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HUMAN NEUROSCIENCE
REVIEW ARTICLE
published: 30 September 2014
doi: 10.3389/fnhum.2014.00742
The role of the hippocampus in flexible cognition and
social behavior
Rachael D. Rubin1*, Patrick D. Watson1,Melissa C. Duff2,3 and Neal J. Cohen1
1Department of Psychology and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA
2Department of Communication Sciences and Disorders, University of Iowa, Iowa City, IA, USA
3Department of Neurology, Division of Behavioral Neurology and Cognitive Neuroscience, University of Iowa, Iowa City, IA, USA
Edited by:
Richard Patterson, Emory
University, USA
Reviewed by:
Stephen V. Shepherd, The
Rockefeller University, USA
Jennifer D. Ryan, Rotman Research
Institute, Canada
*Correspondence:
Rachael D. Rubin, Department of
Psychology and Beckman Institute,
University of Illinois at
Urbana-Champaign, 405 N.
Mathews Ave., Urbana, IL 61801,
USA
e-mail: rrubin2@illinois.edu
Successful behavior requires actively acquiring and representing information about the
environment and people, and manipulating and using those acquired representations
flexibly to optimally act in and on the world. The frontal lobes have figured prominently
in most accounts of flexible or goal-directed behavior, as evidenced by often-reported
behavioral inflexibility in individuals with frontal lobe dysfunction. Here, we propose that
the hippocampus also plays a critical role by forming and reconstructing relational memory
representations that underlie flexible cognition and social behavior. There is mounting
evidence that damage to the hippocampus can produce inflexible and maladaptive behavior
when such behavior places high demands on the generation, recombination, and flexible
use of information. This is seen in abilities as diverse as memory, navigation, exploration,
imagination, creativity, decision-making, character judgments, establishing and maintaining
social bonds, empathy, social discourse, and language use. Thus, the hippocampus,
together with its extensive interconnections with other neural systems, supports the
flexible use of information in general. Further, we suggest that this understanding has
important clinical implications. Hippocampal abnormalities can produce profound deficits in
real-world situations, which typically place high demands on the flexible use of information,
but are not always obvious on diagnostic tools tuned to frontal lobe function. This review
documents the role of the hippocampus in supporting flexible representations and aims to
expand our understanding of the dynamic networks that operate as we move through and
create meaning of our world.
Keywords: hippocampus, flexible cognition, social behavior, relational memory, amnesia
OVERVIEW
“The measure of intelligence is the ability to change.”
-Albert Einstein
Humans are active agents in the world, constantly acquiring
information about their environment, manipulating those rep-
resentations, and synthesizing optimal behavioral and cogni-
tive strategies to modify the world around them. This ability
to flexibly employ different strategies is usually attributed to
executive function and working memory systems supported by
the prefrontal cortex (PFC). However, we suggest that in every-
day, ecologically valid scenarios such flexible cognition places
great demands on memory beyond what can be supported by
PFC-associated working memory, drawing heavily upon memory
representations that capture past experiences to inform future
behaviors and decisions. Accordingly, we use the term flexible
cognition to describe the adaptive process of generating, updat-
ing, modifying, and integrating past and present information
in response to the demands and constraints of both the real-
world environment and the experimental task, and aim to show
its reliance on the hippocampal network. Thus, we suggest that
the hippocampus, which has traditionally been associated with
long-term, declarative, or episodic memory, is actually essential to
the flexible cognition network whenever representations must be
appropriately constructed, manipulated, and updated to respond
to the task at hand, and reflect the social and environmental
context.
We also note that the contribution of the hippocampus to
flexible cognition is perhaps most apparent in the complex
dynamics of social interactions. In everyday social interactions,
subtle contextual differences (e.g., a single prior interaction with
an individual) require extensive and flexible modifications of
our behavior, driving us to select different words, draw upon
shared knowledge, or use entirely different language and social
conventions for interaction. For example, successfully navigating
a dinner party requires making appropriate responses to both
novel and familiar guests and updating representations of
ongoing conversations. The ability to do so relies on information
about the situation no longer in current sensory experience (e.g.,
“Who arrived on time?”), predictions based on prior knowledge
(e.g., “What does Jen want to drink tonight?”), inferences based
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Rubin et al. Hippocampus and flexible cognition
on existing relationships (e.g., “Does Hillary know Debbie?”),
and much more. Hence, we suggest that rather than relying on
memory processes associated with PFC networks that include
executive and working memory functions, successful behavior
increasingly depends upon the constant encoding, updating,
and flexible manipulation of relational memory representations
supported by the hippocampus. Otherwise behavior is driven by
inappropriate, inflexible, and stereotypical behaviors guided by
general knowledge (e.g., pour wine for everyone, regardless of an
individual’s preferences).
In this review, we describe findings from studies that utilize
a variety of cognitive neuroscience methodologies to elucidate
the role of the hippocampus in flexible cognition and social
behavior. We place particular emphasis on findings from patients
with impairments resulting from hippocampal damage that estab-
lish the critical role of the hippocampus in a broad range of
behaviors that require the flexible use of information. These
findings provide unique insight into the nature and time course
of the contribution of the hippocampus to flexible cognition
across everyday tasks and social interactions. These data show that
(1) the hippocampus is a critical component of the large network
of brain structures implementing flexible cognition, and as a
result (2) hippocampal-dependent representations are necessarily
employed in situations requiring the flexible use of informa-
tion. In particular, the hippocampus is critical for performance
in complex and ecologically valid situations that unfold over
time and involve dynamically binding together various pieces of
information.
Disruptions in flexible cognition that result from hippocampal
damage, however, do not always appear on neuropsychological
tests of cognitive flexibility constructed to specifically measure
either executive functions or more traditional forms of declar-
ative memory. Thus, in later sections we outline implications
for the inclusion of the hippocampus in the neural network
supporting flexible cognition and discuss implications for future
research, clinical practice, and re-conceptualizing the relationship
between disorders of the brain and complex behavior. Under-
standing how the hippocampus contributes to adaptive behav-
iors necessary for navigating complex environments and social
interactions is critical for clinicians seeking to understand the
everyday challenges that patients with memory deficits face,
and for investigators seeking to understand the relative contri-
butions of different brain systems during all kinds of flexible
cognition.
THE NETWORK OF BRAIN STRUCTURES SUPPORTING
FLEXIBLE COGNITION AND THE HIPPOCAMPUS
Flexible cognition is often discussed in the context of executive
function, supporting the ability to switch between competing
goals, as well as contributing to high-level human behavior,
such as planning, organizing, and decision-making (e.g., Eslinger
and Grattan, 1993; Eslinger, 1996; Jurado and Rosselli, 2007).
On neuropsychological assessments that rely on executive func-
tions, patients with damage to frontal areas demonstrate impair-
ments, exhibiting various forms of behavioral inflexibility that
include perseveration of behavior, rigid rule structure, and social
inappropriateness (e.g., although see Anderson et al., 1991; Lezak,
1993; Stuss and Alexander, 2000; Stuss and Levine, 2002; Alvarez
and Emory, 2006). Thus, the frontal lobes are properly empha-
sized as making a critical contribution to flexible cognition and
social behavior.
The frontal lobes, however, are part of a large and distributed
network of brain structures that support the flexible use of
information. For example, complex social interactions that rely
on the flexible use of information involve various parts of the
frontal lobes (e.g., medial, dorsolateral, orbital, and ventromedial
prefrontal cortex), as well as structures located in temporal,
parietal, and limbic circuits (e.g., superior temporal sulcus, amyg-
dala, insula, somatosensory cortex, temporoparietal junction)
(Adolphs, 2003; Hari and Kujala, 2009). Thus, there is consensus
that complex information processing draws upon a variety of
brain networks in order to respond to varying task demands; how-
ever, the usual description of the network for flexible cognition
rarely, if ever, includes the hippocampus.
The omission of the hippocampus in descriptions of the flex-
ible cognition network likely results from the strong association
between the hippocampus and long-term memory. Traditional
neuropsychological and laboratory tasks were designed to obtain
process-pure measures that distinguished between executive func-
tion and memory abilities, rather than elucidated interactions
between these functions. Yet, outside of the lab, everyday situ-
ations necessitate active engagement with the environment and
other social agents. In these real-life situations, memory and
executive function must interact seamlessly, and obligatorily,
to meet the demands of a constantly changing environment.
The demand on memory is particularly clear in social interac-
tions that often require learning by observing others in sim-
ilar situations, recognizing the shifting or changing status of
friends and enemies, using language to communicate and re-
describe events from multiple points of view, and imagining
things that might happen to us in the future. These abilities
require integrating information across multiple timeframes that
may stretch from the distant past, to the present moment,
to possible futures (Lemke, 2000; Adolphs, 2003; Cacioppo
et al., 2006). That is, these abilities require representing infor-
mation, such as previous conversations, alternate perspectives,
shared and unshared experiences, and even fictive material that
are not necessarily contained within the present moment or
within the span of working memory. Therefore, the constant
encoding, updating, and flexible expression of relational mem-
ory representations are required for flexible cognition, which
depends heavily upon the hippocampal-dependent memory
system.
THE HIPPOCAMPUS SUPPORTS FLEXIBLE COGNITION
THROUGH THE ENCODING AND FLEXIBLE EXPRESSION OF
RELATIONAL MEMORY REPRESENTATIONS
Early neuropsychological studies in patients with hippocampal
amnesia provided crucial insight into the organization of human
memory and its instantiation in the brain, such that damage
to the hippocampus and related medial temporal lobe (MTL)
structures resulted in a profound but circumscribed amnesia
(e.g., Scoville and Milner, 1957; Cohen and Eichenbaum, 1993).
The memory system selectively affected in amnesia, and critically
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Rubin et al. Hippocampus and flexible cognition
dependent on the hippocampus, is declarative memory (Cohen
and Squire, 1980; Squire, 1992; Cohen and Eichenbaum, 1993;
Gabrieli, 1998; Eichenbaum and Cohen, 2001). This form of
memory represents information about the co-occurrences of
people, places, and things, along with the spatial, temporal, and
interactional relations among them, which often include per-
sonal awareness and social context, that constitute the autobi-
ographical record of our lives (Cohen and Eichenbaum, 1993;
Eichenbaum and Cohen, 2001). That is, the hippocampus is
essential for representing the elements of everyday interactions
and the relations among them, whereas surrounding MTL struc-
tures, the perirhinal cortex and the parahippocampal cortex,
are characterized by the ability to support item (i.e., inflexi-
ble configural relations) and context memory, respectively (e.g.,
Cohen et al., 1997; Davachi, 2006; Eichenbaum et al., 2007;
Ranganath, 2010b; but see Squire et al., 2007). The criti-
cal role of the hippocampus in relational representations has
received considerable support in recent years (Davachi, 2006;
Henke, 2010; Ranganath, 2010a; Olsen et al., 2012; Yonelinas,
2013).
Relational representations supported by the hippocampus are
characterized by two hallmark features: (1) the binding of arbi-
trary relations between the elements of experience into durable
representations of past experiences; and (2) the flexible expression
of these representations, which allow for the search, reconstruc-
tion, and recombination of the information contained within
them (as opposed to a “video-camera”-like recapitulation of prior
events). This representational flexibility permits information to
be searched and accessed across processing systems (e.g., when
a rich, multisensory autobiographical memory is evoked by the
sight of a familiar face or sound of a familiar song) and to be
used in novel situations (e.g., when exploring a new environ-
ment or meeting a new person). Furthermore, the contribution
of the hippocampus to relational representations need not be
limited to the explicit awareness and retention of memory over
long-term delays (Ryan et al., 2000; Eichenbaum and Cohen,
2001; Henke, 2010; Olsen et al., 2012). This conceptualization
has implications for the involvement of the hippocampus dur-
ing tasks on the time-scale of short-term or working memory,
and outside the memory domain, when relational represen-
tations are required. We discuss these points in more detail
later on.
The flexible nature of relational memory representations also
makes contact with a long memory literature that presents mem-
ory as a flexible reconstruction of past events (Bartlett, 1932).
This literature is frequently framed negatively, being primar-
ily concerned with the study of memory’s imperfect accuracy
(Neisser, 1982), such as the imperfect accuracy of eyewitness
testimony (Loftus et al., 2008), or outright “false” memories
(Loftus and Pickrell, 1995). However, the relational memory
framework suggets that it is this same flexible reconstruction
that enables us to update and integrate the information from
previous experiences to other episodes and to generate new
ideas. That is, binding and re-binding the individual elements of
experience compositionally permits the encoding for time- and
place-specific autobiographical experiences, as well as the repre-
sentations of the relationships among different experiences which
are impossible to appreciate a priori (Cohen and Eichenbaum,
1993; Cohen et al., 1997; Ryan et al., 2000; Eichenbaum and
Cohen, 2001; Giovanello et al., 2003; Davachi, 2006; Eichenbaum
et al., 2007; Konkel et al., 2008; Staresina and Davachi, 2009;
Ranganath, 2010b; Olsen et al., 2012; Yonelinas, 2013). These
hippocampal representations provide the basis for the larger
record of one’s life, and as we emphasize, support the ability
to adapt to changing circumstances and engage in complex
social interactions, which are necessary for functioning success-
fully in the real-world. The flexible construction and use of
these representations also implies a persistent need for mem-
ory search, updating, and transformation of previously encoded
information, especially in contexts that require the tracking of
multiple objects, locations, times, and individuals, embedded
in diverse environmental and social contexts. The involvement
of hippocampus in supporting interactions between diverse and
complex elements required for cognitive and social abilities is
well documented (O’Keefe and Nadel, 1978; Cohen, 1984; Squire,
1992; Cohen and Eichenbaum, 1993; Bunsey and Eichenbaum,
1996; Dusek and Eichenbaum, 1997; Eichenbaum and Cohen,
2001).
As mentioned previously, the relational memory frame-
work suggests that the characteristic processing features of the
hippocampus, the ability to bind together arbitrary relations
and to support their flexible expression, occur independent
of timescale. That is, whether the representations are being
accessed on the timescale of long-term or episodic memory,
short-term or working memory, or even during moment-to-
moment processing. Recent findings support this idea: when
tasks are constructed to require relational binding and represen-
tational flexibility, patients with hippocampal amnesia demon-
strate impairments across minimal delays, and even when all
the necessary information to perform the task is perceptually
available (Hannula et al., 2006; Olson et al., 2006a,b; Barense
et al., 2007; Warren et al., 2011; Watson et al., 2013). For
example, we have shown that patients with hippocampal amne-
sia are impaired relative to matched comparison participants
at forming both spatial and non-spatial relations among co-
occurring items (e.g., the elements of furniture in a room and
a face superimposed on a scene) at very short delays that are
considered to be on the time scale of working or short-term
memory (Hannula et al., 2006). Consistent with these find-
ings, evidence from functional neuroimaging reveals hippocam-
pal activations for relational information during these same
short delays (Ranganath and D’Esposito, 2001; Hannula and
Ranganath, 2008).
In light of this evidence, others are also exploring hippocampal
contributions to formatting, updating, and actively using models
of our experiences in navigating our world, social interactions
and relationships (see Spreng, 2013 for introduction to Research
Topic “Examining the role of memory in social cognition”). In the
next section, we examine the contribution of the hippocampus
to flexible and adaptive behavior, and the importance of the
hippocampus to increasingly ecologically valid tasks that require
flexible representations, whether those representations pertain to
remembered events, or supporting online social, linguistic, or
cognitive processing.
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Rubin et al. Hippocampus and flexible cognition
THE HIPPOCAMPUS AND FLEXIBLE MEMORY
REPRESENTATIONS ARE CRITICAL IN MANY COGNITIVE
ABILITIES AND COMPLEX SOCIAL BEHAVIORS
We suggest that the flexibility afforded by hippocampal repre-
sentations permits various pieces of information to be called
upon promiscuously to support diverse and complex cognitive
and social abilities. The importance of flexible representations in
many cognitive and social behaviors has recently been explored in
a number of experimental paradigms in patients with hippocam-
pal amnesia. These paradigms assess the ability of humans with
hippocampal damage to perform tasks that approximate real-
world interactions in which there is a high demand on flexible
representations for adaptive and successful performance. The
performance of humans with hippocampal damage on these tasks
provides useful insight into the specific role that the hippocampus
performs in supporting the flexible use of information. Indeed,
we highlight a variety of findings from patients with hippocampal
amnesia on both tasks in the cognitive and social domains, in
which the basic processing mechanisms are not impaired (e.g.,
basic linguistic abilities are intact as patients with amnesia do not
have aphasia), but the nature of the task places significant process-
ing demands on the flexible use of information (e.g., using lan-
guage flexibly to reflect changes in context or perspective during
social discourse), resulting in abnormal or impaired performance.
Thus, while the PFC may be important for switching between
or integrating abstracted representations, the hippocampus is
required to form and deploy those representations flexibly for use
by other neural systems.
SPATIAL NAVIGATION AND ACTIVE EXPLORATION OF THE
ENVIRONMENT
As we navigate and engage with our world, we are constantly,
automatically, and obligatorily encoding relations (spatial or oth-
erwise), updating mental representations, and using that infor-
mation in real-time to guide our behavior. The contribution of
the hippocampus to spatial information and navigation has an
extensive basis in the literature stemming from early evidence of
location-modulated cells in the rodent hippocampus (for review,
see Burgess et al., 2002). Evidence suggesting the hippocampus
is important for spatial navigation also comes from patients
with hippocampal amnesia (Maguire et al., 2006), as well as
findings from functional neuroimaging studies (Ghaem et al.,
1997; Maguire et al., 1997, 1998; Hartley et al., 2003; Kumaran
and Maguire, 2005; Spiers and Maguire, 2006), especially when
successful navigation requires access to detailed spatial represen-
tations of recently learned information. For example, Maguire
et al. (2006) examined the involvement of the hippocampus in
navigating an environment learned long ago in a taxi driver
with hippocampal amnesia. While performance was relatively
intact on general orientation in the city, knowledge of landmarks
and their spatial relationships, and active navigation along some
routes, hippocampal damage disrupted the ability to navigate
complex environments that required the use of roads that were
not major arties in the city, even though the information had been
learned prior to the onset of amnesia. These findings are broadly
consistent with a theory of hippocampal processing emphasizing
the flexible and dynamic use of information, since representing
spatial information requires constructing and maintaining rela-
tionships between different elements in the environment, estab-
lishing maps, layouts, and spatially arranged compositions of
elements. Once such a configuration has been encoded (such as
the relationships between the buildings and streets that make up
the layout of a city, or the hallways and rooms that make up
the layout of one’s own home), we must continually update our
own position as we move through the map, and compare this
location with the desired destination. These elements are intrinsic
to spatial navigation and place a great demand on the flexible
information supported by the hippocampus (Eichenbaum et al.,
1999; Eichenbaum and Cohen, 2001).
Even outside the realm of navigation, the ability to tailor our
behavior to meet current situational demands and incorporate
immediate sensory input to guide upcoming actions and choices
relies on contributions from both memory and executive control
systems (Squire and Zola-Morgan, 1991; Smith and Jonides, 1999;
Eichenbaum and Cohen, 2001; Tanji and Hoshi, 2008). Recent
neuroimaging research suggests that the hippocampus and areas
of the frontal cortex, including dorsolateral PFC, support active
exploration of the environment and may lead to optimization
of behavior for learning and memory of new information (Voss
et al., 2011a,b). Consistent with these findings, the benefit of
active control during learning is absent in patients with hip-
pocampal damage, suggesting the hippocampus may actually be
a critical component of the network that supports such behaviors
(Voss et al., 2011a). In this task, patients with hippocampal
amnesia studied an array of common objects arranged on a grid
and viewed one object at a time through a small moving windows.
When the patients with amnesia were tested for memory of the
items and their spatial layout, their performance did not improve,
and was actually worse, when they had active control of the
moving window during the study portion of the task. Research
in hippocampal amnesia also suggests the hippocampus has an
active role in acquiring information about the environment and
using that information during ongoing processing to guide what
information should be obtained next based on previous experi-
ence (Voss et al., 2011a,b; Yee et al., 2014). Together, these findings
suggest that actively learning about the environment optimizes
interactions among specialized neural systems and relies critically
on the involvement of the hippocampus. Furthermore, the con-
tribution of the hippocampus is far more immediate than would
be suggested by traditional descriptions of hippocampal function
that are limited to long-term memory. Thus, the contribution
of the hippocampus stems from the fundamental role of the
hippocampus in the flexible use of relational representations.
IMAGINATION AND CREATIVITY
The contribution of the hippocampus in (re)constructing,
manipulating and updating relational information extends to
imaginary and future events. Neuroimaging studies have consis-
tently shown hippocampal activation during tasks that require
participants to create fictional mental scenarios, especially when
they draw upon or dynamically recombine previously encoded
materials (e.g., Addis et al., 2007; Buckner and Carroll, 2007;
Hassabis et al., 2007a; Schacter and Addis, 2007, 2009; Schacter
et al., 2007; Szpunar and McDermott, 2008; Addis and Schacter,
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Rubin et al. Hippocampus and flexible cognition
2008). Consistent with these data, patients with hippocampal
amnesia are impaired at generating descriptions of imaginary and
future events, such that their descriptions are more fragmented,
contain fewer episodic and semantic details, and are poorer in
overall quality than matched comparison participants (Hassabis
et al., 2007b; Kwan et al., 2010; Race et al., 2013). These findings
suggest that the hippocampus is required to manipulate and flexi-
bly express stored memories into novel combinations to create the
elements of imaginary events.
The flexibility afforded by hippocampal representations that
are important for imagination also plays a critical role in the
ability to engage in creative thinking more generally. Creativity
requires the ability to rapidly combine and recombine existing
mental representations in order to create novel ideas and ways
of thinking (Damasio, 2001; Bristol and Viskontas, 2006). While
cognitive flexibility is considered to be an important component
of creativity and is often attributed to frontal lobe function
(Dietrich, 2004; Runco, 2004; Bogousslavsky, 2005; Kowatari
et al., 2009; Dietrich and Kanso, 2010), we have shown that
the hippocampus is also involved in representing ideas that are
important for creativity and is part of a more broadly construed
creative, constructive network (Duff et al., 2013). On a well-
validated, standardized measure of creativity (Torrance Tests of
Creative Thinking), we found patients with hippocampal amnesia
are dramatically impaired, qualitatively and quantitatively, on
measures of verbal and figural creativity, relative to matched
comparison participants (Duff et al., 2013). For example, on the
verbal portion, participants were asked to use written language to
generate creative uses for cardboard boxes during a 10 min time
period. Amnesic participant 2363 produced only two responses
(e.g., recycling the boxes and making a fort), while the age,
education, and IQ matched comparison participant produced
26 responses, 23 of which were determined to be unique, such
as building a suit of armor. We observe the same pattern on
the figural portion where, on one task, participants were pre-
sented with an oval shape and asked to think of a picture that
includes the oval, adding new ideas to the make the picture tell
as interesting and exciting a story as possible (see Figure 1). One
healthy comparison participant made the oval into a giant tick
or “tick-mobile” that, similar to a hot air balloon, takes people
for rides above the city. Another comparison participant used
the oval as part of a golf course complete with signs for parking
and the clubhouse, the CBS sports truck, and Tiger Woods with
this caddy. In striking contrast, amnesic participants 1846 and
1951, despite the same stimulus and amount of time (10 min),
used the oval as an egg with a chicken above it and as a bug,
respectively. This deficit in creativity in amnesia is consistent with
the role of the hippocampus in representational flexibility and
resonates with other similar findings that demonstrate the role
of the hippocampus in imagination (e.g., Addis and Schacter,
2012), making comparisons (Olsen et al., 2012), and inferential
reasoning (Zeithamova et al., 2012).
DECISION-MAKING
The role of the hippocampus in flexibly constructing and manip-
ulating representations to imagine future possibilities and alter-
natives has implications for the contribution of the hippocampus
in decision-making. On one such assessment, the Iowa Gambling
Task (IGT, c.f. Damasio, 1994; Denburg et al., 2007), choices are
associated with different amounts of rewards and punishments.
In the task, participants select from four decks of cards that are
overall advantageous or disadvantageous, such that some decks
are associated with small rewards and also have small punish-
ments, whereas other decks are associated with larger immediate
rewards but also larger long-term punishments. The participant
must learn to select from the decks that are overall rewarding.
Thus, the IGT involves constructing an overall evaluation of the
different decks based on integrating variable positive and negative
outcomes, as well as selectively disregarding information that is
inconsistent with the overall value of the deck.
These attributes make the IGT sufficiently more demanding on
hippocampal representations as compared to other still complex
tasks (e.g., Weather Prediction and the Wisconsin Card Sorting
Task), on which patients with hippocampal amnesia perform suc-
cessfully (Leng and Parkin, 1988; Janowsky et al., 1989; Shoqeirat
et al., 1990; Knowlton et al., 1994). On the IGT (Gupta et al.,
2009), patients with hippocampal damage differ from controls
and from other patient populations. For example, patients with
vmPFC and amygdala damage, known to have difficulties with
real-world decision-making (Eslinger and Damasio, 1985; Stuss
and Levine, 2002; Anderson et al., 2006), develop a preference
for the disadvantageous decks on the IGT (Bechara et al., 1994,
1999, 2003; Fellows and Farah, 2005). Patients with hippocam-
pal damage, however, do not develop a preference for either
the advantageous or disadvantageous deck, even when there is
no interposed delay after the card selection, suggesting these
patients maintain only a momentary response to the outcome
and employ a simplistic “lose-shift” strategy. Thus, the hippocam-
pus is necessary to form, maintain, and update choice-outcome
relations that unfolded over the course of the task, while the
vmPFC and the amygdala are important to successfully integrate
the information into a coherent, positive-payoff strategy. These
findings are also consistent with other research in hippocampal
amnesia (Gutbrod et al., 2006), patients with memory deficits
resulting from Alzheimer’s type mild dementia (Sinz et al., 2008),
and neuroimaging findings in healthy participants (Wimmer and
Shohamy, 2012), which support the role of the hippocampus in
effective decision-making.
Interestingly, one of the patients with hippocampal amnesia
in Gupta et al. (2009) had more extensive bilateral MTL damage
that also encompassed the amygdala. While patients with circum-
scribed amygdala develop a preference for the disadvantageous
deck, this patient performed more like the patients with focal
hippocampal damage than the patients with focal amygdala
damage—failing to develop a preference for either the disadvanta-
geous or advantageous decks. We have interpreted this additional
finding to suggest that the contribution of the hippocampus
may occur earlier and be more fundamental to advantageous
decision-making, since patients with either amygdala or vmPFC
damage are able to use hippocampal representations to develop
a preference for one of the decks, albeit the disadvantageous
one. Together, these findings may also explain real-world chal-
lenges that rely on similar complex decision-making abilities,
such that patients with hippocampal amnesia are often unable
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Rubin et al. Hippocampus and flexible cognition
FIGURE 1 | Creativity. Figural form example: picture construction from
oval stimulus. (A) Comparison participant—Title: The 4th Hole Par 3;
notations read from upper left clockwise: To parking; To clubhouse; Its
Tiger Woods!; No carts. (B) Comparison participant—Title: Tickets for
the Tick-mobile; notations read: Get your tickets here; $10. (C) Amnesic
participant 1951—Title: “Where are those tasty little buggers?”
(D) Amnesic participant 1846—Title: Chicken had laid it’s egg. (Adapted
with permission from Duff et al. (2013)).
to live independently, hold full-time employment, manage their
finances, or navigate flexibility through the world.
CHARACTER JUDGMENTS
The ability to flexibly represent information afforded by the
hippocampus has an important role in a range of social behaviors.
The ability to learn new information about a person, or ourselves,
that is tied to a specific event or experience is a characteristic fea-
ture of hippocampal-dependent memory, and contributes to our
ability to form relationships with others, influences our behaviors
towards others, and affects our judgments and perceptions of
others. For example, hippocampal representations enable us to
access multiple lines of associated information, often remote in
time and space, and flexibly integrate the information with new
experiences, such that the way people have behaved towards us
in the past will influence the way we expect them to act in the
future (Cohen and Eichenbaum, 1993; Eichenbaum and Cohen,
2001; Croft et al., 2010); however, the role of the hippocampus in
social behaviors has only recently been formally investigated (with
limited exceptions, e.g., Johnson et al., 1985; Tranel and Damasio,
1993; Duff et al., 2007, 2008a,b, 2009; Todorov and Olson, 2008;
Croft et al., 2010; Davidson et al., 2012; Beadle et al., 2013).
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Rubin et al. Hippocampus and flexible cognition
FIGURE 2 | Character judgments. Moral updating for valenced scenarios
as a function of group. This figure shows the group changes in moral
judgments (in absolute Likert scale units) for morally good and bad
(valenced) scenarios. Group means represent adjusted values after taking
into account the effects of the covariate. Individual raw data points are
plotted as open circles. Error bars represent SEM. (Adapted with
permission from Croft et al. (2010)).
We investigated the contribution of the hippocampus in form-
ing and updating character judgments by comparing the perfor-
mance of patients with hippocampal amnesia to patients with
damage to the vmPFC (a brain region that contributes to process-
ing of emotional salience and moral information), as well as other
brain damaged controls (Croft et al., 2010). In this study, patients
made character judgments about unfamiliar persons before and
after the presentation of scenarios in which a person was shown
engaging in morally good, bad, or neutral behaviors. The ability
to update the representation of the unfamiliar person, based on
the behavior depicted in the scenario, was reflected by the change
in the participant’s rating of the person (i.e., the change in the
rating from before the presentation of the scenario to after the
presentation of the scenario.) The patients with vmPFC damage
exhibited the least change in character judgments, as expected
due to their impairment in emotional processing; however, the
patients with hippocampal amnesia demonstrated the greatest
change and, after the presentation of the scenario, dramatically
rated the persons as either very good or very bad (see Figure 2).
These findings suggest that the hippocampus provides the spe-
cific contextual information from which to make appropriate
character judgments, flexibly binding together information from
multiple experiences, and without this signal (as well as on
the IGT in Gupta et al., 2009) the patients with hippocampal
amnesia overvalue the present event to make more polarized
judgments.
SOCIAL RELATIONSHIPS AND EMPATHY
The ability to flexibly represent everyday experiences and the rela-
tions among them also impacts the capacity to form relationships
with other people and maintain them overtime. Indeed, research
in patients with hippocampal amnesia suggests that the hip-
pocampus contributes to establishing and maintaining social
bonds (although see Duff et al., 2008c; Davidson et al., 2012;
Warren et al., 2012). In the decades since the onset of their
amnesia, patients report making only a few close new friends and
are less involved with neighbors, as well as religious and com-
munity groups. As a result, their social networks are significantly
smaller than matched comparison participants. The inability to
form, update, and flexibly deploy hippocampal-dependent mem-
ory representations likely contributes to difficultly in maintaining
and developing social relationships. That is, patients with hip-
pocampal amnesia cannot consciously recollect shared experi-
ences, learn the names of new people, or incorporate important
new information about existing relationships into their mental
representations. Consistent with this perspective, performance
in healthy adults on hippocampal-dependent memory tasks has
been shown to predict social network size (Stiller and Dunbar,
2007).
The ability to form and maintain social relationships may
also involve contributions from hippocampal representations that
support the ability to imagine and reflect upon experiences with
other people. That is, to consider the social relationship from
another person’s perspective and exhibit empathy. Empathy is an
important ability that contributes to the quality of human rela-
tionships, life satisfaction, and well-being. The cognitive and neu-
ral substrates of empathy usually include brain regions involved
in processing emotional experience and perspective taking, such
as vmPFC, amygdala, anterior insula, and cingulate; however,
we have shown that the hippocampus is also important (Beadle
et al., 2013). In this study, we measured several aspects of empa-
thy, including perspective-taking, emotion contagion, emotional
responsiveness, and empathic concern, using a variety of standard
questionnaires and in response to a series of empathy inductions.
Relative to matched comparison participants, patients with hip-
pocampal amnesia reported lower cognitive and emotional trait
empathy on questionnaires, and reported no increase in empathy
ratings or prosocial behavior in response to empathy inductions.
For example, on one of the measures of cognitive trait empathy,
perspective-taking, the ratings of the patients with hippocampal
amnesia were three standard deviations, or more, below that of
matched comparison participants. The perspective-taking sub-
scale of the questionnaire was designed to assess the ability of
the individual to adopt the mental perspective of another person
(e.g., “When I’m upset at someone, I usually try to “put myself
in his shoes” for awhile”). These findings suggest that empathy
places a demand on the flexible use of information, especially
in terms of the ability to engage in perspective-taking, and con-
struct and update on-line representations that incorporate new
information from recent interactions—all of which involves con-
tributions from the hippocampus. Similarly, research in healthy
adults suggests that the quality of hippocampal-dependent mem-
ory representations contributes to empathic responses, in terms
of facilitating the desire to endorse prosocial intentions, such
that participants report increased prosocial intentions when they
vividly imagine an event, or remember a past event, helping
another person (Gaesser and Schacter, 2014).
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Rubin et al. Hippocampus and flexible cognition
SOCIAL DISCOURSE AND LANGUAGE USE
The contribution of the hippocampus also extends to what could
be considered the most complex form of flexible cognition: dis-
course and language use in social interaction. We have proposed
that the hippocampus is a key contributor to meeting many of
the demands of social discourse and language use and processing
(Duff and Brown-Schmidt, 2012). Spoken language unfolds over
time requiring rapid and incremental processing as multiple
sources of information are generated, gathered, integrated, and
maintained in real-time to create meaning. Consistent with recent
accounts of hippocampal involvement over very short delays,
or no delays at all, (e.g., Hannula et al., 2006; Warren et al.,
2011), we have found deficits in on-line referential processing
in patients with hippocampal amnesia over very short discourse
histories (e.g., within and across utterances) (Rubin et al., 2011;
Kurczek et al., 2013). For example, in one study we had patients
view a scene while listening to short dialogues introducing two
characters; for example, Melissa is playing violin for Debbie/Danny
as the sun is shining overhead. She is wearing a blue/purple dress
(Kurczek et al., 2013). Healthy comparison participants and
vmPFC patients rapidly identified the intended referent of the
pronoun (she) when gender uniquely identified the referent,
and when it did not, they showed a preference to interpret the
pronoun as referring to the first-mentioned character. Patients
with hippocampal amnesia, however, while exhibiting a similar
gender effect, exhibited significant disruptions in their ability
to use information about which character had been mentioned
first to interpret the pronoun. Findings like this, and others
(e.g., Rubin et al., 2011) suggest that patients with hippocampal
amnesia not only have difficulty remembering a conversation they
had earlier, they also have trouble maintaining and integrating
linguistic representations as they unfold over time and using that
information to guide language processing in the moment.
The hippocampus also contributes to social discourse, which
often requires highly creative and flexible uses of language. Two
examples of creative and flexible uses of language ubiquitous
in social discourse include reported speech, in which speakers
represent or reenact words or thoughts from other times and/or
places (e.g., If I ever have kids I’m going to tell them, please
don’t say mean things to me,Tannen, 1989) and verbal play, in
which speakers play with the sounds and meanings of words
through the use of puns, voices, teasing and telling funny stories
(Crystal, 1998). Both of these discourse features require flexible
access to previous knowledge as well as the ability to flexibly
and creatively generate unique combinations of the reconstructed
elements (what details to represent, what details to omit, to meet
the specific interactional goals of this telling, on this occasion,
with this communication partner). We have suggested that these
processes are hippocampal dependent and we find deficits in the
use of both reported speech and verbal play in individuals with
hippocampal amnesia (Duff et al., 2007, 2009; Duff and Brown-
Schmidt, 2012). That is, patients with hippocampal damage use
significantly less reported speech and verbal play in their social
interactions with either a clinician or familiar communication
partner (see Figure 3) and when they do use reported speech or
verbal play it is qualitatively different from healthy comparison
participants (e.g., rotely produced). Furthermore there is some
FIGURE 3 | Reported speech and verbal play. In conversational
interactions with a clinician, patients with hippocampal amnesia produce
significantly fewer episodes of reported speech (185) than do normal
comparisons (400). In the interactions with a familiar communication
partner while completing trials of a collaborative referencing game,
patients with hippocampal amnesia produced significantly fewer
episodes of verbal play (187) than do normal comparisons (395). Data
presented are group totals for patients with hippocampal amnesia
(Amnesia) and demographically matched healthy normal comparison (NC)
participants. Data of interactional partners (clinician; familiar
communication partner) are not presented.
degree of hippocampal specificity; damage to vmPFC does not
disrupt verbal play (Gupta et al., 2012).
Hippocampal damage is associated with deficits across a range
of linguistic and discursive abilities, although it does not, of
course, affect all aspects of social discourse and language use
(e.g., Gordon et al., 2014). Furthermore, hippocampal damage
does not cause the devastating impairments in basic linguistic
processing associated with aphasia. Yet, when the demands of
social discourse and language use place sufficiently high demands
on the processing features of the hippocampus, we observe deficits
in the capacity to creatively and flexibility deploy the commu-
nicative and cognitive resources necessary to meet many of the
moment-to-moment demands of everyday language use in social
interactions.
RECONCILING ACCOUNTS OF THE FUNCTIONAL ROLE OF THE
HIPPOCAMPUS
The critical claim here is that representations supported by the
hippocampus contribute not only to performance on memory
tasks but also to a diverse set of cognitive abilities, which are
engaged in accomplishing a variety of complex cognitive and
social behaviors. The evidence reviewed above documents the
striking deficits following disruption of the hippocampus or of its
interconnections within a broad network of structures, impairing
a broad array of abilities across multiple domains and paradigms.
This leads to some hard questions: what is in common between
the memory tasks typically associated with the hippocampus
and the much broader range of abilities we now see as also
dependent on the integrity of the hippocampus? And, what does
this apparent expansion of the purview of the hippocampus mean
with regard to accounts of the nature of the critical processing
performed by the hippocampus?
Frontiers in Human Neuroscience www.frontiersin.org September 2014 | Volume 8 | Article 742 |8
Rubin et al. Hippocampus and flexible cognition
On our view, the hippocampus implements a very basic
functionality, but one whose reach has not always been fully
appreciated: it binds together multiple items into composi-
tional, relational representations that are stored, maintained, and
updated, in the interconnections of the hippocampus with neo-
cortical networks (more on this below), in such a way as to be
available for retrieval by multiple brain processors, to be deployed
in service of a wide variety of performances in a broad range
of domains. While the functionality is basic—relational memory
binding and reactivation—its reach is extensive, capable of being
used in service of any performance that challenges or would
benefit from the ability to construct, update, search, compare
and contrast, and flexibly deploy relational representations across
time.
Due to its capacity, in conjunction with the neocortical net-
works to which it is connected, to provide a rich relational
database of information, the hippocampus plays an early and
critical role in the formation, maintenance, and flexible deploy-
ment of representations that are then used by other neural
systems in service of flexible cognition and complex social behav-
ior. More specifically, we propose as an individual navigates
through dynamic spatial and social environments in the world,
the hippocampus is creating rich relational representations of
the present while simultaneously and automatically recovering
previous experiences that are similar in content and/or context
and may generate novel scenarios of possible future events and
outcomes (see Eichenbaum and Cohen, 2014; Wang et al., 2014).
The flexibility afforded by these hippocampal representations
allows them to be made immediately available to other neural
systems promiscuously (Cohen, 1984). Thus, other structures
in the network specialized for weighting social information and
social decision-making (e.g., PFC and amygdala) can then use the
information (i.e., representations of past, present, and possible
future(s)) made available by the hippocampus to make decisions
about the best outcome or course of action. To highlight just
one example emphasizing the critical role of the hippocampus
within a larger brain network, recall from the studies using the
IGT that the hippocampus is necessary to form, maintain, and
update choice-outcome relations that unfolded over the course
of the task, while the vmPFC and the amygdala are critical to
successfully integrate the information into a coherent, positive-
payoff strategy.
The functionality described here is fully consistent with
our previous accounts of the hippocampus (e.g., Cohen
and Eichenbaum, 1993; Eichenbaum and Cohen, 2001, 2014;
Eichenbaum, 2004; Wang et al., 2014). The emphasis here is on
the idea that hippocampal function is not limited to particular
domains of memory (e.g., just space or just explicit remem-
bering), and not limited only to the domain of memory, but
instead is available to and in service of any aspects of behav-
ior or performance that place high demands on the formation
or use of relational and flexible representations. This idea is
also consistent with points of emphasis of other contemporary
investigators, including ideas about the role of the hippocampus
in scene (re)construction (e.g., Maguire and Mullally, 2013),
and in the generation of simulated future events (Buckner and
Carroll, 2007), as well as the functional relationship between
the hippocampus and the PFC in service of episodic memory
(Ranganath, 2010b). Moscovitch (2008) has also talked about
the hippocampus in ways reminiscent of our views on rela-
tional memory binding, and about the critical interaction of
hippocampus with the PFC. He emphasizes that the hippocampus
is a “stupid” module, and attributes to the PFC subsequent and
ostensibly more important processing of the information, with
ultimate decision- and choice-making (Moscovitch, 2008). We
would emphasize that the extent that the hippocampus success-
fully forms and recovers all the pertinent information of the past,
present, and possible future options, in addition to maintaining
that information online and making it available to other neural
systems, has a profound influence on and plays a critical role in
the outcome of what neural systems can accomplish. This is true
not just for memory performance, narrowly, but as we have docu-
mented here, also for flexible cognition and social behavior more
generally. So, while the hippocampus may not make decisions
about what pieces of information to encode or make decisions
about how to act on those representations, its binding, construc-
tion, updating, and reactivation of relational representations are
critical to flexible cognition and social behavior.
A different thread in the current literature on memory and
hippocampus is less focused on the interconnections of the
hippocampus and larger brain networks, and more focused on
the internal structure of, or anatomical subdivisions within, the
hippocampus, emphasizing the memory-related sub-processes of
pattern separation and pattern completion (e.g., Norman and
O’Reilly, 2003; Bakker et al., 2008). But, here, too, such memory
operations are thought to be applicable to all kinds of informa-
tion, contributing to the creation and retrieval of the kinds of
representations that we suggest here have such a broad impact on
flexible cognition and social behavior.
THE HIPPOCAMPUS IS ANATOMICALLY CONNECTED TO
BRAIN REGIONS KNOWN TO SUPPORT FLEXIBLE
COGNITION AND SOCIAL BEHAVIOR
The role of the hippocampus in flexible cognition and social
behavior is further revealed by the neuroanatomical and func-
tional connections between the hippocampus and other brain
structures. While the hippocampus is extensively connected
with surrounding MTL structures, including the entorhinal, the
perirhinal, and the parahippocampal cortices, we focus here on
the connectivity between hippocampus and brain structures that
are traditionally thought to be involved in executive function
and social interactions, such as the PFC, the amygdala, and the
cingulate (Simons and Spiers, 2003; Wood and Grafman, 2003).
Both neuropsychological patient and functional neuroimaging
studies have demonstrated the involvement of the PFC in complex
abilities that require flexible cognition, such as moral reasoning,
social conduct, experiencing and recognition of social emotions,
assigning affective value to mental representations, and social and
emotional decision-making (e.g., Eslinger and Damasio, 1985;
Damasio et al., 1990, 1991; Bechara et al., 1994, 1997; Anderson
et al., 1999; Greene et al., 2001; Gusnard et al., 2001; Berthoz
et al., 2002; Gregory et al., 2002; Shuren and Grafman, 2002; Stuss
and Levine, 2002; Bar-On et al., 2003; Beer et al., 2003; Frith and
Frith, 2003; Sabbagh, 2004; Mah et al., 2005; Moll et al., 2005;
Frontiers in Human Neuroscience www.frontiersin.org September 2014 | Volume 8 | Article 742 |9
Rubin et al. Hippocampus and flexible cognition
Hynes et al., 2006; D’Argembeau et al., 2008). The hippocampus
has extensive connections with the PFC (Simons and Spiers, 2003;
Wood and Grafman, 2003), including direct reciprocal connec-
tions between the medial PFC and the MTL (Simons and Spiers,
2003), reciprocal connections between the PFC and the perirhinal
cortex (Lavenex and Amaral, 2000), unidirectional projections
from the hippocampus to the vmPFC (Rosene and Van Hoesen,
1977; Barbas and Blatt, 1995), and bidirectional connections from
the subiculum and neocortical medial temporal regions to the
vmPFC (Goldman-Rakic et al., 1984; Barbas et al., 1999).
The hippocampus is also extensively involved in the limbic
circuit, with extensive connectivity between the amygdala and
the cingulate. Many research findings have documented the role
of the amygdala social and emotional behavior. The amygdala
is important for the detection and recognition of emotional
facial expressions (Vuilleumier et al., 2001; Adolphs, 2002, 2003;
Adolphs et al., 2005), for the processing of social information
more generally (e.g., Hariri et al., 2002; Norris et al., 2004), for
advantageous complex decision-making (Bechara et al., 1999),
for taking the perspective of others (Baron-Cohen et al., 1999;
Stone et al., 2003), and for fear conditioning (e.g., LeDoux, 2003).
Furthermore, there is clear evidence that the amygdala is critical
for the enhancement of declarative memory by emotion (Bradley
et al., 1992; Buchanan and Adolphs, 2002, 2004; McGaugh, 2004;
Phelps, 2004; Adolphs et al., 2005; LaBar and Cabeza, 2006).
Similarly, the cingulate is involved in both reward processing
(Hadland et al., 2003) and emotional memory (Frankland et al.,
2004), seemingly by transmitting and elaborating information
passing between the hippocampal system and neocortical asso-
ciation areas (Sutherland et al., 1988). Functional neuroimaging
studies have also demonstrated correlated activation in the amyg-
dala and the PFC (Rilling et al., 2002; Greenberg et al., 2005),
correlated activation of the amygdala and the hippocampus for
emotional pictures (Dolcos et al., 2004; Richardson et al., 2004),
and prefrontal-cingulate networks in emotional processing (Etkin
et al., 2011) and decision-making (Elliott and Dolan, 1998; Rogers
et al., 2004).
The hippocampus is anatomically connected to the amygdala
via the basal nucleus, the accessory basal nucleus, and the lateral
nucleus (Pikkarainen et al., 1999). Furthermore, the amygdala
is connected bidirectionally to the PFC, especially the medial
aspects, directly and via the dorsomedial thalamus (Bachevalier,
2000; Öngür and Price, 2000). With regards to the cingulate, the
hippocampal formation sends dense projections to the anterior
cingulate gyrus (Wyass and Van Groen, 1992) and the posterior
cingulate cortex receives direct afferents from the subiculum of
the hippocampus (Adey, 1951).
Thus, the hippocampus is both neuroanatomically and func-
tionally connected with brain structures that are important for
decision-making, adaptive reasoning, executive function, and
social behavior, emphasizing the contribution of the hippocam-
pus to an extensive network of brain structures that enable us
to engage in successful and adaptive behavior. Of course, flexible
cognition requires the orchestration of the full network, yet per-
formance of patients with focal hippocampal and vmPFC damage
suggests that distinct neural systems may differ in the nature
and timing of their contribution (e.g., patients with hippocampal
damage and vmPFC damage show different patterns of deficit on
the IGT task and on the character updating task). Delineating the
nature and time-course of the interactions between hippocampus
and the rest of the network for flexible cognition promises to
offer finer-grained understandings of these complex dynamics.
Development of tasks that are sufficiently complex to recruit
diverse neural systems and data analyses sufficiently sensitive to
detect the timing and contribution of individual systems will also
further our understanding of how the network as a whole operates
in real time and in complex environments in service of adaptive
and social behavior. Indeed, even patients with hippocampal
damage can often rely upon perception and prior semantic knowl-
edge to guide their behavior in many circumstances, causing
investigators to underestimate all the ways in which such patients
might be impaired if properly challenged.
TRANSLATING ADVANCES IN BASIC COGNITIVE
NEUROSCIENCE INTO CLINICAL APPLICATIONS
Converging evidence shows that varying degrees of hippocampal
dysfunction have been implicated in a wide variety of patients
with neurological conditions, such as traumatic brain injury and
Alzheimer’s disease, as well as psychiatric conditions, such as
schizophrenia, post-traumatic stress disorder (PTSD), depression,
anxiety, and autism (Heckers et al., 1998; Nelson et al., 1998;
Campbell and MacQueen, 2004; Schumann et al., 2004; Shin
et al., 2006; Etkin and Wager, 2007). For example, in schizophre-
nia patients we found the same kind of impairment on a
hippocampal-dependent relational memory paradigm (Williams
et al., 2010), though to a lesser degree, than amnesic patients
with profound hippocampal damage (Hannula et al., 2007).
In depressed patients, structural neuroimaging studies revealed
reduced hippocampal volumes relative to control groups (Brem-
ner et al., 2000; Mervaala et al., 2000; but see Posener et al., 2003).
In patients with PTSD, a meta-analysis of functional neuroimag-
ing studies found hypoactivations during fear-conditioning in
a network of structures, including the anterior hippocampus,
relative to a control group (Etkin and Wager, 2007). The
hippocampus also plays a role in regulating the hypothalamic-
pituitary-adrenal axis (Fendler et al., 1961; Jacobson and Sapol-
sky, 1991), which is perturbed in both PTSD (Buckley et al., 2000;
de Kloet et al., 2006) and depression (MacQueen et al., 2003;
Heim et al., 2008). Thus, the evidence that hippocampal dysfunc-
tion can be found in clinical cases more broadly than only those
discussed in the amnesia literature raises an interesting question
as to whether clinicians may be more aware of the larger reach of
the hippocampus, beyond its impact on traditional memory test
performance, than we get from the amnesia literature alone.
Once we understand that hippocampal insult (whether focal
and primary or secondary as part of a more diffuse pathology) is
disruptive to the formation and use of flexible representations in
service of flexible cognition, we see how it can underlie deficits
in the seemingly distinct domains of memory, language, social
interaction, etc. Thus, the patient with hippocampal disruption
who is unable to integrate knowledge during a complex task,
use specific details to plan a future event, track the status of a
social interaction over time, and, more generally, reach outside the
contents of their current experience, will surely exhibit broader
Frontiers in Human Neuroscience www.frontiersin.org September 2014 | Volume 8 | Article 742 |10
Rubin et al. Hippocampus and flexible cognition
disruptions of everyday life. These disruptions will be manifested
in their social behaviors, shrinking the range and quality of their
social interactions, and in their decision-making, resulting in
taking on fewer day-to-day responsibilities and more difficulty
with everyday activities, much of which is likely to be seen by
clinicians in their interactions with these patients. We suggest that
these various deficits or changes in everyday life for such patients
emerge from a common cause, namely the deficit in formation
and use of flexible representations.
This view of how a deficit in what is classically seen as limited
to the domain of memory actually extends across many domains
of cognition is, intriguingly, very much in line with the NIMH’s
recently created Research Domain Criteria (RDoC) project, where
researchers are encouraged to shift from focusing on categorically
distinct mental disorders, such as schizophrenia or major affective
disorder, to instead focus on underlying symptoms, or disruptions
of dimensions of cognition and behavior, such as depression or
hallucinations, that might cut across disease categories. Here,
we are arguing that declarative memory, one of the dimensions
described in RDoC, when impaired, causes deficits that extend
across a range of cognitive domains and impair or disrupt behav-
ior in a wide range of neurological and psychiatric conditions.
Moreover, consistent with the RDoC focus on underlying brain
systems and brain mechanisms, our consideration here of declar-
ative memory, and its various manifestations, is tied squarely to
the hippocampus and the brain networks with which it interacts.
CONCLUSION
Humans interact with and actively participate in the world around
them. The ability to make sense of the events of daily life,
and to act optimally in and on the world requires the constant
creation, modification, and use of flexible representations. The
ability to flexibly manipulate, update, and integrate information
is essential, allowing us to blend past experiences with future
goals to make appropriate decisions. The findings reviewed here
demonstrate that the hippocampus plays a critical role in flexibly
representing information important for many aspects of cogni-
tion and social behavior. The hippocampus supports the ability to
bind and flexibly represent discrete elements of an experience and,
through its interconnections with other neural systems, permits
the expression of flexible and adaptive behavior. Together, these
findings also highlight the unique perspective that research in
patient populations provides, when investigating the contribution
of a specific brain structure to a variety of complex behaviors, and
the translational value of such research to clinical practice. The
flexible cognitive and social abilities reviewed here are required to
successfully engage in everyday activities; however, only recently
has the hippocampus been recognized as one of the brain struc-
tures important for flexible and adaptive human interactions,
which is related to, but beyond its traditionally recognized role
in memory.
ACKNOWLEDGMENTS
Preparation of this manuscript was supported in part by NIH R01
DC011755 to Melissa C. Duff, NIMH RO1 MH062500 to Neal
J. Cohen, and a Carle Foundation Hospital-Beckman Institute
Fellowship to Rachael D. Rubin.
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Conflict of Interest Statement: The authors declarethat the research was conducted
in the absence of any commercial or financial relationships that could be construed
as a potential conflict of interest.
Received: 08 June 2014; accepted: 03 September 2014; published online: 30 September
2014.
Citation: Rubin RD, Watson PD, Duff MC and Cohen NJ (2014) The role of the
hippocampus in flexible cognition and social behavior. Front. Hum. Neurosci. 8:742.
doi: 10.3389/fnhum.2014.00742
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