Representations in the Human Prefrontal Cortex

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 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 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]. CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE Volume 15—Number 4 167 Journal compilation r 2006 Association for Psychological Science. No claim to original U.S. government works. 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 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 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. 168 Volume 15—Number 4 Representations in the Human Prefrontal Cortex