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The Journal of Neuroscience, March 15, 1998, 18(6):2226-2230
Hippocampal Lesions Disrupt an Associative Mismatch Process
R. C.
Honey,
A.
Watt, and
M.
Good
School of Psychology, University of Wales, Cardiff CF1 3YG, United
Kingdom
 |
ABSTRACT |
Novel assays were used to assess inter alia whether the hippocampus
is involved in detecting novelty per se or in an associative mismatch
process. During training, rats received two audiovisual sequences
(tone-left constant light and click-left flashing light). In both
sham-operated control rats and those with excitotoxic hippocampal
lesions, novel visual targets provoked an orienting response that
habituated during training. Moreover, like sham-operated rats, rats
with hippocampal lesions acquired associations between the elements of
two audiovisual sequences. However, subsequent test trials in which the
auditory stimuli preceding the visual targets were switched
(click-left constant light and tone-left flashing light) provoked
renewed orienting to the visual targets in sham-operated rats but not
in hippocampal rats. These results support the view that hippocampal
damage results in a failure to detect (or act on) mismatches that are
generated when an auditory stimulus associatively evokes the memory of
one visual stimulus and a different (familiar) visual stimulus is
present in the environment.
Key words:
hippocampus; rat; orienting response; novelty; associative learning; associative mismatch process
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INTRODUCTION |
The process of novelty detection is
of fundamental importance; novel stimuli are accorded a special status
throughout the animal kingdom. For example, in many species the
presentation of a novel stimulus provokes an orienting response (OR)
(see Fig. 1a) that declines or habituates as the stimulus
becomes familiar. The mechanisms underlying the OR and its habituation
are, therefore, of importance in their own right and also provide a
common means to examine the processes of novelty detection across
different species. Traditional accounts of habituation suppose that the likelihood of an OR is determined by stimulus novelty per se with the
decline in the frequency of the OR simply reflecting an underlying reduction in the efficacy of a link between the neural processes activated by the stimulus and those responsible for generating the OR
(Horn and Hill, 1964 ; Groves and Thompson, 1970; Hawkins and Kandel,
1984) (for review, see Mackintosh, 1987; Hall, 1991). Recently,
however, we have demonstrated that the OR in rats is not solely
dependent on stimulus novelty (Honey et al., 1998). Rats received
habituation training with two audiovisual sequences (tone-left
constant light and click-left flashing light; see Fig. 1c).
After this training, renewed orienting to the visual targets was
observed when rats received mismatch trials on which the auditory stimuli that preceded the visual targets were exchanged (click-left constant light and tone-left flashing light; Honey et al., 1998). Given that this exchange resulted in no change in the physical properties of the visual stimuli, our findings suggest that an OR can
be triggered either when a novel visual stimulus is presented or when
there is an associative mismatch; in this case, a mismatch between the
memory of a visual stimulus that the presentation of the auditory
stimulus evokes by association and the familiar visual stimulus that is
present in the environment (Sokolov, 1963; Konorski, 1967; Wagner,
1981). Although there has been progress in understanding the neural
mechanisms underlying simple habituation phenomena (Horn and Hill,
1964; Groves and Thompson, 1970; Hawkins and Kandel, 1984), the neural
mechanisms that underlie the associative mismatch process are unknown.
Nevertheless, there has been long-standing speculation that the
hippocampus is a component of a novelty or mismatch detection system
(Sokolov, 1963; Vinogradova, 1975; Gray, 1982). This view has received
recent support from functional neuroimaging studies in humans (Squire
et al., 1992; Schacter et al., 1996; Tulving et al., 1996) and
electrophysiological recording in animals (O'Keefe, 1979; Rolls et
al., 1982; O'Keefe and Speakman, 1987) (for review, see Macphail,
1993). Accordingly, this study used rats with excitotoxic lesions of
the hippocampus and the novel procedures developed by Honey et al.
(1998) to examine the role of the hippocampus in novelty detection and
the associative mismatch process.
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MATERIALS AND METHODS |
Subjects and surgery. Sixty-two naive adult hooded
Lister rats served as subjects. Thirty rats received ibotenate acid
lesions of the hippocampus (Jarrard, 1989), and the remainder received sham operations. The surgical procedures were identical to those described by Honey and Good (1993). After a minimum of 2 weeks of
postoperative recovery, rats were gradually reduced to 80% of their
ad libitum weights. They were maintained at these weights throughout the habituation study. Rats were housed in pairs and had
free access to water when they were in their home cages. The colony
room in which the rats were housed was illuminated between the hours of
8:00 A.M. and 8:00 P.M.; training and testing began at ~9:00 A.M.
Behavioral procedures and apparatus. All experimental
sessions were conducted in two standard, experimental chambers (see Fig. 1a) that were identical to those used by Honey et al.
(1998). Aspects of the procedure that are not mentioned below were
identical to those described in Honey et al. (1998).
Training. On the first 2 d, animals were placed in the
experimental apparatus for 30 min. Subsequently, they received 4 d of training with two audiovisual sequences. One auditory stimulus (a 2 kHz tone presented at an intensity of 78 dB) preceded the constant
presentation of a small, 3 W covered light bulb, whereas a second
auditory stimulus (a 10 Hz series of clicks, also 78 dB) preceded the
flashing (alternating 25 csec on and off) presentation of a small 3 W
covered light bulb. All stimuli were 10 sec. For rats in the
associative mismatch condition (sham, n = 16;
hippocampal, n = 14), both visual stimuli emanated from
the left light source (left constant light and left flashing light; see
Fig. 1a), whereas for rats in the control mismatch condition
(sham, n = 16; hippocampal, n = 16),
one type of light was presented from the left source (left constant
light), and the other was presented from the right source (right
flashing light; see Fig. 1c). In the control mismatch condition, the frequency (constant or flashing) of the light that was
presented in a given spatial location was counterbalanced. In both
conditions, the identity of the auditory stimulus that preceded a given
visual target stimulus was counterbalanced. There were 10 presentations
of both audiovisual sequences on each of the first 3 d of training
and six presentations of both sequences on day 4 that served as warmup
trials for the eight test trials that immediately followed. The
interval between adjacent trials was 2 min.
Testing. Rats in both conditions received two types of test
trials, match and mismatch. The order in which the two types of test
trials were presented was counterbalanced. For rats in the associative
mismatch condition, match test trials were presentations of the same
audiovisual sequences that had been presented during training (e.g.,
tone-left constant light and click-left flashing light), whereas on
mismatch trials the auditory stimuli preceding the visual stimuli were
exchanged (click-left constant light and tone-left flashing light).
As we have already argued, the mismatch trials in our standard,
associative mismatch condition involve no change in the physical
identity of the visual target stimuli. Consequently, a restoration of
the OR on these trials must reflect the associative mismatch between
the memory evoked by the auditory stimulus and the familiar visual
stimulus that is presented to the rats. For rats in the control
mismatch condition, match test trials were presentations of the
audiovisual sequences presented during training (e.g., tone-left
constant light and click-right flashing light); however, on mismatch
trials the spatial and temporal properties of the lights were exchanged
(tone-left flashing light and click-right constant light). That is,
in the control mismatch condition, any associative mismatch is
accompanied by a change in the physical properties of the visual target
stimuli. Accordingly, a restoration of the OR on these trials might
simply reflect that the target lights are novel, if only because the
pattern of stimulation a flashing light produces on one side of the
apparatus (during training) will differ from the pattern that it
produces on the other side of the apparatus (on mismatch trials). The
inclusion of this condition thereby allows us to investigate a second
type of mismatch; there is already evidence to suggest such
(perceptual) mismatches are not mediated by the hippocampus (Ennaceur
and Aggleton, 1994).
Behavioral scoring. All experimental sessions were recorded
using a video recorder and subsequently scored by observers who were
blind to the group membership of the rats and the nature of the test
trials (match or mismatch). Our principle interest was in whether rats
oriented toward the visual, target stimuli. An OR was defined as the
tip of a rat's snout being located in the left side of the apparatus
that contained the light sources and pointing in the direction of the
light source (Honey et al., 1998). We were also interested in the
development of associations between the auditory stimuli and the visual
target stimuli during training. The spatial location of the rats during
training in the control mismatch condition provides a sensitive
behavioral index of the acquisition of these associations. Honey et al.
(1998) reported that rats show anticipatory responses during an
auditory stimulus that reflects the spatial location of the light with which it has been paired; for example, rats that have received tone-left constant light pairings and click-right flashing light pairings approach the quadrant of the experimental chamber adjacent to
the left light during the tone and adjacent to the right light during
the click. Accordingly, we also noted the location of the tip of each
rat's snout during the final second of the auditory stimuli,
immediately before presentations of the visual target stimuli. A
correct response was defined as the tip of the rat's snout being in
the quadrant of the experimental chamber adjacent to the light source
that was about to be illuminated; an incorrect response was defined as
the tip of the rat's snout being in the quadrant adjacent to the light
source that was not subsequently illuminated. Interobserver concordance
for each of our measures was >90%.
Water maze study. After the habituation study all rats were
returned to ad libitum food for a minimum of 1 week.
Subsequently, 23 sham-operated rats and 24 hippocampal rats received
training in a spatial, reference memory task in a water maze using an
apparatus and a training protocol identical to those described in Good
and Honey (1997). Briefly, on each of the 6 d of training, rats
received four trials with an intertrial interval of 30 sec. On each
trial the rats were released from a randomly selected point around the perimeter of the pool and were allowed to swim until they located a
hidden platform or until 2 min had elapsed, at which point the rat was
placed on the platform. For half of the rats in each group the platform
was placed in the northwest quadrant of the maze, and for the remainder
it was placed in the southeast quadrant. On day 7 the hidden platform
was removed, and rats were placed in the pool for 1 min. The percentage
of time rats spent in each quadrant of the maze was recorded. Of the
remaining rats that had taken part in the habituation study, one
sham-operated rat that was to receive training in the water maze task
became ill and died, and the other rats received training in a
different spatial learning task that is being developed by our
colleagues. Results from this task will not be reported here.
After the completion of behavioral testing, the lesioned animals
received injections of Euthatal and were perfused, and their brains
were removed and sectioned for histological analysis. A cresyl violet
stain was used to determine the extent of cell loss.
| |
RESULTS |
Histological analysis
Figure 1b shows
photomicrographs of horizontal sections taken at a mid-dorsoventral
level from a representative lesioned animal. All rats with lesions to
the hippocampus sustained >90% cell loss in the CA1-CA4 subfield of
the hippocampus and >90% cell loss in the dentate gyrus. All lesioned
animals showed complete cell loss in the dorsal and mid-dorsoventral
region of the hippocampal formation. Cell loss in the most ventral
aspects of the hippocampus was more variable between animals. More
specifically, cell loss in the CA fields and dentate gyrus in the most
ventral aspects of the hippocampus varied between 0 and 30%. However,
the extent of cell loss in these areas did not correlate with
performance during any part of this study. There was little or no
damage to adjacent areas such as the subiculum and no damage to the
entorhinal cortex.
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Figure 1.
a, Rat orienting toward a light
presented on the left side of the experimental apparatus with the video
camera that was used to record habituation training and test sessions
in the foreground. b, Photomicrographs of horizontal
sections taken at a mid-dorsoventral level from a representative
lesioned animal. c, Summary of the design of the study
in which rats received training with two audiovisual sequences and then
received test trials with the same sequences (match test trials) and
test trials in which the elements of the sequences were rearranged
(mismatch test trials; see Materials and Methods).
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Behavioral analysis
Associative learning
Figure 2a depicts the
mean percentages of trials on which sham-operated rats and hippocampal
rats from the control mismatch condition showed correct and incorrect
responses during the auditory stimuli over the course of training. An
ANOVA revealed an effect of response (correct vs incorrect)
[F(1,30) = 7.76; p < 0.01], an interaction between day and response
[F(2,60) = 3.70; p < 0.05], and no other effects or interactions (F < 1). Simple
main effects revealed differences in the percentages of trials with
correct and incorrect responses on days 2 and 3 [smallest
F(1,30) = 8.52; p < 0.01].
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Figure 2.
Behavior of rats that had received either sham
operations (sham) or excitotoxic lesions of the
hippocampus (hippocampal) during training and
testing. a, Behavior of rats in the control mismatch condition during the auditory stimuli across the 3 d of training. The mean percentages of trials on which rats correctly anticipated (correct response) or failed to anticipate (incorrect response) the
spatial location in which a light was about to be presented during the
terminal portion of the auditory elements of the audiovisual sequences
are shown. b, Behavior of rats in the control mismatch condition and the associative mismatch condition (pooled) during the
visual target stimuli across the 3 d of training. The mean percentages of trials on which the visual stimuli provoked an orienting
response are shown. c, d, Mean
percentages of trials on which the visual stimuli elicited an orienting
response on match and mismatch test trials in c, the
associative mismatch condition and d, the control
mismatch condition (see Materials and Methods).
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Habituation of the OR
The overall tendency for rats to orient toward the visual stimuli
in the two training conditions, 41.19% in sham-operated rats
(n = 32) and 38.52% in hippocampal rats
(n = 30), did not differ (F < 1). Each
day of training was divided into five blocks of four trials to monitor
between-day (long-term) habituation, within-day (short-term)
habituation, and spontaneous recovery of the OR from the end of one day
to the beginning of the next. Figure 2b shows the middle
block of training for the 3 d of training. There was an orderly
decline in the OR across days in both groups of animals. ANOVA revealed
an effect of day [F(2,120) = 4.32; p < 0.02], no effect of group, and no interaction
between these factors (F < 1). The percentages of
trials with an OR on the final block of each day in sham-operated rats
were 39.82% (day 1), 29.69% (day 2), and 39.06% (day 3); on the
first block of the following days they were 58.59% (day 2), 53.12%
(day 3), and 47.66% (day 4). Similarly, for hippocampal rats the
corresponding percentages for the final blocks were 30.83% (day 1),
34.17% (day 2), and 31.67% (day 3); on the first blocks of the
following days they were 51.67% (day 2), 47.50% (day 3), and 47.5%
(day 4). ANOVA revealed an effect of block
[F(1,60) = 42.06; p < 0.001]
and no other significant effects or interactions [largest
F(1,60) = 1.24; p > 0.27].
These results demonstrate that both within-day habituation and
spontaneous recovery of the OR from one day to the next were equivalent
in hippocampal and sham-operated rats.
Match and mismatch test trials
The percentages of trials with an OR during match and mismatch
test trials in the associative mismatch condition are shown in Figure
2c. ANOVA revealed an interaction between group and trial
type [F(1,28) = 7.98; p < 0.01], no effect of group [F(1,28) = 2.02;
p > 0.16], and no effect of trial type
(F < 1). Simple main effects revealed an effect of
trial type in sham-operated rats [F(1,28) = 5.73; p < 0.03], no effect in the hippocampal rats
[F(1,28) = 2.65; p > 0.11],
and a difference between the groups on mismatch trials
[F(1,53) = 8.13; p < 0.01],
but no such difference on match trials (F < 1). The
associative mismatch effect in sham-operated rats was, in fact, most
marked during the first half of the test: mismatch, 53.12%; match,
18.75% [F(1,15) = 8.44; p < 0.02] (see Honey et al., 1998). Associative mismatch trials, those
involving no change in the physical properties of the visual target
stimuli, result in a restoration of the OR in sham-operated rats but
have no such effect in hippocampal rats. A parallel ANOVA conducted on
the scores of the rats in the control mismatch condition shown in
Figure 2d revealed an effect of trial type
[F(1,30) = 9.28; p < 0.005],
no effect of group, and no interaction between these factors
(F < 1). Both groups of rats showed a restoration of
the OR on mismatch trials involving a change in the physical properties
of the visual, target stimuli.
Water maze study
After the habituation study, the majority of rats received
training in the benchmark assay of hippocampal damage, spatial learning
in the water maze. The mean escape latencies during the course of
training were significantly shorter for sham-operated rats
(n = 23; 43.28 sec) than for hippocampal rats
(n = 24; 57.53 sec) [F(1,45) = 10.03;
p < 0.005]. During the probe test, in which the
hidden platform was removed, sham-operated rats spent a significantly greater percentage of their time swimming in the quadrant of the pool
in which the hidden platform had been located previously (n = 23; 40.45%) than hippocampal rats
(n = 24; 26.28%) [F(1,45) = 14.21;
p < 0.001].
| |
DISCUSSION |
The contribution of the present study to our understanding of
hippocampal function is threefold. First, the results of this study
support the general contention that the hippocampus in the rat plays a
critical role in an associative mismatch process (Squire, 1992; Bunsey
and Eichenbaum, 1996) and in doing so provide further evidence that
this structure has a role in mnemonic processes beyond the spatial
domain (O'Keefe and Nadel, 1978; Morris et al., 1990; Gaffan, 1994).
The fact that the involvement of the hippocampus in this process is not
a concomitant of an underlying deficit in spatial information
processing is indicated by the finding that our hippocampal animals
readily responded to and acquired associations involving spatially
separated targets. Thus, insofar as our procedures have a spatial
component, howsoever limited, it is clear that rats with hippocampal
lesions were not affected by it. Second, our results indicate that a
simple process of novelty detection (Horn and Hill, 1964; Groves and
Thompson, 1970; Hawkins and Kandel, 1984) is dissociable from an
associative mismatch process (Sokolov, 1963; Konorski, 1967; Wagner,
1981). Generation of the OR to a novel stimulus and the subsequent
habituation of the OR proceeds normally without the involvement of the
hippocampus (Leaton, 1981; Han et al., 1995), but the influence of
associative mismatches on the OR requires the integrity of the
hippocampus (Vinogradova, 1975; Gray, 1982). This dissociation receives
further support from the observation that a change in the physical
properties of the visual target stimuli is sufficient to restore the
orienting response in hippocampal rats, whereas a purely associative
mismatch is not. Finally, the observation that rats with hippocampal
damage can learn stimulus-stimulus associations (Murray et al., 1993; Bunsey and Eichenbaum, 1996), in our case associations involving the
elements of two audiovisual sequences, is important because it allows
us to be more specific regarding the probable locus of the deficit in
the associative mismatch process. In particular, it suggests that the
deficit reflects that the hippocampus plays a pivotal role in detecting
(or acting on) retrieval-generated mismatches: in this instance,
mismatches between the memory of the visual stimulus associatively
retrieved by the presentation of an auditory stimulus and the visual
stimulus that is currently impinging on the animal. This conclusion is
clearly consistent with the more general suggestion that the
hippocampus is involved in the flexible expression of declarative
memory (Bunsey and Eichenbaum, 1996). Our results illustrate that this
involvement is quite general, occurring with stimuli from different
modalities, and is influential in mediating a response with a
conspicuous stimulus-processing component, the orienting response.
| |
FOOTNOTES |
Received Oct. 23, 1997; revised Dec. 17, 1997; accepted Dec. 22, 1997.
This research was funded by the Biotechnology and Biological Sciences
Research Council (UK), a Royal Society Equipment Grant, a Royal Society
University Research Fellowship, and the Schizophrenia Research Fund. We
thank K. L. Manser for help with the histological analysis.
Correspondence should be addressed to R. C. Honey, School of
Psychology, University of Wales, Cardiff, Tower Building, Park Place,
Cardiff CF1 3YG, UK.
| |
REFERENCES |
-
Bunsey M,
Eichenbaum H
(1996)
Conservation of hippocampal memory function in rats and humans.
Nature
379:255-257[Medline].
-
Ennaceur A,
Aggleton JP
(1994)
Spontaneous recognition of object configurations in rats: effects of fornix lesions.
Exp Brain Res
100:85-92[Web of Science][Medline].
-
Gaffan D
(1994)
Scene-specific memory for objects: a model of episodic memory impairment in monkeys with fornix transection.
J Cognit Neurosci
6:305-320.
-
Good M,
Honey RC
(1997)
Dissociable effects of selective lesions to hippocampal sub-systems on exploratory behavior, contextual learning and spatial learning.
Behav Neurosci
111:487-493[Web of Science][Medline].
-
Gray JA
(1982)
In: The neuropsychology of anxiety: an enquiry into functions of the septo-hippocampal system. Oxford: Oxford UP.
-
Groves PM,
Thompson RF
(1970)
Habituation: a dual-process theory.
Psychol Rev
77:419-450[Medline].
-
Hall G
(1991)
In: Perceptual and associative learning. Oxford: Clarendon.
-
Han J-S,
Gallagher M,
Holland P
(1995)
Hippocampal lesions disrupt decrements but not increments in conditioned stimulus processing.
J Neurosci
15:7323-7329[Abstract].
-
Hawkins RD,
Kandel ER
(1984)
Is there a cell biological alphabet for simple forms of learning?
Psychol Rev
91:375-391[Web of Science][Medline].
-
Honey RC,
Good M
(1993)
Selective hippocampal lesions abolish the contextual specificity of latent inhibition and conditioning.
Behav Neurosci
107:23-33[Web of Science][Medline].
-
Honey RC, Good M, Manser KL (1998) Negative priming in
associative learning: evidence from a serial-habituation procedure. J
Exp Psychol Anim Behav Process, in press.
-
Horn G,
Hill RM
(1964)
Habituation of the response to sensory stimuli of neurones in the brain stem of rabbits.
Nature
202:296-298.
-
Jarrard LE
(1989)
On the use of ibotenic acid to lesion selectively different components of the hippocampal formation.
J Neurosci Methods
29:251-259[Web of Science][Medline].
-
Konorski J
(1967)
In: Integrative activity of the brain. Chicago: University of Chicago.
-
Leaton RN
(1981)
Habituation of the startle response, lick suppression, and exploratory behavior in rats with hippocampal lesions.
J Comp Physiol Psychol
95:813-820[Web of Science][Medline].
-
Mackintosh NJ
(1987)
Neurobiology, psychology and habituation.
Behav Res Ther
12:81-97.
-
Macphail EM
(1993)
In: The neuroscience of learning and memory: from the seahare to the seahorse. New York: Columbia UP.
-
Morris RGM,
Schenk F,
Tweedie F,
Jarrard LE
(1990)
Ibotenate lesions of the hippocampus and/or subiculum: dissociating components of allocentric spatial learning.
Eur J Neurosci
2:1016-1028[Web of Science][Medline].
-
Murray EA,
Gaffan D,
Mishkin M
(1993)
Neural substrates of visual stimulus-stimulus association in rhesus monkeys.
J Neurosci
13:4549-4561[Abstract].
-
O'Keefe J
(1979)
A review of hippocampal place cells.
Prog Neurobiol
13:419-439[Web of Science][Medline].
-
O'Keefe J,
Nadel L
(1978)
In: The hippocampus as a cognitive map. Oxford: Oxford UP.
-
O'Keefe J,
Speakman A
(1987)
Single unit activity in the rat hippocampus during a spatial memory task.
Exp Brain Res
68:1-27[Web of Science][Medline].
-
Rolls ET,
Perret DI,
Caan AW,
Wilson FW
(1982)
Neuronal responses related to visual recognition.
Brain
105:611-646[Abstract/Free Full Text].
-
Schacter DL,
Alpert NM,
Savage CR,
Rauch SL,
Albert MS
(1996)
Conscious recollection and the human hippocampal formation: evidence from positron emission tomography.
Proc Natl Acad Sci USA
10:131-135.
-
Sokolov EN
(1963)
In: Perception and the conditioned reflex. London: Pergamon.
-
Squire LR
(1992)
Memory and the hippocampus: a synthesis from findings with rats, monkeys and humans.
Psychol Rev
99:195-231[Web of Science][Medline].
-
Squire LR,
Ojemann JG,
Miezin FM,
Petersen SE,
Videen TP
(1992)
Activation of the hippocampus in normal humans: a functional anatomical study of memory.
Proc Natl Acad Sci USA
89:1837-1841[Abstract/Free Full Text].
-
Tulving E,
Markowitsch HJ,
Craik FIM,
Habib R,
Houle S
(1996)
Novelty and familiarity activations in PET studies of memory encoding and retrieval.
Cereb Cortex
6:71-99[Abstract/Free Full Text].
-
Vinogradova OS
(1975)
Registration of information and the limbic system.
In: Short-term changes in the neural activity and behavior (Horn G,
Hinde RA,
eds), pp 95-148. Cambridge: Cambridge UP.
-
Wagner AR
(1981)
SOP: a model of automatic memory processing in animal behavior.
In: Information processing in animals: memory mechanisms (Spear NE,
Miller RR,
eds), pp 5-48. Hillsdale, NJ: Erlbaum.
Copyright © 1998 Society for Neuroscience 0270-6474/98/1862226-05$05.00/0
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A. Ploghaus, I. Tracey, S. Clare, J. S. Gati, J. N. P. Rawlins, and P. M. Matthews
Learning about pain: The neural substrate of the prediction error for aversive events
PNAS,
August 1, 2000;
97(16):
9281 - 9286.
[Abstract]
[Full Text]
[PDF]
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Abstract
Introduction
