the summation over
five words enabled us to acquire the slower hemodynamic response, and
it is a valid approximation of the ERP paradigm. In ERP studies it is
difficult to localize the source of encoding-related activity from
scalp recordings alone. Thus, it is not possible to relate
scalp-recorded ERPs to activity in the hippocampus. In contrast, our
fMRI findings show that activity correlated with successful encoding is
localized to the hippocampus, an essential structure for episodic
memory. This localization supports the interpretation that this
enhanced activity is directly related to episodic memory encoding and
not to other processes such as attention, elaboration, or emotional
arousal. Such processes influence subsequent retrievability, but they
are not dependent on the hippocampus.
In addition to the hippocampal activations, we identified clusters of
voxels with significant, positive correlations in cerebellar hemispheres, the precentral gyrus, and the sylvian fissure, which were
less consistent across participants. Activations of the cerebellar hemispheres are common in various different cognitive tasks (for review, see Cabeza and Nyberg, 1997; Shulman et al., 1997). In specific
studies, cerebellar activations were correlated with attentional
processes (Allen et al., 1997), working memory (Desmond et al., 1996),
or subvocal rehearsal (Fiez et al., 1996). Our finding of cerebellar
activations might also be explained by different demands of attention.
In contrast, it seems less likely that they are correlated with working
memory processes, because we tested recall after distraction; thus the
predominant number of recalled words was retrieved from episodic memory
and not from working memory. The concurrent activation of the
cerebellum, the precentral gyrus (primary motor cortex), and the
sylvian fissure (auditory cortex), however, may indicate different
extents of subvocal rehearsal connected with different recall
probabilities (Fiez et al., 1996). It is important to note, however,
that the structures beyond the MTL were not completely imaged.
Therefore, these findings should be evaluated further with a study
optimized to investigate these non-MTL activations.
Although contrasting semantic and perceptual encoding or word
generation and reading lead to reliable differences in episodic encoding success, PET studies comparing theses tasks have not revealed
MTL activations (Petersen et al., 1988; Frith et al., 1991;
Démonet et al., 1992; Kapur et al., 1994; Raichle et al., 1994;
Fletcher et al., 1995). What are the reasons for this apparent paradox
in comparison to our findings? In addition to the general problem of
the subtraction approach, which assumes only additive relations between
cognitive processes (Friston et al., 1996), there are further
possibilities. Control tasks might elicit encoding processes, and this
may lead to hemodynamic changes that are not detectably different from
that of the encoding condition. The findings by Martin and colleagues
(1997) support this interpretation. They revealed an MTL activation
only in comparisons between processing of specific stimuli (words,
nonwords, objects, and nonsense objects) and a baseline without
specific stimulus information (visual noise). Furthermore, the failure
of MTL activations could also be explained by insufficient
signal-to-noise ratios attributable to partial volume effects that
occur when the imaging planes are not aligned with the hippocampus.
Another possibility for failure of previous studies to find MTL
activations related to encoding arises from the fact that in most PET
studies the data are collected across subjects and averaged into a
common stereotactic space. This procedure might lead to an
interindividual mismatch for the MTL and its subregions. Furthermore,
the subtraction approach does not consider each subject's memory
performance; hence, variability of performance may reduce the power to
detect changes in hemodynamic responses. The present study used methods
that eliminated or mitigated the impact of the foregoing problems, and
thus in addition to the parametric analysis we used may have permitted
the activations of the posterior hippocampus to be detected.
The hippocampus receives its input mainly from cells located in layers
II and III of the entorhinal cortex (EC), which give rise to the
perforant path, and it connects the EC with the dentate gyrus, the
hippocampal "gateway" (for review, see Amaral and Insausti, 1990).
The posterior hippocampus, the area that is activated in our study, may
receive its major input from the lateral portion of the EC, because in
primates the lateral EC is mainly connected with the posterior
hippocampus and the medial EC with the anterior hippocampus (Witter et
al., 1989). Patients with Alzheimer's disease show profound neuronal
loss in layer II of the EC (Gómez-Isla et al., 1996), and this
neuronal loss precedes the hippocampal damage (Mizutani and Kasahara,
1997). These findings suggest that the EC plays a crucial role in
episodic memory. However, we did not find an entorhinal activation.
This result may support the hypothesis formulated by Hyman and
collaborators (1984) and further developed by De Lacoste and White
(1993) that neuronal loss within the EC impairs episodic memory
primarily by disconnecting the hippocampus and not by damage of
neuronal circuits directly engaged in episodic memory formation.
Computational models of MTL function hypothesize that the neocortical
activity pattern that represents an episode and finds its way into
memory is first processed by the parahippocampal cortex. The
information then undergoes preliminary storage by pathways between the
EC, dentate gyrus, and CA3 region of the hippocampus, including the
recurrent collaterals, which enable autoassociative encoding, storage,
or binding processes (Alvarez and Squire, 1994; McClelland and Goddard,
1997; Rolls, 1997). As already reported, processing of novel in
comparison to familiar stimuli leads to enhanced neuronal activity in
the posterior parahippocampal gyrus (Gabrieli et al., 1997) or
posterior hippocampus and parahippocampal gyrus (Stern et al., 1996).
These findings may represent a correlate of novelty assessment, whereas
the present findings exhibit activations more purely related to
episodic memory formation. This would provide the first indications
that there are two distinct stages of encoding into episodic memory.
This episodic memory encoding model would distinguish between an
initial encoding process like novelty detection subserved by the
parahippocampal cortex and a process of memory formation subserved by
the hippocampus. This interpretation based on evidence derived across
studies needs further confirmation, but it provides a testable model
for future research.
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FOOTNOTES |
Received Oct. 3, 1997; revised Dec. 15, 1997; accepted Dec. 16, 1997.
H.J.H. is supported by Human Frontier Science Program Grant
RG0136/1997, Deutsche Forschungsgemeinschaft/Sonderforschungsbereich (DFG/SFB) Grant 426,C5, and DFG Grant He1531/4-1; G.R.M. is supported by Human Frontier Science Program Grant RG0136/1997 and National Institutes of Mental Health Grant MH55714; H.H. is supported by DFG/SFB
Grant 426,C5; and G.F. is supported by DFG Grant FE 479/1-1. We thank
James B. Brewer for detailed comments on earlier versions of this
article and instructive discussions about the data.
Correspondence should be addressed to Dr. Guillén
Fernández, Klinik für Neurophysiologie, Otto-von-Guericke
Universität, Magdeburg, Leipziger Strasse 44, 39120 Magdeburg,
Germany.
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Top
Abstract
Introduction
