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CHAPTER 12 Cognitive Control A S EA SO NED NEU ROLOG I ST was caught by surprise when his new patient, W.R., reported his main symptom quite simply: “I have lost my ego.” (R. T. Knight & Grabowecky, 1995...

CHAPTER 12 Cognitive Control A S EA SO NED NEU ROLOG I ST was caught by surprise when his new patient, W.R., reported his main symptom quite simply: “I have lost my ego.” (R. T. Knight & Grabowecky, 1995). A driven child, W.R. decided at an early age that he wanted to become a lawyer. Focused on this plan, he completed college with an excellent GPA and took the right classes for a prelaw student. He was accepted BIG Questions to his first-choice law school and graduated with a solid, if not stellar, What are the computational academic record. But then his life derailed: Suddenly, he seemed to have requirements that enable forgotten his plan to work at a top law firm. Four years later, he had yet organisms to plan and execute to look for a job in the legal profession and, in fact, had not taken the bar complex behaviors? exam. Instead, he was an instructor at a tennis club. What are the neural Accompanying W.R. at the neurologist’s office was his brother, who mechanisms that support reported that the family had found W.R.’s behavior odd but not atypical working memory, and how of the times, perhaps indicative of an early, antimaterialist midlife crisis. is task-relevant information Maybe he would find satisfaction in teaching tennis, his favorite hobby, selected? or perhaps this was just a temporary diversion before he embarked on a career in law after all. But no: W.R. eventually gave up on his job and How does the brain represent even lost interest in playing tennis. His nonchalant attitude frustrated his the value associated with opponents, as he forgot to keep track of the score and whose turn it was different sensory events and to serve. Unable to support himself financially, W.R. hit up his brother experiences, and how does it with increasingly frequent requests for “temporary” loans. use this information to make Clearly a highly intelligent man, W.R. was cognizant that something decisions when faced with was amiss. Though he expressed repeatedly that he wished he could pull multiple options for taking things together, he simply could not take the necessary steps to find a action? job or get a place to live. He had little regard for his own future, for his How do we monitor ongoing successes, even for his own happiness. His brother noted another radi- performance to help ensure the cal change in W.R.: He had not been on a date for a number of years success of complex behaviors? and seemed to have lost all interest in romantic pursuits. W.R. sheepishly agreed. 515 516 | CHAPTER 12 Cognitive Control If this had been the whole story, the neurologist step toward attaining it. Planning how to attain it and might have thought that a psychiatrist was a better then sticking with the plan are also complicated affairs option to treat a “lost ego.” However, during his last involving different cognitive control processes, which year in law school, W.R. had suffered a seizure. An we examine in the final sections of this chapter. extensive neurological examination at the time failed to identify the cause of the seizure, so it was diag- nosed as an isolated event, perhaps related to the fact that on the night before the seizure, W.R. had been 12.1 The Anatomy Behind drinking coffee all night while preparing for an exam. After hearing about the events of the previous 4 years, Cognitive Control the neurologist decided it was time to reconsider the Cognitive control, sometimes referred to as executive cause of the seizure. function, refers to the set of psychological processes that A CT scan confirmed the neurologist’s worst fears. enable us to use our perceptions, knowledge, and goals to W.R.’s brain had an extremely large astrocytoma that bias the selection of action and thoughts from a multitude of possibilities. Collectively, the behaviors thus enabled had traversed along the fibers of the corpus callosum, can be described as goal-oriented behavior, frequently extensively invading the lateral prefrontal cortex in requiring the coordination of a complex set of actions that the left hemisphere and a considerable portion of the may unfold over an extended period of time. The success- right frontal lobe. This tumor had very likely caused ful completion of goal-oriented behavior faces many chal- the initial seizure and over the previous 4 years had lenges, and cognitive control is necessary to meet them. slowly grown. The prognosis was now poor, with a life All of us must develop a plan of action that draws on expectancy of about a year. our personal experiences, yet is tailored to the current W.R.’s brother was devastated on hearing the environment. Such actions must be flexible and adaptive news. W.R., on the other hand, remained relatively to accommodate unforeseen changes and events. We must passive and detached. Though he understood that monitor our actions to stay on target and attain our goal, the tumor was the culprit behind the dramatic life and we may need to inhibit a habitual response in order changes he had experienced, he was not angry or to do so. Although you might want to stop at the dough- upset. Instead, he appeared unconcerned. He under- nut shop when heading to work in the morning, cognitive control mechanisms can override that sugary urge. stood the seriousness of his condition, but the news, As might be suspected of any complex process, cog- as with so many of his recent life events, failed to evoke nitive control requires the integrated function of many a clear response or any resolve to take some action. different parts of the brain. This chapter highlights the W.R.’s self-diagnosis seemed to be right on target: He frontal lobes. As we learned in Chapter 8, the most pos- had lost his ego and, with it, the ability to take com- terior part of the frontal lobe is the primary motor cortex mand of his own life. (see the “Anatomical Orientation” box on p. 517). Ante- In this chapter our focus turns to cognitive control rior and ventral to the motor cortex are the secondary processes, which are essential for the kind of behav- motor areas, made up of the lateral premotor cortex and ior that is uniquely human, be it going to law school, the supplementary motor area. The remainder of the fron- playing tennis, or recognizing that something is amiss tal lobe is termed the prefrontal cortex (PFC). We will in one’s actions or those of a loved one. Cognitive con- refer to four regions of prefrontal cortex in this chapter: trol processes give us the ability to override automatic the lateral prefrontal cortex (LPFC), the frontal pole thoughts and behavior and step out of the realm of (FP), the orbitofrontal cortex (OFC) (sometimes referred to as the ventromedial zone), and the medial habitual responses. They also give us cognitive flexibil- frontal cortex (MFC). ity, letting us think and act in novel and creative ways. In this chapter we concentrate on two prefrontal To facilitate discussion of these functions, we first control systems. The first system, which includes the review the anatomy of the frontal lobe and the behav- LPFC, OFC, and FP, supports goal-oriented behavior. ioral problems that are observed when this region of This control system works in concert with more posterior the brain is damaged. We then focus on goal-oriented regions of the cortex to constitute a working memory sys- behavior and decision making, two complicated pro- tem that recruits and selects task-relevant information. cesses that rely on cognitive control mechanisms to This system is involved with planning; simulating conse- work properly. And deciding on a goal is only the first quences; and initiating, inhibiting, and shifting behavior.  12.1 The Anatomy Behind Cognitive Control | 517 ANATOMICAL ORIENTATION Anatomy of Cognitive Control Squirrel monkey Cat Central sulcus Lateral prefrontal cortex Frontal pole Rhesus monkey Dog Orbitofrontal cortex Secondary Primary motor motor areas cortex Chimpanzee Human Frontal pole FIGURE 12.1 A comparison of prefrontal cortex in different species. The purple region indicates the PFC in six mammalian species. Although the brains are not drawn to scale, the figure makes clear that the PFC spans a much larger percentage of the overall cortex in the chimpanzee and human. Orbitofrontal cortex Because the development of functional capabilities Medial frontal cortex parallels phylogenetic trends, the frontal lobe’s expan- sion is related to the emergence of the complex cog- The prefrontal cortex includes all of the areas in front of the nitive capabilities that are especially pronounced in primary motor cortex and secondary motor areas. The four subdivisions of prefrontal cortex are the lateral prefrontal humans. What’s more, as investigators frequently note, cortex, the frontal pole, the orbitofrontal cortex (which lies “Ontogeny recapitulates phylogeny.” Compared to the above the bony orbits of the eyes), and the medial frontal rest of the brain, prefrontal cortex matures late, in terms cortex. of the development of neural density patterns and white matter tracts. Correspondingly, cognitive control pro- cesses appear relatively late in development, as is evident in the “me-oriented” behavior of infants and teenagers. The second control system, which includes the MFC, The prefrontal cortex coordinates processing across plays an essential role in guiding and monitoring behav- wide regions of the central nervous system (CNS). It ior. It works in tandem with the rest of the prefrontal cor- contains a massively connected network that links the tex, monitoring ongoing activity to modulate the degree brain’s motor, perceptual, and limbic regions (Goldman- of cognitive control needed to keep behavior in line with Rakic, 1995; Passingham, 1993). Extensive, recipro- current goals. cal projections connect the prefrontal cortex to almost The frontal cortex is present in all mammalian spe- all regions of the parietal and temporal cortex, and to cies. Evolutionarily speaking, this part of the brain has prestriate regions of the occipital cortex. The PFC also become much larger in primates relative to other mam- receives a huge input from the thalamus, relaying infor- mals (Figure 12.1). Interestingly, when compared to mation from the basal ganglia, cerebellum, and various other primate species, the expansion of prefrontal cortex brainstem nuclei. Indeed, almost all cortical and sub- in the human brain is more pronounced in the white mat- cortical areas influence the prefrontal cortex either ter (the axonal tracts) than in the gray matter (the cell through direct projections or indirectly via a few syn- bodies; Schoenemann et al., 2005). This finding suggests apses. The prefrontal cortex has many projections to the that the cognitive capabilities that are uniquely human contralateral hemisphere—projections to homologous may be due to how our brains are connected rather than prefrontal areas via the corpus callosum, as well as bilat- an increase in the number of neurons. eral projections to premotor and subcortical regions. 518 | CHAPTER 12 Cognitive Control (Shallice & Burgess, 1991) took three patients with fron- TAKE-HOME MESSAGES tal lesions to a shopping center, assigning each a short shopping list. Obtaining all the items on the list presented Cognitive control is the collection of mental abilities that involve planning, controlling, and regulating the flow of a real problem for the patients. One patient failed to pur- information processing. chase soap because the store she visited did not carry Cognitive control gives us the flexibility required for goal- her favorite brand; another wandered outside the desig- oriented behavior. nated shopping center in pursuit of an item that could The prefrontal cortex includes four major components: easily be found within the designated region. All became lateral prefrontal cortex, frontal pole, orbitofrontal cortex, embroiled in social complications. One succeeded in and medial frontal cortex. These parts of the brain have obtaining a newspaper but was pursued by the merchant become very prominent in mammals, and especially for failing to pay! in primates. Studies in animals with lesions to their prefrontal cor- tex revealed behaviors similar to those exhibited by these patients who were unable to complete a plan and were socially inappropriate. Unilateral lesions of prefrontal 12.2 Cognitive Control cortex tend to produce relatively mild deficits in these animals, but dramatic changes can be observed when Deficits PFC lesions are extended bilaterally. Consider the obser- vations of Leonardo Bianchi (1922), an Italian psychia- People with frontal lobe lesions—like W.R., the wayward trist of the early 20th century: lawyer—present a paradox. From a superficial look at The monkey which used to jump on to the window- their everyday behavior, it is frequently difficult to detect ledge, to call out to his companions, after the a neurological disorder: They do not display obvious defi- operation jumps to the ledge again, but does not cits in any of their perceptual abilities, they can execute call out. The sight of the window determines the motor actions, and their speech is fluent and coherent. reflex of the jump, but the purpose is now lacking, They are unimpaired on conventional neuropsychological for it is no longer represented in the focal point of tests of intelligence and knowledge. They generally score consciousness.... Another monkey sees the handle within the normal range on IQ tests. Their memory for of the door and grasps it, but the mental process previously learned facts is fine, and they do well on most stops at the sight of the bright colour of the handle. tests of long-term memory. With more sensitive and spe- The animal does not attempt to turn it so as to open cific tests, however, it becomes clear that frontal lesions the door.... Evidently there are lacking all those oth- can disrupt different aspects of normal cognition and er images that are necessary for the determination of memory, producing an array of problems. a series of movements coordinated towards one end. Such patients may persist in a response even after being told that it is incorrect; this behavior is known as As with W.R., the monkeys demonstrate a loss of perseveration. They may be apathetic, distractible, or goal-oriented behavior. Indeed, the behavior of these impulsive. They may be unable to make decisions, plan monkeys has become stimulus driven. The animal sees the actions, understand the consequences of their actions, ledge and jumps up; another sees the door and grasps the organize and segregate the timing of events in memory, handle, but that is the end of it. They no longer appear to remember the source of their memories, and follow rules. have a purpose for their actions. The sight of the door is They may disregard social conventions (discussed in no longer a sufficient cue to remind the animal of the food Chapter 13). Ironically, patients with frontal lobe lesions and other animals that can be found beyond it. are aware of their deteriorating social situation, have the A classic demonstration of this tendency for humans intellectual capabilities to generate ideas that may allevi- with frontal lobe injuries to exhibit stimulus-driven ate their problems, and may be able to tell you the pros behavior is evident from the clinical observations of and cons of each idea. Yet their efforts to prioritize and François Lhermitte of the Pitié-Salpêtrière Hospital in organize these ideas into a plan and put them into play Paris (Lhermitte, 1983; Lhermitte et al., 1986). Lher- are haphazard at best. Similarly, although they are not mitte invited a patient to meet him in his office. At the amnesic and can list rules from memory, they may not be entrance to the room, he had placed a hammer, a nail, able to follow them. and a picture. Upon entering the room and seeing these To demonstrate how seemingly subtle deficits in cog- objects, the patient spontaneously used the hammer and nition may snowball into severe limitations in real-world nail to hang the picture on the wall. In a more extreme situations, Tim Shallice of University College London example, Lhermitte put a hypodermic needle on his desk,  12.3 Goal-Oriented Behavior | 519 dropped his trousers, and turned his back to his patient. Whereas most people in this situation would consider TAKE-HOME MESSAGES filing ethical charges, the patient was unfazed. He simply Patients with frontal lobe lesions have difficulty executing picked up the needle and gave his doctor a healthy jab in a plan and may exhibit stimulus-driven behavior. the buttocks! Deficits in cognitive control are found in numerous psychi- Lhermitte coined the term utilization behavior to atric disorders, as well as when mental health is compro- characterize this extreme dependency on prototypical mised by situational factors such as stress or loneliness. responses for guiding behavior. The patients with frontal lobe damage retained knowledge about prototypical uses of objects such as a hammer or needle, saw the stimu- lus, and responded. They were not able to inhibit their response or flexibly change it to fit the context in which 12.3 Goal-Oriented they found themselves. Their cognitive control mecha- nisms were out of whack. Behavior Deficits in cognitive control are also considered Our actions are not aimless, nor are they entirely a hallmark of many psychiatric conditions, including automatic—dictated by events and stimuli immediately depression, schizophrenia, obsessive-compulsive dis- at hand. We choose to act because we want to accom- order (OCD), and attention deficit hyperactivity disor- plish a goal or gratify a personal need. der (ADHD; De Zeeuw & Durston, 2017), as well as Researchers distinguish between two fundamental antisocial personality disorder and psychopathy (Zeier types of actions. Goal-oriented actions are based on the et al., 2012). Even in individuals who do not have clini- assessment of an expected reward or value and the knowl- cally defined conditions, impairments in cognitive control edge that there is a causal link between the action and the become manifest when people experience stress, sad- reward (an action–outcome relationship). Most of our ness, loneliness, or poor health (reviewed in Diamond & actions are of this type. We turn on the radio when getting Ling, 2016). in the car so that we can catch the news on the drive home. A hallmark of drug or alcohol addiction is the sense We put money in the soda machine to purchase a favorite of a loss of control. One model of drug addiction suggests beverage. We resist going to the movies the night before an that disruption of PFC function underlies the charac- exam so that we can get in some extra studying, with the teristic problems addicts have in inhibiting destructive hope that this effort will lead to the desired grade. behaviors and appropriately evaluating the relevance In contrast to goal-oriented actions stand habitual of behavioral cues (Goldstein & Volkow, 2011). Hugh actions. A habit is defined as an action that is no longer Garavan and colleagues at Trinity College in Ireland con- under the control of a reward, but is stimulus driven; as ducted a series of studies to ask whether the cognitive such, we can consider it automatic. The habitual commuter control changes that occur in cocaine users would also might find herself flipping on the car radio without even manifest in the lab (Kaufman et al., 2003). In one task, thinking about the expected outcome. The action is trig- the participants viewed a stream of stimuli that alter- gered simply by the context. Its habitual nature becomes nated between two letters and were instructed to quickly obvious when our commuter reaches to switch on the press a button with the presentation of each letter. In rare radio, even though she knows it is broken. Habit-driven instances, however, the same letter was repeated on suc- actions occur in the presence of certain stimuli that trigger cessive trials. For these “no-go” trials, participants were the retrieval of well-learned associations. These associa- instructed to withhold their response. tions can be useful, enabling us to rapidly select a response, Chronic cocaine users, none of whom had used such as stopping quickly at a red light (S. A. Bunge, 2004). cocaine for 18 hours before testing, were more likely They can also develop into persistent bad habits, however, to respond on the no-go trials than were matched such as eating something every time you walk through the controls—a result that was interpreted as evidence of a kitchen or lighting up a cigarette when anxious. Habitual general problem with response inhibition. The cocaine responses make addictions difficult to break. users also showed lower activation in the medial frontal The distinction between goal-oriented actions and hab- cortex when they produced these erroneous responses. its is graded. Though the current context is likely to dictate As we will see later in this chapter, this pattern suggests our choice of action and may even be sufficient to trigger that they had difficulty monitoring their performance. a habit-like response, we are also capable of being flexible. Thus, even when the drug users were not under the influ- The soda machine might beckon invitingly, but if we are ence of cocaine and were not making choices related to on a health kick, we might just walk past it or choose to their addiction, changes in cognitive control persisted. purchase a bottle of water. These are situations in which 520 | CHAPTER 12 Cognitive Control cognitive control comes into play. Of course, if we make a Working memory task b Associative memory task the water purchase enough times, a new habit can develop. Cognitive control provides the interface through which goals influence behavior. Goal-oriented actions require processes that enable us to maintain our goal, Cue Cue and focus on the information that is relevant to achieving that response goal, ignore or inhibit irrelevant information, monitor our progress toward the goal, and shift flexibly from one sub- goal to another in a coordinated way. Wrong Wrong Food Right Right Cognitive Control Requires Delay Delay Working Memory As we learned in Chapter 9, working memory, a type of short-term memory, is the transient representation of task-relevant information—what Patricia Goldman- Rakic (1992, 1996) called the “blackboard of the mind.” Food These representations may be from the distant past, or they may be closely related to something that is currently in the environment or has been experienced recently. The term working memory refers to the temporary main- Response Cue and tenance of this information, providing an interface that response links perception, long-term memory, and action, thus enabling goal-oriented behavior and decision making. Working memory is critical when behavior is not Right Wrong exclusively stimulus driven. What is immediately in front of us surely influences our behavior, but we are not FIGURE 12.2 Working memory versus associative memory. automatons. We can (usually) hold off eating until all the Two delayed-response tasks. (a) In the working memory task, the guests sitting around the table have been served. This monkey observes one well being baited with food. The location of the food is determined randomly. After a delay period, the animal capacity demonstrates that we can represent informa- retrieves the food. (b) In the associative memory task, the food tion that is not immediately evident (in this case, social reward is always hidden under the same visual cue, and the loca- rules), in addition to reacting to stimuli that currently tions of the two cues are determined randomly. Working memory is dominate our perceptual pathways (the fragrant food and required in the first task because, at the time the animal responds, conversation). We can mind our dinner manners (stored no external cues indicate the location of the food. Long-term memory is required in the second task because the animal must knowledge) by choosing to respond to some stimuli (the remember which visual cue is associated with the reward. conversation) while ignoring other stimuli (the food). This process requires integrating current perceptual informa- tion with stored knowledge from long-term memory. placing a food morsel in one of the two wells (percep- tion). Then the two wells are covered, and a curtain is lowered to prevent the monkey from reaching toward Prefrontal Cortex Is Necessary either well. After a delay period, the curtain is raised and for Working Memory but Not the monkey is allowed to choose one of the two wells to try to recover the food. Although this appears to be a Associative Memory simple task, it demands one critical cognitive capability: The prefrontal cortex appears to be an important interface The animal must continue to retain the location of the between current perceptual information and stored knowl- unseen food during the delay period (working memory). edge, and thus constitutes a major component of the work- Monkeys with prefrontal lesions do poorly on the task. ing memory system. Its importance in working memory was Do the animals fail this task because of a general defi- first demonstrated in studies where animals with prefrontal cit in forming associations or because of a deficit in work- lesions performed a variety of delayed-response tasks. ing memory? To answer this question, a second task is In a test of spatial working memory (Figure 12.2a), a used to test associative memory by pairing the food with monkey is situated within reach of two food wells. At the a distinctive visual cue. The well with the food has a plus start of each trial, the monkey observes the experimenter sign, and the empty well has a minus sign (Figure 12.2b).  12.3 Goal-Oriented Behavior | 521 In this condition, the researcher may shift the food mor- It seems likely that many species must have some sel’s location during the delay period, but the associated ability to recognize object permanence. A species would visual cue—the food cover—will be relocated with the not survive for long if its members did not understand food. Prefrontal lesions do not disrupt performance in that a predator that had stepped behind a particular bush this task. was still there when no longer visible. Evolutionarily sig- These two tasks clarify the concept of working mem- nificant differences between species may be found in the ory (Goldman-Rakic, 1992). In the working memory capacity of the working memory, how long information task, the animal must remember the currently baited can be maintained in working memory, and the ability to location during the delay period, which it fails to do. In maintain attention. contrast, in the associative learning condition in which it succeeds, the visual cue only needs to reactivate a long- term association of which cue (the plus or minus sign) is Physiological Correlates associated with the reward. The food’s location does not need to be kept in working memory. The reappearance of of Working Memory the two visual cues can trigger the association and guide A working memory system requires a mechanism to the animal’s performance. access stored information and keep that information Another, albeit indirect, demonstration of the impor- active. The prefrontal cortex can perform both opera- tance of prefrontal cortex in working memory comes tions. In delayed-response studies, neurons in the prefron- from developmental studies. Adele Diamond of the Uni- tal cortex of monkeys show sustained activity throughout versity of Pennsylvania (1990) pointed out that a com- the delay period (Fuster & Alexander, 1971; Figure 12.3). mon indicator of conceptual intelligence, Piaget’s Object For some cells, activation doesn’t commence until after Permanence Test, is logically similar to the delayed- the delay begins and can be maintained for up to a min- response task. In this task, a child observes the experi- ute. These cells provide a neural correlate for keeping a menter hiding a reward in one of two locations. After a representation active after the triggering stimulus is no delay of a few seconds, the child is encouraged to find longer visible. the reward. Prefrontal cortex (PFC) cells could simply be pro- Children younger than a year are unable to accomplish viding a generic signal that supports representations in this task. At this age, the frontal lobes are still maturing. other cortical areas. Alternatively, they could be cod- Diamond maintained that the ability to succeed in tasks ing specific stimulus features. To differentiate between such as the Object Permanence Test parallels the devel- these possibilities, Earl Miller and his colleagues (Rao opment of the frontal lobes. Before this development et al., 1997) focused on the lateral prefrontal cortex takes place, the child acts as though the object is “out of (LPFC). They trained monkeys on a working memory sight, out of mind.” As the frontal lobes mature, the child task that required successive coding of two stimulus can be guided by representations of objects and no longer attributes: identity and location. Figure 12.4a depicts requires their presence. the sequence of events in each trial. A sample stimulus 10 s Cue Delay Go FIGURE 12.3 Prefrontal neurons can show sustained activity during delayed-response tasks. Each row represents a single trial. During the cue interval, a cue was turned on, indicating the location for a forthcoming response. The monkey was trained to withhold its response until a go signal (arrows) appeared. Each vertical tick represents an action potential. This cell did not respond during the cue interval. Rather, its activity increased when the cue was turned off, and the activity persisted until the response occurred.  522 | CHAPTER 12 Cognitive Control Fixation Sample “What” delay Test objects “Where” delay Choice a ts ts de e” de e” e e lay lay ec ec lay lay t” t” pl pl r r ha he ha he j j de de st st m m ob ob Te Te Sa Sa “W “W “W “W 100 70 90 Good location 60 Response (spikes/s) Response (spikes/s) 80 Good object 70 50 60 40 50 30 40 Poor object 20 30 Poor location 20 10 0.0 0.5 1.0 1.5 2.0 2.5 0.0 0.5 1.0 1.5 2.0 2.5 Time from sample onset (s) Time from sample onset (s) b c FIGURE 12.4 Coding of “what” and “where” information in single neurons of the LPFC in the macaque. (a) Sequence of events in a single trial. See text for details. (b) Firing profile of a neuron that shows a preference for one object over another during the “what” delay. The neuronal activity is low once the response location is cued. (c) Firing profile of a neuron that shows a preference for one location during the “where” delay. This neuron was not activated during the “what” delay. is presented, and the animal must remember the identity These results indicate that, in terms of stimulus of this object for a 1-second delay period during which attributes, cells in the LPFC exhibit task-specific selec- the screen is blank. Then, two objects are shown, one of tivity. What’s more, these LPFC cells remain active which matches the sample. The position of the matching only if the monkey uses that information for a future stimulus indicates the target location for a forthcoming action. That is, the activity of the LPFC cells is task response. The response, however, must be withheld until dependent. If the animal only has to passively view the the end of a second delay. stimuli, the response of these cells is minimal right after Within the LPFC, cells characterized as “what,” the stimulus is presented and entirely absent during the “where,” and “what–where” were observed. For delay period. Moreover, the response of these cells is example, “what” cells responded to specific objects, malleable. If the task conditions change, the same cells and this response was sustained over the delay period become responsive to a new set of stimuli (Freedman (Figure 12.4b). “Where” cells showed selectivity to et al., 2001). certain locations (Figure 12.4c). In addition, about half These cellular responses by themselves do not tell us of the cells were “what–where” cells, responding to spe- what this protracted activity means. It could be that long- cific combinations of “what” and “where” information. term representations are stored in the LPFC, and the A cell of this type exhibited an increase in firing rate activity reflects the need to keep these representations during the first delay period when the target was the pre- active during the delay. However, patients with frontal ferred stimulus, and the same cell continued to fire during lobe lesions do not have deficits in long-term memory. An the second delay period if the response was directed to a alternative hypothesis is that LPFC activation reflects a specific location. representation of the task goal and, as such, serves as an  12.3 Goal-Oriented Behavior | 523 the processing demands on working memory. After an Location: 8-second delay, a face stimulus—the probe—was pre- Parietal sented, and the participant had to decide whether the probe matched one of the faces presented during the Goal encoding period. representation The BOLD response in the LPFC bilaterally began to rise with the onset of the encoding period, and this response was maintained across the delay period, even Shape: though the screen was blank (Figure 12.6b). This lat- Inferior temporal eral prefrontal response was sensitive to the demands Color: Temporo-occipital on working memory. The sustained response during the delay period was greater when the participant had to remember three or four intact faces as compared to just one or two intact faces. We walked across By using faces, the experimenters could also compare the beautiful Golden Gate Bridge! activation in the LPFC with that observed in the fusiform face area (FFA), the inferior temporal lobe region that was discussed in Chapter 6. The BOLD responses for these two regions are shown in Figure 12.6c, where the data are combined over the different memory loads. When the stimuli were presented, either during the encoding phase or for the memory probe, the BOLD response was much stronger in the FFA than in the LPFC. During the delay FIGURE 12.5 Working memory arises from the interaction period, as noted already, the LPFC response remained of goal representations and the activation and maintenance high. of long-term knowledge. Note, however, that although a substantial drop In this example, the woman’s goal is to tell her friend about the in the FFA BOLD response occurred during the delay highlights of her recent trip to San Francisco. Her knowledge of the period, the response did not drop to baseline, thus Golden Gate Bridge requires activation of a distributed network of cortical regions that underlie the representation of long-term suggesting that the FFA continued to be active dur- memory. ing the delay period. In fact, the BOLD response in other perceptual areas of the inferior temporal cortex (not shown) actually went below baseline—the so- interface with task-relevant long-term representations in called rebound effect. Thus, although the sustained other neural regions (Figure 12.5). response was small in the FFA, it was considerably This goal representation hypothesis jibes nicely with higher than what would have been observed with non- the fact that the prefrontal cortex is extensively con- facial stimuli. nected with postsensory regions of the temporal and pari- The timing of the peak activation in the LPFC and etal cortex. By this view, we can conceptualize working the FFA is also intriguing. During encoding, the peak memory as the interaction between a prefrontal repre- response was slightly earlier in the FFA as compared sentation of the task goal and other parts of the brain that to the prefrontal cortex. In contrast, during memory contain perceptual and long-term knowledge relevant to retrieval, the peak response was slightly earlier in the that goal. This sustained interaction between prefrontal prefrontal cortex. Although this study does not allow cortex and other brain regions facilitates goal-oriented us to make causal inferences, the results are consistent behavior. with the general tenets of the model sketched in Figure This hypothesis is supported by many functional 12.5. The LPFC is critical for working memory because imaging studies. In one representative study, researchers it sustains a representation of the task goal (to remember used a variant of a delayed-response task (Figure 12.6a). faces) and works in concert with inferior temporal cortex On each trial, four stimuli were presented successively to sustain information that is relevant for achieving that for 1 second each during an encoding interval. The stimuli goal across the delay period. were either intact faces or scrambled faces. The partici- Working memory, by definition, is a dynamic pro- pants were instructed to remember only the intact faces. cess. Not only must task-relevant information be main- Thus, by varying the number of intact faces presented tained, but it is also usually important to manipulate that during the encoding interval, the researchers manipulated information. A favorite experimental task for studying  524 | CHAPTER 12 Cognitive Control Encoding Delay Retrieval + 0 2 4 6 8 10 12 14 16 Time (s) a LPFC 1.6 Encoding Delay Retrieval 1.4 LPFC FFA 0.8 BOLD signal change (%) One face 1.2 BOLD signal change (%) 0.6 Two faces 1 Three faces 0.8 0.4 Four faces 0.6 0.2 0.4 0.2 0 0 –0.2 –0.2 0 4 8 12 16 20 24 28 0 4 8 12 16 20 24 28 Time (s) Time (s) b c FIGURE 12.6 Functional MRI study of working memory. (a) In a delayed-response task, a set of intact faces and scrambled faces is presented during an encod- ing period. After a delay period, a probe stimulus is presented, and the participant indicates whether that face was part of the memory set. (b) The BOLD response in the lateral prefrontal cortex (LPFC) rises during the encoding phase and remains high during the delay period. The magnitude of this effect is related to the number of faces that must be maintained in working memory. Dotted lines indicate peaks in hemodynamic responses for encoding and retrieval. (c) The BOLD response in the LPFC and the fusiform face area (FFA) rises during the encoding and retrieval periods. The black and red dashed lines indicate the peaks of activation in the FFA and LPFC. During encoding, the peak is earlier in the FFA; during retrieval, the peak is earlier in the LPFC. the manipulation of information in working memory is Organizational Principles the n-back task (Figure 12.7). In an n-back task, the dis- play consists of a continuous stream of stimuli. Partici- of Prefrontal Cortex pants are instructed to push a button when they detect The prefrontal cortex covers a lot of brain territory. a repeated stimulus. In the simplest version (n 5 1), Whereas much of the posterior cortex can be organized responses are made when the same stimulus is presented in terms of sensory specializations (e.g., auditory versus on two successive trials. In more complicated versions, n visual regions), understanding the functional organiza- can equal 2 or more. tion of the prefrontal cortex has proved to be more chal- With n-back tasks, it is not sufficient simply to main- lenging. One hypothesis is that the anterior–posterior tain a representation of recently presented items; the gradient across the PFC follows a crude hierarchy: For working memory buffer must be updated continually to the simplest of working memory tasks, activity may be keep track of what the current stimulus must be com- limited to more posterior prefrontal regions or even sec- pared to. Tasks such as n-back tasks require both the ondary motor areas. maintenance and the manipulation of information in For example, if the task requires the participant to working memory. Activation in the LPFC increases as press one key upon seeing a flower and another upon n-back task difficulty is increased—a response consistent seeing an automobile, then these relatively simple with the idea that this region is critical for the manipula- stimulus–response rules can be sustained by the ven- tion operation. tral prefrontal cortex and lateral premotor cortex. If the  12.3 Goal-Oriented Behavior | 525 1-Back condition 2-Back condition As a heuristic, we can think of PFC function as orga- nized along three separate axes (see O’Reilly, 2010): K K 1. A ventral–dorsal gradient organized in terms of S S maintenance and manipulation, as well as in a S Response K Response manner that reflects general organizational prin- ciples observed in more posterior cortex, such as M M the ventral and dorsal visual pathways for “what” R R versus “how.” T T 2. An anterior–posterior gradient that varies in abstraction, where the more abstract representa- L L tions engage the more anterior regions (e.g., frontal Response L Response T pole), and the less abstract engage more posterior A A regions of the frontal lobes. In the extreme, we might think of the most posterior part of the frontal P P lobe, the primary motor cortex, as the point where abstract intentions are translated into concrete FIGURE 12.7 n-Back tasks. movement. In n-back tasks, responses are required only when a stimulus 3. A lateral–medial gradient related to the degree to matches one that was shown n trials earlier. The contents of work- which working memory is influenced by information ing memory must be manipulated constantly in this task because the target is updated on each trial. in the environment (more lateral) or information re- lated to personal history and emotional states (more medial). In this view, lateral regions of the PFC stimulus–response rule, however, is defined not by the integrate external information that is relevant for objects themselves, but by a color surrounding the object, current goal-oriented behavior, whereas more medial then the more anterior frontal regions are also recruited regions allow information related to motivation and (S. A. Bunge, 2004). When such contingencies are made potential reward to influence goal-oriented behavior. even more challenging by changes in the rules from one block of trials to the next, activation extends even For example, suppose it is the hottest day of summer more anterior into the frontal pole (Figure 12.8). These and you are at the lake. You think, “It would be great complex experiments demonstrate how goal-oriented to have a frosty, cold drink.” This idea starts off as an behavior can require the integration of multiple pieces of abstract desire but then is transformed into a concrete information. idea as you remember root beer floats from summer days past. This transformation entails a spread in activation Anterior from the most anterior regions of PFC to medial regions, Premotor cortex Caudal LPFC Rostral LPFC as orbitofrontal cortex helps in recalling the high value you associate with previous root beer float encounters. More posterior regions become active as you begin to develop an action plan. You become committed to the root beer float, and that goal becomes the center of working memory and thus engages the LPFC. You think about how good these drinks are at A&W restaurants, Posterior drawing on links from more ventral regions of the PFC to long-term memories associated with A&W floats. You FIGURE 12.8 Hierarchical organization of the prefrontal cortex. also draw on dorsal regions that will be essential for form- Prefrontal activation in an fMRI study began in the more posterior premotor cortex and moved anteriorly as the experimental task ing a plan of action to drive to the A&W. It’s a compli- became more complex. Activation in the premotor cortex (shown cated plan, one that no other species would come close in green) was related to the number of stimulus–response map- to accomplishing. Luckily for you, however, your PFC pings that had to be maintained. Activation in caudal LPFC (shown network is buzzing along now, highly motivated, with in yellow) was related to the contextual demands of the task. For the ability to establish the sequence of actions required example, a response to a letter might be made if the color of the to accomplish your goal. Reward is just down the road. letter were green, but not if it were white. Activation in rostral LPFC (shown in red) was related to variation in the instructions from one Network analyses have also been employed to depict scanning run to the next. For example, the rules in one run might organizational principles of brain connectivity. Jessica be reversed in the next run. Cohen and Mark D’Esposito constructed connectivity 526 | CHAPTER 12 Cognitive Control 3.0 Task Number of provincial hubs 2.5 Rest 2.0 1.5 Rest Finger tapping n-Back task 1.0 Functional Finger n-Back relatedness tapping task Number of connector hubs 16.0 12.0 8.0 4.0 Anatomical locations 0.0 Finger n-Back tapping task a b FIGURE 12.9 Changes in functional connectivity during different task states. (a) Each color represents a network of regions in which the BOLD response was correlated between nodes during rest (left), finger tapping (middle), or performance of an n-back task (right). Black lines indicate between-network edges. The top row shows the nodes in a functional space, with distances indicating the similarity between networks. The same nodes are replotted in the bottom row to depict the anatomical location of each node. A cognitive control network (red), spanning prefrontal, parietal, and temporal cortex, is much more pronounced in the n-back task. (b) Within-network connections (pro- vincial hubs, top) and between-network connections (connector hubs, bottom) are shown for each task relative to its associated rest condition. Finger tapping is associated with an increase in provincial hubs, whereas the n-back task is associated with an increase in connector hubs. maps to show the cortical networks at work during rest, during a simple motor task (finger tapping), and dur- TAKE-HOME MESSAGES ing an n-back task (J. R. Cohen & D’Esposito, 2016). Working memory can be conceptualized as the informa- Figure 12.9a shows the organization of nine anatomi- tion formed by the combination of a task goal and the cal networks in each of the three conditions (recall from perceptual and long-term knowledge relevant for achieving Chapter 3 that the number of networks varies with the that goal. This form of dynamic memory emerges from the criteria used to select them). interactions of prefrontal cortex and the rest of the brain. While the overall structure persists across the three Neurons in the PFC of monkeys show sustained activity tasks, there are some systematic differences. In particu- throughout the delay period in delayed-response tasks. lar, during the demanding n-back task, the dorsolateral These cells provide a neural correlate for keeping a represen- PFC network expands, showing marked connectivity with tation active after the triggering stimulus is no longer visible. parietal regions and areas in the ventral visual pathway. Various frameworks have been proposed to uncover Not only does the cognitive control network become functional specialization within the prefrontal cortex. more expansive during the n-back task, but the connec- Three gradients have been described to account for tion strength between networks increases, with more PFC processing differences: ventral–dorsal, anterior– voxels now classified as connector hubs (Figure 12.9b). posterior, and lateral–medial. The working memory demands of the n-back task require maintaining the goal, staying on task (attention), and keeping track of the visual stimuli. A very different pat- tern is seen in the finger-tapping task: Here, connection strength becomes greater within a network (provincial 12.4 Decision Making hubs). Thus, with the motor task, segregation of dis- Go back to the hot summer day when you thought, tinct networks is increased; in contrast, the more cogni- “Hmm... that frosty, cold drink is worth looking for. tively demanding n-back task requires integration across I’m going to get one.” That type of goal-oriented behavior networks. begins with a decision to pursue the goal. We might think  12.4 Decision Making | 527 of the brain as a decision-making device in which our that we often make decisions by following simple, effi- perceptual and memory systems evolved to support deci- cient rules (heuristics) that were sculpted and hard-coded sions that determine our actions. Our brains start making by evolution. The results of these decisions may not seem decisions as soon as our eyes flutter open in the morning: rational, at least within the context of our current, highly Do I get up now or snooze a bit longer? Do I wear shorts mechanized world. But they may seem more rational if or jeans? Do I skip class to study for an exam? Though looked at from an evolutionary perspective. humans tend to focus on complex decisions such as who Consistent with this point of view, the evidence indi- will get their vote in the next election, all animals need cates that we reach decisions in many different ways. to make decisions. Even an earthworm decides when to As we touched on earlier, decisions can be goal oriented leave a patch of lawn and move on to greener pastures. or habitual. The distinction is that goal-oriented deci- Rational observers, such as economists and math- sions are based on the assessment of expected reward, ematicians, tend to be puzzled when they consider human whereas habits, by definition, are actions taken that are behavior. To them, our behavior frequently appears in- no longer under the control of reward: We simply execute consistent or irrational, not based on what seems to be a them because the context triggers the action. A some- sensible evaluation of the circumstances and options. For what similar way of classifying decisions is to divide them instance, why would someone who is concerned about into action–outcome decisions or stimulus–response eating healthy food consume a jelly doughnut? Why would decisions. With an action–outcome decision, the deci- someone who is paying so much money for tuition skip sion involves some form of evaluation (not necessarily classes? And why are people willing to spend large sums of conscious) of the expected outcomes. After we repeat money to insure themselves against low-risk events (e.g., that action, and if the outcome is consistent, the pro- buying fire insurance even though the odds are overwhelm- cess becomes habitual; that is, it becomes a stimulus– ingly small that they will ever use it), yet equally willing to response decision. engage in high-risk behaviors (e.g., texting while driving)? Another distinction can be made between decisions The field of neuroeconomics has emerged as an inter- that are model-free or model-based. Model-based means disciplinary enterprise with the goal of explaining the that the agent has an internal representation of some neural mechanisms underlying decision making. Econ- aspect of the world and uses this model to evaluate dif- omists want to understand how and why we make the ferent actions. For example, a cognitive map would be a choices we do. Many of their ideas can be tested both model of the spatial layout of the world, enabling you to with behavioral studies and, as in all of cognitive neuro- choose an alternative path if you found the road blocked science, with data from cellular activity, neuroimaging, as you set off for the A&W restaurant. Model-free means or lesion studies. This work also helps us understand the that you have only an input–output mapping, similar to functional organization of the brain. stimulus–response decisions. Here you know that to get Theories about our decision-making processes are to the A&W, you simply look for the tall tower at the cen- either normative or descriptive. Normative decision ter of town, which is right next to the A&W. theories define how people ought to make decisions Decisions that involve other people are known as that yield the optimal choice. Very often, however, such social decisions. Dealing with other individuals tends to theories fail to predict what people actually choose. make things much more complicated—a topic we will Descriptive decision theories attempt to describe return to in Chapters 13 and 14. what people actually do, not what they should do. Our inconsistent, sometimes suboptimal choices pre- sent less of a mystery to evolutionary psychologists. Our Is It Worth It? Value modular brain has been sculpted by evolution to optimize reproduction and survival in a world that differed quite and Decision Making a bit from the one we currently occupy. In that world, A cornerstone idea in economic models of decision mak- you would never have passed up the easy pickings of a ing is that before we make a decision, we first compute jelly doughnut, something that is sweet and full of fat, the value of each option and then compare the different or engaged in exercise solely for the sake of burning off values in some way (Padoa-Schioppa, 2011). Decision valuable fat stores; conserving energy would have been a making in this framework is about making choices that much more powerful factor. Our current brains reflect will maximize value. For example, we want to obtain the this past, drawing on the mechanisms that were essential highest possible reward or payoff (Figure 12.10). It is not for survival in a world before readily available food. enough, however, to think only about the possible reward Many of these mechanisms, as with all brain functions, level. We also have to consider the likelihood of receiv- putter along below our consciousness. We are unaware ing the reward, as well as the costs required to obtain 528 | CHAPTER 12 Cognitive Control External Commodity Quantity Delay Risk Ambiguity Cost Risk Ambiguity Internal Motivation Patience attitude attitude Integration Option 1 Option 2 Comparison Choice outcome FIGURE 12.10 Decisions require the integration and evaluation of multiple factors. In this example, the person is asked to choose between two options, each of which has an inferred value. The values are determined by a weighted combination of multiple sources of information. Some sources are external to the agent— for example, will I gain (commodity), how much reward will be obtained (quantity), will I get the reward right away (delay), and how certain am I to obtain the reward (risk)? Other factors are internal to the agent—for example, am I feeling motivated (motivation), am I willing to wait for the reward (patience), is the risk worth it (risk attitude)? that reward. Although many lottery players dream of win- land a small trout or perhaps a bream. At the other spot, ning the million-dollar prize, some may forgo a chance at you’ve caught a few largemouth bass. the big money and buy a ticket with a maximum payoff Probability. How likely are you to attain the reward? You of a hundred dollars, knowing that their odds of winning might remember that the current spot almost always are much higher. yields a few catches, whereas you’ve most often come back empty-handed from the secret hole. COMPONENTS OF VALUE To figure out the neural Effort or cost. If you stay put, you can start casting right processes involved in decision making, we need to away. Getting to the fishing hole on the other side of the understand how the brain computes value and pro- lake will take an hour of scrambling up and down the cesses rewards. Some rewards, such as food, water, hillside. One form of cost that has been widely studied or sex, are primary reinforcers: They have a direct is temporal discounting. How long are you willing to wait benefit for survival fitness. Their value, or our response for a reward? You may not catch large fish at the current to these reinforcers, is, to some extent, hardwired in spot, but you could feel that satisfying tug 60 minutes our genetic code. But reward value is also flexible and sooner if you stayed where you are. shaped by experience. If you are truly starving, an item Context. This factor involves external things, like the of disgust—say, a dead mouse—suddenly takes on time of day, as well as internal things, such as whether reinforcing properties. Secondary reinforcers, such you are hungry or tired, or looking forward to an after- as money and status, are rewards that have no intrinsic noon outing with some friends. Context also includes value themselves, but become rewarding through their novelty—you might be the type who values an adventure association with other forms of reinforcement. and the possibility of finding an even better fishing hole Reward value is not a simple calculation. Value has on your way to the other side of the lake, or you might various components, both external and internal, that are be feeling cautious, eager to go with a proven winner. integrated to form an overall subjective worth. Consider Preference. You may just like one fishing spot better than this scenario: You are out fishing along the shoreline and another for its aesthetics or a fond memory. thinking about whether to walk around the lake to an As you can see, many factors contribute to subjective out-of-the-way fishing hole. Do you stay put or pack up value, and they can change immensely from person to person your gear? Establishing the value of these options requires and hour to hour. Given such variation, it is not so surprising considering several factors, all of which contribute to the that people are highly inconsistent in their decision-making representation of value: behavior. What seems irrational thinking by another indi- Payoff. What kind of reward do the options offer, and vidual might not be, if we could peek into that person’s how large is the reward? At the current spot, you might up-to-date value representation of the current choices.  12.4 Decision Making | 529 REPRESENTATION OF VALUE How and where is value neural regions. For example, in one study, OFC activa- represented in the brain? Jon Wallis and his colleagues tion was closely tied to variation in payoff, whereas acti- (Kennerley et al., 2009) looked at value representation vation in the striatum of the basal ganglia was related to in the frontal lobes of monkey brains, targeting regions effort (Croxson et al., 2009). In another study, LPFC associated with decision making and goal-oriented activation was associated with the probability of reward, behavior. While the monkey performed decision- whereas the delay between the time of the action and the making tasks, the investigators used multiple electrodes payoff was correlated with activity in the medial PFC and to record from cells in three regions: the anterior cingu- lateral parietal lobe (J. Peters & Buchel, 2009). late cortex (ACC), the lateral prefrontal cortex (LPFC), A classic finding in behavioral economics, temporal and the orbitofrontal cortex (OFC). Besides comparing discounting, is the observation that the value of a reward cellular activity in different locations, the experiment- is reduced when we have to wait to receive that reward. ers manipulated cost, probability, and payoff. The key For example, if given a choice, most people would prefer question was whether the different areas would show to immediately receive a $10 reward rather than wait a selectivity to particular dimensions. For instance, would month for $12 (even though the second option translates OFC be selective to payoff, LPFC to probability, and into an annual interest rate of 240 %). But make people ACC to cost? Or, would there be an area that coded choose between $10 now or $50 in a month, and almost overall “value” independent of the variable? everyone is willing to wait. For a given delay, there is As is often observed in neurophysiology studies, the some crossover reward level where the subjective value results were quite nuanced. Each of the three regions of an immediate reward is the same as that of a larger included cells that responded selectively to a particular amount to be paid off in the future. What would that dimension, as well as cells that responded to multiple number be for you? dimensions. Many cells, especially in the ACC, responded Given the association of the OFC with value repre- to all three dimensions (Figure 12.11). A pattern like this sentation, researchers at the University of Bologna tested suggests that these cells represent an overall measure people with lesions encompassing this region on tempo- of value. In contrast, LPFC cells usually encoded just a ral discounting tasks (Sellitto et al., 2010). For both food single decision variable, with a preference for probability. and monetary rewards, the OFC patients showed abnor- This pattern might reflect the role of this area in working mal temporal discounting in comparison to patients with memory, since probability judgments require integrating lesions outside the OFC or healthy control participants the consequences of actions over time. In contrast, OFC (Figure 12.12). Extrapolating from the graph in Figure neurons had a bias to be tuned to payoff, reflecting the 12.12c, we can see that a control participant is willing to amount of reward associated with each stimulus item. Similar studies with human participants have been 75 conducted with fMRI. Here the emphasis has been on 70 how different dimensions preferentially activate different 65 60 55 Percentage of neurons ACC 50 45 OFC 40 LPFC 35 30 25 20 15 10 +32 mm 1.0 cm 5 Probabillity Payoff Cost a b FIGURE 12.11 Cellular representation of value in the prefrontal cortex. (a) Simultaneous recordings were made from multiple electrodes that were positioned in lateral prefrontal cortex (red), orbitofrontal cortex (blue), or anterior cingulate cortex (green). (b) Cellular correlates were found for all three dimensions in each of the three regions, although the number of task-relevant neurons is different between regions. The dimensional preference varies between regions, with the LPFC preferring probability over payoff, and the OFC preferring payoff over probability.  530 | CHAPTER 12 Cognitive Control “$10 now...” “... or $12 a month from now?” –23 –17 –9 –2 6 15 23 1 7 –23 a b FIGURE 12.12 Patients with OFC lesions strongly prefer immediate rewards over delayed rewards. (a) The participant must choose either to receive an immediate 1.0 reward of modest value or to wait for a specified delay period in order With an OFC lesion, Non-FC to receive a larger reward. (b) The locations of orbitofrontal lesions in patience runs out 0.8 Healthy cotrols seven individuals are all projected here onto each of seven different after 2 weeks. OFC horizontal slices. The color bar indicates the number of lesions affect- Subjective value ing each brain region. The white horizontal lines on the sagittal view 0.6 (bottom right) indicate the level of the horizontal slices, where 23 is the most dorsal. (c) Temporal discounting function. The curve indi- 0.4 cates how much a delayed reward is discounted, relative to an imme- diate reward. The dashed line indicates when the delayed option is 0.2 discounted by 50%. For example, the healthy controls (green) and patients with lesions outside the frontal cortex (non-FC, blue) are will- 0.0 0 30 90 180 360 ing to wait 4 to 6 months to receive $100 rather than receiving an immediate payoff of $50. The patients with OFC lesions (red) are will- Time (days) c