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CU R RE N T D I R E CT I O NS IN P SYC H OL OGI C AL SC I EN C E
Representations in the Human
Prefrontal Cortex
Edward D. Huey, Frank Krueger, and Jordan Grafman
Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, Maryland
ABSTRACT—The
prefrontal cortex (PFC) in humans has
been studied for more than a century, but many crucial
questions about its functions remain unanswered. This
paper will highlight a few key differences between human
and animal PFCs, and between the human PFC (HPFC)
and other parts of the human brain. We then make a case
that the HPFC is critically important for executing behaviors over time and integrating disparate information
from throughout the brain. Finally, we will focus on our
position in the current debate regarding how the HPFC
performs its functions and discuss future directions for
research.
KEYWORDS—human
prefrontal cortex; frontal lobes
In humans, the prefrontal cortex (PFC) occupies approximately
one third of the entire cerebral cortex, consisting of the area
anterior to the supplemental motor area and the premotor cortex
(see Fig. 1). The human PFC (HPFC) is central to many of the
behaviors that make us ‘‘human,’’ including language, reasoning, decision making, social interactions, planning, and creativity. This review will discuss some of the differences between
human and animal PFCs and between the HPFC and other areas
of the human brain. We will then review a current debate about
how the HPFC functions in light of its unique characteristics. We
conclude with a discussion of some suggested future directions.
UNIQUE CHARACTERISTICS OF THE HPFC
COMPARED TO THE PFC IN OTHER ANIMALS
The neurobiological basis of the unique intelligence of humans
is complex (see Roth & Dicke, 2005, for a complete review). The
intelligence of a species is associated with its overall brain size,
the size of its PFC relative to the rest of its brain, the number of
Address correspondence to Jordan Grafman, Cognitive Neuroscience
Section, National Institute of Neurological Disorders and Stroke,
Bldg. 10; Room 5C205; MSC 1440, National Institutes of Health,
Bethesda, Maryland 20892-1440; e-mail: [email protected].
Volume 15—Number 4
neurons in its brain, and its neuronal interconnectivity (Roth &
Dicke, 2005). Humans do not have the largest brains in the
animal kingdom (some larger mammals, such as elephants and
whales, have larger brains). Humans have one of the largest
relative PFC sizes in the animal kingdom, but other animals (for
example, some species of whale) arguably have a larger relative
PFC. The human brain appears to be unsurpassed in overall
number of neurons (although the African elephant is very close)
and in its degree of neuronal interconnectivity, especially in the
PFC (Elston, 2003). Likely, human intelligence is related to a
combination of large brain and relative PFC size and high neuron
number, density, and interconnectedness (Roth & Dicke, 2005).
UNIQUE ATTRIBUTES OF THE HPFC COMPARED TO
OTHER AREAS OF THE BRAIN
The HPFC evolved recently and rapidly compared to other areas
of the brain. Within a few million years, the human brain has
tripled in size, with the largest proportion of that increase occurring in the frontal regions—especially Brodmann’s area 10
(part of the anterior PFC including the frontal pole; Roth &
Dicke, 2005). This increase in size and complexity of the HPFC
is associated with tool use, art, language, culture, consciousness,
and other uniquely human abilities. The PFC likely evolved from
adjacent posterior structures such as the premotor cortex and the
supplemental motor area.
The HPFC also has a high degree of interconnectivity. This
applies both to individual HPFC neurons as compared to neurons from other areas of the human brain (Elston, 2003) and to
the connectivity of the systems and structures of the HPFC with
each other and with more posterior brain structures (Wood &
Grafman, 2003). The HPFC’s high interconnectivity on cellular
and structural levels likely contributes to its ability to integrate
input from many sources in order to implement more abstract
behaviors.
The PFC is uniquely oriented to time. Almost 70 years ago,
Jacobson made the important observation that monkeys with
damaged PFCs had difficulty remembering which container held
Journal compilation r 2006 Association for Psychological Science. No claim to original U.S. government works.
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Representations in the Human Prefrontal Cortex
Fig. 1. Anatomy of the human prefrontal cortex (HPFC). The HPFC can be divided into the anterior PFC
(APFC), dorsolateral PFC (DLPFC), ventrolateral PFC (VLPFC), and medial PFC (MPFC). From ‘‘Prefrontal
and Medial Temporal Lobe Interactions in Long-Term Memory,’’ by J.S. Simons and H.J. Spiers, 2003, Nature
Reviews Neuroscience, 4, p. 638. Copyright 2003, Macmillan Magazines Ltd. Reproduced with permission.
Figure derived from Neuroanatomy: Text and Atlas (2nd Ed.), by John H. Martin, 1996, Stamford, CT:
Appleton & Lange, pp. 458–459. Copyright 1996, McGraw-Hill companies. Used with permission.
food if there was a delay between observing the researcher place
food in a container and choosing a container to open (Jacobsen &
Nissen, 1937). Later researchers discovered a unique property
of neurons in the PFC of monkeys that related to this early
finding: The neurons can continuously fire during an interval
between a stimulus and a delayed judgment about the stimulus.
Neurons in other brain areas of monkeys are directly linked to
the presentation of a single stimulus, and if they demonstrate
continuous firing, it is probable that they are driven by neurons
in the PFC or by continuous presentation of the stimulus. In
functional magnetic resonance imaging (fMRI) studies, humans
also demonstrate continuous PFC activation between a stimulus
and a delayed judgment about the stimulus (Curtis & D’Esposito,
2003). If the firing of neurons in the PFC is linked to activity that
‘‘moves’’ the subject toward a goal rather than reacting to the
appearance of a single stimulus, then potentially those neurons
could continuously fire across many stimuli or events until the
goal is achieved or the behavior of the subject is disrupted. This
observation of sustained firing of PFC neurons across time and
events has led many investigators to suggest that the HPFC must
be involved in maintaining a stimulus across time.
CURRENT APPROACHES: PROCESS VERSUS
REPRESENTATION
A key debate in current research on the HPFC is whether a
process or a representational view best explains its function.
Traditionally, HPFC function has predominantly been studied
with a processing approach. Such an approach takes the view
that cognition in the PFC can primarily be described in terms of
cognitive processes independent of the material (representations) being processed. In this view, PFC processes such as
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switching, maintenance, and inhibitory control are computational procedures or algorithms operating upon knowledge
stored in other, posterior parts of the brain. The representational
view, in contrast, focuses on unique kinds of knowledge hypothesized to be stored as memories in the HPFC. A representation can be strengthened by repeated exposure to the same or
similar knowledge element and is a member of a psychological
and neural network in the HPFC composed of multiple similar
representations. One or more representations can remain activated over a period of time and compete with activation of other
sets of representations by facilitation or inhibition of neural
activity. In this view, a process such as ‘‘inhibition’’ can be reinterpreted as the activation of knowledge stored in the prefrontal cortex that enforces long-term goals based on prior
experience and suppresses activation in those brain regions
concerned with rapid responses that may be inappropriate to
achieving those goals.
Models of HPFC function can take a primarily processing or
representational approach, or can take a hybrid of the two approaches. An example of a processing model is the adaptivecoding model. This model proposes that HPFC neurons are
substantially adaptable or programmable to meet current behavioral demands (Duncan & Miller, 2002). It emphasizes global
attention—the selective focusing on relevant stimuli and the
role of the HPFC in directing the activity of other brain systems.
In support of this model, a high proportion of PFC neurons show
activity in monkeys performing disparate tasks. The adaptivecoding model is an example of a processing model because it
emphasizes the lack of regional specialization in the PFC and
instead posits a nonspecific general processing role.
An example of a hybrid model is the temporal-organization
model (Fuster, 2002). This model emphasizes the role of the PFC
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Edward D. Huey, Frank Krueger, and Jordan Grafman
in the temporal organization of speech and behavior. It distinguishes between PFC representations and processing but asserts
that the PFC is both a permanent memory store and the site of
processes such as working memory, attention, monitoring, and
planning. (See Wood & Grafman, 2003, for further discussion
and comparison of different models of PFC function.)
As an example of a representational model, we will discuss a
particular model proposed by our laboratory. Our group has
suggested that the HPFC stores a unique type of knowledge in
the form of structured event complexes (SECs). SECs are representations composed of goal-oriented sequences of events that
are involved in planning and monitoring complex behavior.
Aspects of SECs are represented independently in the HPFC but
are encoded and retrieved as a single episode. The stored
characteristics of the SEC representations (e.g., frequency of
exposure) form the bases for the strength of representation in
memory (e.g., higher frequency of exposure leads to stronger
representations) and the relationships between SEC representations (e.g., high-frequency representations are likely to inhibit
low-frequency representations).
According to this theory, the representations in the HPFC differ
from the type of representational memory people are more used to—
e.g., semantic memories contained in the inferolateral temporal
lobe. Semantic memories (e.g., the memory that allows one to name
the capital of France) are explicit (associated with conscious
awareness) and declarative (consciously recalled), but can be implicitly primed. Memories in the HPFC are established by abstracting information across time and events that integrates elements
of knowledge (e.g., themes that cannot be further reduced to their
simpler elements without losing their meaning). The representations
are usually implicitly executed (especially since they are activated
over long periods of time even in the absence of directly relevant
stimuli) and are typically goal related. However, we can also explicitly access these memories via translational and time-compressed mechanisms (e.g., describing a plan by listing events,
creating a cartoon, or in modern times, creating a video).
In our opinion, the processing approach to PFC function is a
fundamental shift away from how cognitive neuroscientists understand other types of brain function. Processing models suggest
that the PFC is minimally committed to long-term storage of
knowledge, as compared to posterior cortical regions in the temporal, parietal, and occipital lobes. We argue that representational
models of the HPFC may be superior to process models for theoretical and empirical reasons: Representational models are more
consistent with evolutionary theory, they make testable predictions, and they too can be supported by the experimental evidence.
First, much of the cortex other than the PFC is organized on a
representational model, with more posterior parts of the cortex
processing simpler information and more anterior parts of the
cortex processing more complex information. For example, in
the visual system, cells in the primary visual cortex are activated
by simple patterns, whereas cells in more anterior visualprocessing areas of the brain respond to more complex, inte-
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grated patterns. It seems likely that the development of the PFC
would follow the same representational model as the more
posterior cortex from which it was derived, especially given the
rapid increase in PFC size and complexity that occurred with the
evolution of modern humans. A parsimonious hypothesis is that
the PFC encodes unique representations of complex behaviors
(e.g., social inferences) in a manner similar to the posterior
cortex. According to this hypothesis, the HPFC would contain
integrative representations more complex than those contained
in more posterior brain areas, and yet would access representations contained in posterior areas, similar to the way visual
stimuli are processed. For example, an HPFC encoding of a plan
that takes place in an office could integrate the goal-directed use
of a telephone, but the memory of the appearance and simple
function of telephones would be contained in more posterior
structures. Representational stores in different locations in the
PFC (and elsewhere) would then become bound together as part
of an episode, with the involvement of memory structures such as
the hippocampus (O’Reilly & Rudy, 2000). As discussed earlier,
the properties of the HPFC—that it integrates and maintains
information about stimuli over time—make it uniquely suited to
store representations of episodes that unfold temporally.
Second, a representational approach forces investigators to
define the nature and location of memories in the HPFC, and this
is well suited for generating testable hypotheses. Processing
models less often suggest specific hypotheses or brain regions
involved because, by definition, the processes are independent
of the specific stimuli being processed. We also have wondered
why such a proportionally large brain region as the PFC would be
the repository of so few ‘‘processes.’’
Third, there is growing empirical data supporting representational models. SECs appear to be selectively processed by
anterior PFC regions. Errors in event sequencing can occur with
preservation of aspects of event knowledge. Thematic knowledge can be impaired even though single-event knowledge is
preserved. Additionally, SEC frequency can affect the ease of
retrieval of SEC knowledge (Grafman, in press).
REGIONAL PREDICTIONS
Because representations are stored in specific brain areas, we
can use our SEC model to make predictions, based on current
data, about the regions of the PFC associated with different aspects of specific PFC functions such as planning. For this purpose, we can crudely divide the prefrontal cortex into left and
right, medial and lateral, dorsal and ventral, and anterior and
posterior sectors. There is evidence that the left PFC focuses on
the specific features of individual events (including features and
meanings) that make up a plan whereas the right PFC mediates
the integration of information across events (including making
sense of the plan as a whole and features at the macro-plan level
such as themes and morals; Grafman, Spector, & Rattermann,
2005). We hypothesize that the medial PFC stores key features
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Representations in the Human Prefrontal Cortex
of predictable overlearned cognitive plans that have a contingent relationship with sensorimotor processes and are rarely
modified. The lateral PFC would store key features of plans that
are frequently modified to adapt to special circumstances. The
ventral PFC is concerned with social-category-specific plans,
which often have an emotional component (e.g., how to ask a
member of the opposite sex for a date). The dorsal PFC is concerned more with aspects of plans representing mechanistic
activities without a social component (e.g., repairing a food
processor). Finally, the anterior PFC tends to represent plans of
long duration composed of many events, whereas the posterior
PFC tends to represent plans and actions of short duration and
fewer events (e.g., a simple overlearned association).
Since no single PFC region would represent all features or
components of a plan, specific plans tend to evoke selected
patterns of PFC activation. Any region could participate in plan
processing depending on the type of plan, with the different plan
(and cortical) subcomponents being differentially weighted in
importance (and activation) depending on the kind of plan, the
moment-by-moment demands of the plan, and previous experience with the plan. For example, the left anterior ventromedial
PFC would be expected to represent a long, multi-event sequence of social interactions (i.e., a social plan) with specialized
processing of single component events including the computation of their temporal and sequential dependencies and primary
meanings (Grafman et al., 2005).
We have begun investigating these proposed differential
contributions of PFC subregions. Positive evidence has been
found for the representation of several different SEC components
within the HPFC. For example, one of us (Frank Krueger)
performed an fMRI study in humans that detected that highfrequency SECs are encoded in the posterior medial Brodmann’s
area 10 and low-frequency SECs are encoded in the anterior
medial Brodmann’s area 10. There is little in the way of negative
studies of this framework, but many predictions of the SEC
framework have not been fully explored to date and could
eventually be falsified.
testable hypotheses. For example, a general prediction would be
that patients with HPFC damage should show selective deficits
in performance in novel situations for which they cannot access
representations to aid them. Furthermore, the pattern of deficits
should show regional specificity depending on the location of the
lesion in the HPFC. For example, a specific prediction would be
that damage to the left anterior ventromedial PFC would impair
access to long multi-event sequences of social information and
cause special difficulty processing the meaning and features of
single events within such sequences, including difficulty computing their sequential dependencies.
The development of normed and validated research tools to investigate tasks such as social interactions performed by the HPFC
will be required to better investigate the neuropsychology of this
brain area. Experiments using virtual-reality technology have the
potential to delineate the functions of the HPFC in a controlled yet
more naturalistic manner than conventional neuropsychological
testing. Innovative imaging technologies have great potential; for
example, simultaneous fMRI scanning of multiple subjects (termed
‘‘hyperscanning’’) allows real-time imaging of the neural correlates
of social interactions. The elucidation of genetic influences on the
HPFC is also an important research topic.
Because of the role of the HPFC in storing and executing
social behavior, findings on the HPFC have important ethical
and societal implications. For example, if a set of clearly articulated and understood social behaviors are found to be additively and significantly associated with particular imaging
findings, such findings could be used by the legal system or
potential employers to evaluate and screen for those behaviors.
And because of its standing in the hierarchy of cognitive abilities, the HPFC is an ideal target for interdisciplinary investigations by, for example, economists, political scientists,
historians, and educators. Although the HPFC has been researched for more than a century, there remain many important
unanswered and socially relevant questions about the functions
of this, the most ‘‘human’’ of brain areas.
SUMMARY
Recommended Reading
Miller, E.K., & Cohen, J.D. (2001). An integrative theory of prefrontal
cortex function. Annual Review of Neuroscience, 24, 167–202.
Moll, J., Zahn, R., de Oliveira-Souza, R., Krueger, F., & Grafman, J.
(2005). Opinion: The neural basis of human moral cognition.
Nature Reviews Neuroscience, 6, 799–809.
Stuss, D., & Knight, R. (Eds.). (2002). Principles of frontal lobe function.
Oxford, England: Oxford University Press.
Wood, J.N., & Grafman, J. (2003). (See References)
The HPFC appears to be important for executing behaviors over
time and integrating disparate information from throughout the
brain. Although the prevailing view of the HPFC is that of a
functional processor region (in contrast to the view of posterior
brain structures), we have instead hypothesized that these
functions are based on a large set of associative and integrative
representations ranging from social attitudes to long-term plans.
OUTSTANDING ISSUES/FUTURE DIRECTIONS
Further data are required to resolve the process-versus-representation debate over HPFC function. Representational models
such as the SEC framework discussed above provide many
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REFERENCES
Curtis, C.E., & D’Esposito, M. (2003). Persistent activity in the prefrontal cortex during working memory. Trends in Cognitive Sciences, 7, 415–423.
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Edward D. Huey, Frank Krueger, and Jordan Grafman
Duncan, J., & Miller, E.K. (2002). Cognitive focus through adaptive
neural coding in the primate prefrontal cortex. In D. Stuss &
R. Knight (Eds.), Principles of frontal lobe function (pp. 278–291).
Oxford, England: Oxford University Press.
Elston, G.N. (2003). Cortex, cognition and the cell: New insights into the
pyramidal neuron and prefrontal function. Cerebral Cortex, 13,
1124–1138.
Fuster, J.M. (2002). Physiology of executive functions: The perception–
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lobe function (pp. 96–108). Oxford, England: Oxford University
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Grafman, J. (in press). Executive Functions. In M. Rizzo & R. Parasuraman (Eds.), Neuroergonomics: The brain at work. Oxford,
England: Oxford University Press.
Grafman, J., Spector, L., & Rattermann, M. (2005). Planning and
the Brain. In R. Morris & G. Ward (Eds.), The Cognitive Psy-
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chology of Planning (pp. 181–198). Hove, England: Psychology
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