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This chapter presents a brief overview of the neural representations in the rat prefrontal cortex and striatum in spatial tasks. While both structures appear to be strongly affected by position information (and possibly hippocampal input), the nature of their representation is deeply different from the map-like structure of hippocampal-system activity. Both structures seem to be affected by combinations of factors such as task phase, current motor behavior, reward or lack thereof, and task-relevant locations. The prefrontal cortex is sensitive to the task-relevant cues, and exhibits a large deal of flexibility in changing its response characteristics when the reward contingency is changed, in accordance with its proposed role in attentional shifts. Spatial modulation of activity is often present in these two structures, but most likely in conjunction with some other influence, such as the factors mentioned above.

This chapter reviews data from a range of disciplines and, in particular, the comparison of lesion effects with those of anti-anxiety drugs. It presents an essentially two-dimensional picture of the neurology of defense that matches the two ethological dimensions described in Chapter 2. Small defensive distances are dealt with by lower neural levels and large ones by higher neural levels following the hierarchy: periaqueductal gray; hypothalamus; amygdala/hippocampus; cingulate cortex; prefrontal cortex. Different streams within these levels control fear and anxiety, respectively.

This chapter examines the role of the cerebral cortex in the control of autonomic function. Prefrontal and insular cortical regions are key components of the cortical pathways that are recruited during stress as well as influencing blood pressure, sympathetic vasomotor drive, cardiovascular reflex function, vasopressin secretion, gastrointestinal motor function, and micturition. A description of the neuroanatomical connections of the cortex with other central autonomic circuits underpins the discussion of the role of the cerebral cortex in central autonomic control mechanisms. In addition, the sources of afferent input to cortical regions known to influence autonomic function are described. In man, early clues pointing to a role for the cortex in autonomic function came from patients affected by cerebral trauma or seizures. Today, the role(s) of the prefrontal cortex and insular cortex in human autonomic function is emerging from functional magnetic resonance imaging studies.

The decades since Luria's seminal work in neuropsychology have brought tremendous advances in the understanding of prefrontal cortex (PFC) function. This chapter reviews meta-analytic, functional neuroimaging, and other neuropsychological and neuroscience data in order to discuss the putative functions of a set of PFC regions involved in cognition, motivation, and emotion. It is argued that PFC function is best understood by looking at the involvement of specific regions across a wide range of tasks, rather than restricting interpretations of function to specific task domains (e.g. working memory, task switching, etc.). In this light, processing in PFC is proposed to be roughly hierarchical, with posterior PFC regions being involved in motor response selection while more anterior regions carry out a set of specific higher-order processes commonly associated with working- and long-term memory tasks. Finally, orbitofrontal cortex and ventromedial PFC are involved in specific aspects of emotion processing.

Recent research on action selection suggests that a useful distinction may be drawn between two systems centered on the ventrolateral prefrontal cortex (PFv) and anterior cingulate cortex (ACC). The PFv is concerned with the selection of actions in response to visual stimuli (stimulus‐response mappings) and according to learned arbitrary rules. The ACC is more concerned with reward‐guided action selection. This is especially the case when a judgment must be made about whether a reward is worth pursuing, given the probability that the reward will follow the action, or given the effort that will have to be exerted before the reward is obtained. Three lines of evidence supporting this contention are reviewed.

Working memory is an elaboration short term memory, the capacity to hold items briefly in consciousness and then repeat or identify them, and involves the important addition of mental “work”, that is, cognitive processing and its combination with “memory”. In addition, working memory is a form of declarative memory, because this sort of processing goes on in consciousness and involves relational and inferential judgments, and is accessible to explicit forms of expression. Working memory relies critically on the functions of the prefrontal cortex, which studies on humans and animals show is essential to executive functions involving holding and manipulating information in mind, and for searching for stored memories and formulating appropriate behavioral strategies.

This chapter sets the stage for the rest of the book, presenting anatomical and clinical distinctions that serve as organizational and memory “hooks” for reading many of the other chapters. It discusses how massive damage to the frontal lobes can cause dramatic changes in personality and comportment while keeping sensation, movement, consciousness, and most cognitive faculties. It addresses questions such as: Is there a unitary “frontal lobe syndrome” encompassing all signs and symptoms? Are there regional segregations of function within the frontal lobes? Is it possible to identify a potentially unifying principle of organization which cuts across the heterogeneous specializations attributed to the frontal lobes?

This chapter reviews the current neuropsychological and physiological evidence linking lateral and orbital prefrontal cortex (PFC) to human cognition and social interchange in an attempt to provide a summary of much of the work presented in this book and elsewhere. It begins with a review of the findings concerning the role of lateral PFC in executive control of cognition, and then discusses the relevant literature on the contributions of orbital PFC to social and emotional control.

This chapter summarizes current knowledge of dopamine (DA) and DA receptor localization in primate prefrontal cortex (PFC), and the powerful influences of DA on PFC physiology and cognitive function. It begins with an overview of PFC function, physiology, and circuitry. It then discusses the anatomy of DA and its receptors in the primate PFC, the effects of DA on PFC physiology and function, and the role of changes in DA transmission in PFC in several neuropsychiatric disorders.

This chapter presents what is known about the anatomy and function of the executive processes to provide a better understanding of them. The discussion covers the sensory and mnemonic representations that remain in posterior cortex, the ensemble of executive processes, the anatomy and physiology of the prefrontal cortex, whether active prefrontal connections necessary for posterior conscious states, access consciousness versus phenomenal consciousness, and bare consciousness.

In traditional animal learning theory, stimuli, responses, and outcomes determine an animal's behavior. But how can animals, or people, for that matter, make decisions regarding stimuli they have never encountered? One way involves abstract response strategies. These strategies are considered abstract because they do not depend on experience with particular, previously experienced stimulus‐response mappings. This chapter reviews relevant neurophysiological data from macaque monkeys and addresses the following questions: (1) What is a strategy? (2) How, if at all, do strategies differ from rules? (3) Does the idea that prefrontal cortex subserves strategies contribute to contemporary ideas about its evolutionary history? (4) What are the adaptive advantages of a strategy‐implementing prefrontal cortex for those animals that have one?

This chapter first summarizes the anatomy of the prefrontal cortex. It then reviews the functional role of the prefrontal cortex, including a consideration of whether it is involved in memory per se or other cognitive processes related to memory, and whether this expansive area has specialized subdivisions between or within the hemispheres. This is followed by considering the parcellation of functions and cooperation between the prefrontal cortex and other higher-order cortical areas, including a review of findings on how the prefrontal cortex interacts with the medial temporal lobe in support of long-term declarative memory.

This chapter shows that key higher-level cognitive functions known as the executive functions are strongly associated with the human prefrontal cortex (HPFC). It argues that an important way to understand the functions of the HPFC is to adapt the representational model that has been the predominant approach to understanding the neuropsychological aspects of, for example, language processing and object recognition. The representational approach developed is based on the structured event complex framework. This framework claims that there are multiple subcomponents of higher-level knowledge that are stored throughout the HPFC as distinctive domains of memory. The chapter also argues that there are topographical distinctions in where these different aspects of knowledge are stored in the HPFC.

Dopamine and serotonin have been implicated in a wide variety of cognitive and emotional control processes. This chapter reviews the evidence that these two neuromodulators differentially regulate two distinct forms of cognitive flexibility in marmoset monkeys, namely, attentional set‐shifting and discrimination reversal learning, through their independent actions within the lateral prefrontal cortex and orbitofrontal cortex, respectively. Consideration is given to the psychological and cellular mechanisms that may underlie their effects, not only at the level of the prefrontal cortex, but also at other neural sites known to contribute to these forms of flexibility, namely, the striatum and amygdala.

This chapter discusses the executive functions of the prefrontal cortex against the background of its position in the neocortical map of cognitive representations. It attempts to place prefrontal functions within the broad framework of the cortical substrate of long-term memory, which is formed by a complex array of widely distributed, overlapping, and intersecting neuronal networks in the neocortex of association. The chapter then presents a conceptual model of the distribution of long-term memory in the neocortex. The chapter concludes with a brief discussion of microelectrode data from the lateral prefrontal cortex that not only reaffirm the anchoring of its functions in long-term memory but also provide insight into the mechanisms of temporal integration, which is cardinal among those functions.

The chapter describes the structural organization of the orbital cortex (OFC), together with the medial prefrontal cortex. It reviews previous areal maps of this cortex, and provides a description of architectonic divisions of the cortex based on analysis of eight staining methods in nonhuman primates and humans. Twenty-two areas were recognized, most of which are subdivisions of previously described areas. Distinct subregions were found ranging from several agranular insular areas in the posterior orbital region, through a dysgranular zone in the central region (subdivisions of area 12 and 13), to a granular region in more rostral portions of cortex (subdivisions of areas 10 and 11). The comparable regions in humans are presented with reference to stereotaxic space. An analysis of the comparable regions in rodents is also provided.

To understand how humans use rules to determine actions, it is critical to learn more about how they select responses on the basis of associations in long‐term memory. This chapter discusses what has been learned thus far about the neural substrates of rule storage, retrieval, and maintenance. This chapter presents evidence that rule knowledge associated with environmental cues is stored in areas of the posterior temporal lobes, such as the middle temporal gyrus. It also provides evidence that ventrolateral prefrontal cortex is engaged in the effortful retrieval of rule meanings from long‐term memory. During initial rule retrieval, there is some evidence that different brain structures are recruited, depending on the type of rule retrieved. In contrast, during rule maintenance, brain activation in prefrontal cortex and other brain regions appears to be sensitive to the amount of information to be held in mind, rather than the type of rule or instructional cue.

The prefrontal cortex (PFC) undergoes one of the longest periods of development of any brain region, taking over two decades to reach full maturity in humans. This chapter focuses on normal development, dividing it into the following epochs: 0-1 years, 1-3 years, 3-7 years, and 7 years through early adulthood. For each epoch, it summarizes some of what is known about (a) the development of the working memory and inhibitory control functions that depend on PFC and (b) the anatomical and biochemical developmental changes in PFC during that period.