3 1 rostral prefrontal cortex (brodmann area 10)

31 ROSTRAL PREFRONTAL CORTEX (BRODMANN AREA 10) METACOGNITION IN THE BRAIN

Paul W. Burgess and Hsuan-Chen Wu Burgess, P. W. & Wu, H-C. (2013) Rostral prefrontal cortex (Brodmann area 10): metacognition in the brain. Chapter 31 in: Principles of Frontal Lobe Function, 2 edition (Editors: Donald T. Stuss & Robert T. Knight) pp. 524-534. New York: OUP nd

INTRODUCTION

size (Semendeferi, Armstrong, Schleicher, Zilless, & Van Hoesen, 1998).

The study of rostral prefrontal cortex (PFC) must count now as perhaps the fastest-growing new area of cognitive neuroscience. Until approximately 10 years ago, virtually nothing was known about this huge brain region (actually the largest architectonic subregion of the PFC). Now we have evidence that stretches across neuroanatomy, anthropology, brain development, cognitive neuroscience, neuropsychology, neuropsychiatry (adults and children), and, most recently, even behavioral neuroscience (Tsujimoto, Genovesio, & Wise, 2011). The purpose of this chapter is to lay out, in as straightforward a way as possible, the current state of our knowledge about this fascinating brain region. We will conclude by suggesting that perhaps the best description for the overall function of this brain region in humans would be that it is a hub for metacognition. So, what do we currently know about rostral PFC, especially as it relates to cognition?

IT HAS AN U N U S U A L L Y

LOW N E U R O N A L

DENSITY

(POINT 2)

Rostral PFC is not only unusual in terms ofits size, but also in terms of neuronal density. In humans, its density is particularly low (Semendeferi et al., 2001). However, the number of dendritic spines per cell and the spine density are higher than those of comparable areas (Jacobs et al., 2001). These differences may be of anthropological significance. Semendeferi et al. (2011) compared the horizontal spacing distance of neurons in different regions of the cortex across primates (including humans). They found that it is only after the split from our last common ancestor that BA 10 neuronal spacing became the largest in humans compared with the other apes. THERE ARE DIFFERENT

CYT0ARCHITECTURAL

S U B R E G I O N S WITHIN BA 10 ( P O I N T 3 ) ROSTRAL

P F C IS A V E R Y B I G B R A I N R E G I O N ,

Rostral PFC is a complex structure from a cytoarchitectural viewpoint. There appear to be at least three different Confusingly, in the literature, rostral PFC (approxi- subregions in humans (with only two in, e.g., the macaque; mating Brodmann area [BA] 10) is referred to by many Carmichael & Price, 1994). According to Ongiir, Ferry, and names. These include "frontopolar cortex," "frontal pole," Price (2003), there is a large and highly differentiated region "anterior prefrontal cortex," and so forth. A l l these terms in humans that covers the frontal pole itself (i.e., the most are used to refer to a large part of the cortex that sits at anterior section), extending across both medial and lateral the very front of the brain, and given our current state of aspects. This region has a thick, highly granular cortex with knowledge, these terms are all virtually interchangeable. a well-developed sublaminated layer I I I . Ongur et al. term Rostral PFC is conspicuously large in humans, compris- this region " lOp." The other two subregions ofBA 10 occupy ing approximately 500 million neurons spread over an the medial surface only. Ongiir et al. describe how the first area of roughly 28,000 mm (Semendeferi, Armstrong, of these regions lies directly behind (i.e., caudally) lOp and Schleicher, Zilles, & Van Hoesen, 2001). Indeed, it is larger is termed "lOr." This has granular layers I I and IV, with a in humans, both relatively and absolutely, than in any other moderately developed layer I I I . The most caudal subregion animal. This is especially noteworthy since this is not the of BA 10 lies behind lOr and is termed "10m." This is granucase for all subregions of PFC. For instance, BA 13 is actu- lar, but with a thinner layer I V and radial and horizontal ally smaller than would be expected given overall brain striations. It is located ventral to BA 24 and ventral and E S P E C I A L L Y IN HUMANS ( P O I N T 1)

3

524

anterior to BA 32 but superior to BA 11 and 13, extending anteriorly to the level of the genu of the corpus callosum. What are we to make of this, as researchers interested in determining the cognitive functions supported by this intriguing brain region? Should we take this information as relevant for constraining theories about the functional organization of rostral PFC (i.e., mapping between structural and functional levels of explanation)? It is unwise to expect a straightforward relation between structure and function, at least using the forms of data currently available to us. Nevertheless, perhaps the fact that there are distinct cytoarchitectonic subregions within rostral PFC might be taken to be congruent with a general notion that there may be differences between these regions in the way they operate, the contributions they make to cognition, or the behaviors or mental abilities afforded by them. In fact, as we shall see later, these anatomical subdivisions appear to be remarkably well reflected in the different functional specializations of these subregions. It is also the case that a number ofthese abilities, while not perhaps entirely unique to humans, nevertheless would be among those that we might think of as strongly typifying what is more characteristic of them than of other primates.

the brain, does not in fact stop in the early 20s, as has been assumed, and the later stages of this process might afford some kind of protection against undesirable cognitive phenomena. A C T I V A T I O N S OF R O S T R A L P F C CAN B E FOUND D U R I N G A L M O S T ANY

KIND OF C O G N I T I V E

TASK

(POINT 5)

As Burgess, Simons, Dumontheil, and Gilbert (2005) pointed out, local hemodynamic (e.g., blood flow, blood oxygenation) changes occur in BA 10 during the performance of a very wide variety of cognitive tasks, from the simplest (e.g., conditioning paradigms; Blaxton et al., 1996) to highly complex tests involving memory and judgment (e.g., Burgess, Quayle, & Frith, 2001; Burgess, Scott, & Frith, 2003; Frith & Frith, 2003; Koechlin, Basso, Pietrini, Panzer, & Grafman, 1999) or problem solving (e.g., Christoff et al., 2001). Indeed, one can find activation of the rostral PFC in just about any kind of task—for example, verbal episodic retrieval (Rugg, Fletcher, Frith, Frackowiak, & Dolan, 1996; Tulving, Markowitsch, Criak, Habib, & Houle, 1996), nonverbal episodic retrieval (Haxby et al. 1996; Roland & Gulyas, 1995), semantic memory (Jennings, Mcintosh, Kapur, Tulving, & Houle, 1997; R O S T R A L P F C (BA 10) D E V E L O P S LATE Martin, Haxby, Lalonde,Wiggs, & Ungerleider 1995), IN L I F E ( P O I N T 4) language (Bottini et al., 1994; Klein, Milner, Zatorre, I f this is true, then perhaps it would not be surprising i f Meyer, & Evans, 1995), motor learning (Jenkins, Brooks, the development of rostral PFC showed a particularly pro- Nixon, Frackowiak, & Passingham, 1994), rule learning tracted course. After all, the most subtle faculties of the (Strange, Henson,Friston,&Dolan, 2001), shock/tone conhuman mind are generally thought to be acquired after ditioning (Hugdahl et al., 1995), nonverbal working memchildhood. And rostral PFC obliges (see Dumontheil, ory (Gold, Berman, Randolph, Goldberg, & Weinberger, Burgess, & Blakemore, 2008, for review): It is a cortical 1996; Haxby, Ungerleider, Horwitz, Rapoport, & Grady, region that displays an unusually large degree of brain 1995), verbal working memory (Petrides, Alivisatos, growth between the ages of 5 and 11 years (Sowell et al., Meyer, & Evans, 1993), spatial memory (Burgess, Maguire, 2004) . But the changes do not stop there. There are large Spiers, & O'Keefe, 2001), auditory perception (Zatorre, decreases in gray matter density in this region between Halpern, Perry, Meyer, & Evans, 1996), object processadolescence (12-16 years old) and young adulthood ing (Kosslyn et al., 1994; Kosslyn, Alpert, & Thompson, (23-30 years old; Sowell, Thompson, Holmes, Jernigan, 1995), the Tower of London Test (Baker et al., 1996), &c Toga, 1999), with maturation of dendritic systems con- the Wisconsin Card Sorting Test (Berman et al., 1995), tinuing into late adolescence (e.g., Travis, Ford, & Jacobs, reasoning tasks (Goel, Gold, Kapur, & Houle, 1997), and 2005) . The developmental changes in gray matter volume intelligence tests such as Raven's Progressive Matrices might be consequent upon an increase in cortical myelina- (Christoff et al., 2001; Prabhakaran, Smith, Desmond, tion (Paus, 2005), which for many years has been thought Glover, & Gabrieli, 1997). Indeed, it might be more of a challenge to find a task to be particularly late in this region (Bonin, 1950). Then there appear to be sharp changes in early adulthood as well: that does not activate some subregion of rostral PFC at least John et al. (2009) compared the volume of rostral PFC as some of the time. This means that the scientific emphasis, in a proportion of total brain volume in healthy people 20 to the struggle to determine the functions of the brain region, 40 years old. They found a sharp decrease in relative vol- turns to (1) those paradigms where there is an usually freume over this period. Moreover, this normally occurring quent finding of rostral PFC activation and (2) those where decrease was absent in people with schizophrenia. So, it is performance on the paradigm is directly related to these tempting to speculate that the "sculpting" of rostral PFC activations. Fortunately, there are some, which will be outthat we see throughout childhood and into early adult- lined in the section dealing with the specific functions of roshood, which is part of the normal developmental course of tral PFC.

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L E S I O N S TO R O S T R A L P F C DO NOT

CAUSE

D E F I C I T S IN A W I D E R A N G E OF T A S K S BUT S E E M R E L A T I V E L Y C I R C U M S C R I B E D (WITHIN THE L I M I T S OF THE F U N C T I O N S THAT WE C U R R E N T L Y T E S T ) ( P O I N T 6)

A natural expectation from the finding of activity in rostral PFC duringjust about any class of cognitive task might be that damage to rostral PFC in humans should cause a very wide range of deficits. However, this does not seem to be the case, as revealed by both single-case and group studies in humans. Probably the first group human lesion study of this type was carried out by Asenath Petrie in 1952. Petrie was a clinical psychologist who had initially studied at University College London and subsequently received clinical training at the Maudsley Hospital in London. In her groundbreaking book, written while she was at Pennsylvania State University (and surely deserves greater recognition), she reported a study of the effects of leucotomy upon her patients at St. George's Hospital in London. More specifically, she compared the effects of two different leucotomy procedures upon cognition in participants with "neurotic" symptoms. The standard procedure at that time was to make an incision at a rostral-caudal plane that, if extended to the outer surface of the brain, would have bisected BA 45,47,46,9, and 8. Petrie compared the effects of this intervention with the effects of a more rostral incision, where the cut was made just behind BA 10. The results were, prima facie, surprising. This rostral operation actually led to improvements in a range of tasks, notably manual dexterity, less perseveration, greater concentration, and better performance on the Wechsler Adult Intelligence Scale (WAIS) Digit Symbol and Similarities subtests. It is tempting to ascribe these improvements to the effects of alleviation of many of the neurotic symptoms that Petrie reports (1952, p. 98). However, this must remain conjecture since the sample was not large enough for formal analysis of this type. Nevertheless, one might perhaps conclude that this pattern would be very unlikely to occur if rostral PFC supports to a very substantial degree the mental faculties tapped by these tests. On other tests, relative to preoperative ability, there was no change. These included the Porteus Mazes, WAIS verbal I Q (VIQ), performance IQ(PIQ), full-scale IQ(FSIQ), Cattell fluency, and proverb interpretation tests. Indeed, out of the substantial battery that Petrie administered, postoperative decrements were detected on only two tests. First, there was a varied response to distraction. Second, the patients seemed to experience the sense that time passed more quickly, as measured by unfilled estimation of the passage of 60 s. Since the publication of Petrie's study, a substantial body of further evidence from human lesion studies has accumulated that also demonstrates that patients with 526

rostral PFC damage are not typically impaired across a wide range of tasks, and their performance on IQtests can remain unimpaired. Many single cases have been reported in which patients have scored in the superior range on I Q tests, despite extensive rostral PFC involvement (e.g., Goel & Grafman, 2000; Goldstein, Bernard, Fenwick, Burgess, & McNeil, 1993; Shallice & Burgess, 1991; see Burgess et al., 2009, for review). In fact, Uretzky and Gilboa's (2010) patient, ZP (WAIS-III V I Q 121, PIQ 104, FSIQ 113), who has circumscribed right frontopolar atrophy following a road traffic accident, gained degrees in civil engineering and business administration after his injury, which would seem unlikely i f rostral PFC dysfunction causes a marked decrement in general intellectual capabilities. Group studies have largely supported these observations. For instance, Dreher et al. (2008) compared patients with rostral PFC lesions (N= 7; called " frontopolar lesions" by Dreher et al.) and patients whose lesions affected the frontal lobes but not the rostral aspects of it (A^= 5). There was no significant difference in the performance of the two groups in terms of WAIS-III FSIQ scores (rostral patients' mean 110.43, SD 20.4; nonrostral patients 103.20, SD 8.35). Moreover, the largest study of its kind (to our knowledge) also supports this contention. Warrington, James, and Maciejewski (1986) examined 656 patients with unilateral cerebral lesions on a shortened version ofperhaps the most widely used neuropsychological test of intelligence, the WAIS. They found that V I Q was impaired following left hemisphere lesions, regardless of where the lesion was located within the hemisphere. Performance I Q was only impaired following lesions affecting the right parietal lobe. In an analysis by individual subtest, only a relationship between Block Design and Picture Arrangement decrement and right parietal involvement was found. There was no specific deficit for lesions in the frontal lobe. Glascher et al. (2009) carried out a similar study, using the more sophisticated lesion imaging methods now available and examining 241 patients with focal brain damage on the WAIS-III. They found a statistically significant lesion-deficit relationship in left inferior frontal cortex for verbal comprehension scores, with an association between lesions in left lateral frontal and parietal cortex for the working memory index and in right parietal cortex for perceptual organization. Again, there was no evidence for a link between rostral PFC lesions and a generalized cognitive impairment, as one might perhaps have expected from a simple-minded extrapolation from the neuroimaging findings of activations across a wide range of tasks. Indeed, those who have specifically addressed this matter reinforce the idea that whatever role it is that processes supported by rostral PFC play in cognition, it is not strongly linked to notions of "general intelligence." Roca et al. (2010) studied the relationship between measures of "fluid intelligence" (e.g., Cattell's Culture Fair Test) and performance on a range of measures of executive functions. P R I N C I P L E S OF FRONTAL L O B E FUNCTION

In their first experiment, the sample was 44 patients with chronic lesions affecting the frontal lobes. For two of the most commonly used executive function tasks (Wisconsin Card Sorting Test [WCST], Nelson version, and Verbal Fluency), they found that although the patients were significantly poorer than a group of matched healthy controls in terms of raw performance on all three tests, once the variance attributable to "fluid intelligence" was accounted for by covariance, this difference disappeared. However, in their second experiment, Roca et al. (2010) administered a wider range ofexecutive and social function tasks to 21 patients. Most of these were performed more poorly by the patient group. This time, however, Roca et al. found that for some of the executive tasks, adjusting for fluid intelligence didnot remove the group difference. These tests were Go-no go (Dubois, Slachevsky, Litvan, & Pillon, 2000; Luria, 1966), proverb interpretation (Hodges, 1994), the Hayling Sentence Completion Task (Burgess & Shallice 1996,1997), the Hotel Task (Manly, Hawkins, Evans, Woldt, & Robertson, 2002), aversion ofShallice and Burgess's Six Element Task (Shallice & Burgess, 1991), and the Faux Pas Test (Stone, Baron-Cohen, & Knight, 1998). Roca et al. (2010) then devised a score that represented the mean residual from these tests (i.e., a score that represented the degree of impairment on the tests that could not be explained by fluid intelligence). When they examined the lesion overlaps for the six patients who showed the greatest negative value, they found that the location of the overlap was in rostral PFC, especially in the right hemisphere. In summary, then, Roca et al. showed that rostral PFC lesions caused an impairment that showed up on a number of executive tasks but that could not be explained by changes in fluid intelligence.

On the Specificity of the Deficit Following Rostral PFC Lesions Roca et al.'s (2010) study moves the argument about the specificity of functions supported by rostral PFC away from notions of "intelligence" (i.e., a construct involved in the performance of virtually all tasks). Yet their study still showed that rostral PFC lesions caused deficits larger than can be explained by intelligence across a range of tasks. So, perhaps rostral PFC lesions in humans still cause widespread cognitive problems of some sort, but these problems are just not well measured by IQtests. An analysis that speaks to this issue is presented by Burgess, Gonen-Yaacovi, and Voile (2012). They carried out a meta-analysis of the set of group human lesion studies carried out over many years by Donald T. Stuss and Michael Alexander and their colleagues in Toronto. They applied similar methods to the analysis of their data over a long period of time, and some of the cases were shared across studies, which made this dataset particularly valuable for 31.

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assessing the overall impact of lesions within the PFC on a range of cognitive domains. The question Burgess et al. (2012) were trying to address in their meta-analysis was whether lesions affecting rostral PFC cause a breadth of deficits comparable to that of lesions elsewhere within the frontal cortex. This is an important issue for knowing where to start about theorizing about functional specialization of the region (see Burgess et al,. 2012, for further explanation). Broadly, Stuss and Alexander tested patients whose lesions involved the frontal lobes, and collected sets of data from nonpatient control subjects matched as closely as possible to the patients for sex, age, and education. The lesions were acute, andincluded infarction, hemorrhage (including ruptured aneurysms), trauma, and tumors. Most patients with tumors had resection of meningiomas or low-grade gliomas and had not been treated with radiation. Stuss and Alexander avoided patients in the very acute phase of their illness (e.g., less than two months' onset) and also excluded patients with significant aphasia, visual neglect, apraxia, or any other significant neurological or psychiatric disorders. Further, the patients tended to have I Q scores within the normal range. Incidentally, it should be mentioned that in these studies, and in comparable ones where rigorous neuropsychological screening is used to remove potential confounds (e.g., Burgess, Veitch, de Lacy Costello, & Shallice, 2000), no simple link between etiology and cognitive results is found: it is the location of the lesion that is the principal determining factor. Burgess et al. (2012) presented an analysis of the results from a range of the published papers by the Stuss/ Alexander team over roughly a 10-year period, using this population. This analysis looked at how many variables showed impairment following lesions to different parts of the frontal lobes out of44 under consideration (see Burgess et al., 2012, for a list of them). The 44 variables were scores from a range of tests and paradigms, including the WCST, various verbal fluency measures, humor measurement, the Stroop Test, simple and choice reaction time tests under various conditions, inhibition, and various measures of attentional performance. The meta-analysis shows two clear results. The first is that rostral PFC lesions did not cause deficits on more of the measurements than lesions elsewhere within the frontal lobes. For both left and right hemispheres, lateral and medial surfaces, deficits were noted on the range ofvariables examined by Stuss and Alexander less frequently than for some other frontal lobe regions; indeed, with the possible exception of some aspects of ventral PFC, cognitive deficits associated with BA 10 lesions, regardless of hemisphere or surface, were consistently among the leastfrequent findings in this series of studies stretching over 10 years. The second finding from the Stuss/Alexander meta-analysis is that the deficits that can be exclusively attributed to rostral PFC lesions seem to relate to quite 527

only partly complete one task and move to another task before returning to the first one. Much of the complex behavior in work and family situations is of this form. For instance, one might start preparing a meal until such time as a phone call has to be made, then break off to make the call and return to preparing the meal. Often each day will be composed of many of these routines and subroutines, which have to be dovetailed i f one is to use one's time effectively. This type of scheduling is called "multitasking." It is distinguished from "multiple-task performance" (e.g., trying to type something while holding a conversation) by the characteristic that only one task is trying to be accomplished at any one time. (The relations between the processes and brain regions involved in these two behaviors are, however, not well established.) In other words, multitasking is the ability to sequence the performance of a series of subtasks, which in practice means performing one task with the intention of switching to another in the future or rehearsing information relevant to one task while performing another. This type of behavior—multitasking—was probably the first for which a case was made for a link with rostral PFC structures. How this came about is documented by Burgess et al. (2009). The first historical stage was the demonstration that some patients with frontal lobe damage showed multitasking impairments in the context of normal performance on most, if not all, of the traditional tests of neuropsychological function used at the time (e.g., memory, language, perception, executive function). The second stage was the demonstration that this pattern was caused most frequently by lesions to rostral PFC. Regarding the first stage, the pattern of relatively isolated behavioral disorganization in everyday life had been observed clinically for many years. For instance, Penfield and Evans (1935) described the symptoms that Penfield's sister was experiencing after the removal of a right frontal glioma: "She had planned to get a simple supper for one guest and four members of her family. She looked forward R O S T R A L P F C IS I N V O L V E D IN THE to it with pleasure and had the whole day for preparation. M E T A O R G A N I Z A T I O N OF B E H A V I O R When the appointed hour arrived she was in the kitchen, ( M U L T I T A S K I N G AND P R O S P E C T I V E M E M O R Y ) the food was all there, one or two things were on the stove, ( P O I N T 7) but the salad was not ready, the meat had not been started and she was distressed and confused by her long continued Multitasking effort alone" (p. 131). This impairment was not caused by problems with Virtually all meaningful behavior has a structure to it, and so could be said to be organized at some level. This is memory, language, or perception, or by gross intellectual true of even relatively simple goal-directed behaviors such decline, but instead seemed to be more specifically related as reaching for a cup of tea. However, at the heart of most to prefrontal lobe function—although none ofthe theorists influential models of the role of frontal lobe processes in at the time attempted either to characterize the problem in human cognition is the notion of a division between behav- information processing terms or describe the characterisioral routines that have become automated through repeti- tics of the situation in which the disability was shown. This tion (like the ability to reach for an object and grasp it) and situation changed in the mid-1980s. Eslinger and Damasio those one-time sequences of behavior that are created to (1985) described the case of EVR, who had undergone deal with novel situations. One of the most common forms surgical removal of a large bilateral frontal meningioma. of the latter behavioral sequences is where one wishes to At the time of his operation, EVR was a financial officer

specific situations. I f one considers just those variables where rostral PFC (BA 10) lesions caused an impairment that was significantly worse than the impairments in patients with lesions elsewhere, the result is a very restricted subset of the 44 variables indeed. Patients with rostral PFC lesions showed impairments in humor judgment in two (only) of the 10 WCST variables considered by Stuss and Alexander, and in maintaining performance in time-keeping tasks, and were worst during slow conditions of sustained attention tasks. With this latter finding, there is an interesting concordance with the findings of Petrie (1952), more than 50 years earlier (described above), which suggested that rostral PFC lesions can lead to a variable response to distraction, and the sense that time passes more quickly, but leaves other cognitive abilities intact. This helps a great deal in the search to discover the cognitive functions supported by rostral PFC. Rostral PFC lesions do not usually cause serious deficits in primary sensory functions, or in the "routinized" learned skills such as basic aspects of language processing, motor or visuo-perceptual abilities, reading, writing, simple aspects of memory (e.g., knowledge; episodic recognition memory), and so forth, since virtually all the studies reviewed here describe patients who have rostral PFC damage but whose abilities in these domains are unaffected. Nor do rostral PFC lesions cause widespread cognitive decline. Instead, they seem to cause deficits on quite a restricted set of tasks. Putting these findings from human neuropsychology together with those from neuroimaging, it seems likely that whatever the functions of rostral PFC are, they (1) are critical to the actual performance of only a restricted range of tasks and (2) are nevertheless operational during a much wider range of tasks. So, what kind of processing could fulfill these criteria? We will argue later that this kind of processing can best be described as "metacognition."

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with a small company and a respected member of his community. He was married and the father of two children; his brothers and sisters considered him a role model and a natural leader. After the operation, however, EVR lost his job, went bankrupt, was divorced by his wife, and moved in with his parents. He subsequently married a prostitute and was divorced again within two years. Extensive psychological evaluations found no deficit; in fact, he was superior or above average on most tests (e.g., V I Q o f 125; PIQof 124; no difficulty on the WCST). He was also able to discuss intelligently matters such as the economy, foreign affairs, financial matters, and moral dilemmas. Despite these normal findings, EVR was often unable to make simple everyday decisions, such as which toothpaste to buy, what restaurant to go to, or what to wear. He would instead make endless comparisons and contrasts, often being completely unable to come to a decision at all. Further, Eslinger and Damasio report prospective memory problems:" it was as if he forgot to remember short- and intermediate-term goals" (p. 1737). Eslinger and Damasio's (1985) study was the first empirical demonstration that this level of behavioral disorganization could occur in the context of intact intellect and intact performance on some tests traditionally thought to be sensitive to deficits in "frontal lobe" executive functions; previously, there had only been observational reports. However, although Eslinger and Damasio quantified the degree of specificity of the impairment (i.e., by showing normal performance on many neuropsychological tests), they did not quantify the actual impairment itself. Shallice and Burgess (1991) addressed this lacuna. They presented the cases of three patients who had all suffered frontal lobe damage following traumatic brain injury. A l l three had no significant impairment on formal tests of perception, language, and intelligence, and two performed well on a variety of traditional tests of executive function. Indeed, one of these patients (AP) was probably the best example of the syndrome so far reported (this patient was later called " N M " by Metzler & Parkin, 2000). AP had sustained an open head injury in a road traffic accident when he was in his early 20s. The injury caused a virtually complete removal of the rostral PFC bilaterally plus damage to surrounding regions. On standard neuropsychological measures of intellectual functioning, memory, perception, and even traditional tests of executive function, AP performed within the superior range. However, AP did show cognitive impairment in other situations (Metzler & Parkin, 2000; Shallice & Burgess, 1991). The most noticeable of these in everyday life was a marked multitasking and prospective memory problem. This manifested itself as tardiness and disorganization, the severity of which ensured that despite his excellent intellect and social skills, he never managed to return to work at the level he had enjoyed premorbidly. Shallice and Burgess (1991) invented two new tests of multitasking to 31

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assess these problems. The first of these tests, called the "Multiple Errands Test" (MET), was a real-life multitasking test carried out in a shopping precinct. Participants have to complete a number of tasks, principally involving shopping in an unfamiliar shopping precinct while following a set of rules (e.g., no shop should be entered other than to buy something). The tasks vary in complexity (e.g., buy a small brown loaf of bread vs. discover the exchange rate of the euro yesterday), and there are a number of "hidden" problems in the tasks that have to be appreciated and the possible course of action evaluated (e.g., on one task, participants must write and send a postcard, yet they are given no pen, and although they cannot use anything they haven't brought during the test to help them, they are also told that they need to spend as little money as possible). In this way, the task is quite open-ended or ill-structured (i.e., there are many possible courses of action, and it is up to the individual to determine which one he or she will choose). The second task that Shallice and Burgess invented was a more controlled experimental task (the "Six Element Test" [SET]). This required subjects to shift efficiently between three simple subtasks, each divided into two sections, within 15 mins, while following some arbitrary rules (e.g., "You cannot do part A of a subtask followed immediately by part B of the same subtask"). There are no cues as to when to switch tasks, and although a clock is present, it is covered, so that checking it has to be a deliberate action. Thus, this paradigm has a strong component of voluntary time-based task switching, that is, one form of prospective memory. Despite their excellent general cognitive skills, AP and the other cases reported by Shallice and Burgess all performed these tasks below the 5% level compared with ageand IQ-matched controls. On the MET the subjects made a wide range of errors. Many of these could be interpreted as problems with prospective memory. For instance, they had to go into the same shop more than once to buy items that could all have been bought at one visit; they forgot to carry out tasks that they had previously learned that they needed to do, and they forgot to follow task rules. They also made a range of social behavior errors (e.g., leaving a shop without paying; offering sexual favors in lieu of payment). Shallice and Burgess (1991) rather inelegantly termed this kind of behavioral disorganization in the context of preserved intellect and other cognitive functions the "Strategy Application Disorder." It was not possible, on the basis of Shallice and Burgess's data, to speculate on the anatomical localization of the lesion critical for this pattern of deficit, since the patients had large traumatic lesions that invaded many subregions. Two years later, however, Goldstein et al. (1993) described a case that began to suggest a possible locus. A 51-year-old right-handed man (GN) had undergone a left frontal lobectomy 2.5 years earlier following the discovery of a frontal lobe tumor (mixed astrocytoma-oligodendroglioma). 529

A 5 cm resection of the left frontal lobe from the frontal pole was undertaken. This surgery made little difference to his general cognitive abilities (e.g., WAIS-R V I Q 129, PIQ 111; story recall immediate 75th-90th percentile, delayed 50th-70th percentile; Rey Osterreith delayed figure recall 80th-90th percentile; Trail-making 70th-75th percentile). However, it was clear from his everyday behavior that something was seriously wrong. He had held a senior management position in an international company, but two years after surgery he had to take medical retirement because of increasing lethargy. He worked from home as a free-lance management consultant, but had difficulty making decisions, culminating in his taking two weeks to decide which slides to use for a work presentation but never actually reaching a decision. He also experienced anger control difficulties. Goldstein et al. (1993) administered Shallice and Burgess's (1991) MET. GN made significantly more errors than controls, being less efficient (e.g., havingto return to a shop), breaking tasks rules (e.g., using a stamp that another customer gave him), and misinterpreting tasks (e.g., sticking the stamp on the wrong card), as well as failing to complete some tasks altogether, reporting that he knew he had to do them but somehow "forgot" them. He also showed some "social rule" breaks. For instance, he had omitted to find out the price of tomatoes earlier in the fruit and vegetable shop, and realizing that he should not go back there unless he wanted to buy something, he very conspicuously climbed onto the fruit display outside the shop and peered in the window. It was not until the study of Burgess et al. (2000), however, that the link between multitasking deficits and rostral PFC damage was formally demonstrated by the principal localizingmethod in neuropsychology: agroup lesion study. Sixty patients with acute neurological damage from an unselected series of referrals (approximately three-quarters ofwhom were suffering from brain tumors) and 60 age- and IQ-matched healthy controls were administered a multitasking test called the "Greenwich Test." This test follows the principles of the SET but, in contrast, the majority of the variance in test performance comes from rule infractions rather than task-switchingproblems. Participants are presented with three different simple tasks and told that they have to attempt at least part of each of the tasks within 10 min while following a set of rules. One of these rules relates to all subtests ("In all three tasks, completing a red item will gain you more points than completing an item of any other color"), and there are four task-specific rules (e.g., "In the tangled lines test you must not mark the paper other than to write your answers down"). The test was administered in a form that allowed consideration of the relative contributions of task rule learning and remembering, planning, plan following, and remembering one's actions in relation to overall multitasking performance. Specifically, before participants began the test, their ability to learn 530

the task rules (by both spontaneous and cued recall) was measured. They were then asked how they intended to do the test, and a measure of the complexity and appropriateness of their plans was calculated. This enabled us to look at whether their failures could be due to poor planning. The participants then performed the task itself, and by comparing what they did with what they had planned to do, a measure of plan following could be determined. Multitasking performance was measured as the number of task switches minus the number of rule breaks. After these stages were finished, subjects were asked to recollect their own actions by describing in detail what they had done. Finally, delayed memory for the task rules was examined. Burgess et al. (2000) found that lesions in different brain regions were associated with impairment at different stages in the multitasking procedure. For instance, lesions to a large region of superior posterior medial cortex including the left posterior cingulate and forceps major led to deficits on all measures except planning. Remembering task contingencies after a delay was also affected by lesions in the region of the anterior cingulate. Critically, however, Burgess et al. found that patients with rostral PFC lesions in the left hemisphere, when compared with patients with lesions elsewhere, showed asignificant multitaskingimpairment despite no significant impairment in planning, or in remembering what they had done, or the task rules. Indeed, the left rostral prefrontal patients showed no significant impairment on any variable except the one reflecting multitasking performance. In other words, despite being able to learn the task rules, form a plan, remember their actions, and say what they should have done, they nevertheless did not do what they said that they intended to do. The Burgess etal. (2001) result—an association between rostral PFC lesions and multitasking impairments—has now been replicated several times (e.g., Dreher et al., 2008; Roca et al., 2010,2011) and thus seems secure. These studies have also opened up an entirely new area of inquiry (the cognitive [neuro] science of multitasking) that did not exist just a few years ago. But what is the nature of the critical processing impairment shown by these patients? The multitasking situations presented to a participant by the two experimental paradigms developed by Burgess and Shallice (MET and SET) share a number of similarities. These are: 1. A number of discrete and different tasks have to be completed. 2. Performance on these tasks needs to be dovetailed in order to be time effective. 3. Due to either cognitive or physical constraints, only one task can be performed at any one time. 4. The times for returns to task are not signaled directly by the situation. P R I N C I P L E S OF FRONTAL LOBE FUNCTION

5. There is no moment-by-moment performance feedback of the sort that participants in many laboratory experiments receive. Typically, failures are not signaled at the time they occur. 6. Unforeseen interruptions, sometimes of high priority, will occasionally occur, and things will not always go as planned. 7. Tasks usually differ in terms of priority, difficulty, and the length of time they will occupy. 8. People decide for themselves what constitutes adequate performance. A key component of dealing with situations that have these characteristics (and that, incidentally, are very common in everyday life) is that they make demands upon prospective memory. "Prospective memory" (PM) is the ability to enact delayed intentions, that is, to remember to carry out an intended act in the future, while engaged in another task (referred to as the "ongoing task"). Prospective Memory There are three main forms of the PM situation: event-based, time-based, and activity-based. In event-based PM situations, one intends to carry out the action (or thought) in response to an event, typically a prospective memory "target" or "cue". In time-based PM conditions, the intention is to carry out the act at a particular time (e.g., at 3 p.m. or 30 min from now), regardless of what else is occurring. These are by far the most commonly studied forms. The third, and less well understood PM situation, activity-based PM, is where the intention is to do something when one is engaged in a particular activity (e.g., "The next time I go surfing (regardless of when or where), I will do X"), or at the start or cessation of it. The link between PM and rostral PFC was first highlighted by Burgess and colleagues (e.g., Burgess, Quayle, & Frith, 2001; Burgess, Scott, & Frith, 2003) using functional neuroimaging. Subsequent studies by this group and others have shown this to be a remarkably consistent association. Indeed, all currently published neuroimaging studies in which a straightforward comparison has been made between a condition requiring the maintenance of a delayed intention and ongoing task performance only have shown activation within rostral PFC (see Burgess et al., 2011, for review). A full review of what we have learned so far from this technique about the role of rostral PFC in PM is given in Burgess et al. (2011). Some of the most consistent or promising findings are outlined in Table 31-1. A key finding is that PM performance does not activate all subregions within rostral PFC equally. As shown in Figure 31-1, during event-based tasks, maintenance of the intention over the delay period while the participant is occupied with another task tends to be associated 31.

ROSTRAL PREFRONTAL CORTEX

with activation in lateral aspects of rostral PFC (Burgess, Quayle, & Frith, 2001; Burgess, Scott, & Frith, 2003; den Ouden, Frith, Frith, & Blakemore, 2005; Gilbert et al., 2009; Okuda et al., 2011; Reynolds, West, & Braver, 2009; Simons, Schoivinck, Gilbert, Frith, & Burgess, 2006. By contrast, ongoing tasks tend to activate medial rostral PFC structures more than during the PM conditions (Burgess et al., 2001, 2003; Hashimoto, Umeda, & Kojima, 2011; Okuda et al., 2007; Simons, Schoivinck, Gilbert, Frith, & Burgess, 2006). Many of these rostral PFC activations (either medial or lateral) seem surprisingly insensitive to the form of stimulus material presented, the nature of the ongoing task, how easy or hard the PM cue is to detect, or how easy or hard the intended action is to recall (Burgess et al, 2001; 2003; Simons, Schoivinck, Gilbert, Frith, & Burgess,). Second, there does seem to be functional specialization for different components, forms, and types of PM for some regions within rostral PFC (Gilbert et al., 2009; Hashimoto, Umeda, & Kojima, 2011; Haynes et al., 2007; Okuda et al., 2007; Simons, Schoivinck, Gilbert, Frith, & Burgess, 2006). For instance, it appears that there might be activation pattern differences during event-based versus time-based paradigms. It is too early in the course of investigations in this field to be certain, but it is possible, on the basis of current evidence, that the rostral PFC activations that occur during time-based PM conditions tend to be more medial than those occurring during eventbased conditions. Other factors that seem to affect rostral PFC activations during PM paradigms include variation in implicit cues (Hashimoto et al., 2010), the nature of the intention itself (Haynes et al., 2007), the form of the instruction given (Gilbert et al., 2009), and the characteristics of intention retrieval (Simons, Schoivinck, Gilbert, Frith, & Burgess, 2006). In general, the patterns of rostral PFC activation seem less affected by differences in the particular stimuli used (e.g., words, pictures) than they do by other aspects of the paradigm, such as those that affect higher-level aspects of cognition. This may be the reason why apparently small changes in task instruction can have a marked effect upon the patterns of activation in rostral PFC (Gilbert et al., 2009) and why broader environmental aspects that might affect strategic behavior may also have an effect (e.g., whether a clock is present or not during timebased PM tasks; Okuda et al., 2007). But perhaps the biggest clue to the nature of the cognition that at least some of these rostral PFC activations are indexing is given by the fact that they can be seen during PM tasks even when no targets are encountered (Burgess et al., 2001); it is enough that participants merely expect a target to occur. However, these patterns of activation can be so specific that one can use them to predict which intentions a participant is considering (Haynes et al., 2007). Moreover, this appears not to be reducible to the notion of "working memory" in one of its many guises. There are regions of lateral rostral 531

TABLE 3 1 - 1

PRINCIPLES OF ROSTRAL PFC ACTIVATION IN PROSPECTIVE MEMORY TASKS ACCORDING TO BURGESS,

GONEN-YAACOVI, AND VOLLE (2011) Seemingly Secure Findings 1 . Performance of prospective memory paradigms, relative to the ongoing task alone, is typically accompanied by activations within rostral PFC (approximately, BA 10; Burgess et al., 2 0 0 1 , 2003; den Ouden et al., 2005; Gilbert et al., 2009; Hashimoto et al., 2010; Haynes et al., 2007; Okuda et al., 1998, 2007; Poppenk et al., 2010; Reynolds et al., 2009; Simons, Schoivinck et al., 2006). 2. Activations during ongoing or (most) control tasks in medial rostral PFC structures tend to be higher than during PM conditions (Burgess et al., 2 0 0 1 , 2003; Hashimoto et al., 2010; Okuda et al., 2007; Simons, Schoivinck et al., 2006). 3. Maintenance of an intention over a delay period during which the participant is fully occupied with another task tends to be associated with activation in lateral aspects of rostral PFC (Burgess et al., 2 0 0 1 , 2003; den Ouden et al., 2005; Gilbert et al., 2009; Okuda et al., 2 0 1 1 ; Reynolds et al., 2009; Simons, Schoivinck et al., 2006). 4.

Some of these rostral PFC activations (either medial or lateral) seem remarkably insensitive (at least with event-based tasks) to the form of stimulus material presented, the nature of the ongoing task, how easy or hard the PM cue is to detect, or how easy or hard the intended action is to recall (Burgess et al., 2 0 0 1 , 2003; Simons, Schdlvinck et al., 2006).

5.

However, for other regions within rostral PFC, there does seem to be functional specialization for different components, forms, and types of PM. For instance, activation in subsections of this region can be sensitive to changes in the nature of what is intended (Haynes et al., 2007); in target recognition versus intention retrieval demands (Simons, Schoivinck et al., 2006); whether the task is time-based or event-based (Okuda et al., 2007); and the nature of the PM cueing procedure (spontaneous vs. cued; Gilbert et al., 2009). There is frequent activation of the precuneus, parietal lobe (BA 7 and 40) and often also of the anterior cingulate (BA 32) during the performance of PM tasks (Burgess et al., 2 0 0 1 ; den Ouden et al., 2005; Eschen et al., 2007; Gilbert et al., 2009; Hashimoto et al., 2010; Okuda et al., 1998, 2007, 2 0 1 1 ; Poppenk et al., 2010; Reynolds et al., 2009; Simons, Schoivinck et al„ 2006). Some of these regions are often coactivated with rostral PFC during many types of cognitive tasks, not just PM ones (Gilbert et al., 2010). But the significance of these coactivations remains to be discovered.

6.

Promising Findings That Could Benefit from Replication 7. In event-based PM tasks, apparently small changes in task instruction can have a marked effect upon the patterns of activation in rostral PFC (Gilbert et al., 2009). 8. (Related to [5] above.) There is a difference in activations in rostral PFC according to whether the PM task is time- or event-based (Okuda et al., 2007). 9. 10. 11. 12.

13. 14.

(Related to [5] above.) In time-based tasks, activation patterns in rostral PFC may change according to whether a clock is available for the participant to use (Okuda et al., 2007). This may be due to differences in clock monitoring or time estimation caused by such manipulation. Rostral PFC activations can be seen during PM tasks even when no targets are encountered (Burgess, Quayle & Frith, 2001); it is enough that participants merely expect targets (see also Martin et al., 2007). There are regions of lateral rostral PFC (BA 10) that are activated during event-based PM tasks that are not also activated during working memory demands (Reynolds et al., 2009). Some activation patterns within PFC (including regions of medial and rostrolateral PFC) are so task-specific that one can use them to predict which intentions a participant is considering (Haynes et al., 2007). However, activation in other rostral regions (with possibly a more anterior lateral location) is unrelated to the specifics of the intention; instead, these areas are coactivated with more posterior regions within the brain that are related to the intention (Gilbert, 2011). Rostral PFC activations are not necessarily synonymous with "conscious thought" (Okuda et al., 2 0 1 1 ; Hashimoto et al., 2010) since they can occur alongside behavioral (and presumably therefore mental) changes (e.g., reaction time) of which the participant is unaware. Some investigators have found lateral BA 10 sustained responses during PM conditions (Burgess, Quayle & Frith, 2 0 0 1 ; Reynolds et al., 2009, Table 1 , p. 1215). However, others have found lateral BA 10 to be transiently associated with detection of PM targets (Gilbert et al., 2009, in Table 2, p. 9 1 1 , explicitly discussed on p. 912). There is thus evidence for both sustained and transient effects in lateral BA 10 during PM tasks. The reason for these differences between sustained or transient activations across studies is not currently well understood but seems a promising avenue for future study.

PFC (BA 10) that are activated during event-based PM tasks that are not also activated during working memory demands (Reynolds et al., 2009). Furthermore, the activations that occur during PM tasks are not necessarily synonymous with "conscious thought": Okuda et al. (2011) have shown that changes in target frequency can provoke both activation of some subregions of rostral PFC and significant behavior changes, yet the participant may be completely unaware (in the sense of being able to verbally report) of the effect of these contingency changes upon his or her behavior or mental life. Very recently, human group lesion studies have confirmed that rostral PFC damage is not only involved in PM performance but is necessaryforit. Umeda et al. (2011) asked a group of 74 patients with traumatic brain injury to 532

remember to hand back to the examiner, at the end of testing, a card given to them at the beginning. They examined the relation between performance on this task and damage to 12 different brain regions previously identified by neuroimaging studies as involved in PM. Using discriminant function analysis, Umeda et al. reported that damage to three brain regions was particularly associated with PM failure: right dorsolateral PFC, involving sections of BA 9 and the superior sections of BA 10 and 46; right ventromedial PFC, involving B A 11 and 47 and inferior parts ofBA 10 and 46; and left dorsomedial PFC, involving BA 9 and superior parts of BA 10. Interestingly, as predicted by both the single-case studies (e.g., Shallice & Burgess, 1991) and the group lesion studies (e.g., Burgess et al., 2000), Umeda et al. also found no difference between those who failed the P R I N C I P L E S OF FRONTAL LOBE FUNCTION

PM task and those who passed on a range of neuropsychological tests not involving PM. The degree of specificity of this cognitive deficit is amply demonstrated in another recent group lesion study (Voile, Gonen-Yaacovi, de Lacy Costello, Gilbert, & Burgess, 2011). We assessed both time-based and event-based PM using two types of material, words and pictures, for each. In addition, we administered tests of time estimation, sustained attending, target detection, inhibition, and ability to deal with multiple instructions. These tests were given to 45 patients with focal brain lesions and 107 healthy control subjects. We found that lesions in the right rostral (polar) prefrontal region (in BA 10) were specifically associated with a deficit in time-based PM tasks for both words and pictures. This deficit could not be explained by impairments in attending, target detection abilities, inhibition, or ability to deal with multiple instructions, and there was also no significant deficit in event-based PM conditions. (This may be particularly noteworthy in reference to the predominantly right lateralized finding of Umeda et al. [2011] with their activity-based PM task.) In addition to their PM difficulties, the patients with right rostral frontal lobe lesions were significantly impaired in time estimation ability compared to other patients. Thus, Voile et al.'s (2011) findings suggest that time-based and event-based PM might be supported at least in part by distinct brain regions, and that the same cognitive mechanisms that are required for estimating the unfilled passage of time (especially when changes of timing are involved) might also be involved in time-based PM (although the design did not, of course, enable us to exclude the possibility that this finding is an epiphenomenon). More generally, the cognitive neuroscience of PM, and especially the role of rostral PFC in it, is an area of inquiry that is moving extremely rapidly, and where there is good concordance between the indications from neuroimaging and those from lesion studies. This seems very promising for future discoveries (see Burgess et al., 2011, for further discussion). R O S T R A L P F C IS I N V O L V E D

IN I M A G I N I N G THE

F U T U R E ( P R O S P E C T I O N ) ( P O I N T 8)

Aside from the (largely) rather experimentally constrained paradigms from the cognitive neuroscience literature (see, e.g., the large body of work relating to Shallice and McCarthy's Tower of London test; Shallice, 1982; see Burgess, Simons, Coates, & Channon, 2005, for review), relatively little attention has been given, until recently, to investigation of how people plan for and envisage future situations. However, in the last few years there have been exciting developments on this front (Addis, Pan, Vu, Laiser, & Schacter, 2009; Schacter, Addis, & Buckner, 2007, 2008; Szpunar, Watson, McDermott, 2007; Weiler, Suchan, & Daum, 2010a,b; Williams et al., 1996). 31.

ROSTRAL PREFRONTAL CORTEX

And there is a meeting point between studies of these cognitive phenomenon and prospective memory not only in a conceptual sense, but also in the prominent findings of rostral PFC activation when people are imagining future scenarios (e.g., Addis, Wong, & Schacter, 2007). Burgess et al. (2011) present a meta-analysis of neuroimaging studies involving future thinking (see Figure 31-1). A considerable caveat needs to be applied to this analysis: the field of "future thinking" or, perhaps more elegantly, "prospection" (also sometimes called "mental time travel"), is in its infancy, so it would be premature to draw strong conclusions from the patterns of activation demonstrated so far. However, as Figure 31-1 shows, rostral PFC activations appear to be extremely common in studies of prospection; this frequency may be higher than for perhaps any other function examined so far in this context, except perhaps prospective memory. But as there are currently few if any comprehensive information processing models of the demands made by prospection, it is difficult to ascertain the significance of this finding for understanding either prospection or the role of rostral PFC structures in supporting it. However, the consistency of the findings is striking, and this bodes well for future discoveries. R O S T R A L P F C IS I N V O L V E D S O U R C E AND C O N T E X T

IN

METAMEM0RY:

M E M O R Y AND

REALITY

M O N I T O R I N G ( P O I N T 9)

The term "metamemory" refers to a range of cognitive operations during which a person deliberates over their own memory processes or traces, searching, editing, reconfiguring, and recombining traces or representations to form new insights. This is often prompted by a failure of more automatic recognition and recall processes. Many examples of this kind of processing in everyday life recollection are given in Burgess and Shallice (1996a). This kind of processing is typically measured experimentally using paradigms tapping constructs such as "source memory," "context memory," or "reality monitoring." A l l of these paradigms provoke high-level memory control/metamemory processing because they ask for information that was not central to the representation (indeed, was often incidental) when it was encoded. A fairly typical example is given by Simons, Gilbert, Owen, Fletcher, and Burgess (2005), a study in which two temporally distinct lists of items were presented. In each list, participants were cued to make one of two different kinds of semantic judgments about people identified either by their face or by their name. Then the participants were asked either whether a particular stimulus had appeared in the first or second list of stimuli (i.e., to test temporal source memory) or which of the two semantic judgments they had made in response to it (context recollection). By contrast, in a reality monitoring paradigm, the key component is that the participant is required to distinguish 533

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Time-based

Event-based

Ongoing

Figure31-1 Panel C shows the typical pattern of rostral PFC activations found during event-based prospective memory tasks. The top panel shows activations occurring while maintaining an intention; the bottom panel shows the higher medial rostral PFC activations that occur when performing the ongoing task only (compared with performing the ongoing task + maintaining an intention). Panel A: meta-analysis from Burgess etal. (2011) showing consistent rostral PFC activations from neuroimaging studies of prospection (e.g., future thinking). Panel B: meta-analysis from Burgess etal. (2011) of activations during both time-and event-based PM experiments in the literature, where simple contrasts between PM conditions and the ongoing task have been made.

between something that was witnessed and something that was just imagined. An example is given in Simons, Davis, Gilbert, Frith, & Burgess (2006). Participants first studied either well-known word pairs or the first word of a word pair accompanied by a question mark, which were presented either on the left or right side of a monitor screen. They were cued to view each word pair and either to look at, or to imagine, the second word of each pair and to count the number of letters it contained. In the subsequent test phase, the first word of each word pair was presented again, and participants were asked to say either whether the second word in the word pair had been seen or imagined (reality monitoring) or, in a contrast condition, whether the word pair had been presented on the left or right side of the screen (i.e., testing position context memory). The remarkable aspect of all these paradigms from the point of view of rostral PFC is that, despite varying greatly in the nature of the stimuli presented, the questions asked of the participants, what they had to remember, and how they gave their answer, every paradigm activates (when contrasted with a suitable baseline) very similar parts of rostral PFC (e.g., Cansino, Maquet, Dolan, & Rugg, 2002; Dobbins, Foley, Schacter, & Wagner, 2002; Fan, Snodgrass, & Bilder, 2003; Mitchell, Johnson, Raye, & Greene, 2004; Nolde, Johnson, & D'Esposito, 1998; Ranganath, Johnson, & D'Esposito, 2000; Raye, Johnson, Mitchell, Nolde, & D'Esposito, 2000; Rugg, Fletcher, Chua, & Dolan, 1999). Turner etal. (2008) shows the typical pattern. They used event-related functional magnetic resonance imaging (fMRI) to contrast two forms of source 534

recollection: recollection of whether stimuli had previously been perceived or imagined and recollection of which of two temporally distinct lists where the stimuli belonged. Lateral regions of rostral PFC were activated in both tasks. However medial regions of rostral PFC were activated only when participants were required to recollect source information for self-generated, "imagined" stimuli (see also Simons, Davis, Gilbert, Frith, & Burgess, 2006). In addition, reduced activity in a region of medial ventrocaudal PFC/basal forebrain was associated with making "imagined-to-perceived" confabulation errors. Thus, it seems at present that lateral rostral PFC is involved in a very broad way with performance of this whole class of metamemory tasks, and that there appears to be an additional more specific relation between medial rostral PFC (and adjoining medial PFC regions) and making perceived/imagined judgments (i.e., "reality monitoring") (see Figure 31-2). But if these lateral rostral PFC activations in particular are the signature of a cognitive process that is used across all of these tasks, what might this process be? We will address this further below. However, it might be noted at this point that what participants report about their thought processes when trying to answer these context-type questions is similar to the processes that Burgess and Shallice (1996a) identified in their study of the control of recollection of everyday life events. One participant described it as "walking around the mind's eye," that is, a disengagement from attending to the external world, and attempted generation of the desired representation in the imagination, with the aim of seeing i f this process might yield information to PRINCIPLES OF FRONTAL LOBE

FUNCTION

(A) Perceived/Imagined & Temporal Order > New

(B)

Task & Position Memory > Baseline

(C)

List & Task Memory : Baseline

(E) Activation in the mPFC (pictured) significantly correlated with the likelihood of misattributing imagined items as perceived (D)

Imagined at study > Perceived at study

-.10 -.05 -.00 -.05 -.10 -.15 -.20 -.25 -.30 -.35 Percent signal change in medial anterior pretrontal cortex

Typical rostral activations during source and context memory experiments. Panel B shows a contrast from Simons, Owen, etal. (2005) where memory for the task someone had performed with a stimulus was contrasted with recalling where on the screen the stimulus had appeared. Panel C shows activations from Simons, Gilbert, etal. (2005) where list and task memory were contrasted. Although these two studies tested different samples of participants and made different source/context memory contrasts, the lateral rostral PFC activations are very similar. Panel A: results from Turner etal. (2008). Lateral rostral PFC is also commonly activated when making temporal order and perceived/imagined judgments. But medial regions of rostral PFC are activated when participants are required to recollect source information for self-generated, "imagined" stimuli (Panel D, Turner etal., 2008). Finally, Panel E shows results adapted from Simons Davis, Gilbert, Frith, & Burgess, (2006): significant correlation across participants between reduced activation in medial anterior PFC (pictured) and misattributions of imagined stimuli as having been perceived, reinforcingthe role of medial rostral PFC in this ability. Figure 31-2

answer the question. But there are other strategies people seem to use as well. Sometimes people will report, especially during reality monitoring paradigms, alternating between attending intently to the stimuli and introspecting on the level of familiarity it provokes, with the aim of getting a " feeling" for the answer.

they were that they were correct. Using the accuracy of these judgments as a measure of introspection, Fleming et al showed a correlation between this behavioral measure and gray matter volume in rostral PFC (BA 10; peak voxel coordinates: 24,65,18). A similar principle was followed by Miele et al. (2011). In their task, participants used a trackball to move a cursor to touch certain objects scrolling down a screen R O S T R A L P F C IS I N V O L V E D IN I N T R O S P E C T I O N and avoid others. The program sometimes introduced AND A W A R E N E S S OF C O M P E T E N C E ( P O I N T 1 0 ) noise geared to the degree of precision with which the The argument, therefore, is that at least some of the activa- cursor followed the inputs to the trackball so that the partions seen during the paradigms mentioned above are due ticipant would feel out of control. During these phases, to this introspective process of walking around the mind's Miele et al. found increased activity in the right temporopaeye. This interpretation is given more plausibility by the rietal junction and other nonfrontal regions. By contrast, evidence of involvement of rostral PFC activation during when participants were more in control, activity was seen in paradigms that aim directly to instigate a mental state of regions linked to self-initiated action (e.g., the pre-suppleintrospection. An example of this latter mental state might mentary motor area, dorsal striatum, anterior cingulate). be a situation where you are asked to rate your confidence However, importantly, when the activation that occurred that you are correct about something. during participants' judgments about the extent to Fleming et al. (2010) designed a task of this kind. which they were in control was contrasted with activation They showed people perceptually similar displays, but during their judgments about their own performance, one of them had a distinct feature they had to detect (a Miele et al. found increased activity in rostral PFC (—20, high-contrast Gabor patch). They varied the difficulty of 50, 20) during the former compared with the latter situthis task to ensure that for all participants, performance ation. So, at least in this context, this region seems to be remained about 71%. Each time after the participants had more involved in judgments of agency rather than of given their answer, they were asked to rate how confident performance. 31.

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535

R O S T R A L P F C IS I N V O L V E D

IN

MENTALIZING

yes," "unsure no," "sure no"). So, the correct response was "yes" only for old/same words but "no" for both old/different and new words, and participants would only respond The intriguing differences between the locations of the "old," if the word was previously seen in the specified task. regions identified by Fleming et al. (2010) and Miele et al. For example, they might have encountered the trait "edu(2011) perhaps create the possibility that different forms of cated" during a Self Study phase and "modest" during an introspection, metacognition, or self-judgment may actiOther Study phase before seeing both words again during a vate different subregions of rostral PFC. self test phase. In this case, they would have had to respond One can see local hemodynamic changes with very "yes" to the old/same word "educated" but "no" to the old/ fine-grained differences in the type of judgment that is different word "modest." being made when one turns to the arena of "mentalizing" We found that there was a positive correlation between or "self-judgment." Schmitz et al. (2004) employed a parasignal change in medial rostral PFC for self versus friend digm that requiredpeople to make decisions about how well judgments and subsequent memory for the reference adjectives that were presented to them described themselves of such judgments. So, these results link hemodynamic or other people they knew (plus a purely semantic positive changes in medial rostral PFC to both personality judgvalence judgment control condition). These adjectives comments about oneself and subsequent episodic memory prised a wide selection ofpersonality traits such as "daring" retrieval of these judgments. But the hemodynamic effects or "intelligent" as well as physical traits such as "weak." showed even greater specificity. The degree to which blood Comparing the self-evaluation with the semantic control oxygen level-dependent (BOLD) signal in this region was condition, Schmitz et al. found significant activation in a associated with thinking about others correlated with the network that involved medial rostral PFC (x,y, z ofmaxima perceived similarity of the traits to oneself in both tasks. = 6, 56, 4) and medial orbitofrontal cortex (-4, 18, -10), Moreover, participants who perceived themselves as having as well as retrosplenial cortex (2, -60, 16) and thalamus traits similar to those of their friend tended to be poorer at (2, -24, 2). A very similar pattern was found when people remembering whether they had made trait judgments in made judgments about other people (compared with the reference to themselves or their friend. So, the behavioral same control condition), with activation in rostral medial effect was reflected in the BOLD signal in medial rosPFC (-4, 58, 4), retrosplenial cortex, and thalamus. But tral PFC: there was a positive correlation between signal direct comparison of judgments about oneself versus judgchange for self versus friend judgments and subsequent ments about other people revealed activation bilaterally in memory for the reference of such judgments. These results dorsolateral PFC and parahippocampal gyrus, with higher therefore suggest a link between medial rostral PFC activactivation for self-judgments. So, these results perhaps sugity and a "psychological similarity" effect in making pergest that (medial) rostral PFC is involved in personality sonality judgments. trait judgments in a fairly broad way. AND S E L F - J U D G M E N T ( P O I N T

11)

However, Benoit et al. (2010) showed a more specific relation. Their study built upon that of Schmitz et al. (2004), also using fMRI. Functional M R I was used while two factors were crossed: (1) engaging in personality trait or episodic source memory judgments and (2) the source memory for these judgments (i.e., oneself or a friend). Participants alternated between study and test phases. In a "self" study condition, they judged how well a set of personality traits described them. In a second, "other" study condition, they made similar judgments in reference to their best friend. There was also a control condition during which participants were asked to judge the number of syllables of the trait words (i.e., two, three, four, or five syllables). Test phases also consisted of self, other, and syllables conditions. For each condition of the test phase (i.e., self, other, syllables), words were presented that were either previously encountered in the respective study condition (old/same words) or in the other two study conditions (old/ different words) or were not shown before (new words). Participants were asked to accept only old/same words and reject both old/different and new words. Responses were always given on a 4-point scale ("sure yes," "unsure 536

R O S T R A L P F C IS I N V O L V E D ANALOGICAL INTEGRATION

IN M E T A L E A R N I N G :

R E A S O N I N G AND (POINT

RELATIONAL

12)

How do we learn from our experience ? I f each lesson learned resided as a unique experience, to be considered only when exactly the same situation that had provoked it recurred, then humans would be limited in their development purely by time and experience, and imagination would count for nothing. But this is not how we learn. Instead, we are constantly detecting similarities between situations and looking for parallels between them in order to apply lessons learned from one situation to another. This is the crux of "analogical reasoning." In this form of thought, a familiar situation (referred to as the "source") is used to make inferences about a less familiar situation (called the "target"), and out of this process can emerge a more abstract schema that encompasses structural aspects of both. Thus, two of the most influential theories, the "structure mapping theory" of Gentner and colleagues (e.g., Gentner 1983; Gentner & Holyoak, 1997; Gentner, Ratterman, & Forbus, 1993) and the "multiconstraint theory" of Holyoak and P R I N C I P L E S OF FRONTAL LOBE

FUNCTION

colleagues (e.g., Holyoak & Thagard 1995,1997), mapping between source and target, involves seeking commonalities not only in elements between the two situations, but also between relations that link those elements. In this sense, analogical reasoning shares considerable overlap with "relational integration" (see Voile et al., 2010, for further detail). There is good evidence for the involvement of rostral PFC in both analogical reasoning and relational integration. As Voile et al. (2010) point out, although there have been relatively few studies of analogical reasoning and relational integration, those that have been performed have consistently suggested that rostral PFC structures support some aspect of the processing that is involved (e.g., Bunge, Helskog, & Wendelken, 2009; Bunge, Wendelken, Badre, & Wagner, 2005; Christoff et al., 2001; Green, Fugelsang, Kraemer, Shamosh, & Dunbar, 2006; Kroger et al., 2002; Prabhakaran et al., 1997; Wendelken, Nakhabenko, Donohue, Carter, & Bunge, 2008). Furthermore, development of these abilities throughout childhood has been associated with the maturation of this region (Crone et al., 2009; Dumontheil et al., 2008). However, a recent study has cast doubt upon some of the more straightforward interpretations of findings of hemodynamic change during analogical reasoning, especially where it is assumed that those changes that are concomitant with performance of the task reflect the process of target-source mapping. Voile et al. (2010) designed an analogical reasoning paradigm that separated in time the presentation of the source and the presentation of the target, thus allowing examination of the similarities and differences in activation patterns (compared to the control) during these phases. I f rostral PFC is involved in analogical reasoning per se, it should not be seen before the target is presented, since prior to this stage no analogy can be drawn. In fact, a lateral rostral PFC (BA 10) region was found to be activated dur'mgany phase of analogical reasoning (compared with a control task that involved attribute matching only). Unlike other rostral prefrontal regions, this region was activated right from the initial time of the presentation of the source. Thus, while it may be the case that this activation indexes a process that is important to analogical reasoning, it is not specific to the phase where an analogy is drawn, but it may play a much more general (perhaps fundamental) role. By contrast, a more dorsomedial region of BA 10 was specifically activated when the target was presented, and not during the source period. This may suggest that this region is associated with comparison or mapping processes. Overall, the study of Voile et al. (2010) confirms that there seems to be an interesting relation between performance of analogical reasoning and activation of rostral PFC. However, it also suggests that different subregions may play distinct roles, with some perhaps more broadly involved not only in analogical reasoning, but also playing 31.

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CORTEX

a more general role in cognition. So, what might this more general role be? ROSTRAL

P F C IS I N V O L V E D IN

DIRECTING

A T T E N D I N G E I T H E R TO THE E X T E R N A L OR TO OUR OWN ROSTRAL

INNER

MENTAL

PFC ATTENTI0NAL

LIFE

WORLD (THE

GATEWAY)

(POINT 13)

Burgess and colleagues (e.g., Burgess, Simons, Dumontheil, & Gilbert, 2005; Burgess, Dumontheil, & Gilbert, 2007; Burgess, Gilbert, & Dumontheil, 2007; Burgess, Gilbert, Okuda, & Simons, 2006) sought to try to discover whether the involvement of rostral PFC in all of the cognitive abilities outlined above (e.g., multitasking, prospective memory, metamemory, competence judgments, mentalizing, self-judgment, analogical reasoning, relational integration) might reflect the operation of a cognitive system that is common to dealingwith all these situations. Burgess and colleagues hypothesized that this common cognitive system might be one involved in controlling the direction of attending, allowing us to engage novel amounts of either "stimulus-oriented" (S) or "stimulus-independent" (SI) attending. In SO attending, our attentional focus is directed toward the external environment; we are simply paying attention to the things we can see, hear, and so on. By contrast, in SI attending, we are caught up with the "thoughts in our head," that is, self-generated and/or maintained representations. Burgess and colleagues called the notion that at least some parts of rostral PFC support a system that exerts control over the degree of SO or SI attending the "gateway hypothesis" of rostral PFC. In the first of a series of experiments (Gilbert, Frith, & Burgess, 2005), Burgess and colleagues tested this hypothesis. We designed a range of tasks contrasting the activations that occur in the brain while people are attending to external stimuli with those that occur while people are doing exactly the same tasks but have to imagine the stimuli in their heads. We used a "conjunction-type" design using a series of tasks that measure the construct of interest (SI/SO attending control or, as we have rather inelegantly called it, the "supervisory attentional gateway"; Burgess, Dumontheil, & Gilbert, 2007) but that differ in as many other ways as possible (e.g., in terms of the stimuli encountered, the question that has to be answered). Then, by looking at the activations that were common across the tasks, we could determine the pattern that is true for this whole class of tasks rather than being true of only one (see Figure 31-3). The results from Gilbert et al. (2005) confirmed the hypothesis. Lateral aspects of rostral PFC (BA 10) were activated when people switched from either SO to SI or from SI to SO modes of attending (i.e., switching between attending to external stimuli or doing the task "in one's 537

(A)

Stimulus-Oriented Attending (SO)

Stimulus-Independent Attending (SI)

o

(B)

BBMBBBB 1 Task 1

Task 2

WBM

Bit P I G

\I B

15

LO •5

Si blocks

II 111 B B

Task 3

RSB Sal •

^

'6 4

0

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Figure 31-3 Rostral PFC structures play a role in the control of SO versus SI attending. Panel A shows the three different tasks used by Gilbert etal. (2005) to measure these constructs. Task 1 required participants to anticipate when a clock hand would reach a certain point; they were either able to seethe clock (SO phases) or they were distracted by irrelevant information (SI phases). Task 2 involved navigating around a figure that the participant could either see (SO) or not (SI). Task 3 required making judgments about the shape of letters of the alphabet, which were either displayed or had to be imagined by the participant. Panel B shows the typical activations in rostral PFC during SO versus SI phases; results from Gilbert, Williamson, etal. (2007).

head only, or vice versa). An anterior region of medial BA 10 was active specifically in the SO conditions (i.e., when attending to external stimuli rather than doing the same task in one's head). This basic pattern has recently been confirmed by a separate research group in a clever study by Henseler, Kriiger, Dechent, and Gruber (2011). We have now conducted a series of experiments that have examined the dynamics of the hemodynamic changes that occur while variously stressing the supervisory attentional gateway. The three main conclusions so far, very briefly, are: 1. Lateral aspects of rostral PFC are activated not only at the SO/SI attending switch points, but also during longer phases of SI attending (Gilbert, Williamson, Dumontheil, Simons, Frith & Burgess, 2007). 2. The rostral PFC activations seem remarkably invariant to the stimulus you are attending to or what you are thinking about (Dumontheil, Gilbert, Frith, & Burgess, 2010). 3. The medial anterior rostral activation increases seen with these types of tasks are associated with faster reaction times. 4. The same regions involved in this form of attentional control are also involved in prospective memory. The last point (4) will be covered in the next section. Point 2 deserves a caveat: So far we have only examined tasks that present stimuli visually. It is possible that auditory or tactile presentations, for example, may reveal a different pattern (this would be a very interesting finding in terms 538

of understanding the functional organization of rostral PFC). Point 3 is an important finding because of the debate surrounding the role of medial PFC structures in supporting mind wandering or other off-task processing. It would appear, prima facie, that the findings presented here are in conflict with those of authors who maintain that this medial PFC region is part of a "default mode network," which typically shows decreased activation during the performance of demanding cognitive tasks. A full appraisal of the vigorous debate surrounding this apparent conflict is beyond the scope of this chapter, and the reader is referred to Mason et al. (2007), Gilbert, Dumontheil, Simons, Frith, and Burgess (2007), and Gilbert, Bird, Frith, and Burgess (2012). However, not only have we shown in previous studies that the anterior medial PFC activation during our reaction time tasks is performance-related, but we have also examined the possibility of a relation with task difficulty. In a very recent study (Gilbert, Bird, Frith, and Burgess, 2012), we used f M R I to study 18 participants performing two "stimulus-oriented" (SO) tasks where responses were directly cued by visual stimuli, as well as an "stimulus-independent" (SI) task with greater reliance on internally generated information. The SI task was intermediate in difficulty, as measured by response time and error rate, relative to the two SO tasks. The BOLD signal in medial rostral PFC, despite claims that this region is part of the default mode network, was reduced in the SI condition in comparison with both the more difficult and less difficult SO conditions. This result suggests that task difficulty PRINCIPLES OF FRONTAL LOBE FUNCTION

(as measured by response time and error rate) does not provide a comprehensive account of signal change in medial PFC; instead, it is the relative demand made upon SI and 5 0 attendingsystems that is thebetter predictor. This latter study is important because it is possible to argue from the evidence from our earlier simple reaction time tasks that good performance indicates that the task is well within the capabilities of the participant, and so would also provide the opportunity for mind wandering (i.e., that mind wandering and fast reaction times might be correlated in some circumstances). But it is much more difficult to square the evidence from this latter study on task difficulty with the default mode hypothesis.

jointly recruited during (1) mere ongoing task activity versus additional engagement in a PM task and (2) SO versus SI processing. This is congruent with the notion that some of the processes mediating PM performance can be characterized by relative differences in these attentional modes, as proposed by the gateway hypothesis (Burgess, Gilbert, and Dumontheil, 2007; Burgess et al., 2009). At the same time, the PM contrast was consistently associated with more dorsal peak activation than the stimulus contrast, perhaps reflecting engagement of additional processes. It would be interesting, and theoretically noteworthy, to see similar methods applied to the mapping of rostral PFC activations during prospection versus PM.

S O M E R E G I O N S OF R O S T R A L P F C A R E I N V O L V E D IN M O R E THAN O N E C O G N I T I V E

DOMAIN

(POINT 14)

A natural question emerging from the finding of rostral PFC involvement in supporting a broad function like an attentional gateway is whether these same regions are involved in the other functions identified as associated with this brain region. One might suppose, perhaps on information processing grounds, that an ability such as maintaining an intention in the face of demands associated with competing external stimuli might require a high degree of control over SO versus SI attending. Thus, the hypothesis that there might be a corresponding overlap in the brain regions involved is an obvious one. Ideally perhaps, distinguishing between the foci of activation involved during performance of these kinds of cognitive activities would be tested using a direct within-subjects comparison. This is exactly the kind of design that Benoit et al. (2012) have attempted with prospective memory. Their study aimed to discover whether functional imaging data are consistent with the idea that the rostral PFC attentional gateway is involved in performance of prospective memory paradigms. As mentioned above, the supervisory (or rostral PFC) attentional gateway is a hypothetical cognitive mechanism proposed by the gateway hypothesis of rostral PFC function (Burgess, Simons, Dumontheil, & Gilbert, 2005; Burgess, Dumontheil, & Gilbert, 2007; Burgess, Gilbert, & Dumontheil, 2007; Burgess et al., 2006). This asserts that aprincipal purpose of rostral PFC is to control differences in attending between 51 thought (i.e., inner mental life) and SO thought (i.e., attending to the external world). Benoit et al. (2012) used a factorial design, crossing prospective memory (PM vs. no-PM) with mode of attending (stimulus-oriented [SO] vs. stimulus-independent [SI]; e.g., Gilbert et al., 2005; see Figure 31-3). The purpose of the experiment was to determine whether the foci of activations in PM were the same as those activated by SI/SO attention changes. Benoit et al. (2012) found that parts of medial rostral PFC were 31.

R O S T R A L PREFRONTAL CORTEX

CONCLUSION: IS ROSTRAL PFC A HUB FOR METACOGNITION? Stuss and Alexander (2007) have characterized the functions supported by rostral PFC as being involved in "metacognitive" processing. This label has considerable appeal given the foregoing review. There is, however, no agreed set of abilities or behaviors that this label might encompass. For instance, Shammi and Stuss (1999) showed that humor appreciation is affected by lesions involving the right rostral PFC region. Should this cognitive ability be considered to have a strong metacognitive component? We know of no comprehensive information processing model for humor appreciation, or for many of the other cognitive abilities reviewed above, which might allow a firm decision on this point. For this reason, it may be better to start with an account of metacognition developed without knowledge of the cognitive neuroscience of rostral PFC and judge retrospectively whether the functions outlined above (i.e., for which there is strong reason to believe that supporting structures are located in rostral PFC) fit within the framework. I f there is a remarkable coincidence between the functions we have recently found to be supported at least in part by rostral PFC structures and the functions that have been described as requiring metacognition from another field, then this may give the label more credence for its application in cognitive neuroscience. Such a prior framework does exist, although perhaps not always with the form ofspecification that might be ideal for cognitive neuroscience purposes. "Metacognition" is commonly defined as "thinking about thinking," that is, reflecting or introspecting upon one's own thoughts. But while most theorists would indeed count such a mental experience as metacognition, the person widely credited with the introduction of the term to the psychological literature (J. H . Flavell) provided a much broader and more practical definition. For instance, his widely cited 1979 paper, titled "Metacognition and Cognitive Monitoring: A 539

New Area of Cognitive Developmental Inquiry," opens thus:

to the intended outcome of one's actions. The fourth was "actions and strategies," referring to the behaviors and cognitive operations required in order to achieve one's goals. Preschool and elementary school children were Flavell (1979) describes the situations in which such asked to study a set of items until they were sure they cognitions are most likely to occur. He says, "my present could recall them perfectly (Flavell, Friedrichs, & guess is that metacognitive experiences are especially likely Hoyt, 1970). The older subjects studied for a while, to occur in situations that stimulate a lot of careful, highly said they were ready, and usually were, that is, they conscious thinking: in a job or school task that expressly showed perfect recall. The younger children studied demands that kind of thinking; in novel roles or situafor a while, said they were ready, and usually were not. tions, where every major step you take requires planning In another study, elementary school children were beforehand and evaluation afterwards; where decisions asked to help the experimenter evaluate the commuand actions are at once weighty and risky; where high affecnicative adequacy of verbal instructions, indicating tive arousal or other inhibitors of reflective thinking are any omissions and obscurities (Markman, 1977). absent Such situations provide many opportunities for Although the instructions were riddled with blatant thoughts and feelings about your own thinking to arise omissions and obscurities, the younger subjects were and, in many cases, call for the kind of quality control that surprisingly poor at detecting them. They incorrectly metacognitive experiences can help supply" (p. 908). thought they had understood and could follow the Given that a key aspect of Flavell's characterization of instructions, much as their counterparts in the study metacognitive processes was that they are used in a very by Flavell et al. (1970) incorrectly thought they had wide range of situations (e.g., oral communication and memorized and could recall the items, (p. 906) comprehension, language acquisition, attention, memory, problem solving, social cognition, self-control, and From these examples, it is clear that it is not thinking self-instruction), i f rostral PFC structures were part of a about thinking that is the immediate focus for Flavell, system that supported these forms of cognition, then we but issues such as awareness of competence, knowledge would expect activations in this region to occur in a wide about one's tendency to err, and knowing when you know range of situations. And this is, of course, what point 5 something—or do not. Indeed, Flavell goes on to define above outlines. But how would this then be squared with metacognition very broadly, indeed, as "knowledge and the apparently contradictory finding that lesions to rostral cognition about cognitive phenomena" (1979, p. 906). He PFC do not cause deficits in a correspondingly large (or gives as examples of situations where metacognition plays often even similar) range of tasks (point 6) ? an important role "oral communication... [and] persuaOne explanatory hypothesis might be that some prosion, oral comprehension, reading comprehension, writ- cessing carried out by rostral PFC may not necessarily be ing, language acquisition, attention, memory, problem reflected in task performance. Many metacognitive expesolving, social cognition and various types of self-control riences may bear only a passing relation to behavior seen and self-instruction" (ibid.). It would seem, therefore, that on a moment-by-moment basis. This is because much of it the principal source of the term "metacognition" refers to a may relate to consideration of future, rather than present, far wider range of cognition than introspection upon one's actions (see points 7 and 8) or consideration of many posthoughts. sibilities for immediate action that are then not enacted Indeed, Flavell described four broad classes of men- (see point 12). Further, judgments arising from reflections tal phenomenon which together might be thought of as upon one's own performance are known to be not necessaran operational definition. The first was "metacognitive ily closely related to "objective" (e.g., normative) estimates, knowledge," referring to knowledge about individuals so they are not necessarily helpful to test scores (although as cognate agents, and their diverse and individual goals, in some circumstances they might be more so to future actions, and experiences, including, for example, how good performance perhaps, which may be their utility). There is or bad people are at things. The second class of mental phe- also the possibility sometimes of mind wandering, as highnomenon was "metacognitive experiences," which were lighted above. thoughts provoked by, or accompanying, any kind of intelIn this way, the possibility that rostral PFC (BA 10) lectual operation, such as the "sudden feeling that you do structures support metacognition may help to explain not understand something another person has said" (1979, perhaps the principal puzzle of current rostral PFC findp. 906). It is noteworthy here that the example involves a ings (i.e., that rostral PFC activation occurs during a very spontaneous realization rather than something that one wide range of tasks, but lesions to the region may not has had to work toward: similar effects accompany many cause impairments in many of those tasks). Further, there behavioral phenomena associated with the realization of are obvious parallels between the core components of delayed intentions (e.g., Okuda et al., 2011). Flavell's the Flavell's metacognitive knowledge and more recent conthird component of metacognition was "goals," referring ceptions of theory of mind and mentalizing (see point 11). 540

P R I N C I P L E S OF FRONTAL LOBE FUNCTION

And metacognitive experiences, (goals, actions, and strategies) all sound like descriptions of processes that could be impaired in the patients we have reviewed who have suffered rostral PFC damage, or processes that are the focus of neuroimaging experiments attempting to characterize the functions of rostral PFC (see points 7 and 12 in particular). The emphasis on controlled processing and reflecting upon one's performance is not only reminiscent of most conceptualizations of prefrontally supported cognitive systems, but is also more specifically echoed in the tasks described in points 10 and 11 here. There are many other parallels also. Altogether, these are probably enough to postulate (in agreement with Stuss & Alexander, 2007) that a substantial amount of the processing supported by rostral PFC structures is highly relevant to Flavell's notions of metacognition. These notions were advanced long before techniques like functional imaging were generally available. It may be that cognitive neuroscience is finally starting to discover their full significance for understanding brain function—and indeed, perhaps vice versa.

offigurativeaspects of language: A positron emission tomography activation study. Brain, 117(pt 6), 1241-1253. Bunge, S. A., Helskog, E . H., & Wendelken, C . (2009). Left, but not right, rostrolateral prefrontal cortex meets a stringent test of the relational integration hypothesis. Neuroimage, 46(1), 338-342. Bunge, S. A., Wendelken, C , Badre, D., & Wagner, A. D. (2005). Analogical reasoning and prefrontal cortex: Evidence for separable retrieval and integration mechanisms. Cerebral Cortex, 15(3), 239-249. Burgess, N., Maguire, E. A., Spiers, H . J., & O'Keefe, J. (2001). A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events. Neuroimage, 14(2), 439-453. Burgess, P. W, Alderman, N., Voile, E„ Benoit, R. G., & Gilbert, S. J. (2009). Mesulam's frontal lobe mystery re-examined. Restorative Neurology and Neuroscience, 27(5), 493-506. Burgess, P. W, Dumontheil, I., & Gilbert, S. J. (2007). 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