DOI 10.1515/revneuro-2012-0049 Rev. Neurosci.

2012; 23(5-6): 627643

Jarid Goodman, Kah-Chung Leong and Mark G. Packard*

Emotional modulation of multiple memory

systems: implications for the neurobiology
of post-traumatic stress disorder
Abstract: In lower animals and humans, stress/anxiety
can enhance dorsal striatal-dependent habit memory,
Introduction
at the expense of hippocampal-dependent cognitive
A major goal of the behavioral sciences is to identify the
memory. The present review considers the potential for
contributing factors in the development and persistence
this stress/anxiety-induced habit bias to explain some
of human psychopathologies. In the context of learning
aspects of post-traumatic stress disorder (PTSD). In rats,
theory, researchers have developed various stimulus
anxiety induced by peripheral or intra-amygdala infu-
stimulus or stimulus-response (S-R) learning paradigms
sions of anxiogenic drugs can enhance habit memory and
that putatively generate experimental neuroses in
impair cognitive memory. In tasks in which both habit
lower animals and have suggested that learning in these
and cognitive memory processes may provide a learned
situations may reflect the development of neuroses in
solution, stress and drug-induced anxiety favors the use
humans as well (Mowrer, 1947; Wolpe, 1952; Eysenck,
of habit memory. The effect of stress and anxiety on the
1976). Building on these earlier models and considering
use of multiple memory systems in rats depends on the
the modern multiple brain systems approach to learn-
functional integrity of the basolateral amygdala. Thus,
ing and memory, recent theories have proposed that the
under robust emotional arousal, amygdala activation can
development and persistence of some psychopathologies
modulate the relative use of memory systems in a manner
may arise from the differential involvement of neuroana-
that favors habit memory. We propose a similar mecha-
tomically distinct memory systems (e.g., White, 1996;
nism may underlie the development and persistence of
McDonald et al., 2004; Packard, 2009). More specifically,
some PTSD symptoms. The traumatic memories of PTSD
it has been suggested that some psychological disorders,
patients can be deficient in hippocampus-dependent
particularly those characterized by strong habit-like
contextual or autobiographical aspects, and enhanced
behavioral features, may reflect a shift from the use of
in responding to trauma-related cues, which we suggest
a hippocampal-dependent cognitive memory system
may reflect increased involvement of the dorsal striatum.
towards a dorsal striatal-dependent habit memory
We briefly consider the potential role of a stress/anxiety-
system.
induced habit bias with regard to other psychopatholo-
In dual solution tasks that can be solved adequately
gies, including obsessive-compulsive disorder and drug
with either a habit- or cognitive-based learning system,
addiction.
pre-training, post-training or pre-retrieval drug-induced
anxiety biases animals towards the use of habit memory
Keywords: anxiety; brain; memory; stress; posttraumatic
(for a review, see Packard, 2009). This anxiety-induced
stress disorder.
habit bias may be mediated by a dynamic interplay among
the amygdala, hippocampus and dorsal striatum (Packard
*Corresponding author: Mark G. Packard, Department of and Wingard, 2004; Elliot and Packard, 2008; Wingard and
Psychology, Texas A&M University, College Station, TX 77843, USA, Packard, 2008; Packard and Gabriele, 2009). Specifically,
e-mail: mgp@psyc.tamu.edu in some learning situations that occur under high levels of
Jarid Goodman: Department of Psychology, Texas A&M University,
emotional arousal, activation of the amygdala can modu-
College Station, TX 77843, USA
Kah-Chung Leong: Department of Psychology, Texas A&M late memory in a manner that favors the use of dorsal str-
University, College Station, TX 77843, USA iatal-dependent habit memory over hippocampal-depend-
ent cognitive memory. Considering both the potential
role of anxiety and S-R learning in post-traumatic stress
disorder (PTSD), it is possible that interactions among the
amygdala, hippocampus, and dorsal striatum may under-

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628 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
lie some aspects of the disorder (Packard, 2009). In the
present review, we further examine the stress-induced
habit bias as a potential model for the development, per-
sistence and expression of some PTSD symptoms.
We begin by considering the literature on the emo-
tional modulation of multiple memory systems in lower
animals, describing research indicating that stress/
anxiety can facilitate dorsal striatal-dependent habit
memory, and that this effect depends on a modulatory
influence of the basolateral amygdala (BLA). In some
learning situations, the stress/anxiety-induced bias
towards the use of habit memory may arise via an impair-
ing effect on hippocampal-dependent memory. Recent
evidence indicating that the stress-induced habit bias
observed in lower animals may also exist in humans is
briefly discussed. The symptomatology and diagnostic
criteria for PTSD are summarized, and various models
of PTSD that implicate multiple memory systems are
described. Considering both the animal literature and
the symptomatic features of PTSD, we propose that the
stress/anxiety-induced habit bias observed in lower
animals may underlie some PTSD symptoms, namely
the acquisition and expression of maladaptive behavio-
ral responses to trauma-related cues. In this context, we
review findings from relevant human behavioral and neu-
roimaging experiments. It is important to note that a wide
variety of brain structures have been implicated in PTSD
(for a recent review, see Hughes and Shin, 2011) and that
this review will focus selectively on the potential roles
of the amygdala, hippocampus and dorsal striatum in
PTSD. Finally, whether the stress/anxiety-induced habit
bias may influence the neurobiological and behavioral
aspects of other human psychopathologies (e.g., drug
addiction and relapse, obsessive-compulsive disorder,
etc.) is briefly considered.
Multiple memory systems in the
mammalian brain
The hypothesis that memory is organized in multiple
systems in the mammalian brain is supported by exten-
sive evidence from studies in lower animals and humans
(for reviews, see White and McDonald, 2002; Squire,
2004). Numerous theories describing the psychological
operating principles that may distinguish different forms
of memory have been proposed (e.g., Hirsh, 1974; OKeefe
and Nadel, 1978; Mishkin and Petri, 1984; for a review, see
Kesner, 1998). Several of these theories typically draw a
distinction between a Tolmanian (Tolman, 1932) or cog-
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nitive form of learning and memory mediated by a brain
system that includes the hippocampus as a critical com-
ponent, and a Hullian (Hull, 1943) or S-R habit form of
learning mediated by a non-hippocampal-based memory
system. Subsequent neurobiological studies employing
dissociation methodology provide evidence that the hip-
pocampus and dorsal striatum mediate cognitive and
S-R habit forms of memory, respectively. For example, in
rats, lesions of the hippocampal system selectively impair
the acquisition of cognitive tasks that require learning
relationships among multiple stimuli in both spatial (for
a review, see OKeefe and Nadel, 1978) and non-spatial
(Bunsey and Eichenbaum, 1996) domains. In contrast,
lesions of the caudate-putamen (i.e., dorsal striatum)
selectively impair the acquisition of several S-R or habit-
learning tasks (for a review, see Packard and Knowlton,
2002).
An early experiment in rats demonstrating a double
dissociation between the mnemonic functions of the hip-
pocampal system and dorsal striatum used two versions
of a radial maze task. In the win-shift or cognitive version
of the task (Olton and Samuelson, 1976), each maze arm
is baited once during a daily session and rats learn to
forage among the various spatial locations and to not
return to those maze arms in which food has already been
acquired. Acquisition of this task is severely impaired by
lesions of the hippocampal system (Olton et al., 1979), but
not by lesions of the dorsal striatum (Packard et al., 1989;
McDonald and White, 1994). In a win-stay or S-R habit
version of the task, rats are reinforced for learning to
selectively approach illuminated maze arms. Acquisition
of this task is severely impaired by lesions of the dorsal
striatum, but not by lesions of the hippocampal system
(Packard et al., 1989). Similarly, in a dual-solution plus-
maze task that can be acquired using either Tolmanian
place or Hullian response learning, neural inactivation
of the dorsal hippocampus selectively blocks the use of
place learning, whereas neural inactivation of the dor-
solateral striatum selectively blocks the use of response
learning (Packard and McGaugh, 1996).
Double dissociations between the roles of the hip-
pocampus and dorsal striatum in cognitive and habit
memory are also observed following post-training intrac-
erebral drug injections (e.g., Packard and White, 1991;
Packard et al., 1994; Packard and Teather, 1997, 1998).
Thus, post-training intra-hippocampal injections of
dopaminergic agonists selectively facilitate memory in the
win-shift radial maze task described above, whereas
similar injections into the dorsal striatum selectively facil-
itate memory in the win-stay radial maze task (Packard
and White, 1991).
 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
Importantly, when considered across studies, double
dissociations between the mnemonic functions of the hip-
pocampus and the dorsal striatum in cognitive and habit
memory have also been demonstrated in other mam-
malian species, including monkeys and humans (for a
review, see Packard, 2010).
Emotional arousal and the relative
use of multiple memory systems
In view of the evidence that the hippocampus and dorsal
striatum mediate cognitive and habit memory respectively,
studies have begun to focus on factors that can influence
the relative use of these two memory systems in various
learning situations. In our laboratory we have investigated
the hypothesis that robust emotional arousal induced by
stress or anxiety can influence the use of multiple memory
systems in rats. The results of several studies now indicate
that in learning situations in which both the hippocam-
pal and dorsal striatal memory systems can provide an
adequate learned solution, acute stress or drug-induced
anxiety can bias animals towards the use of dorsal stri-
atal-dependent habit memory. In one study (Packard and
Wingard, 2004) rats were trained in a dual-solution water
plus-maze task to swim from the same start position on
each trial (i.e., the south arm), and reach a hidden escape
platform that was always located in the same location
(i.e., the west arm). In this task, making the same body
turn response and approaching the same spatial location
are reinforced, and thus this task can be acquired using
either hippocampal-dependent place learning or dorsal
striatal-dependent response learning. Following acquisi-
tion, the use of these learning strategies can be assessed
on a probe trial in which rats are started from the oppo-
site start arm of the plus-maze (i.e., the north arm). In the
probe trial, rats that swim to the maze arm that contained
the platform during training were designated place learn-
ers, whereas rats that made the same body turn response
that was consistently reinforced (in this example, a left
turn at the maze choice point) were designated response
learners. In order to assess the effect of drug-induced
anxiety on the use of these two learning strategies, rats
received pre-training peripheral injections of yohimbine
or RS 79948197, two drugs that act as -2 adrenorecep-
tor antagonists and possess anxiogenic properties in rats
(e.g., Handley and Mithani, 1984; Guy and Gardner, 1985;
White and Birkle, 2001). On a drug-free probe trial follow-
ing task acquisition, vehicle-treated rats predominantly
displayed place learning. In contrast, rats treated with
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629
the anxiogenic drugs predominantly displayed response
learning (Packard and Wingard, 2004). A bias towards the
use of response learning in the dual-solution water maze
task is also observed if an anxiogenic dose of RS 79948
197 is peripherally injected prior to memory retrieval
(Elliot and Packard, 2008).
Consistent with these findings, rats exposed to a
pre-training stress regimen consisting of restraint stress
and intermittent tail-shock also displayed a bias towards
the use of dorsal striatal-dependent habit learning (Kim
et al., 2001), and lower levels of trait anxiety positively
correlated with place recognition memory and with a pref-
erence for the use of hippocampal-dependent place learn-
ing (Hawley et al., 2011). Taken together, experiments in
lower animals involving exposure to acute stress or drug-
induced anxiety suggest that in some learning situations,
robust levels of emotional arousal can bias the brain
towards the use of a habit memory system.
Emotional modulation of cognitive
and habit memory: role of the
basolateral amygdala
We have recently investigated the BLA as a potential
neural site of action that mediates the modulatory influ-
ence of drug-induced anxiety on the relative use of multi-
ple memory systems. A possible role for this brain region
is suggested by evidence that the BLA is involved in
mammalian emotional behavior, including the ability of
various drugs to produce anxiety (e.g., Kluver and Bucy,
1939; Nagy et al., 1979; Scheel-Kruger and Petersen, 1982;
Sanders and Shekhar, 1991). In addition, the BLA exerts a
modulatory influence on memory processes occurring in
several other brain structures, including the hippocam-
pus and dorsal striatum (Packard et al., 1994, 1996;
Packard and Teather 1998; Roozendaal and McGaugh,
1996, 1997). In an experiment investigating the effect of
pre-training injections of RS 79948197 directly into the
BLA, we observed that this treatment was sufficient to
produce the same bias towards the use of response learn-
ing in a dual-solution plus-maze task that is produced by
peripheral injections of the drug (Packard and Wingard,
2004). Thus, in a task in which both hippocampal-
dependent place learning and dorsal striatal-dependent
response learning can provide an adequate solution,
peripheral or intra-BLA injections of an anxiogenic dose
of RS 79948197 favors a facilitated use of response
learning.
630 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
One possible explanation for this modulatory influ-
ence of anxiogenic drugs in the dual-solution plus maze
task is that the drug activates BLA efferent projections and
directly enhances dorsal striatal-dependent memory pro-
cesses. Alternatively, it is possible that the drug activates
BLA efferents in a manner that impairs hippocampal-
dependent memory processes, effectively allowing the
dorsal striatum to guide the expression of learned behav-
ior. In order to examine these two possibilities, rats were
trained in single-solution plus-maze tasks that required
animals to employ either response or place learning. In
the single-solution water plus-maze tasks, the start points
varied across trials between north and south. For the
place task, rats learned to approach the same spatial loca-
tion to reach the escape platform (i.e., the west arm), and
the body turn response at the choice point (i.e., the left or
right) was equally reinforced across trials. Thus, response
learning could not provide an adequate solution. For the
response task, rats were required to always make the
same body turn response (i.e., left) at the choice point to
reach the escape platform, and the spatial location of the
platform varied equally across trials. Post-training intra-
BLA injections of an anxiogenic dose of RS 79948197
enhanced acquisition of the response learning task and
impaired acquisition of the place learning task (Wingard
and Packard, 2008). Interestingly, the same pattern of
results in these two tasks was observed following post-
training neural inactivation of the dorsal hippocampus
(Schroeder et al., 2002). Therefore, the bias towards the
use of response learning produced by intra-BLA injections
of RS 79948197 was effectively mimicked by a reversible
lesion of the hippocampus. Taken together, these findings
suggest that intra-BLA administration of this anxiogenic
drug impairs the modulatory influence on hippocampal-
dependent cognitive memory, resulting in a reliance on
dorsal striatal-dependent habit memory. Consistent with
this suggestion, neural inactivation of the BLA blocks both
the impairing and enhancing memory modulatory effects
of peripheral injections of RS 79948197 on response and
place learning, respectively (Packard and Gabriele, 2009).
Emotional arousal and multiple
memory systems in humans
Recent research suggests that the effects of emotional
arousal on multiple memory systems observed in lower
animals may also exist in humans. Specifically, in some
learning situations, acute or chronic stress can bias
humans towards the use of a S-R habit-learning strategy,
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at the expense of a more cognitive learning strategy. For
example, when trained to locate a win-card in a three-
dimensional model of a room, humans exposed to an
acute stressor (i.e., public speaking) were more likely to
associate a proximal cue with the location of the win-card
(i.e., a S-R strategy), as opposed to integrating the contex-
tual elements of the room to locate the card (i.e., a spatial
strategy; Schwabe et al., 2007). Subjects with higher
scores on a chronic stress questionnaire were also more
likely to be S-R learners, as opposed to spatial learners, in
a two-dimensional version of the win-card task (Schwabe
et al., 2008). Thus, consistent with the lower animal find-
ings described earlier, both acute and chronic stress may
shift humans towards the use of habit learning in dual
solution tasks.
Consistent with these findings, emotional arousal
at the time of encoding enhances retention in a proba-
bilistic classification weather prediction task (Steidl
et al., 2006, 2011). In addition, human subjects exposed to
the socially-evaluated cold pressor test were more likely to
engage in habitual behavior as opposed to goal-directed
behavior in a food-devaluation paradigm (Schwabe and
Wolf, 2009). Importantly, learning in the weather predic-
tion task and habitual behavior in the food-devaluation
paradigm depend, in part, upon the dorsal striatum
(Knowlton et al., 1996; Poldrack et al., 1999; Tricomi et al.,
2009).
As suggested in lower animals, the stress/anxiety-
induced facilitation of habit memory in humans may
also stem from an impairment of hippocampal-depend-
ent memory. Several studies in humans indicate that
high levels of stress at the time of encoding or retrieval
impair learning in hippocampal-dependent memory tasks
(Schwabe et al., 2009; Merz et al., 2010; Schwabe and
Wolf, 2010; Thomas et al., 2010). Interestingly, subjects
with lower scores in episodic memory tasks were more
likely to be response learners in a dual-solution virtual
maze task (Bohbot et al., 2011). The observation that
impaired hippocampal-dependent memory may result in
a greater use of an S-R strategy suggests that the stress-
induced facilitation of habit memory may arise indirectly,
i.e., through stress-induced impairments of the hippocam-
pal-dependent memory system. Consistent with this
interpretation, stressful life events have been associated
with reduced gray matter volume of the hippocampus
in humans (Papagni et al., 2011), and lower gray matter
volume of the hippocampus has been associated with
the use of an S-R strategy in a dual-solution virtual maze
(Bohbot et al., 2011).
Taken together, findings from investigating the effects
of emotional arousal on multiple memory systems in
 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
humans reflect the lower animal literature. In humans
and lower animals, acute or chronic stress can produce a
bias towards the use of striatal-dependent habit memory,
at the expense of hippocampal-dependent cognitive
memory. The existence of a stress/anxiety-induced habit
bias in humans provides further reason for considering
the phenomenon as a potential mechanism underlying
some human psychopathologies.
We now consider the hypothesis that a stress-induced
bias towards the use of dorsal striatal-dependent habit
memory may underlie some of the symptomatology of
PTSD. We begin with a review of PTSD symptomatology
and a description of multiple memory systems theories
of PTSD. Subsequently, we briefly review evidence from
human neuroimaging studies indicating a role for the
amygdala, hippocampus and dorsal striatum in PTSD
symptoms. Finally, we consider the converging evidence
indicating a stress-induced bias towards the use of habit
memory and its implications for PTSD.
Introduction to PTSD
symptomatology
The Diagnostic and Statistical Manual of Mental Dis-
orders text revision (DSM IV-TR; American Psychiatric
Association, 2000) classifies PTSD as an anxiety disorder
that may develop after experiencing a traumatic event.
According to the DSM IV-TR, the traumatic episode itself
must have included actual or anticipated threats of death
or serious injury to oneself or others, and the traumatic
episode must have instilled within the patient intense
feelings of fear, helplessness or horror. In addition, the
patient must persistently re-experience the traumatic
episode. This re-experiencing may occur through intru-
sive recollections of the event (taking the form of mental
images, thoughts, or perceptions), a sense that the trau-
matic event is actually recurring, emotional or physiolog-
ical reactivity to internal or external cues that somehow
represent the traumatic event, or recurrent nightmares
of the event. Importantly, these recollections often arise
involuntarily. In fact, in many cases, a patients ability
to recall the event voluntarily proves to be impaired.
The phenomenon of impaired recall falls under the fol-
lowing criterion: in order to make a PTSD diagnosis, a
patient must display several avoidance behaviors; this
avoidance may include efforts to avoid stimuli that might
incite involuntary recollection, or may manifest itself as
the inability to voluntarily recall important aspects of the
traumatic event.
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631
When considering the PTSD symptoms that relate
to memory processes, an interesting paradox emerges.
Specifically, the DSM IV-TR suggests that PTSD patients
may potentially exhibit both enhanced and impaired
memory of the traumatic event. Enhancements of the
traumatic memory become evident through the excep-
tionally vivid and involuntary re-experiencing, or flash-
backs, of the event. Such flashbacks are characterized
as being triggered by trauma-related internal cues (e.g.,
anxiety) or external cues (e.g., loud noises) and as con-
taining vivid perceptual features from the event, such as
sounds, smells, and images. Importantly, when a patient
experiences a flashback, he or she feels the event is actu-
ally recurring, as if it were part of the present instead of
the past. These observations suggest that the version of
the traumatic memory that is readily and involuntarily
invoked by cues fails to acknowledge the spatial or tem-
poral context in which the event originally took place.
This lack of contextual content may be viewed as one of
the many impairments commonly observed in traumatic
memories. Other impairments in traumatic memory
become evident through the patients inability to recall
certain aspects of the event. Thus, amnesia, memory gaps
and fragmentary recall of the traumatic event are rela-
tively common features in PTSD (van der Kolk and Fisler,
1995; Koss et al., 1996; Shalev et al., 1996; Tichenor et al.,
1996; Mechanic et al., 1998; Yovell et al., 2003). Although
a concomitant enhancement and impairment of traumatic
memory may be difficult to explain via a unitary model
of memory, these seemingly antagonistic effects may
be explained more readily through a multiple memory
systems approach.
Multiple memory systems in PTSD
In view of the evidence reviewed earlier indicating that
the mammalian brain contains multiple memory systems,
the enhancement and impairment of traumatic memory
in PTSD may be explained by hypothesizing differen-
tial involvement of distinct memory systems. Thus, one
memory system may be highly active and lead to biased
encoding of certain features, and another memory system
may be relatively inactive and fail to encode other features
of the traumatic event. Interestingly, evidence that more
than one memory system encode traumatic memories in
PTSD arises from case studies involving traumatic brain
injury (TBI). TBI occurring during a traumatic event may
produce both anterograde and retrograde amnesia for the
event. However, in some cases patients with TBI-induced
632 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
amnesia may also develop PTSD-like symptoms, and these
symptoms may prove sufficient for making a full (or at
least partial) diagnosis of PTSD (Horton and Barrett, 1991;
McMillan, 1991; Layton and Wardi-Zonna, 1995; Bryant,
1996; McMillan, 1996; King, 1997; McGrath, 1997; Warden
et al., 1997; Krikorian and Layton, 1998; Podoll et al.,
2000a, b; Creamer et al., 2005; Bryant et al., 2009). Although
TBI may prevent conscious recall of the traumatic event, a
patient may re-experience the trauma through recurrent
nightmares or through emotional and physiological reac-
tivity to cues that in some manner represent the trauma. For
example, in one case study, a 19-year-old male developed
PTSD symptoms after a motor vehicle accident that caused
TBI and consequent amnesia of the event (see Podoll
et al., 2000a). Despite having no memory of the accident,
the patient experienced recurrent nightmares involving
two lights appearing like the headlights of an approach-
ing motor vehicle and the feeling of a shock or concussion
going through the whole body. The patient would also
experience intense psychological distress when driving
past the location of the accident or when seeing another
accident on the road, and he avoided riding in vehicles
of the same make and model as the one he was driving
during the crash. The patient displayed all these symptoms
without having any conscious memory of the accident.
Case studies such as this suggest that although a traumatic
memory may not be stored or recalled at a conscious level,
some remnants of the event may be preserved at a com-
paratively less conscious level. This view is consistent with
the idea of at least two distinct memory systems: one medi-
ating conscious memory of the event (a cognitive, declara-
tive, explicit system) and another mediating latent memory
of the event (a habit, non-declarative, implicit system).
Thus, TBI may impair the ability of the cognitive system to
encode and consciously recall the traumatic event, while
sparing the non-declarative/habit memory systems ability
to encode and store the memory at a relatively unconscious
level (Layton and Wardi-Zonna, 1995). The unimpaired
non-declarative/habit system may then in part subserve
the avoidance and emotional reactivity to trauma-related
cues. Finally, it is also important to note that TBI-induced
amnesia resembles the memory impairments observed in
PTSD patients without TBI. For example, in both PTSD
patients with TBI and PTSD patients without TBI, volun-
tary recall of certain aspects proves to be impaired, while
involuntary re-experiencing remains intact (e.g., Podoll
et al., 2000b; Yovell et al., 2003). Therefore, an impairment
of the cognitive/declarative memory system and a concom-
itant preservation of the non-declarative/habit memory
system may be relatively common processes underlying
traumatic memories in PTSD.
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Interestingly, contemporary psychological theories
surrounding PTSD often implicate more than one memory
system to explain the development and persistence of
PTSD symptoms. For example, the dual representation
theory (Brewin et al., 1996) suggests the existence of a ver-
bally accessible memory (VAM) system and a situation-
ally accessible memory (SAM) system. The VAM system
mediates memories that are easily retrieved through
voluntary recall. These memories often contain contex-
tual aspects of the event (i.e., time and place) and are
usually integrated with other autobiographical memories.
However, the VAM system can only encode information
that is consciously attended to during the event. There-
fore, considering that a person amidst trauma may focus
his or her attention selectively on the immediate source of
the threat, the VAM system may fail to encode the contex-
tual aspects (i.e., time and place) surrounding the trauma.
Unlike the VAM system, the SAM system is postulated to
mediate memories that fail to be recalled voluntarily. Mem-
ories mediated by the SAM system are instead triggered
involuntarily through situational reminders (e.g., internal
or external cues). These memories may contain informa-
tion from lower-level processes (e.g., sights, sounds and
smells), the emotions felt during the experience (e.g., fear
and helplessness), and the bodys initial responses to the
trauma (e.g., a change in heart rate). Therefore, when the
SAM memory is later triggered by a situational reminder,
the patient re-experiences the perceptions, emotions and
bodily responses from the traumatic event. These features
recalled through the SAM system culminate into a highly
distressing flashback.
Similarly, Ehlers and Clark (2000) propose a cogni-
tive model for PTSD that implicates two distinct systems.
The authors suggest that, like other memories, trauma
memory may be encoded through either conceptual or
data-driven processing. Through conceptual processing,
the mind encodes the meaning of the event and organizes
the memory within its appropriate context, allowing the
memory to be voluntarily retrieved at a later time. Accord-
ing to the authors hypothesis, trauma victims that use
conceptual processing during the event do not develop
persistent PTSD. In contrast, through data-driven pro-
cessing the mind encodes the sensory impressions of the
event, priming the individual to later readily respond to
cues that resemble these impressions. Trauma victims
that had used data-driven processing during the event fail
to recall the event voluntarily, yet show enhanced invol-
untary recall when cued. According to the model, more
data-driven processing (relative to conceptual processing)
increases the chance that a trauma victim will develop
long-lasting PTSD symptoms. Consistent with this inter-
 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder 633

pretation, several studies using analogues of traumatic Evidence the amygdala has a role
experiences (e.g., watching a traumatic film) found that
a tendency to use data-driven processing was associated in PTSD
with greater PTSD-like symptoms, most notably the devel-
In view of the role of the mammalian amygdala in stim-
opment of intrusive recollections (Halligan et al., 2002;
ulus-affect learning (for reviews, see Maren, 2001; White
Evans et al., 2007; Kindt et al., 2008; McKinnon et al.,
and McDonald, 2002; Davis, 2003; LeDoux, 2003) and in
2008; Ehlers et al., 2010; Laposa and Rector, 2012; Regam-
the emotional modulation of multiple memory systems
bal and Alden, 2012).
(for reviews, see Packard and Cahill, 2001; McGaugh,
There are several neurobiological models of PTSD
2004), it is perhaps not surprising that numerous studies
that incorporate more than one memory system (Layton
have implicated this brain structure in PTSD symptoma-
and Wardi-Zonna, 1995; Nadel and Jacobs, 1998; Brewin,
tology. Using various neuroimaging techniques, studies
2001; Layton and Krikorian, 2002; Rauch et al., 2006).
have consistently revealed increased activation of the
These neurobiological theories suggest, in part, that the
amygdala in PTSD subjects (Hughes and Shin, 2011). For
concomitant impairment and enhancement of traumatic
example, amygdala activation is increased in combat
memory observed in PTSD may be explained through dif-
veterans with PTSD in response to both combat-related
ferential involvement of the hippocampus and amygdala.
noises (Liberzon et al., 1999) and odors (Vermetten et al.,
For example, Layton and Krikorian (2002) propose that
2007), suggesting that the amygdala may be involved in
as a situation increases in emotional intensity the amyg-
the discrete-cued recall of the traumatic event. In another
dala becomes progressively more involved in the encod-
study, Vietnam veterans with PTSD listened to a script
ing process. At moderate levels of arousal, the amygdala
describing a traumatic event that the subject had actually
enhances hippocampal function, thus strengthening the
experienced during the war (Shin et al., 2004). Positron
consolidation of aspects of the event dependent on the
emission tomography scans revealed that the regional cer-
hippocampus (e.g., contextual aspects, integration of
ebral blood flow in the right amygdala maintained a posi-
the event into autobiographical memory, etc.). However,
tive correlation with the severity of PTSD symptoms. Using
at extreme levels of emotional intensity (such as those
similar techniques, several other studies have established
experienced under trauma) the amygdala inhibits hip-
positive correlations between amygdala activation and
pocampal function, thus leading to impairments in the
PTSD symptom severity (Rauch et al., 2000; Pissiota
consolidation of hippocampal-dependent features of
et al., 2002; Armony et al., 2005; Bryant et al., 2005;
the event. At the same time, the amygdala encodes and
Protopopescu et al., 2005; Dickie et al., 2008; Brunetti
consolidates its own version of the traumatic event,
et al., 2010). Conversely, there is evidence that in sub-
serving as the predominant locus of consolidation of
jects exposed to trauma, decreased amygdala activation
the traumatic memory. According to this hypothesis, the
may actually be associated with a failure to develop PTSD
traumatic memory mediated by the amygdala remains
(Britton et al., 2005; Osuch et al., 2008). Taken together,
noncontexual and highly emotional (two characteris-
the evidence suggests that the amygdala is likely to be
tics that are common to PTSD flashbacks). It should be
involved in the development, and potentially the expres-
noted that this view of the mnemonic role of the amyg-
sion, of PTSD symptoms. As the amygdaloid nuclei project
dala in PTSD is consistent with extensive research in
to several brain structures related to different types of
lower animals indicating that this brain structure has a
learning and memory (McGaugh, 2004), it may also be
role in fear conditioning (e.g., Davis, 1992; Maren, 2001;
reasonable to infer that heightened amygdala activation
LeDoux, 2003). In addition, neurobiological models of
during and after a traumatic event may modulate memory
PTSD (e.g., Layton and Krikorian, 2002) remain con-
via an interaction with other brain structures as well.
gruent with contemporary psychological theories. For
example, both VAM vs. SAM and conceptual vs. data-
driven theories of PTSD may potentially be understood
as complex interactions between hippocampal-depend-
ent and amygdala-dependent memory processes (Brewin
Evidence the hippocampus has
and Holmes, 2003). Lastly, it has been hypothesized that a role in PTSD
a failure to inhibit distressing flashbacks and avoidance
behaviors in PTSD may reflect an impairment of execu- As mentioned previously, several studies report impair-
tive control resulting from hypofunction of the prefrontal ments in the traumatic memories of PTSD patients (e.g.,
cortex (Aupperle et al., 2012). van der Kolk and Fisler, 1995; Koss et al., 1996; Shalev

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634 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
et al., 1996; Tichenor et al., 1996; Mechanic et al., 1998;
Yovell et al., 2003). These impairments include a lack of
temporal or spatial context, failure to integrate the event
into autobiographical memory, inability to intentionally
recall important aspects of the traumatic event, and frag-
mented or disorganized recall of the traumatic memory.
Also, relative to healthy controls, PTSD patients tend to
perform poorly on declarative memory tasks (for a brief
review, see Bremner, 2006). Considering their character-
istics, these memory impairments may reflect a functional
decline of hippocampal-dependent cognitive memory pro-
cesses in PTSD (Bremner, 2006). There are several lines of
research in support of this idea that indicate abnormali-
ties of the hippocampus in PTSD patients. For example,
several neuroimaging studies suggest that patients with
PTSD have a reduced hippocampal volume (for a review,
see Bremner, 2007; and also Bonne et al., 2001; Carrion et
al., 2001; De Bellis et al., 2001; Fennema-Notestine et al.,
2002; Pederson et al., 2004; Golier et al., 2005). Moreover,
neuroimaging studies have established a negative corre-
lation between hippocampal volume and the severity of
PTSD symptoms (Gilbertson et al., 2002; Villarreal et al.,
2002; Bremner et al., 2003).
In view of extensive evidence that behavioral stress-
ors and stress hormones can be detrimental to hip-
pocampal structure and morphology (Watanabe et al.,
1992; Gould et al., 1998; Kim and Diamond, 2002), it
is possible that the traumatic event and the distress it
may engender reduces the volume of the hippocampus.
However, there is also evidence that a prior reduction
in hippocampal volume may serve as a risk factor for
developing PTSD (e.g., Pitman et al., 2006). Indeed,
whether the reduction in hippocampal volume pre-
cedes or follows the traumatic event and the develop-
ment of PTSD symptoms remains debatable (Bremner,
2001; Pitman, 2001). Results in favor of the latter view
(i.e., that traumatic stress reduces hippocampal volume)
came from one study that measured hippocampal gray
matter volume in healthy human subjects at two dif-
ferent time points, separated by a three-month interval
(Papagni et al., 2011). The number of stressful life events
that a participant experienced during the three-month
interval was positively correlated with a reduction in
gray matter volume of the right hippocampus, suggest-
ing that the stressful life events preceded and contrib-
uted to the reduction in hippocampal volume. Experi-
ments in animals yield potentially similar results (Kim
and Diamond, 2002). For example, rats subjected to
21 days of chronic restraint stress showed a 3% reduc-
tion in hippocampal gray matter volume relative to non-
stressed controls (Lee et al., 2009).
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In addition to reduced hippocampal volume, neu-
roimaging studies reveal decreased activation of the
hippocampus in patients with PTSD (for reviews, see
Francati et al., 2007; Hughes and Shin, 2011). Typically,
these experiments measure hippocampal activation while
the subject performs a hippocampal-dependent memory
task. For example, researchers trained individuals with
PTSD and healthy individuals who had not been exposed
to trauma on a virtual version of the Morris water maze
(Astur et al., 2006). While performing the task, the PTSD
group showed no significant activation in the hippocam-
pus, whereas individuals without PTSD showed a robust
increase in hippocampal activation. Moreover, a negative
correlation between hippocampal activation and sever-
ity of PTSD symptoms was observed (Astur et al., 2006).
It should be noted that, although reduced hippocampal
activation is often observed, some studies have reported
increases in hippocampal activation in PTSD patients
(Werner et al., 2008; Whalley et al., 2009). The reason for
this discrepancy remains uncertain, but it may depend on
the features of the particular learning task or the analyses
used for the scans (Francati et al., 2007; Hughes and Shin,
2011).
Evidence the dorsal striatum has
a role in PTSD
As described earlier, there is extensive evidence from
studies in lower animals and humans indicating that
the dorsal striatum has a selective role in S-R/habit
learning and memory. In PTSD, the learning of behav-
ioral responses to trauma-related cues may be a form
of S-R learning. PTSD patients may learn in part to
associate discrete stimuli/cues surrounding the trauma
(e.g., loud noises) with the trauma itself and have sub-
sequently learned to respond to the cues as if the cues
themselves posed a serious threat. This automatic/habit-
ual responding to cues without regard to the spatial or
temporal context in which they occur is characteristic
of both PTSD symptomatology and S-R (or habit) learn-
ing. Indeed, the idea that S-R learning may be associ-
ated with PTSD pathology is not a new concept. In the
1980s, drawing from Mowrers earlier (1960) two-factor
learning theory, researchers attempted to describe the
development of PTSD as involving two distinct learning
phases, one characterized by classical conditioning and
the other by instrumental learning (for a review, see Foa
et al., 1989). In the initial phase, a trauma victim learns
to associate spatially or temporally proximal sounds,
 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder 635

smells and images (i.e., the conditioned stimuli; CSs) Evidence the noradrenergic system
with the central threat (i.e., the unconditioned stimulus;
US) so that when the person later encounters the previ- has a role in PTSD
ously neutral CSs he or she re-experiences the tremen-
In lower animals, the effect of anxiety on the relative use
dous fear and anxiety originally elicited by the US. This
of memory systems can be produced by drugs that increase
may be viewed as a representation of Pavlovian classi-
norepinephrine release and hence can activate adreno-
cal conditioning. In the second phase, the trauma victim
receptors in the BLA (Packard, 2009). Consistent with
learns to react to the CSs through maladaptive condi-
the hypothesis that this anxiety-mediated habit bias may
tioned responses, treating the CSs like USs, avoiding
underlie some PTSD symptoms, converging evidence indi-
them at any cost. It is this second phase of Mowrers two-
cates that PTSD patients have increased basal norepineph-
factor learning theory that may be viewed as a represen-
rine levels and show exaggerated noradrenergic responses
tation of S-R learning. Despite some explanatory power,
to trauma-related stimuli (for reviews, see Pitman and Dela-
conditioning theories of PTSD have been criticized in
hanty, 2005; Strawn and Geracioti, 2008). Pitman (1989)
part due to their inability to explain more complex PTSD
advanced a pathophysiological model of PTSD suggesting
symptoms, such as emotional numbness, hyperarousal
that stress hormones released during and after a traumatic
and memory impairment (Foa et al., 1989; Brewin and
event may lead to an overconsolidation of the traumatic
Holmes, 2003). However, S-R learning may nonetheless
memory, precipitating the intrusive recollections and con-
operate alongside other learning processes and in part
ditioned emotional responses observed in PTSD. Aside
mediate the learning of behavioral responses to trauma-
from the consolidation of traumatic experiences, it has
related cues (Ehlers and Clark, 2000; Pitman et al., 2000;
also been suggested that the retrieval of traumatic memo-
Bryant, 2005).
ries may depend on noradrenergic mechanisms (Pitman,
Consistent with the neurobehavioral findings in
1989; Pitman and Delahanty, 2005). Considering the puta-
lower animals and humans implicating the dorsal stria-
tive role of the noradrenergic system in PTSD, several
tum in S-R habit learning and with the idea that S-R
studies have investigated the treatment efficacy of antiadr-
learning may underlie some PTSD symptoms, recent neu-
energic agents (for reviews, see Pitman et al., 2006; Stein,
roimaging studies indicate that the dorsal striatum has a
2006; Strawn and Geracioti, 2008). For example, treatment
role in PTSD symptomatology. For example, researchers
with the -adrenoreceptor blocker propranolol in the acute
played personalized auditory scripts to traumatized train
aftermath of trauma or after the development of the disor-
drivers and asked them to re-imagine the traumatic event
der has been shown to reduce PTSD symptoms (Famularo
as if it were actually recurring (Nardo et al., 2011). Sub-
et al., 1988; Pitman et al., 2002; Vaiva et al., 2003; Brunet et
sequent single-photon emission computed tomography
al., 2008; Krauseneck et al., 2010). Considering the effects
analyses revealed increased regional cerebral blood flow
of norepinephrine on the relative use of memory systems
in the caudate and putamen of train drivers with PTSD,
(Packard, 2009), it is tempting to speculate that exagger-
relative to train drivers without PTSD. An additional
ated norepinephrine release during and after a traumatic
study using script-driven imagery established a positive
event may increase amygdala activation, thus mobilizing
correlation between regional cerebral blood flow in the
a shift from a hippocampal-dependent memory system
right putamen and self-reported intensity of the flash-
towards a dorsal striatal-dependent system. Disrupting
back (Osuch et al., 2001). Script-driven activations of the
the noradrenergic system with drugs like propranolol may
caudate head and putamen have also been correlated
prevent or reverse this shift to habit memory.
positively with the severity of PTSD symptoms (Mickle-
borough et al., 2011). Other findings indicate increased
activation of the caudate and putamen in PTSD patients
subjected to electrical stimulation or heat pain (Geuze
et al., 2007; Linnman et al., 2011; Mickleborough et al.,
The stress-induced habit bias:
2011). In addition to increased activation, it should be implications for PTSD
noted that some neuroimaging studies of PTSD patients
report decreased activation in regions of the dorsal stria- Research in lower animals described earlier indicates
tum as well (e.g., Lucey et al., 1997; Lindauer et al., 2004). that anxiety-induced impairment of the hippocampal-
In summary, there is a developing and increasing body dependent memory system enhances dorsolateral stri-
of evidence indicating that the dorsal striatum may be atal-dependent habit memory and that this enhancement
involved in PTSD symptoms. depends on the integrity of the basolateral amygdala. We

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636 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
propose that a similar mechanism may in part underlie
the development, persistence and expression of some
PTSD symptoms. More specifically, we suggest that during
a traumatic event the amygdala becomes highly active and
modulates memory of the experience by impairing modu-
latory influence on the hippocampus, essentially allowing
the dorsal striatum to play a prominent role in encoding
and consolidating trauma-related cues. The prominence
of the dorsal striatal-dependent S-R learning system
may manifest in part as enhanced learning of malada-
ptive avoidance behaviors in response to these cues. In
addition, considering that pre-test anxiety also induces
a habit bias in lower animals (Elliot and Packard, 2008),
we suggest that the anxiety-driven retrieval of traumatic
memory may similarly engage the dorsal striatum to guide
the automatic-like avoidance behaviors observed in PTSD
patients. Support for these ideas comes from human neu-
roimaging research and neurobehavioral studies in lower
animals suggesting potential roles for the amygdala, hip-
pocampus and dorsal striatum in PTSD symptomatology.
As described previously, a recurrent finding among
PTSD patients is an impaired hippocampus. The hip-
pocampal impairments commonly observed in PTSD
include reductions in volume, lower activation levels and
relatively poor performance in hippocampal-dependent
memory tasks. Likewise, common deficits observed in
traumatic memory may reflect hippocampal impairment.
Although the mechanism underlying these impairments
remains uncertain, contributing factors may include the
high levels of stress experienced both during and after the
traumatic episode (Bremner, 2001). Interestingly, in lower
animals, stress-induced impairments of hippocampal
long-term potentiation or neurogenesis have been asso-
ciated with the use of an S-R strategy in dual solution
tasks (Kim et al., 2001; Ferragud et al., 2010). Similarly, in
healthy human subjects, lower hippocampal volume and
poor performance in episodic memory tasks have been
associated with an S-R strategy in a dual solution virtual
maze (Bohbot et al., 2007, 2011). With this evidence, it is
tempting to speculate that trauma-induced impairments
in hippocampal structure and function may promote a
habit bias in PTSD patients.
The recent neuroimaging evidence we have summa-
rized indicates that the dorsal striatum may have a role in
PTSD symptoms. Further evidence such a role exists may
be gleaned from fear conditioning experiments in lower
animals. It should be noted that auditory fear conditioning
fails to mimic all the symptoms of PTSD (e.g., emotional
numbness, memory impairment, recurrent nightmares,
etc.). In addition, we might speculate that this model fails
to replicate the hippocampal memory impairment com-
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monly observed in PTSD, because footshock treatment may
not elicit the same high levels of stress or the prolonged
nature of traumatic experiences. Despite these inefficien-
cies, auditory fear conditioning may nevertheless serve as
a useful model for understanding other major PTSD symp-
toms, in particular the learning of emotional and behavioral
responses to trauma-related cues (Foa et al., 1992; Rasmu-
sson and Charney, 1997; Siegmund and Wotjak, 2006; for
a recent review of PTSD animal models, see Berardi et al.,
2012). Consistent with the dorsal striatum having a role
in PTSD, pre-training or post-training lesions delivered
to the dorsal striatum in rats impaired conditioned freez-
ing behavior in response to an auditory cue, while having
no effect on freezing behavior in response to the context
(Ferreira et al., 2003, 2008). Thus, dorsal striatal lesions
selectively impaired learning to freeze in response to a dis-
crete cue (i.e., S-R learning). Post-training amphetamine
infused directly into the dorsal striatum enhanced freez-
ing in both auditory and contextual versions of the task
(White and Salinas, 2003). Interestingly, it has been dem-
onstrated more recently that an amygdala-dorsal striatum
system is necessary for auditory fear conditioning (Ferreira
et al., 2008). A pre-training unilateral lesion to the central
amygdaloid nucleus and contralateral lesion to the dorsal
striatum impaired conditioned freezing, while ipsilateral
lesions had no effect. Lastly, the contralateral lesions did
not affect conditioned freezing in a contextual version of
the task, suggesting that the amygdala-dorsal striatum
system may mediate conditioned freezing selectively to
discrete cues (i.e., stimulus-response learning). Taken
together, these experiments suggest that the acquisition of
behavioral responses to fear-conditioned cues may depend
on an indirect pathway from the amygdala to the dorsal
striatum (Ferreira et al., 2008). Considering the parallels
between auditory fear conditioning and some PTSD symp-
tomatology, we might also speculate that the development
of avoidance behaviors to trauma-related cues in PTSD
may depend on an amygdala-dorsal striatum system.
The stress-induced habit
bias: implications for other
psychopathologies
In addition to PTSD, other human psychopathologies
may similarly reflect a stress-induced facilitation of the
dorsal striatal-dependent habit memory system. Consid-
ering both the role of anxiety and the habit-like nature of
compulsions in obsessive-compulsive disorder (American
 J. Goodman et al.: Multiple memory systems and post-traumatic stress disorder
Psychiatric Association, 2000), the stress-mediated habit
bias observed in lower animals may also underlie at least
some symptoms of the disorder (McDonald et al., 2004).
More specifically, the anxiety arising from obsessions or
stressful/traumatic life events may lead to the compul-
sive behavior observed in obsessive-compulsive disorder
patients, and this process may depend on an interaction
between the amygdala, hippocampus and dorsal striatum.
When exposed to distressing life events or obsessions,
the amygdala may become highly active and, through
its inputs to different learning and memory structures,
modulate which behavioral strategy becomes employed
to relieve the anxiety. In this situation, a highly active
amygdala may favor the use of a habit learning strategy
mediated by the dorsal striatum, as opposed to a more
cognitive strategy, which would be mediated in part by the
hippocampus. In a recent study, researchers trained obses-
sive-compulsive disorder patients on a set of instrumental
learning tasks and found that relative to healthy individu-
als they demonstrated deficient knowledge of action-out-
come relationships and were more likely to rely on habit-
like responses to the stimuli (Gillan et al., 2011). These
results may represent the impairment of a cognitive, goal-
directed learning system and consequent reliance on the
habit memory system in obsessive-compulsive disorder. In
addition, a number of studies report that environmental
factors contributing to the development and persistence
of obsessive-compulsive disorder symptoms may include
stressful or traumatic life events (Happle, 2005; Sasson et
al., 2005; Cromer et al., 2007a,b; Tolin et al., 2010; Landau
et al., 2011). Lastly, several neuroimaging studies have pro-
vided evidence of abnormal structure and function of the
amygdala, hippocampus and regions of the dorsal stria-
tum in obsessive-compulsive disorder patients (for recent
reviews, see Del Casale et al., 2011; Milad and Rauch, 2012).
In drug abuse, the acquisition and subsequent relapse
of drug-seeking behaviors may be attributed to aberrant
or maladaptive functioning of different memory systems
(White, 1996; Di Chiara, 1999; Everitt and Robbins, 2005;
Schwabe et al., 2011). Whereas the initial acquisition of drug-
taking behavior may depend on a hippocampal-dependent
memory system, extended drug use may shift the control of
drug-taking behavior to a dorsal striatal-dependent system,
increasing the rigid and habit-like nature of these behaviors
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637
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The effect of stress/anxiety on the relative use of memory
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