Psychological Bulletin 1996. Vol. 120, No.

2, 272-292

Copyright 1996 by the American Psychological Association, Inc. 0033-2909/96/S3.00

An Application of Prefrontal Cortex Function Theory to Cognitive Aging

Robert L. West
University of South Carolina
The purpose of this review is to extend the existing application of the frontal lobe hypothesis of cognitive aging beyond the limited work on inhibitory control (F. N. Dempster, 1992) to include memory processes supported by the prefrontal cortex. To establish a background for this analysis, I review existing models of prefrontal cortex function and present a synthesized model that includes a general function of temporal integration, supported by 4 specific processes: prospective memory, retrospective memory, interference control, and inhibition of prepotent responses. I found the frontal lobe hypothesis to perform well, with the exception of an inability to account for age-related declines in item recall and recognition memory, possibly a result of age-related declines in medial temporal function.

In the past decade, a rapidly expanding body of evidence from the field of geriatric neuropsychology has provided evidence suggesting a selective, age-related decrease in performance on neuropsychological measures diagnostic of frontal lobe insult. In studies on the affect of increasing age on tasks sensitive to damage of a number of brain regions, older adults have been found to perform poorly, relative to younger adults, on measures of frontal lobe function, while performing comparably on tasks of nonfrontal function (Ardila & Rosselli, 1989; Whelihan & Lesher, 1985). Findings from these large-scale studies have been supported by additional research on age-related differences on single tasks sensitive to frontal lobe insult. For instance, the Self-Ordered Pointing Task (SOFT) has consistently been found to reveal age-related performance decline as early as the 6th decade of life (Daigneault & Braun, 1993; Shimamura & Jurica, 1994). These findings have led a growing number of researchers and theorists to suggest that the cognitive processes supported by the frontal lobes, and more specifically the prefrontal cortex, are among the first to decline with increasing age (Albert & Kaplin, 1980; Daigneault, Braun, & Whitaker, 1992; Dempster, 1992). One of the key assumptions of the frontal lobe hypothesis of aging is that cognitive functions supported by the prefrontal cortex should reveal decline at an earlier age than those supported by other brain regions. Whereas the number of studies directly addressing this issue is limited, there is some evidence indicating early decline of prefrontal cognitive function. Daigneault et al. (1992) reported that a group of individuals with a mean age of

Robert L. West, Department of Psychology, University of South Carolina. I thank Gordon Baylis and Martha Ann Bell for their insightful commentary provided on drafts of this article. I also thank Bruce Pennington for his comments during the review process. Correspondence concerning this article should be addressed to Robert L. West, who is now at Rotman Institute, Baycrest Centre for Geriatric Care, 3560 Bathhurst Street, North York, Ontario, Canada M6A 2E1. Electronic mail may be sent via Internet to westr@black.cla.sc.edu.
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56.62 years were "impaired" relative to a group of individuals with a mean age of'27.71 years on 10 of 12 measures of prefrontal cortex function. Investigations of age-related differences on the SOFT have also provided some measure of support for early decline in prefrontal cortex function. Daigneault and Braun (1993) reported that late middle-aged adults (mean age 60) committed more errors than a group of young middle-aged adults (mean age 36). Investigating the SOFT, Shimamura and Jurica (1994) found that age-related differences in pointing errors emerged as early as age 61, whereas age-related differences in item recognition were only observed after age 71. Similar findings are reported in a study of source memory, where older adults demonstrated equivalent recall of fact material when compared with younger adults but were impaired in the recall of source information (Schacter, Kaszniak, Kihlstrom, & Valdiserri, 1991). Both of these findings are of considerable importance for the frontal lobe hypothesis because they provide evidence for declining frontal lobe function with commensurate maintenance of nonfrontal function, in this case, temporal lobe function (Kolb & Whishaw, 1990). Whereas the existing evidence does provide tentative support for the idea of an early, selective decline of cognitive functions associated with the prefrontal cortex, more studies, like those of Shimamura and Jurica and Schacter et al., are warranted to further establish this dissociation. An application of the frontal lobe hypothesis to the problem of cognitive aging, and cognitive development in general, appeared in a series of reviews by Dempster (1991, 1992, 1993). The major premise of this work is that age-related differences from childhood to old age, in a variety of cognitive domains, can be interpreted to arise from ontogenetic differences in the efficiency of inhibitory processes that are supported by the prefrontal cortex (Dempster, 1991; Harnishfeger & Bjorklund, 1993), a hypothesis consistent with the earlier work of Albert and Kaplin (1980) indicating that older adults demonstrate age-related performance deficits on a number of tasks related to frontal lobe function. Within the area of cognitive aging, the inhibition deficit hypothesisproposed by Hasher and Zacks (1988)suggests that age-related impairments observed in a

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number of tasks result from a weakening of inhibitory processes in working memory with old age. This hypothesis has generally been supported by findings from a variety of experimental paradigms, including negative priming (Kane, Hasher, Stoltzfus, Zacks, & Connelly, 1994; Tipper, 1991), text processing (Hamm & Hasher, 1992), and speech production (Arbuckle & Gold, 1993). Whereas the importance of the prefrontal cortex in supporting inhibitory processes is well-established, inhibition is not the only cognitive process believed to be supported by the prefrontal cortex. Extensive literature suggests that the prefrontal cortex plays an intimate role in the maintenance of representational memory on-line during task-related processing (Fuster, 1980; Goldman-Rakic, 1987). The role played by the prefrontal cortex in age-related declines in memory has not been extensively considered, although a number of researchers have found significant correlations between standard neuropsychological measures of frontal lobe function and measures of source and episodic memory (Craik, Morris, Morris, & Loewen, 1990; Parkin & Walter, 1992; Troyer, Graves, & Cullum, 1994), suggesting that the declining efficiency of the prefrontal cortex may contribute to some forms of age-related memory impairment. Whereas the empirical evidence above does provide reasonable support for the frontal lobe hypothesis, this evidence has only been loosely tied to theories of prefrontal cortex function and existing neurobiological evidence regarding selective agerelated declines of the prefrontal cortex. Dempster (1991, 1992) has focused primarily on the role of the prefrontal cortex in protecting the individual from the potential effects of interfering stimuli, whether generated internally or present in the environment. Inhibitory control is but one of the cognitive functions believed to be supported by the prefrontal cortex. Extensive work in the areas of animal neuroscience and human neuropsychology has indicated that the prefrontal cortex is also intimately involved in memory processes, including the integration of information into an enduring memory trace and the maintenance of information on-line during task performance, suggesting that any account of the relationship among aging, cognition, and the prefrontal cortex must address processes of memory as well as of inhibition. With these considerations in mind, the goals of this review are threefold: (a) to provide a review of extant neurobiological evidence relevant to the selective age-related decline of the prefrontal cortex, (b) to provide a summary of the theoretical formulations of the nature of prefrontal cortex cognitive function, and (c) to provide an analysis of the cognitive aging literature in the context of prefrontal cortex theory.

Neurobiology of the Aging Prefrontal Cortex Structural Changes in the Aging Brain
Morphological studies of the aging brain have focused on multiple levels of analysis, ranging from measurement of the gross anatomical volume of various regions to the consideration of neurochemistry and synaptic density and integrity (Goldman-Rakic & Brown, 1981; Haug & Eggers, 1991;

Scheibel, Lindsay, Tomiyasu, & Scheibel, 1975; see Table 1). Numerous researchers have found evidence for a general reduction in gross brain volume becoming significant in the 7th decade of life (Haug & Eggers, 1991). For the entire brain, this reduction in volume has been estimated to be approximately 6% from young adult levels. One of the more striking findings from this line of research is that of regional differences in the degree of reduction across the cortex. In the temporal, parietal, and occipital cortices, the degree of reduction has been estimated to be approximately 1%, compared with volume reduction in the frontal cortex and corpus striatum, estimated to be 10%-17% and 8%, respectively (Haug et al., 1983; Haug & Eggers, 1991). This reduction in brain volume appears to result more from a reduction in neuron size than from an actual loss of neurons (Haug & Eggers, 1991). Shrinkage of cells in the frontal cortex appears to begin earlier and be more severe than in other areas. Haug and Eggers reported that, below the age of 45, there was little reduction in cell size in any area of the cortex measured. Within the 5th to 7th decades of life, shrinkage of cortical neurons appeared to begin and was greater in the extrapyramidal cells of the prefrontal cortex (22%) than in the parietal, orbital prefrontal, or primary visual cortex (6%, 3%, and 9%, respectively). Above the age of 65, the reduction in cell size became more pronounced in all regions and continued to dominate in the prefrontal region (43%, 11%, 25%, and 13%, in the extrapyramidal prefrontal, parietal, orbital prefrontal, and primary visual regions, respectively; Haug & Eggers, 1991). These findings suggest that neural aging was characterized by a reduction in the size of neurons and not a loss in the number of neurons, one may ask, What could have led to the reduction in cell volume observed in these studies? Reduction in cell volume could have resulted from numerous sources, including the loss of dendritic extensions and a reduction in the number of synapses. Scheibel et al. (1975) reported that the neuron proceeds through a series of degenerative changes with advancing age. They reported that the "loss of horizontal elements of the dendritic array is accompanied or preceded by the irregular swelling of the soma and major dendrites" (p. 399). With a loss of dendritic processes, the neuron would decrease in both size and effectiveness. A reduction in the number of synapses could also account for some of the neuronal shrinkage observed during the aging process. Huttenlocher (1979) reported that synaptic density was significantly reduced within the middle frontal gyrus in a group of four individuals ages 74-90 years, compared with individuals ages 16-72 years. Unfortunately, this was the only region sampled from in the study, so between-region comparisons were not possible. It is difficult to ascertain the causal order of neuronal changes at this or any level. For instance, does a decrease in the number of synapses result in a decrease in the number of dendritic processes or do shrinking dendritic processes limit the number of synapses? It does seem safe to suggest that a reduction in neuronal size could result from a loss of connective processes of the neuron. Consistent with findings from studies of gross regional volume and synaptic density, there also appears to be a number of region-specific declines in the concentration, synthesis, and number of receptor sites for some neurotransmitters. In an extensive study of both the concentration and biosynthesis of do-

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Table 1 Age-Related Neurobiological Changes

Change Structural Volume reduction Neuronal atrophy Synapse loss Changes in neurochemistry Senile plaques Functional Oxygen utilization Cerebral blood flow Glucose metabolism Cerebral metabolic rate Note. DA = dopamine. Characteristic 43% extrapyramidal prefrontal, 25% orbital prefrontal, 11 % parietal, 13% primary visual Loss of dendritic processes, enlargement of soma Reduction in number of synapses in midfrontal gyrus Reduced numbers of DA receptors Most prevalent in prefrontal and temporal Greatest reduction in prefrontal enhanced by age-related pathology Nonsignificant age-related effects Study Haug & Eggers (1991) Scheibel et al. (1975) Huttenlocher (1979) Suharaetal. (1991) Struble et al. (1985) Shaw etal. (1984) de Leon etal. (1983)

pamine (DA), norepinephrine ( N E ) , and serotonin (5-HT), Goldman-Rakic and Brown (1981) reported a high degree of both transmitter and regional specificity with regard to the effects of increasing age. In the prefrontal cortex, the concentration of DA was found reduced by 56% in monkeys 18 years of age and older, while levels of NE and 5-HT remained stable in this same group. A similar pattern was found in the superior and posterior inferotemporal cortex, where DA was reduced on average by 39% and 35%, respectively, and 5-HT remained stable across the range of ages tested. In the posterior inferotemporal cortex, a significant reduction in the concentration of NE was also observed. These findings can be contrasted with those revealed by analyses of the parietal and occipital cotices and the hippocampus, where levels of all three neurotransmitters remained unchanged with increasing age. In addition to the reduction in concentration of DA in the prefrontal and temporal cotices, Goldman-Rakic and Brown also reported a significant reduction in neurotransmitter synthesis in the prefrontal, temporal, and parietal regions. Work with humans suggest that age-related changes in neurochemistry are observed as both a reduction in the number of receptors (de Keyser, Backer, Vauquelin, & Ebinger, 1990) and a reduction in the concentration of neurotransmitters (Adolfsson, Gottfries, Roos, & Winblad, 1979). In an in vivo study using PET, Suhara et al. (1991) reported a 39% reduction in the binding potential of D, receptors in the frontal cortex and a 35% reduction in binding potential of D, receptors in the striatum with increasing age. Similarly, de Keyser et al. reported a significant correlation between D, receptor concentration and increasing age ( r = .57) in a postmortem study. In comparison, Adolfsson et al. found a significant relationship between age and the concentration of DA in a number of subcortical structures, including the hypothalamus, caudate nucleus, and hippocampus but not the cortex, in a postmortem study. Not finding a significant age-related effect in the cortex should be interpreted cautiously as the low level of monoamines in the cortex and the often extended period between death and tissue fixation Adolfsson et al. found an average of 27.2 hrmake accurate postmortem estimates of neurotransmitter concentration in the cortex difficult. Rinne (1987) had also reported a reduction in the number of muscarinic receptors with increasing age that was greatest in the frontal and hippocampal regions.

The consequences of this reduction in neurotransmitter-receptor concentration have been considered in studies incorporating various transmitter agonist and antagonist. Arnsten, Cai, Murphy, and Goldman-Rakic (1994) reported that the administration of the D! antagonist SCH23390 impaired performance on a delayed response task in young animals but had no effect on the performance of older animals. In contrast, the administration of a D, agonist improved the performance of the older animals and those treated with reserpine, a DA suppressant (Arnsten et al., 1994). In a study of the effects of administration of a NE agonist and antagonist to younger and older animals, similar performance improvements and deficits were discovered (Arnsten & Goldman-Rakic, 1985). The reduction in cortical volume observed with advancing age is accompanied by an increase in the number of pathological structures present in the brain (Kubanis & Zornetzer, 1981). The presence of senile plaques has been documented in humans and nonhuman primates. This review is not as concerned with the causal origins of such plaques but instead focuses on the regional distribution of these structures. Evidence from the nonhuman primate literature suggests that there is an identifiable regional distribution of senile plaques in healthy animals. A study designed to measure both the origin and regional distribution of plaques revealed greater numbers in the prefrontal and temporal cortices compared with the posterior, frontalparietal, or hippocampal regions (Struble, Price, Cork, & Price, 1985). Furthermore, these researchers suggested that the oldest or most mature plaques were found within these two regions. Similar findings are reported in another nonhuman primate study, noting that the highest concentrations of plaques were in the frontal areas and that significantly fewer plaques were observed in the hippocampus and primary visual and auditory cortices (Heilbroner & Kemper, 1990). These findings suggest that, regardless of the origin of senile plaques in the cortex, they exist in greater concentrations within the frontal and temporal regions in healthy nonhuman primates. This can be contrasted with Alzheimer's disease (AD), where plaques are predominantly found in the hippocampus, association cortex, locus coeruleus, and nucleus basalis (Horvath & Davis, 1990). The findings above support the hypothesis that the frontal cortex is more sensitive to the effects of aging than other cortical regions (Dempster, 1991; Haug & Eggers, 1991). The frontal

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cortex demonstrates accelerated volume loss, resulting from a reduction in cellular size. This reduction in cellular volume may be due to a decrease in the number of synapses, the atrophy of dendritic processes, or a reduction in cellular mechanisms that support the synthesis and transmission of various neurotransmitters. Along with the reduction in cellular volume, an increase in the number of senile plaques is frequently observed within this region. The functional significance of these changes is not fully known. It could be that the brain maintains a relatively stable level of function in the presence of the described structural changes or that these structural changes could result in a decline in the functional integrity of the aging cortex.

Functional Changes in the Aging Brain

Investigations of the functional integrity of the aging brain have primarily incorporated one of two different methods of neuroimaging, the Xenon 133 inhalation (Xe 133 ) method or the positron emission tomography (PET) method. The Xe 133 method used extensively in the study of functional brain aging is believed to measure to the rate of regional cerebral blood flow (rCBF) or oxygen use in the cortex (Roland, 1984). The PET method, developed more recently, can be used to measure both cerebral blood flow and cerebral metabolism of glucose and has been incorporated less frequently into the study of aging (de Leon et al., 1983). Both of these methods have been used to study the effects of aging as well as pathologies often associated with the aging process, including cardiovascular disease (CVD) and AD. Unfortunately, these two methods have not always provided concordant results with regard to the effects of increasing age. Studies incorporating the Xe 133 and the PET methods have in general found age-related decreases in oxygen use, whereas PET studies do not typically demonstrate significant age-related differences in glucose metabolism (Gur, Gur, Orbist, Skolnick, &Reivich, 1987; de Leon etal., 1983). Studies of functional brain aging using the Xe 133 and the 15oxygen PET methods have provided evidence suggesting a decrease in the functional integrity of the cortex with increasing age, characterized by a decline in rCBF. The correlation ( r ) between age and rCBF ranges from -.34 to .70 in samples of healthy adults ages 18-100 (Melamed, Lavy, Shlomo, Cooper, & Rinot, 1980; Naritomi, Meyer, Sakai, Yamaguchi, & Shaw, 1979; Shaw et al., 1984). This age-related reduction in rCBF has been estimated to exceed 27% in some cortical regions (Melamed et al., 1980; Shaw et al., 1984). Whereas reduction in rCBF has been observed over the entire cortex, there is evidence suggesting regionally enhanced decline in blood flow. In young and early middle-aged individuals, a pattern of hyperfrontality, characterized by greater blood flow in the anterior as compared with posterior cortical regions, is frequently observed in studies of rCBF (Gur etal., 1987; Melamed et al., 1980).In older individuals, this pattern is often reversed, a state known as hypofronlality. Findings supporting a selective reduction of blood flow to the frontal cortex have been reported in both cross-sectional and longitudinal studies (Gur et al., 1987; Shaw et al., 1984). Cross-sectional studies suggest that the greatest reduction in rCBF was observed in the prefrontal and temporal cortices, the prefrontal and parietal cortices, or selectively in the left-anterior cortex (Gur et al., 1987; Melamed et al., 1980;

Shaw et al., 1984; Warren, Butler, Katholi, & Halsey, 1985). The longitudinal data suggest that, over a 4-year period of maintained health, significant reduction in rCBF was only observed in the prefrontal cortex, whereas only nominal declines were observed in the motor, frontotemporal, occipital, or temporal regions (Shaw et al., 1984). Taken together, these findings provide support for the somewhat selective reduction in rCBF with increasing age; the common denominator in all of this research is the frontal cortex, with reduction appearing less consistently in the temporal and parietal cortices. One of the fundamental focuses in the study of aging has been an attempt to distinguish the effects of aging from those of various pathological states frequently associated with the aging process, such as CVD, stroke, and AD. Some models suggest that there is an interaction between the effects of increasing age and many age-related pathologies (Houx, Jolles, & Vreeling, 1993). Researchers studying functional brain aging have typically taken one of two positions with regard to this question: (a) the exclusion of any individual demonstrating signs of potential risk factors and (b) the inclusion of individuals exhibiting pathological conditions in separate groups. This second approach allows the researchers to compare the effect of aging against those of pathological states and to consider the possible interaction of the two. In one large study on both healthy adults and those with various pathological conditions, Shaw et al. (1984) found evidence for an interaction between the effects of normal aging and the degree of CVD in relation to rCBF. These researchers suggested that, between the ages of 40-70, the presence of increasingly severe CVD resulted in enhanced declines in the rCBF. However, this interaction was not observed in individuals ages 70-90, suggesting that the affect of CVD may be more detrimental during the middle and early-late adult years. In addition to examining the rate of rCBF while the individual is in a resting state, researchers of functional brain aging studies have also examined the increase in rCBF associated with performing a cognitive task. These researchers have required individuals to perform multiplication problems of varying difficulty, verbal analogies, and spatial-line orientation tasks (Gur et al., 1987; Warren et al., 1985). Paradoxically, these studies do not demonstrate age-related differences in the magnitude or pattern of activation observed in response to cognitive demands, while demonstrating consistent declines in resting rate of rCBF (Gur et al., 1987; Warren et al., 1985). Unfortunately the behavioral significance of these findings cannot be determined from the reported studies. In the Warren et al. study, the groups received different problems designed to equate them on task difficulty. Likewise, in the Gur et al. study, the behavioral performance was not discussed, only the change in rCBF associated with the different task conditions was. This leaves open the possibility that activational deficits could be observed on tasks where younger and older adults differ in behavioral performance. Researchers using the PET technique of neuroimaging and 18 F-2-deoxy-2-fluoro-D-glucose (FDG) as the radioactive tracer generally did not reveal significant age-related differences in the functional capacity of the cerebral cortex (de Leon et al., 1983; Duara et al., 1983). Duara et al. reported that, in a sample of 21 healthy men, there were no significant correlations between age and cerebral metabolic rate at any examined loca-

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tion. Researchers reported similar findings in a study on both the structural and functional changes associated with aging, where a significant correlation was discovered between age and brain structure as measured by computerized tomography, whereas the relationship between age and functional integrity, as measured by PET, was not significant (de Leon et ah, 1984). Additional evidence suggesting preserved glucose metabolism in healthy older adults can be found in a study comparing cerebral metabolic rate (CMR) in younger adults, older adults, and individuals diagnosed as having AD. In this study, the younger and older adults did not differ in cerebral metabolic rate; in comparison, those individuals with probable AD demonstrated reduced CMR rates at all measured locations (de Leon et al., 1983). Whereas none of these studies revealed any significant relationships between increasing age and cerebral glucose metabolism, there are a number of interesting trends worth noting. When younger adults are compared with individuals in their 6th and 7th decade of life, a consistent but nonsignificant increase in CMR is observed (de Leon et al., 1983). In contrast, when younger-older and older-older are compared, there tends to be a consistent trend toward reduced rates of cerebral metabolism, with some studies suggesting that this reduction may be concentrated within frontal regions (de Leon et al., 1983; Duaraet al., 1983; Kuril, Metier, Rieger, & Hawkins, 1984). The evidence above suggests an inconsistency between studies of functional brain aging based on the Xe 133 method, indicating considerable reduction in resting rCBF with increasing age, and the PET method, indicating preserved glucose metabolism in surviving cortex. The question then becomes, Are there clear methodological or theoretical explanations that could account for these differences? One possible difference could be in the theoretical process measured. PET using FDG is believed to provide a measure of the regional metabolism of glucose by the brain, whereas Xem and PET using 15O are believed to reflect the use of oxygen in the brain (Duara et al., 1983; Roland, 1984). Whereas some research has suggested that these two processes are closely related in young and early middle-aged adults (Roland, 1984), it could be that glucose metabolism and oxygen use become decoupled with increasing age. This decoupling could in part account for the increased rates of CMR observed in young older adults if the aging brain were attempting to compensate for reduced oxygen resources. A less interesting explanation of the paradox observed between PET, using DFG, and Xe' 33 studies could arise from differences in sample characteristics. It could be that individuals participating in Xe 133 studies were not as strictly screened as those in PET studies, although this seems unlikely given the number of Xe 133 studies reporting age-related differences. Another methodological concern in the PET studies is the use of relatively small samples, due to the economic and ethical cost of the research, resulting in insufficient power to detect a significant difference between younger and older adults. This is a plausible hypothesis, given the number of nonsignificant trends observed which is suggestive of a small age-related decline. The evidence above suggests that there are both structural and functional changes in the cerebral cortex associated with aging. These changes appear in older individuals who are essentially free of any pathological conditions, including CVD and various dementias. Furthermore, some evidence indicates that

pathological conditions may enhance or accelerate the changes observed in aging. In addition, the structural and functional changes related to aging demonstrate some degree of regional specificity, with some areas appearing more sensitive to increasing age than others. The prefrontal cortex has been consistently implicated as one of the areas most sensitive to the effects of aging in both morphological and functional studies. Within the prefrontal cortex, there also is some evidence suggestive of regional differences in the effects of increasing age, with the dorsolateral prefrontal region demonstrating a linear decline throughout adulthood and the orbital prefrontal region showing evidence of decline only during the late 7th decade and beyond.

Prefrontal Cortex Cognitive Function Description of the Prefrontal Cognitive Deficit

Since the earliest descriptions by Harlow (1868) of the changes in personality and behavior resulting from significant damage to the left-frontal region of his now famous (or infamous) patient Phineas Gage, researchers and clinician have speculated as to the nature of function supported by the prefrontal cortex. Some have suggested that the prefrontal cortex supports the highest level of cognitive organization, serving as the central executive of the brain (Luria, 1980). Others, more reserved in their attribution of function to this region, have been quick to point out that frequently little or no change in behavior is observed after a prefrontal insult (for reviews, see, Fuster, 1980; and Luria, 1980). From the time of Harlow (1868) until the middle of the 20th century, most of the theoretical work in the area of prefrontal function was derived from clinical reports of individuals surviving extensive damage to their frontal region or from animal studies where the entire region of the frontal cortex had been removed (Luria, 1980). This reliance on description of individuals with massive, poorly defined damage resulted in early ideas of prefrontal function being poorly specified regarding the nature of a prototypical prefrontal deficit. Two methodological improvements that emerged around the middle of the 20th century fostered the refinement of theoretical ideas regarding the function of the prefrontal cortex. First, the study of individuals with discrete focal lesions, resulting from planned psychosurgery, the increased survival of individuals sustaining focal warrelated cerebral injuries, and the refinement of radiographic techniques have allowed researchers to classify individuals based on lesion site with a precision not previously possible (Luria, 1973; Milner, 1964). The second methodological improvement came in the area of nonhuman primate studies, when researchers began to focus on the effects of precisely defined lesions of cortical structures, to apply the newly developed techniques of radioactive isotope imaging, and to record the activity of individual cells concurrent with task performance (Fuster, 1980; Passingham, 1993). Even with these methodological advances, as recently as a decade ago, the prefrontal cortex continued to be characterized as the "uncharted province" of the brain (Goldman-Rakic, 1984). Clinical reports of the behavior of individuals sustaining focal damage to the prefrontal cortex have produced a wealth of descriptive literature defining the nature of the prefrontal deficit.

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Disruptions of attention, memory, and planning have been stated characteristics of individuals sustaining prefrontal damage (Duncan, 1995; Luria, 1980; Stuss & Benson, 1987). One of the more interesting deficits ascribed to prefrontal damage is the fragmentation of complex action sequences. This type of deficit is observed when an individual is asked to perform a complex sequential task composed of a series of discrete component behaviors. The individual units that make up the structured whole may be performed to perfection, while lacking any semblance of goal directedness or structure (Luria, 1973), a disruption of the temporal gestalt (Fuster, 1989). This disintegration of organized behavior can be manifest in a number of ways. Shallice and Burgess (1991) reported that, when individuals sustaining prefrontal injury were given a list of routine errands to perform, they experienced considerable difficulty in completing the task requirements. The researchers commented that patients could perform any of the constituent acts required to complete the errands but they seemed to be unable to organize the requirements of the list to efficiently complete the task. This fragmentation of complex sequential behavior appears to result from an inability to form a temporal gestalt to guide the isolated behavioral units required for task completion (Fuster, 1989). The inability to guide behavior by temporal gestalts may give rise to a number of behavioral deficits that are frequently observed in individuals sustaining prefrontal damage. One of the most consistently reported outcomes of prefrontal damage is the emergence of what Stuss and Benson (1987) have called a dissociation between self-consciousness and self-knowledge. This disorder can be observed in the patient who demonstrates full awareness of the occurrence of errors in behavior based on some external criteria but is unable to modify behavior based on this knowledge. Common examples of this type of behavior are observed in a number of classic neuropsychological tests sensitive to prefrontal damage. In the Stroop Color-Naming Task, the patient with prefrontal damage frequently reports the rule requiring the naming of the color and ignoring the word, even as the word continues to be named on successive trials (Duncan, 1995; Ferret, 1974). The Wisconsin Card Sorting Test (WCST) is another instrument in which this type of behavior can be observed. In the WCST, the individual is required to sort a series of cards based on a continually changing rule. When a category shift occurs, patients frequently continue to sort the cards to the now incorrect category, even as they express with each sort that this behavior is inappropriate (Duncan, 1995; Heaton, 1981). Performance on both of these tasks suggests that the individual knows what to do but is unable to use that knowledge to guide his or her behavior. A similar impairment is considered in the production model of Kimberg and Farah (1993), where a prefrontal insult was proposed to result in the weakening of associations within working memory (see Memory-Based Model of Prefrontal Function). This form of "goal neglect" can lead to two other types of behavior that are frequently ascribed to prefrontal damage: perseveration and distractability. At first glance, perseveration and distractability may appear to be very different behavioral deficits. However, within the context of prefrontal theory, both can be seen as an inability to suppress a prepotent response, resulting in a disruption of the

temporal gestalt (Diamond, 1990b; Fuster, 1989; Stuss & Benson, 1987). Perseveration, manifest as a tendency to persist in some prepotent or rewarded response when that response becomes inappropriate, can be thought of as the capturing of an action sequence by one of its constituent units. Distractability, manifest as a tendency to respond to external stimuli not goal related, can be thought of as the capturing of an action sequence by an irrelevant element of the external environment (Knight &Grabowecky, 1995; Luria, 1980). In this way, both distractability and perseveration can be conceptualized to result from the disruption and disintegration of an action sequence or temporal gestalt (Diamond, 1990b; Fuster, 1989). Research in the areas of recency discrimination and frequency estimation has provided additional support for the idea that damage to the prefrontal cortex may result in a decreased sensitivity to the temporal structure of external events. In recency discrimination studies, a series of stimuli were presented to an individual, with the instructions that at some point during the series the individual will be asked to identify which of two stimuli occurred most recently in the list; when asked to make this type of judgment about a set of stimuli, patients with prefrontal damage performed poorly relative to controls (Milner, Petrides, & Smith, 1985). This discrimination inability cannot be attributed solely to a memory deficit because these same individuals performed comparably to controls on tests of simple recognition memory (Milner, 1982). Therefore, the deficit in recency discrimination appears to result from an insensitivity to the temporal structure of information. Deficits in frequency judgments may also arise from a similar insensitivity. In a typical frequency judgment study, the individual is presented with a list of words, in which several words appear different numbers of times. On completion of the list, the individual is asked to estimate the frequency with which a set of words appeared in the list. Patients with prefrontal damage tend to perform similar to controls and patients with other etiologies for words appearing infrequently in the list but are relatively insensitive to increasing frequency of occurrence for words appearing five to nine times in the list (Milner et al., 1985). This can be compared with the performance of patients with damage to the temporal cortex who tend to underestimate the frequency of word presentation relative to controls but demonstrate increasing estimates with increasing frequency of occurrence. Again, patients with prefrontal damage perform similarly to controls on tests of item recognition (Milner, 1982). Models of Prefrontal Cortex Function From the research above, there appears to be a distinct set of cognitive disturbances attributable to damage of the prefrontal area of the cerebral cortex for which a theory of prefrontal cortex function must account. First, a theory of prefrontal function must be able to account for the fragmentation of complex sequential behavior that gives rise to many of the other deficits related to the prefrontal cortex (Fuster, 1989; Luria, 1980). Such a theory must also be able to explain both the increases in distractability as well as the tendency to perseverate in some behaviors (Stuss & Benson, 1987). Finally, any theory of prefrontal function must provide an account of the insensitivity to external stimuli frequently observed in patients with prefrontal

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damage, manifest as an inability to modify behavior based on verbal instructions, inability to differentiate novel from familiar events, and a decreased sensitivity to the temporal characteristics of information retained from the environment (Duncan, 1995; Milner, 1982; Yajeya, Quintana, & Fuster, 1988). Researchers of theoretical models in this area of study have generally attempted to attribute the complex of deficits observed after prefrontal insult to the disruption of a relatively small number of processes. Whereas it becomes clear from the review of existing models that no single model can account for all the deficits believed to arise from prefrontal damage, it is argued that each has provided valuable advances in the field and that, through an integration or synthesis of existing ideas, new insights can be gained.

Memory-Based Model of Prefrontal Function

One influential model of prefrontal function has focused on the role of representational or working memory in understanding prefrontal deficits (Goldman-Rakic, 1987). Memory-based models have been based largely on evidence from nonhuman primate studies in which researchers used variations of the delayed response (DR) task. In the typical DR task, a monkey watches while a desired reward is hidden at one of a number of locations; a delay is then imposed in which the location of the reward is hidden from the animal. After the delay has passed, the barrier is removed, and the animal is allowed to retrieve the reward (Fuster, 1980). In this model, success on a DR task is dependent on the animal's ability to maintain an internal representation of the hiding location of the reward over the delay because there are no external cues to guide behavior at the time a response is required. Representational memory is proposed to perform, bridging the temporal gap between hiding and responding, the dual roles of and the suppression of inappropriate responses on termination of the delay (Goldman-Rakic, 1987). The disruption of representational memory gives rise to secondary deficits, including distractability and perseveration. An inability to use a context-specific representation to guide behavior at the termination of the delay resigns the animal to base responding on prepotent habits, leading to perseverative behavior, or on external cues, leading to stimulus-bound behavior manifest as distractability (Goldman-Rakic, 1987). Evidence supporting a representational memory deficit as the principle determinant of prefrontal dysfunction is found in a number of studies. Perhaps the most intuitive evidence for a primary memory deficit resulting from prefrontal insult is the common finding of increased DR errors with increased delay periods (Goldman-Rakic, 1987). Additional research has demonstrated that behavioral deficits are not observed when memory requirements can be "circumvented" through the elimination of the delay period or postural alignment of the body in the direction of the correct response (Diamond, 1990a; Fuster, 1985). Studies of cellular activity within the prefrontal cortex have also provided some measure of support for the memory hypothesis. Kojima and Goldman-Rakic (1982) found that 32% of the cells recorded from in the dorsolateral prefrontal cortex (DLPFC) demonstrated changes in firing patterns as a function of the duration of delay. The representational memory hypothesis of prefrontal func-

tion has been expressed and tested in two computational models designed to simulate nondeficit and deficient performance on a number of tasks sensitive to the effects of prefrontal insult (J.D. Cohen & Servan-Schreiber, 1992; Kimberg & Farah, 1993). In the Kimberg and Farah model, prefrontal insult is proposed to result in a functional impairment of the strength of various associations active in working memory, including task goals, information about stimuli in the environment, and stored declarative knowledge. Damage to the system produces a reduced ability to determine the relevance of specific goals, environmental information, and declarative knowledge for task performance, allowing behavior to be guided by dominant but possibly inappropriate sources of information. This somewhat general model successfully simulates performance of patient populations on a variety of tasks, including the Stroop ColorWord Task, the WCST, a context memory task, and a motor sequencing task, which suggests that the weakening of associative strength as a result of prefrontal insult does provide an accurate account of many of the performance deficits observed following prefrontal insult. J. D. Cohen and Servan-Schreiber (1992) proposed that disruption of the fronto-striatal DA system results in impairment of a prefrontal mechanism that serves to maintain an appropriate internal representation of context. In this model, the action of DA is represented by adjustments made to a gain parameter that can modulate the state of information processing over the brain through the potentiation of inhibitory and excitatory mechanisms. By varying the efficiency of the gain parameter, the researchers successfully model performance on the Stroop Color-Word Task, the Continuous Performance Task, and a lexical disambiguation task. In comparison, manipulation of the cascade rate in the Stroop task, to simulate changes in information-processing rate, did not successfully model the human data, producing a general increase in response time that did not vary in congruent, control, and incongruent task conditions. Whereas the representational memory model of prefrontal function is attractive on grounds of parsimony, a number of findings question the adequacy of this single process approach. First, the DR deficit is not observed in the absence of competing response alternatives or external distracting stimuli. If the animal is contained in a darkened compartment during the delay period or the hiding locations are spatially distant from one another, the DR deficit is not observed or is manifest to a lesser degree (Fuster, 1985; Pribram, 1973). If the simple passage of time and loss of access to representational memory were sufficient to elicit the DR deficit, then it should be observed under both of these experimental conditions. A second source of evidence against a solely memory-based deficit is found in studies of the A-not-B taska task similar to the DR taskfrequently tested on human infants. In this task, infants can still make errors, even when transparent covers are used over the hiding locations and the object to retrieve is in plain view (Diamond. 1988). If a deficit in representational memory is not sufficient to account for the behavioral deficits related to insult of the prefrontal cortex, then what additional process or processes could be enlisted to resolve these discrepancies? From the evidence above, the representational memory impairment following prefrontal insult appears to be accompanied by a tendency to base

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responding on either highly salient features in the environment or previously rewarded behavioral patterns, suggesting the need for some process that acts to inhibit prepotent response tendencies cued by stimuli in the environment or emerging from within the organism. A number of theorists have suggested the existence of just such a process based on findings from research with human infants, human patients of prefrontal insult, and nonhuman primates (Diamond, 1988; Knight & Grabowecky, 1995;Shimamura, 1995;Stuss, 1991). Evidence supporting the existence of a process that acts to suppress previously rewarded behavior can be found in studies of human infants and infant monkeys, using the A-not-B task described above. Recall that on the first trial of this task, there is no previously rewarded response and, therefore, no prepotent response tendency, only the requirement to maintain the memory over the course of the delay. On this trial, retrieval errors are infrequent with delays of 1-5 s (Diamond, 1990a). In contrast, errors emerge when the object is hidden at a new location, and success becomes dependent on both memory of the correct location and inhibition of the prepotent response to reach back toward the previously rewarded location (Diamond, 1988). This, however, is not conclusive evidence for a dual process theory of prefrontal function. A proponent of the memory-based model could argue that the representational memory required to guide the response had been lost in the course of the delay, resulting in behavior becoming based on the prepotent response tendency (Goldman-Rakic, 1987). There is, however, evidence that the influence of an active inhibitory process is at work. In the Anot-B task, a number of behavioral observations support a dual process explanation. One such piece of evidence is the observation that infants and monkeys with dorsolateral prefrontal lesions often perform a corrective reach to the appropriate location immediately following the execution of the prepotent reach to the inappropriate location (Diamond, 1990b). An even more striking observation is the tendency of individuals to look directly at the appropriate location, while reaching back to the prepotent location (Diamond, 1990b). Both of these behavioral patterns suggest that the individual does have on-line access to the appropriate response but is unable to supplant the overwhelming lure back to a previously rewarded location (Diamond, 1990b). These findings can be taken as an ontogenetically early demonstration of the distinction drawn by Stuss and Benson (1987) of self-consciousness and self-knowledge. Similar forms of behavior can be observed in adults, who have sustained lesions to the prefrontal cortex, performing the WCST and the Stroop Color-Naming Task in their frequent reporting of the rules determining appropriate behavior in the midst of continued errors (Stuss & Benson, 1987). Inhibition of Prepotent Response Model of Prefrontal Cortex Function These findings and others have led a number of researchers to suggest that the inhibitory role of the DLPFC may be its principal function and that memory deficits may be a secondary outcome (Diamond, Cruttenden, & Neiderman, 1994; Posner & Rothbart, 1991; Stuss, 1991). Inhibitory control influences behavior in two interdependent ways. Inhibition of prepotent responses keeps highly salient but inappropriate responses from

gaining control of the action sequence (Dempster, 1991; Norman & Shallice, 1980). In addition, there is an inhibitory influence that acts to sustain attention to task-relevant information in the midst of distraction from the environment or the waning of attention over some extended time period (Posner & Peterson, 1990; Stuss, 1991; Wilkins, Shallice, & McCarthy, 1987). Both of these inhibitory functions have typically been localized within the DLPFC (Diamond, 1990b; Posner & Rothbart, 1991). Evidence for a dual process model of inhibitory control can be found in studies using a number of different research paradigms. Diamond (1990b) has suggested that damage to or underdevelopment of the DLPFC can result in an inability to overcome prepotent response tendencies. Research incorporating PET technology has provided support for the influence of the sustained attention aspect of inhibitory control (Posner & Rothbart, 1991). This research indicates that an increase in activity in the midprefrontal region is accompanied by a reduction of activity in the anterior cingulate, proposed to act to prepare the individual for some anticipated event. Evidence from human neuropsychology also suggests that damage to the right dorsolateral region disrupts performance on tasks requiring sustained attention (Wilkins et al., 1987). An extreme form of the inhibitory control model would suggest that prefrontal function can be solely captured through the process responsible for inhibition of prepotent responses and sustained attention and that memory has only a secondary role in a model of prefrontal function. Whereas none of the theorists above have taken this radical a position, some would be not far from it. Novelty Detection and Inhibition of the Prepotent Response Model of Prefrontal Cortex Function A nonmemory dual process model of prefrontal function suggests that insult to the DLPFC results in a decrease in inhibitory control and an impairment in the detection of novelty in the environment (Knight & Grabowecky, 1995). The role of novelty in prefrontal function has been described by a number of researchers within the fields of human and animal neuroscience (Fuster. 1985; Knight & Grabowecky, 1995; Pribram, 1973). Individuals with DLPFC damage typically demonstrate a reduction in amplitude of the P3a component of the eventrelated potential in response to novel stimuli in a stream of familiar stimuli (Knight, 1991). This reduced capacity for novelty detection results in an inability to encode the behaviorally relevant aspects of an event. To make matters worse, Fuster (1985) suggested that novelty within a given task or situation may be more relative than absolute:
Events or actions, even though not new to the organism, are unpredictable or unforeseen; . . .(when) events or actions that have a low probability of occurrence in the context in which behavior takes place, or else, that compete with others which have a high probability of occurrence in that same context. (Fuster, 1985, p. 170)

This deficit in novelty detection "hampers the ability to code the beginning and end of discrete events and tags them with appropriate temporospatial information" (Knight & Grabowecky, 1995, p. 1357). In this model, the inhibitory process is similar to that described previously, serving to suppress the

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influence of potentially distracting stimuli. In this dual process model, any observed deficit in memory would arise from an inability to encode distinct temporal events or a reduced inhibitory capacity and not the loss of access to an existing representation.

Hierarchical Model ofPrefrontal Cortex Function

In addition to the single and dual process models above, one theorist has suggested a hierarchical organization of function in the prefrontal cortex. At its highest, the role of the prefrontal cortex is to provide the "temporal organization of behavior" (Fuster, 1989). This process allows the organism to develop high-level behavioral structures to guide behavior. The temporal organization process is subserved by three secondary processes: two memory based and the third an inhibitory (interference) control process (Fuster, 1989). The two memory processes within this model represent a parceling of the representational memory aspect of prefrontal function proposed by Goldman-Rakic (1987). The first memory process, provisional memory, is very similar to the idea of short-term or primary memory represented in numerous cognitive models of memory function. Provisional memory permits referencing of some event to past experience or to some future goal or action sequence. This type of memory may consist of a newly acquired representation or the reactivation of some existing memory trace. What is unique about this type of memory is that it provides the foundation or reference on which the action sequence is constructed. Under normal circumstances, this form of memory is maintained in an active state only as long as it serves to build the action sequence. This continued activation is believed to be supported by an excitatory influence of the DLPFC on representations stored within the temporal and parietal association cortices (Fuster, Bauer, & Jervey, 1985; Quintana & Fuster, 1993). The second memory function associated with the DLPFC has been described as prospective memory or preparatory set (Fuster, 1980, 1989). This aspect of memory can be thought of as expectancy based or action oriented. The function of this process is to operate on information derived from the provisional process to prepare the individual for some impending response. The necessary duration of this type of memory is dependent on the interval between the initial activation of provisional memory and the time the action sequence is executed. This distinction between two types of prefrontal memory provides an account of the frequently observed result of frontal insult of expressed knowledge of the requirements of a given task and an inability to act in accordance with that knowledge (Diamond, 1990a; Stuss & Benson, 1987). In this case, the provisional aspect of memory is relatively preserved, hence the ability to verbally express the requirements of the task, whereas the prospective aspect of memory is impaired, resulting in an inability to incorporate task-relevant knowledge in the direction of behavior (Fuster, 1989). This dissociation of impairment between the two types of memory may result from the functional organization of the two systems. The DLPFC probably does not store the actual representation used to guide behavior but rather supports the maintenance of this representation stored in temporal and parietal cortices through an interac-

tion with subcortical structures. In contrast, the prospective aspect of memory may be more highly dependent on the DLPFC and, therefore, more susceptible to prefrontal insult. In this model, the role of the inhibitory process in prefrontal function is somewhat different from that outlined in the previous models. In this case, the interference control process is proposed as located within the orbital and perhaps medial prefrontal regions (Fuster, 1990). This process serves to suppress the influence of potentially interfering stimuli existing in the external environment or arising from internal sources. The current model suggests that the inability of this interference control process results in inappropriate stimuli gaining access to the prospective memory process and then guiding behavior (Fuster, 1989). In summary, this model of prefrontal function suggests that the primary role of the cortical region is to support the temporal organization of behavior through the formation and execution of temporal gestalts or complex behavioral sequences that are both novel to the organism and complex in nature. This temporal organization of behavior is supported by three secondary processes: provisional memory, prospective memory, and interference control. Provisional memory serves to maintain taskrelevant information in an active state while the behavioral structure is constructed. Prospective memory serves to construct and execute temporal gestalts from the information derived from the provisional process. Finally, interference control serves to suppress the activation of task-irrelevant representations, keeping them from gaining access to the prospective memory process and influencing the formation of the action sequence (Fuster, 1989; for similar models, see Moscovitch, 1994; and Norman & Shallice, 1980).

Specialization of Function Within the Prefrontal Cortex

One issue that emerges from a consideration of the prefrontal models outlined above is that of specialization of function within the region of the prefrontal cortex. The prefrontal cortex is generally divided into two or three distinct areas: the dorsolateral, the orbital, and the medial (Fuster, 1980; GoldmanRakic, 1987). Furthermore, at least four rather distinct regions have been identified within the DLPFC of the primate: the region surrounding the principle sulcus, the inferior convexity, the region surrounding the accurate sulcus, and the frontal eye field (Goldman-Rakic, 1987). From the work above, one could speculate that the various functions ascribed to the prefrontal cortex could be localized within these given regions. Extensive work with nonhuman primates suggests that the principal sulcus and inferior convexity participate in the maintenance of representational memory during some DR tasks (Wilson, O'Scalaidhe, & Goldman-Rakic, 1993). The distinction between these two regions appears in the type of representation that each supports. Numerous studies have suggested that the region around the principal sulcus serves in the maintenance of spatial information through its interaction with the parietal cortex (Mishkin & Manning, 1978). In comparison, extensive research has indicated that the inferior convexity serves in the maintenance of nonspatial stimulus characteristics, such as color or form (Wilson, et al., 1993). Whereas the localization of memory-related processes within

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the prefrontal cortex is generally well-accepted, the localization of inhibitory control processes has been somewhat more controversial. Some researchers have suggested that inhibitory control, as memory-related processes, are localized within the dorsolateral region (Diamond, 1990a; Knight, 1991), whereas others have suggested that inhibitory control is a function of the orbital prefrontal region (Fuster, 1989, 1990). Still other researchers have suggested that both memory and inhibitory control processes are "mediated by the modular and laminar substructure within each area (dorsolateral and orbital) rather than distributed across the prefrontal cortex in distinctly different memory and motor-control centers" (Goldman-Rakic, 1987, p. 402). Part of the confusion surrounding the localization of inhibitory control may arise from differences in the type of inhibition exerted by the orbital or dorsolateral regions. Most researchers who have ascribed inhibitory control functions to the DLPFC tend to describe the active inhibition of a prepotent response tendency (Diamond, 1990b; Diamond et al., 1994; Knight, 1991). In this case, inhibitory control serves to guard the individual's behavior from becoming based on dominant response patterns or highly salient environmental stimuli. This type of inhibitory control deficit could be observed in any task requiring the suppression of a dominant response, such as the A-not-B task, WCST, or Stroop task (Diamond, 1990a; Drewe, 1974; Ferret, 1974), and would also be involved in tasks requiring sustained attention over an extended time period. If the inhibitory control role of the DLPFC is to suppress taskirrelevant orienting responses to internal and external stimuli, what then is the role of the orbital prefrontal cortex? Fuster (1980, 1989, 1990) has consistently argued that the function of inhibitory or interference control is localized within the orbital region of the prefrontal cortex. If there are at least two rather different forms of inhibitory control supported by the prefrontal cortex in general, how then does the form of inhibitory control ascribed to the orbital region differ from that ascribed to the dorsolateral region? In the hierarchical model of prefrontal function described above, it was suggested that the inhibitory control process serves to limit the access of currently task-irrelevant information to the prospective memory process. In this case, interference control would serve to return internalized representations to a nonactivated state, thereby permitting the prospective memory process to plan the next behavior sequence based on newly activated, relevant information. This would serve the dual functions of preparing the individual to respond to current task demands based on event-specific information and separating events into distinct temporal units. Tentative support for this view of orbital interference control is found in a study by Stuss (1991). A group of individuals with prefrontal lesions predominantly of the orbital region performed comparably to controls on tasks measuring short-term sustained attention, suppression of prepotent responses, and new learning. However, the patients with orbital damage did not demonstrate release from proactive interference (Stuss, 1991; see Shimamura, Janowsky, & Squire, 1991, for similar findings). This is exactly the pattern of results that could be expected if the inhibitory role of the orbital prefrontal cortex is to suppress information no longer relevant to task performance and not the suppression or control of prepotent response tendencies. Whereas this dual process view of inhibitory control

within the dorsolateral and orbital regions of the prefrontal cortex is at best tentative, it does provide a plausible resolution to the discrepancies in current models of prefrontal function regarding the localization of inhibitory control within the prefrontal cortex. One could now ask, How the prefrontal region interacts with the rest of the brain in accomplishing its task of guiding purposeful behavior? Prefrontal Interactions With Other Cortical Regions Clearly the prefrontal cortex is active in both the maintenance of task-relevant information and the construction of complex action sequences, but does the prefrontal cortex actually house the representation of an event while the action sequence is formed or does the prefrontal cortex merely support the maintenance of a representation stored in some other location of the cortex? Evidence supports the latter of these two hypotheses. Fuster et al. (1985) reported that prefrontal neurons demonstrate poor intrastimulus selectivity when all targets are represented within the same dimension, such as color. In contrast, cells in the inferotemporal cortex react selectively to different stimulus colors, and cooling of the prefrontal cortex results in a decline in this selective reaction to color (Fuster et al., 1985). Cooling of the inferotemporal cortex results in increased firing rates in prefrontal cells in response to target choice, regardless of stimulus color, suggesting that prefrontal cells respond to the informational value of a stimulus and not its featural characteristics (Yajeya et al., 1988). These findings suggest that some of the specific characteristics of a stimulus are maintained in the inferotemporal cortex, which supplies the prefrontal cortex information relevant to the construction of the action sequence. In return, the prefrontal cortex appears to provide energy to the inferotemporal cortex to sustain the activation of a representation until it is no longer needed. Dissociation of Prefrontal From Nonprefrontal Function This interaction between prefrontal and other cortical structures raises the final issue which any theory of prefrontal function must address, dissociation of function from prefrontal and other cortical regions. For instance, can the memory deficits ascribed to prefrontal insult be differentiated in some way from memory deficits believed to arise from damage to other cortical regions? The acceptance of any argument for localization of function within the cortex relies heavily on such a dissociation of deficits arising from insult to different areas. There is extensive evidence suggesting a dissociation in the types of memory deficits that are ascribed to damage of the prefrontal cortex and damage to other cortical regions, primarily the inferotemporal cortex and hippocampus. In studies of monkeys, Diamond (1988) reported that the specific pattern of the A-not-B error attributed to prefrontal insult can be distinguished from errors that arise after insult to the hippocampus. Removal of the DLPFC results in errors after delays of 1 to 2 s, whereas errors following hippocampal lesions do not arise until delays of 10 s or more are interposed between object hiding and retrieval (Diamond, 1990a). The pattern of errors following prefrontal and hippocampal lesions is also markedly different. Errors after prefrontal lesions follow the characteristic pattern of predict-

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ably returning to previously well-rewarded objects. In contrast, errors following hippocampal lesions are unrelated to previous reward (Diamond, 1990a). Work with humans has revealed similar dissociations of impairment following prefrontal or temporal cortex insult. Shimamura (1995) reported that individuals sustaining DLPFC damage outperformed those with damage to the medial temporal lobe on tasks of paired associate learning, story recall, and diagram recall tasks. In addition, the prefrontal group performed similarly to control groups on both story and diagram recall tasks (Shimamura, 1995). In contrast, on recall tasks where structure was not inherent in the materials and must be supplied by the individual, the prefrontal group performed rather poorly (Stuss, 1991). Patients with prefrontal damage have also performed poorly on tasks requiring recency discriminations, even when their ability to recognize the materials as previously presented does not differ from controls. In comparison, individuals with damage to the inferior and medial temporal cortex made accurate discriminations of the materials that they were able to recognize. Recognition memory was impaired, however, relative to patients with prefrontal damage and controls (Milner, 1982; Milneret al., 1985). Studies involving the short-term maintenance of information have also provided evidence for a dissociation between impairments resulting from frontal insult and those resulting from damage to other cortical regions. Performance on tasks requiring the short-term retention of information, such as the Digit Span Forward Test and the Knox Cube Imitation Test, generally show little decrease following prefrontal insult. In comparison, damage in the area of the inferotemporal junction can severely disrupt performance on these tasks (Stuss, 1991). Other tasks requiring the short-term retention of information, such as the Brown-Peterson task and a release from proactive interference (PI) task, have revealed interesting performance deficits with regard to prefrontal damage. Individuals with damage localized predominantly to the DLPFC have been found to demonstrate similar patterns of buildup and release as individuals with damage to the medial temporal lobe and controls (Shimamura, 1995). Individuals with damage to the orbital region of the prefrontal cortex, however, typically do not demonstrate release from PI (Stuss, 1991). This evidence suggests that the prefrontal cortex may become critical in the maintenance of information on-line only when the potential for interference exists. Whereas the evidence above does provide a measure of support for the notion that clear dissociations can be made between cognitive processes supported by the prefrontal cortex and other brain regions, there are a number of findings suggesting that localization may not be as defined as one might believe. Work with both humans and animals suggest that damage to the medial temporal area can result in functional impairments similar to those arising from prefrontal insult. Winocur (1988) suggested that removal of the hippocampus can result in an increased susceptibility to interference in learning paradigms and that similar deficits are observed in senescent rats. Damage to the hippocampus in humans has also been demonstrated to result in performance deficits on the WCST, which are similar to deficits observed in individuals sustaining damage to the frontal cortex (Corcoran & Upton, 1993). Whereas these findings suggest that performance deficits of individuals with medial temporal and prefrontal insults may be comparable, other evidence

suggest that these similarities may result from different sources. Incisa della Rocchetta and Milner (1993) have demonstrated that individuals with left-frontal or hippocampal excisions demonstrate similar impairments of free recall in unstructured situations and that impairment is resolved in frontal, but not hippocampal, patients when encoding and retrieval strategies are supplied by the experimenter, suggesting that similar functional impairments may arise from different sources in various patient populations. An extensive review of the source memory literature leads me to arrive at a comparable conclusion in suggesting that disruptions of memory for context in individuals with medial temporal insults seem to occur in some cases along side content memory deficits; whereas in individuals with frontal insult memory, impairment appears to be specific to context information, with recall of content information generally preserved (Johnson, Hashtroudi, & Lindsay, 1993).

Proposed Model of Prefrontal Function

On the basis of the evidence above, a model of prefrontal cortex function can be proposed that incorporates a number of ideas (see Table 2). First, the function of the prefrontal cortex is organized into a hierarchy of interactive processes. At a general level, the prefrontal cortex supports the integration, formation, and execution of complex, novel behavioral structures or temporal gestalts (Fuster et al., 1985), which support the direction of behavior in an orderly, purposeful manner. This integrative function is supported by four secondary processes: retrospective (provisional) memory, prospective memory, interference control, and inhibition of prepotent responses (Diamond, 1990b; Fuster, 1989;Goldman-Rakic, 1987). The retrospective memory process serves to maintain on-line, task-relevant information on which the temporal gestalt is constructed. The prospective memory process serves to prepare the individual for the execution of the temporal gestalt in response to appropriate internal or external cues. The interference control process serves to clear current task inappropriate information from the retrospective memory store. Finally, the inhibition of prepotent responses process serves to keep behavior from being captured by dominant internal response patterns or highly salient environmental stimuli. Three of these processesretrospective memory, prospective memory, and inhibition of prepotent responsesare proposed to be supported by the DLPFC and the fourthinterference controlby the orbital prefrontal cortex (Diamond, 1990a; Fuster, 1989). The action and interaction of these four processes support a wide variety of cognition, including the selection of task-relevant information, the integration of semantic and contextual information into discrete memory traces, and the planning and execution of complex purposeful behavior (Dempster, 1991; Foster, Eskes, & Stuss, 1994; Milner etal., 1985; Shallice& Burgess, 1991).

Requirement of a Theory of Cognitive Aging

The value of any theory or model of cognitive aging can only be demonstrated by the ability of such a model to accurately represent findings from a broad range of empirical work and to accurately predict when age-related deficits should be observed at both a general and specific level (i.e., between tasks and

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Table 2 Models of Prefrontal Function

Process Study Goldman-Rakic(l987) Diamond (1990b) Knight (Knight & Grabowecky, 1995; Pribram, 1973) Fuster(l989) Current review Primary Representational memory Representational memory Prepotent inhibition Novelty detection Prepotent inhibition Temporal organization of behavior Organization of behavior Secondary Inhibition Memory Provisional memory Prospective memory Interference control Retrospective memory Prospective memory Interference control Prepotent inhibition Cortical location Dorsolateral Dorsolateral Dorsolateral Dorsolateral Dorsolateral Orbital Dorsolateral Dorsolateral Orbital Dorsolateral

within tasks). At the between-tasks level, a theory of cognitive aging should provide an account of the types of tasks that should demonstrate evidence of age-related decline and those which are age insensitive. At the within-task level, a theory of cognitive aging must be able to distinguish those task conditions that produce age-related deficits from those that do not produce agerelated deficits. In addition to accurately predicting withinand between-tasks differences, the current neuropsychological model should be able to differentiate age-related declines arising from functional impairment of the prefrontal cortex from those possibly resulting from functional decline of other brain structures or from some general process, such as age-related slowing. For instance, some work has suggested that damage to the hippocampus may result in behavioral impairments similar to those observed following prefrontal insult (Corcoran & Upton, 1993) and that much of the age-related variance in a number of tasks sensitive to damage of the frontal, parietal, and temporal regions is largely mediated by age-related differences in basic processing speed (Salthouse, Fristoe, & Rhee, 1996). Next, I apply the prefrontal cortex model to relevant findings from a broad range of experimental paradigms used by researchers of age-related declines in the efficiency of cognition.

proposed model of prefrontal cortex function suggests that as these processes are compromised with increasing age, behavior becomes increasingly characterized by a tendency to respond based on dominant behavioral patterns or current task-inappropriate information. With this general set of predictions established, a consideration of the age-related declines in specific paradigms can be undertaken. This analysis provides an account of the presence or absence of age-related task decline within the context of the established prefrontal cortex model. When age-related deficits are manifest but not consistent with a prefrontal interpretation of cognitive aging, an alternative explanation is considered when possible. First, the evidence from three paradigmsprospective memory, frequency estimation, and source memoryincorporated in the investigation of agerelated declines in memory processes is considered in light of the proposed model of prefrontal cortex function. This is followed by the consideration of three paradigmsproactive interference, Stroop color-naming, and sustained attention commonly used by researchers of age-related changes in attention (see Table 3).

Prospective Memory
Investigation of the relationship between aging and prospective memory function has garnered extensive empirical consideration. Prospective memory, or memory for activities to perform, has been studied in both laboratory and natural setting through various techniques (Maylor, 1993; West, 1988). Although the number of studies whose researchers examined the effects of increased age on prospective memory is somewhat limited, a number of variables relevant to this discussion have been considered, including the type of cue used to elicit the prospective action, the complexity of prospective response to make, the time elapsing between prospective instruction and action, and the use of external memory aids (Maylor, 1993; McDaniel & Einstein, 1992). The type of cue used to elicit the prospective action has taken one of two forms: event or time based (McDaniel & Einstein, 1992). In event-based prospective memory tasks, the individual is required to perform some actionfor example, pressing a

Predictions for Cognitive Aging

Before undertaking an analysis of specific tasks or paradigms, a general foundation must be supplied identifying the conditions under which age-related deficits in cognition might arise. On the basis of the proposed model of prefrontal cortex function, a number of predictions can be made regarding the emergence of age-related cognitive deficits. In the context of retrospective memory, deficits can be expected to arise when performance on a task becomes dependent on the retrieval of contextual information about an event and less related to the semantic content of memory. Deficits in prospective memory can be expected to occur when task performance cannot be supported by external cues or reminders. These deficits may be exacerbated by contextually impoverished episodic memory from which distinctive temporal cues are absent. With regard to interference control and inhibition of prepotent responses, the

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Table 3 Summary of Findings From Cognitive Aging Literature
Topic Memory Prospective Frequency estimation Source Attention Short-term interference Stroop color naming Sustained

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Relevant findings Time- versus event-based cues Single versus multiple prospective cues and targets Use of external memory aids Age-related deficit with high frequency of occurrence Age-related deficit with novel stimuli Persistence of deficit with equal item recall Source discriminability Greater build-up and less release Decreased maintenance over brief interval Increases between age 50 and 60 Age-related differences persist with practice Age-related decrement with high event rate or difficult target discrimination Preserved in low resource demanding tasks

Study McDaniel & Einstein (1992) Hasher &Zacks( 1979) Schacteretal.(1991) Hashtroudi et al. (1989) Puglisi (1980) Parkin & Walter (1991) Comallietal. (1962) Dulaney & Rogers (1994) Parasuraman & Giambra (1991) Gridleyetal. (1986)

keyfollowing the presentation or occurrence of some event for example, a target word in a series of words. In contrast, in a time-based prospective memory task, the prospective action is performed after the passage of a prespecified amount of time. An example of a time-based task might be pressing a key every 10 min. Current theory in this area of research suggests that time-based tasks place greater demands on the individual by requiring both the maintenance of the prospective action to perform and the generation of an internalized monitoring scheme (Einstein & McDaniel, 1990). Support for the distinction between event- and time-based prospective memory tasks has been limited. In two studies differing only in the type of cue (event or time based) used to elicit the prospective action, older adults were found to be less accurate than younger adults in the time- but not the event-based task (McDaniel & Einstein, 1992). In another time-based study of prospective memory, researchers did not find differences between younger and older adults in task performance (Patton & Meit, 1993). The findings of this study should be interpreted cautiously because only a single prospective response was measured and the standard deviations of the groups were large, potentially obscuring an agerelated difference. This model of prefrontal cortex function predicts that time-based tasks should demonstrate greater age-related decline than event-based tasks because time-based tasks are presumably devoid of external cues that support prospective action. The complexity of the prospective cue or prospective action have also been explored in several event-based prospective memory studies. Complexity has been manipulated by increasing the number of prospective cues, while maintaining a single prospective action, decreasing the typicality of the prospective cue, and increasing the number of prospective actions to perform (Einstein, Holland, McDaniel, &Guynn, 1992; Mantyla, 1994). Einstein et al. found that younger and older adults performed similarly when there was a single prospective cue and action but that older adults were impaired relative to younger adults when the task required monitoring four prospective cues. A similar finding suggests that older adults were impaired relative to younger adults only when an atypical prospective cue was used in a multicue, multiaction task (Mantyla, 1994). In these

studies, older adults demonstrated poor memory for both prospective cues and actions relative too younger adults, suggesting that part of the age-related effect may have resulted from an inability to remember the prospective cues and actions, a deficit attributable to medial temporal lobe function. This prospective deficit cannot, however, be fully explained by a retrospective inability because other studies have found older adults impaired in prospective performance, while maintaining equivalent levels of cue and action memory following completion of the task (Maylor, 1993), a pattern consistent with the prefrontal model under consideration. The effects of increasing delay between receiving the prospective instructions and the cue to perform the prospective action have also been considered in the study of prospective memory. Einstein et al. (1992) found that increasing the delay from 15 to 30 min between the time task instructions were given and the time the task was performed did not influence performance of the prospective action and that this increase in delay did not interact with age. This same pattern of results has generally been found in naturalistic studies, including intervals of several days (Patton & Meit, 1993; West, 1988). This suggests that increasing delay does result in poorer performance of the prospective memory task in younger and older adults. The stability of performance with increasing delay would be anticipated as long as the amount of potentially interfering stimulation was equal across the two delays. One final variable that has received considerable attention in the prospective memory literature is the use of external memory aids to support task performance. Generally, these studies suggest that the use of an external memory aid improves the performance of both younger and older adults (Einstein & McDaniel, 1990; West, 1988). However, there are a number of issues surrounding the use of memory aids that need to be addressed before this benefit can be firmly accepted. Most prominently, memory aids have been used only in experimental tasks found not to reveal age-related deficits in prospective memory without external cues, so an Age X Memory Aid interaction would not necessarily be expected. One could suggest that differences in memory-aid use between younger and older adults might arise in more demanding tasks, although the di-

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rection of this change is difficult to predict. It could be that older adults would rely more on memory aids as task difficulty increased or older adults would not use memory aids as effectively as task demands increased. Either of these outcomes would be a meaningful finding within the context of prospective memory research. The effectiveness of external aids in supporting prospective memory would certainly be predicted by the prefrontal cortex model, in that part of the role of the prefrontal cortex had been replaced by the external aid.

Frequency Estimation
The study of frequency estimation has received considerable attention in the aging literature. In the typical frequency estimation task, the individual first studies a list of words for a time period and is then asked to make frequency judgments about the studied stimuli in a test phase. Assessment of frequency knowledge primarily has taken one of three forms: absolute, relative, or preference ratings. In an absolute frequency judgment task, the individual is given a stimulus and asked to estimate the number of times it appeared in the study list. In comparison, relative frequency estimation tasks contain two stimuli from which the individual must then determine which appeared most frequently. The preference rating task is similar, in that the individual is presented with pairs of stimuli and asked to judge which of the two is preferred most. In a seminal article, Hasher and Zacks (1979) argued that the encoding of frequency information was an automatic process and should, therefore, be immune to the effects of increasing age. Since that time, empirical evidence has been presented that both supports and questions the age insensitivity of the encoding of frequency information. From this work, a number of variables have emerged that appear to mediate the relationship between increasing age and frequency estimation ability, including the type of task used, the absolute and relative frequency of occurrence of a given stimuli, the rate of stimuli presentation, the familiarity of the stimuli, and the effect of the presence of nontarget distractors at encoding, all interpretable within the current prefrontal cortex model. One of the key variables that appears to influence the effects of increasing age on frequency estimation is the absolute and relative frequency with which stimuli appear in the study list. In absolute frequency judgment tasks, this effect is manifested as an Age X Frequency of Occurrence interaction, with older and younger adults making comparable estimates at low frequencies of occurrence and older adults being impaired at higher frequencies (Freund & Witte, 1986; Hasher & Zacks, 1979; Kausler, Salthouse, & Saults, 1987). Older adults have also demonstrated impaired performance for high-frequency stimuli on a relative frequency task (Freund & Witte, 1986, Experiment 3), a pattern similar to findings reported with patients having frontal lesions (Milner et al., 1985). The current model of prefrontal function would suggest that this deficit results from an inability to form discrete context-dependent memory traces of the study stimuli with increasing frequency of occurrence or to update existing representations. In comparison, individuals with temporal lobe lesions demonstrate estimates that increase with frequency of occurrence (Milner et al., 1985). The inability to form, maintain, or both discrete memory

traces of stimulus material can also account for the age-related deficits in the estimation of frequency of occurrence when target materials are accompanied by nontarget materials and when the rate of presentation of study list information is shortened. Kausler and Hakami (1982) predicted that introducing nontarget stimuli into the study list would be more detrimental to task performance for older than younger adults. Specifically, they suggested that older adults would demonstrate poor performance for target words and demonstrate greater evidence of encoding the nontarget information. These predictions were partially supported as older adults performed poorly in the estimation of target frequency; however, the older adults were no better than the younger adults at estimating the frequency of the nontarget words. Additional support for this finding comes from a study where the target information served as distractors for a delayed recall task. Researchers of this study did not find an Age X Frequency interaction in a relative frequency estimation task (Kausler, Lichty, & Hakam, 1984), suggesting that whereas the presence of nontarget information can disrupt the encoding of target frequency information in the older adults, the distractors did not receive any greater encoding by older adults. A second variable that reduces the discrete encoding of a target event is an increase in the rate of presentation, resulting in a decrease in the temporal distinctiveness of target stimuli. Freund and Witte (1986) reported that decreasing the delay between stimulus presentation from 5 to 1 s produced an Age X Delay interaction, where younger and older adults performed equally at the 5-s delay and older adults were impaired at the 1 s delay in frequency estimation. Younger and older adults did not differ in item recognition memory at either delay, suggesting that decreasing delay only disrupted the encoding of contextual information and not stimulus encoding in general, an important finding in light of the model of cognitive aging under consideration. A similar finding has been reported in the nonhuman primate literature, where increasing the period between trials can serve to ameliorate DR errors in monkeys with prefrontal lesions (Fuster, 1989). The finding that target familiarity can differentially influence frequency estimation ability in younger and older adults is in agreement with existing ideas of prefrontal function. Several researchers in the area of prefrontal cortex function have suggested that efficiently dealing with novel information is commonly disrupted by prefrontal insult (Fuster, 1989; Knight & Grabowecky, 1995). In a series of experiments, researchers examined the affect of target novelty on frequency estimation in younger and older adults and found that older and younger adults did not differ in their accuracy of estimation for English words but that the older adults were significantly impaired in estimation when Japanese ideograms were used as stimuli (Wiggs, 1993). These findings suggest that older adults, like patients with frontal lesions, may experience difficulty when novel stimuli must be incorporated into memory. One is compelled to ask, If the current model of cognitive aging can account for instances of age invariance in frequency estimation. Di Pellegrino, Nichelli, and Faglioni (1988) reported that younger and older adults did not differ in frequency estimation accuracy when word frequencies of only one to four were used. From findings with patients having frontal lobe damage, these frequencies may not be sufficiently demanding to re-

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veal an age-related deficit. A study incorporating frequencies from 1 to 11 in the study list also found no age-related differences between younger and older adults, a finding inconsistent with the predictions of the current model (Sanders, Wise, Liddie, & Murphy, 1990). Unfortunately both younger and older adults performed only slightly above chance, so not finding agerelated differences may have resulted from a floor effect. Wiggs (1993) also did not find a predicted interaction between age and frequency of occurrence. This may have resulted from insufficient experimental power as examination of the reported cell means suggests that younger adults' accuracy was nearly twice that of older adults on more difficult relative frequency judgments. Therefore, existing instances of age invariance in frequency estimation appear either to be predicted by the prefrontal cortex model or to have resulted from methodological problems, such as floor effects or lack of statistical power due to small sample size.

Source Memory
Studies of age-related differences in episodic memory and source amnesia have suggested that older adults are impaired relative to younger adults in their ability to remember the source of newly acquired information. This reduction in source memory has been attributed to a diminished effectiveness in the ability to integrate events with their temporal context in memory (Mclntyre & Craik, 1987). Investigations of source memory have incorporated a number of different stimuli, but all require the individual to recall the context in which some fact was learned or action performed to succeed at the task. The variables that appear to influence performance on source memory tasks include the length of time between initial exposure to the material and recall of source information and the discriminable salience of informational sources. Age-related source memory deficits have been observed in tasks requiring various types of information to learn or actions to perform. Researchers of a number of studies have found that older adults demonstrated poor source memory in tasks requiring learning of both real and fictitious facts about famous, nonfamous, and fictitious persons (Mclntyre & Craik, 1987; Schacter et al., 1991). The ability of older adults to distinguish between performed, observed, and imagined actions has also been found impaired relative to younger adults (G. Cohen & Faulkner, 1989). When required to read sentences or to generate the final word of a sentence, control older adults tend to make fewer correct identifications of which endings were read and which were generated than younger adults (Mitchell, Hunt, & Schmitt, 1986). Older adults also more often tend to incorrectly distinguish between actions actually performed and those only imagined (G. Cohen & Faulkner, 1989; Guttentag& Hunt, 1988). The current model of prefrontal function would suggest that the source memory deficits observed in older adults results from the impoverished integration of context and content information at encoding and possibly recall. Investigations of the length of delay between information acquisition and information recall do not provide consistent findings in relation to age-related differences between younger and older adults. In an early study of source memory, Mclntyre and Craik (1987, Experiment 2) reported that older adults demon-

strated greater source amnesia than younger adults in a study using delays of 10 min and 1 week. This decrease in source memory with increasing delay was accompanied by a decrease in item recognition for the older adults at the 1-week follow-up, so it is possible that the poor performance of the older adults at 1 week may have resulted from poorer memory overall. Evidence counter to this position is found in a study revealing no effect of increasing delay on source memory when younger and older adults did not differ in fact recall (Schacter et al., 1991). This latter finding suggests two important points. First, the effect of increasing delay on source memory appears to be tied to a concurrent reduction in overall recall. Second, source memory differences between younger and older adults persisted even when no item recall deficit was observed. The importance of this finding is paramount with regard to the current model of cognitive aging under consideration because deficits in item recognition would almost certainly be tied to impairment of function supported by the temporal and not the prefrontal cortex (Kolb&Whishaw, 1990). Other factors proposed to influence the effect of increasing age on source memory include the discriminable salience of informational sources and the focus of attention within the encoding phase of the task. Hashtroudi, Johnson, and Chrosniak (1989) found that age-related differences between younger and older adults were only evident for within-class discrimination and not between-class discriminations. Thus, older adults were only impaired when forced to discriminate between two words both of self origin and not when one was self-produced and the other provided by the experimenter. The direction or focus of attention within the encoding phase of the experiment, directing attention to the source or fact information, has not been found to produce differences in memory of source information for younger and older adults (Schacter, Osowiecki, Kaszniak, Kihlstrom, & Valdiserri, 1994). This suggests that age-related differences in source memory do not result from differences in younger and older adults' focus of attention during the task. The current model of prefrontal function would predict the increased difficulty experienced for within-class as compared with between-class sources. Within-class sources would require more extensive encoding and retrieval of more detailed temporal and contextual information for successful source attribution because they share greater similarity to one another and, therefore, fewer defining (unique) characteristics than between-class sources.

Interference in Short- Term Memory

The influence of interference on short-term memory has been the focus of a number of studies within the area of cognitive aging. Whereas several different tasks have been used to study interference in short-term memory, the two most commonly incorporated have been the Brown-Peterson Consonant Trigram Task and variations of a release from the PI task. In the Brown-Peterson, individuals are given three stimuli, typically words or numbers, to remember over some retention interval. During this retention interval, the individual is required to perform a secondary task, such as counting backwards by 3s. At the end of the interval, the individual is required to recall the trigram presented for memory. The release from PI task is sim-

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ilar to the Brown-Peterson in that individuals are required to remember a short list of stimuli. On the first three to four trials of each block of trials, all stimuli are similar in some way, for instance, they are each from the same taxonomic category. This similarity results in decreasing recall over trials until the category is switched, resulting in release from the effects of interference. The release from PI task provides two measures that are of interest: an index of the amount of interference buildup before category shift and an index of the amount of release following the category shift. Investigation of the effects of increasing age on performance in both of these paradigms has provided mixed evidence with regard to an age-related deficit. Researchers examining age-related performance declines on the Brown-Peterson task have generally indicated that older adults tend to demonstrate poorer recall than younger adults and that this age-related deficit does not interact with the length of the retention interval (Dobbs & Rule, 1989; Parkin & Walter, 1991). This suggests that increasing age is associated with a decline in the number of items maintained on-line but that this information is relatively stable within the retention intervals considered, consistent with extensive work in which researchers examined the effects of increasing age on working memory span (Salthouse, 1994). One potential confound in these findings is not considering the possible effects of interference on recall, as performance is averaged across trials, making it impossible to distinguish between a pure memory deficit and the effects of interference on recall. This dissociation can, however, be considered by examining performance on the first trial of the release from PI task, where no interference should exist. If there is a pure memory deficit, younger and older adults should differ on this trial. However, if the deficit is interference dependent, as would be predicted by the current and other models of prefrontal cortex function, then group differences should not arise until later trials. Unfortunately, the evidence supporting either position is ambiguous. Schonfield, Davidson, and Jones (1983) reported that age differences only emerge on Trials 2-4, supporting a memory plus interference interpretation. In comparison, Elias and Hirasuna (1976) reported that younger and older adults differed on the initial trial, making the acceptance of either position premature. Researchers investigating the effects of increasing age on susceptibility to PI have also provided mixed results. When the buildup of interference has been considered in studies of aging, older adults generally demonstrate greater buildup of interference over trials (Dobbs, Aubrey, & Rule, 1989; Schonfield et al., 1983), at least when taxonomic categories are used (Elias & Hirasuna, 1976). This finding can be accounted for by a decreased ability to clear information from working memory, a deficit of the interference control process. In contrast to the greater buildup of PI demonstrated by older relative to younger adults, these groups do not appear to differ in the amount of release from PI when the stimulus category is shifted (Elias & Hirasuna, 1976; Moscovitch & Winocur, 1983; Puglisi, 1980). However, in a review of the existing literature, Dobbs et al. (1989) concluded that when an appropriate measure of release (the Wickens ratio) is used, older adults demonstrated reduced release from PI in each of the five studies considered. A prefrontal interpretation of this data seems consistent with existing neurospychological data, suggesting that individuals with or-

bital frontal damage did not demonstrate release from PI (Stuss, 1991), whereas patients with medial temporal damage display release patterns similar to those of controls (Shimamura, 1995). Stroop Color-Naming Task Research incorporating the Stroop Color-Naming Task has provided a number of findings related to the effects of increasing age on the ability to suppress a prepotent response. In the Stroop task, an individual is asked to perform a series of related word-reading and color-naming conditions. In the word-reading condition of the task, the individual is required to read as quickly as possible a series of color names printed either in black or some other color. The individual is then asked to name the color of a series of colored blocks or patches. The naming of colors is typically slower than the reading of words. In the colorword-naming condition, the individual is required to name the color of a series of words presented in an opposing color, for instance, the word red presented in blue ink. The naming of colors in this condition is generally slowed relative to the naming of color blocks, resulting from the conflict between the color and word information. The effects of increasing age on this task are almost universal, with older adults slowed significantly more by color-word stimuli than younger adults (Conn, Dustman, & Bradford, 1984). Lifespan cross-sectional studies of the Stroop effect indicate that age-related increases in the effect begin to appear in the 6th and 7th decades of life and continue to increase into old age (Comalli, Wapner, & Werner, 1962; Houx et al., 1993). In addition to the age-related effect, a number of variables have been shown to interact with the effects of increasing age, including health status, education, and the spatial location of the color and word information. The interaction between health status and age suggests that there is an accelerated increase with age in the Stroop effect for individuals with even relatively minor health problems. In contrast, higher levels of education have been found to provide some protection against the slowing seen with aging (Houx et al., 1993). In addition, Hartley (1993) suggested that age-related differences in the Stroop effect can be ameliorated by spatially separating color and word information. Over the years, a number of theoretical explanations of the Stroop effect have been proposed and tested in relation to the effects of increasing age. Panek, Rush, and Slade (1983) suggested that older adults exhibit greater Stroop interference due to an increase in response dominance for word reading over color naming with increasing age. Other researchers have suggested that age-related increases in the Stroop effect result from an inability on the part of older adults to use a reading suppression response (Dulaney & Rogers, 1994). Also, Spieler, Balota, and Faust (1996) have demonstrated that age-related differences in the Stroop effect persist after controlling for generalized slowing effects. Unfortunately, none of these models has been able to provide a full account of age-related increases in the Stroop effect, leaving open the possibility that at least part of the age-related Stroop effect can be attributed to a reduced efficiency of the inhibition of prepotent response process supported by the DLPFC.

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Sustained A ttent ion

The study of sustained attention or vigilance has been of keen interest to researchers of the effects of increasing age on cognition. Like many other areas of cognitive aging, investigation of the evidence suggesting either the decline or maintenance of sustained attention capacity has been mixed. In a typical sustained attention task, an individual is required to monitor a form of external stimuli, generally auditory or visual, for the occurrence of a selected target. Target stimuli have included tones, letters, words, and irregular movements of a clock hand (Parasuraman & Giambra, 1991). Optimal performance on sustained attention task is generally considered a function of the ability to focus attention over time, discriminate between target and nontarget stimuli, maintain preparatory set, and respond quickly and accurately (Gridley, Mack, & Gilmore, 1986). The prefrontal cortex has been implicated in the support of each of these skills believed necessary for successful sustained attention (Fuster, 1980; Posner & Rothbart, 1991). Parasuraman and Giambra (1991) found evidence for an age-related decline in target hit rate that was exacerbated by increased event rate and was not attenuated with extensive practice. This decreased hit rate was proposed to arise from an Age X Time on Task interaction, with older adults demonstrating faster rates of attention decrease than younger adults (Parasuraman, Nestor, & Greenwood, 1989) and is thought to emerge in the 7th decade of life (Quilter, Giambra, & Benson, 1983). Preserved sustained attention capacity in older adults has been reported in studies using tasks that place fewer demands on a potentially limited capacity attentional mechanism. These studies have differed from those revealing age-related deficits in that they use highly discriminable targets and nontargets, short testing periods, and relatively low event rates (Giambra & Quilter, 1989; Gridley et al., 1986). This suggests that age-related deficits in sustained attention can be expected to arise under task conditions, placing high demands on a limited capacity attentional system, and this system is increasingly susceptible to failure as the time on task is extended (Parasuraman etal., 1989). Summary The frontal lobe hypothesis of aging suggests that the area of cortex anterior to the central sulcus, the region of the prefrontal cortex, is the "first to malfunction in normal aging" (Fuster, 1989, p. 31), indicating that those cognitive abilities supported by this cortical region should demonstrate signs of age-related decline at an earlier time and to a greater degree than cognitive abilities supported by other cortical and noncortical structures. To evaluate the value of the frontal lobe hypothesis in interpreting age-related changes in cognition, a model of prefrontal cognitive function was applied to the existing evidence from two broad areas of cognitive aging: memory and attention. From the vast literature on the effects of increasing age on memory, three areas were determined relevant to the current review: prospective memory, estimation of frequency of occurrence, and source monitoring. The existing evidence from the study of prospective memory, or remembering to remember to act, suggests that older adults

can be expected to make prospective errors when the reliance on external cues is limited and when maintenance of multiple cues or actions is required (McDaniel & Einstein, 1992). These findings were interpreted to have resulted from a decreased efficiency in both the prospective and retrospective processes supported by the prefrontal cortex. Age-related deficits in frequency estimation were found to arise for study items high in frequency of occurrence (Hasher & Zacks, 1979), similar to findings reported in a study of estimation by patients with frontal lesions (Shimamura, 1995). The effect of increasing age on frequency estimation was also found to vary as a function of degree of novelty of stimulus materials (Wiggs, 1993), consistent with suggestions that the prefrontal cortex is important when novel information is encountered (Fuster, 1980; Knight & Grabowecky, 1995). Age-related deficits in source monitoring or memory were found in a number of studies and seemed to exacerbate when multiple sources of information were highly similar (Hashtroudi etal., 1998; Mclntyre &Craik, 1987), indicating that age-related deficits may arise from the inefficient integration of semantic and contextual information at the time of encoding. This seems consistent with the current model of prefrontal function in which one of the activities supported by the prefrontal cortex is the integration of temporal and contextual information into discrete memory traces (Fuster, 1989). The consistent findings of reduced levels of item or semantic information recall and recognition by older adults across the areas of prospective memory, frequency estimation, and source memory are not consistent with the predictions of the current model of prefrontal function or with findings from studies of individuals with focal frontal lesions (Shimamura, 1995). These findings are, however, consistent with findings from studies of individuals with damage to the medial temporal lobe (Kolb & Whishaw, 1990; Shimamura, 1995). The reduced levels of recall observed in older adults could be hypothesized to account for performance deficits in each of the memory paradigms considered above and could be attributable to a temporal lobe deficit. This is an unfounded position, however, as a number of studies show age-related deficits in memory-related prefrontal tasks concurrent with control levels of recall and recognition (Schacter et al., 1991; Shimamura, 1995). Instead, these findings suggest that a full neuropsychological model of cognitive aging would have to include predictions relevant to both frontally and temporally supported cognitive processes. The study of age-related changes in attention can also be widely interpreted within the context of the present model of prefrontal cortex function. The effects of age on the performance of tasks sensitive to the effects of interference in the short-term retention of information, the ability to suppress a dominant response, and the ability to sustain attention over time can all be interpreted within the current theoretical framework. In studies of the effect of interference on the ability to maintain target information over brief time periods, older adults generally performed poorly relative to younger adults. This age-related increase in susceptibility to interference can be observed when the Brown-Peterson task is applied as reduced recall of target words over varying delays in which a distractor task must be performed and when the release from PI task is applied as the greater buildup of interference precedes a cate-

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gory shift (Parkin & Walter, 1991; Puglisi, 1980). These agerelated deficits can be seen to result from an inability to maintain task-relevant information on-line when resources must be allocated to the performance of a secondary task and a diminished capacity to clear task-irrelevant information from a heightened state of activation (Allen, Madden, Weber, & Crozier, 1992; Cowan, 1995;Fuster, 1989). Evidence from the Stroop Color-Naming Task suggests that the ability to suppress prepotent response tendencies is also sensitive to the effects of increasing age. Findings from the Stroop task indicate that older adults are less efficient than younger adults at dealing with the effects of conflicting color and word information (Cohn et al., 1984; Comalli et al., 1962) and that this deficit remains constant when both younger and older adults receive extensive practice (Dulaney & Rogers, 1994). The current model of prefrontal cortex function would suggest that this deficit results from an age-related decline in the efficiency of the inhibition of prepotent response process. Finally, the effects of increasing age on the ability to sustain attention over an extended time period were interpreted within the context of the prefrontal cortex model. Findings from this area indicate that clearly there are some task conditions under which consistent age-related deficits can be expected to emerge, including tasks using high event rates and tasks with demanding target discriminations (Parasuraman & Giambra, 1991; Parasuraman et al., 1989). These findings indicate that the ability to maintain focused attention over an extended time period in a resource-demanding task is susceptible to the effects of increasing age. The link between this ability and the prefrontal cortex emerges from the extensive work of Posner and numerous colleagues (Posner & Rothbart, 1991) on the vigilance network, supported by the right-prefrontal region. Conclusions The goal of this review was to extend the existing application of the frontal lobe hypothesis of aging beyond the rather limited existing work on interference control and inhibition to include memory processes proposed to be supported by the prefrontal cortex. To support this extension, models of prefrontal cortex function were reviewed and a synthesized model was presented that included a general function of temporal integration supported by four specific processes: prospective memory, retrospective memory, interference control, and inhibition of prepotent responses. The proposed model was found to perform well in accounting for numerous findings of age-related decline in cognition, with one exception: This age-related decline in item recall and recognition suggests that the frontal lobe hypothesis of aging provides a useful but incomplete neuropsychological model of cognitive aging. References
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Received June 19, 1995 Revision received January 16, 1996 Accepted January 29, 1996