Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.     

Evaluating choices by single neurons in the frontal lobe: outcome value encoded across multiple decision variables

Damage to the frontal lobe can cause severe decision-making impairments. A mechanism that may underlie this is that neurons in the frontal cortex encode many variables that contribute to the valuation of a choice, such as its costs, benefits and probability of success. However, optimal decision-making requires that one considers these variables, not only when faced with the choice, but also when evaluating the outcome of the choice, in order to adapt future behaviour appropriately. To examine the role of the frontal cortex in encoding the value of different choice outcomes, we simultaneously recorded the activity of multiple single neurons in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and lateral prefrontal cortex (LPFC) while subjects evaluated the outcome of choices involving manipulations of probability, payoff and cost. Frontal neurons encoded many of the parameters that enabled the calculation of the value of these variables, including the onset and offset of reward and the amount of work performed, and often encoded the value of outcomes across multiple decision variables. In addition, many neurons encoded both the predicted outcome during the choice phase of the task as well as the experienced outcome in the outcome phase of the task. These patterns of selectivity were more prevalent in ACC relative to OFC and LPFC. These results support a role for the frontal cortex, principally ACC, in selecting between choice alternatives and evaluating the outcome of that selection thereby ensuring that choices are optimal and adaptive.     

Distinct roles of three frontal cortical areas in reward-guided behavior

Functional magnetic resonance imaging was used to measure activity in three frontal cortical areas, the lateral orbitofrontal cortex (lOFC), medial orbitofrontal cortex (mOFC)/ventromedial frontal cortex (vmPFC), and anterior cingulate cortex (ACC), when expectations about type of reward, and not just reward presence or absence, could be learned. Two groups of human subjects learned 12 stimulus-response pairings. In one group (Consistent), correct performances of a given pairing were always reinforced with a specific reward outcome, whereas in the other group (Inconsistent), correct performances were reinforced with randomly selected rewards. The mOFC/vmPFC and lOFC were not distinguished by simple differences in relative preference for positive and negative outcomes. Instead lOFC activity reflected updating of reward-related associations specific to reward type; lOFC was active whenever informative outcomes allowed updating of reward-related associations, regardless of whether the outcomes were positive or negative, and the effects were greater when consistent stimulus-outcome and response-outcome mappings were present. A psychophysiological interaction analysis demonstrated changed coupling between lOFC and brain areas for visual object representation, such as perirhinal cortex, and reward-guided learning, such as the amygdala, ventral striatum, and habenula/mediodorsal thalamus. In contrast, mOFC/vmPFC activity reflected expected values of outcomes and occurrence of positive outcomes, regardless of consistency of outcome mappings. The third frontal cortical region, the ACC, reflected the use of reward type information to guide response selection. ACC activity reflected the probability of selecting the correct response, was greater when consistent outcome mappings were present, and was related to individual differences in propensity to select the correct response.     

Neuronal activity of the anterior cingulate cortex during an observation-based decision making task in monkeys

The medial prefrontal cortex (mPFC) including the anterior cingulate sulcus is implicated in both decision-making and social cognition, suggesting that this area may play a central role in decision-making based on social context. In the present study, neural activity was recorded from the monkey anterior cingulate cortex (ACC) while the monkeys chose one of two identical figures based on the choice previously made by a robot arm. Monkeys observed that the robot touched one of the two figures in the left or right side of a touch screen. Every time the robot chose the correct option, the same pair appeared on another touch screen for the monkey. Then, the monkey had to touch the figure in the same side to obtain reward. Neuronal responses were compared by one-way ANOVA among 17 intervals distributed in 4 phases: baseline before the trial, observation phase (robot arm choices and feedback signals), inter-phase interval (between observation and following execution phases), and execution phase (monkeys choices and associated outcomes). Of 264 neurons recorded, 164 (62.12%) responded in one or more intervals of the task. Of these, 16 responded during the observation-phase, 5 during the inter-phase interval, 98 during the execution-phase and 18 on both observation and execution phases. Furthermore, neuronal activity of 69 (26.14%) neurons during action observation was correlated with that during real action (execution). This type of neurons might correspond to mirror neurons. The results indicated that the ACC processes information about self and others actions and outcomes, which may support social-based decision-making.     

Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents.

BACKGROUND: Functional disturbances in reward-related brain systems are thought to play a role in the development of mood, impulse, and substance-abuse disorders. Studies in nonhuman primates have identified brain regions, including the dorsal/ventral striatum and orbital-frontal cortex, in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level-dependent (BOLD) responses in these regions during functional magnetic resonance imaging (fMRI) paradigms; however, no previous studies indicate whether comparable modulations of neural activity exist in the brain reward systems of children and adolescents. METHODS: We used event-related fMRI and a behavioral paradigm modeled on previous work in adults to study brain responses to monetary gains and losses in psychiatrically healthy children and adolescents as part of a program examining the neural substrates of anxiety and depression in youth. RESULTS: Regions and time-courses of reward-related activity were similar to those observed in adults with condition-dependent BOLD changes in the ventral striatum and lateral and medial orbital-frontal cortex; specifically, these regions showed larger responses to positive than to negative feedback. CONCLUSIONS: These results provide further evidence for the value of event-related fMRI in examining reward systems of the brain, demonstrate the feasibility of this approach in children and adolescents, and establish a baseline from which to understand the pathophysiology of reward-related psychiatric disorders in youth.     

Common and distinct networks underlying reward valence and processing stages: a meta-analysis of functional neuroimaging studies

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore take distributed and interrelated representations of reward valuation and valence assessment into account.     

Enhanced affective brain representations of chocolate in cravers vs. non-cravers

To examine the neural circuitry involved in food craving, in making food particularly appetitive and thus in driving wanting and eating, we used fMRI to measure the response to the flavour of chocolate, the sight of chocolate and their combination in cravers vs. non-cravers. Statistical parametric mapping (SPM) analyses showed that the sight of chocolate produced more activation in chocolate cravers than non-cravers in the medial orbitofrontal cortex and ventral striatum. For cravers vs. non-cravers, a combination of a picture of chocolate with chocolate in the mouth produced a greater effect than the sum of the components (i.e. supralinearity) in the medial orbitofrontal cortex and pregenual cingulate cortex. Furthermore, the pleasantness ratings of the chocolate and chocolate-related stimuli had higher positive correlations with the fMRI blood oxygenation level-dependent signals in the pregenual cingulate cortex and medial orbitofrontal cortex in the cravers than in the non-cravers. To our knowledge, this is the first study to show that there are differences between cravers and non-cravers in their responses to the sensory components of a craved food in the orbitofrontal cortex, ventral striatum and pregenual cingulate cortex, and that in some of these regions the differences are related to the subjective pleasantness of the craved foods. Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.     

The influence of emotion regulation on decision-making under risk

Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison with trials where decisions were made in the absence of cognitive regulation. Additionally, BOLD responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum) and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse).     

Dissociation of BOLD responses to reward prediction errors and reward receipt by a model comparison

The representation of reward anticipation and reward prediction errors is the basis for reward-associated learning. The representation of whether or not a reward occurred (reward receipt) is important for decision making. Recent studies suggest that, while reward anticipation and reward prediction errors are encoded in the midbrain and the ventral striatum, reward receipts are encoded in the medial orbitofrontal cortex. In order to substantiate this functional specialization we analyzed data from an fMRI study in which 59 subjects completed two simple monetary reward paradigms. Because reward receipts and reward prediction errors were correlated, a statistical model comparison was applied separating the effects of the two. Reward prediction error fitted BOLD responses significantly better than reward receipt in the midbrain and the ventral striatum. Conversely, reward receipt fitted BOLD responses better in the orbitofrontal cortex. Activation related to reward anticipation was found in the orbitofrontal cortex. The results confirm a functional specialization of behaviorally important aspects of reward processing within the mesolimbic dopaminergic system.     

The affective and cognitive processing of touch, oral texture, and temperature in the brain

Some of the principles of the representation of affective touch in the brain are described. Positively affective touch and temperature are represented in parts of the orbitofrontal and pregenual cingulate cortex. The orbitofrontal cortex is implicated in some of the affective aspects of touch that may be mediated through C fibre touch afferents, in that it is activated more by light touch to the forearm (a source of C-tactile (CT) afferents) than by light touch to the glabrous skin of the hand. Oral somatosensory afferents implicated in sensing the texture of food including fat in the mouth also activate the orbitofrontal and pregenual cingulate cortex, as well as the insular taste cortex. Top-down cognitive modulation of the representation of affective touch produced by word labels is found in parietal cortex area 7, the insula and ventral striatum. The cognitive labels also influence activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum.     

TOWARD THE APPLICATION OF FUNCTIONAL NEUROIMAGING TO INDIVIDUALIZED TREATMENT FOR ANXIETY AND DEPRESSION

Functional neuroimaging has led to significant gains in understanding the biological bases of anxiety and depressive disorders. However, the ability of functional neuroimaging to directly impact clinical practice is unclear. One important method by which neuroimaging could impact clinical care is to generate single patient level predictions that can guide clinical decision‐making. The present review summarizes published functional neuroimaging studies of predictors of medication or psychotherapy outcome in major depressive disorder, obsessive‐compulsive disorder (OCD), posttraumatic stress disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder. In major depressive disorder and OCD, there is converging evidence of specific brain circuitry that has both been implicated in the disordered state itself, and where pretreatment activation levels have been predictive of treatment response. Specifically, in major depressive disorder, greater pretreatment ventral and pregenual anterior cingulate cortex (ACC) activation may predict better antidepressant medication outcome but poorer psychotherapy outcome. In OCD, activation in the ACC and orbitofrontal cortex has been inversely associated with pharmacological treatment response. In other anxiety disorders, research in this area is just beginning, with the ACC potentially implicated. However, the question of whether these results can directly translate to clinical practice remains open. In order to achieve the goal of single patient level prediction and individualized treatment, future research should strive to establish replicable models with good predictive performance and clear incremental validity.     

Reward-related neural responses are dependent on the beneficiary

Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons’ gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship.     

Emotion regulation reduces loss aversion and decreases amygdala responses to losses

Emotion regulation strategies can alter behavioral and physiological responses to emotional stimuli and the neural correlates of those responses in regions such as the amygdala or striatum. The current study investigates the brain systems engaged when using an emotion regulation technique during financial decisions. In decision making, regulating emotion with reappraisal-focused strategies that encourage taking a different perspective has been shown to reduce loss aversion as observed both in choices and in the relative arousal responses to actual loss and gain outcomes. In the current study, we find using fMRI that behavioral loss aversion correlates with amygdala activity in response to losses relative to gains. Success in regulating loss aversion also correlates with the reduction in amygdala responses to losses but not to gains. Furthermore, across both decisions and outcomes, we find the reappraisal strategy increases baseline activity in dorsolateral and ventromedial prefrontal cortex and the striatum. The similarity of the neural circuitry observed to that seen in emotion regulation, despite divergent tasks, serves as further evidence for a role of emotion in decision making, and for the power of reappraisal to change assessments of value and thereby choices.     

Choice selection and reward anticipation: an fMRI study

We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA 11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation.     

Outcome representations, counterfactual comparisons and the human orbitofrontal cortex: implications for neuroimaging studies of decision-making

Recent research suggests that the primate orbitofrontal cortex (OFC) is critical for representations of outcomes of actions and their subsequent impact on the control of behavior. In parallel, a recent theory of decision-making called decision affect theory (Mellers, Schwartz, and Ritov, Psychological Science, 1997) emphasizes the role of anticipated affective impact of outcomes in guiding choices, and the effects of comparisons with alternative outcomes (i.e., counterfactual effects). In the context of decision affect theory, we present results from two event-related functional MRI experiments consistent with two hypotheses regarding the role of the human OFC in guiding behavior through outcome representation: (1) counterfactual effects are manifested in the human OFC during expectation of outcomes, such that the anticipated affective impact of outcomes is modulated by the nature of the various possible alternative outcomes; (2) a regional specialization exists in the human prefrontal cortex, such that affective impact of potential negative outcomes of actions is represented mainly by the lateral areas of the OFC, while areas situated progressively more medial and dorsal on the ventral and medial PFC are specifically involved in representing the impact of positively valenced outcomes. We also discuss some of the implications that these hypotheses have for neuroimaging studies of reward processing and decision-making, and for studies of neuropsychiatric disorders in which these processes are thought to be disturbed.     

Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement

The orbitofrontal cortex and adjacent ventromedial prefrontal cortex carry reward representations and mediate flexible behaviour when circumstances change. Here we review how recent experiments in humans and macaques have confirmed the existence of a major difference between the functions of the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex (mOFC) on the one hand and the lateral orbitofrontal cortex (lOFC) on the other. These differences, however, may not be best accounted for in terms of specializations for reward and error/punishment processing as is commonly assumed. Instead we argue that both lesion and functional magnetic resonance imaging studies reveal that the lOFC is concerned with the assignment of credit for both reward and error outcomes to the choice of specific stimuli and with the linking of specific stimulus representations to representations of specific types of reward outcome. By contrast, we argue that the ventromedial prefrontal cortex/mOFC is concerned with evaluation, value-guided decision-making and maintenance of a choice over successive decisions. Despite the popular view that they cause perseveration of behaviour and inability to inhibit repetition of a previously made choice, we found that lesions in neither orbitofrontal subdivision caused perseveration. On the contrary, lesions in the lOFC made animals switch more rapidly between choices when they were finding it difficult to assign reward values to choices. Lesions in the mOFC caused animals to lose their normal predisposition to repeat previously successful choices, suggesting that the mOFC does not just mediate value comparison in choice but also facilitates maintenance of the same choice if it has been successful.     

Altered neural reward and loss processing and prediction error signalling in depression

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.     

Neurons in the frontal lobe encode the value of multiple decision variables

A central question in behavioral science is how we select among choice alternatives to obtain consistently the most beneficial outcomes. Three variables are particularly important when making a decision: the potential payoff, the probability of success, and the cost in terms of time and effort. A key brain region in decision making is the frontal cortex as damage here impairs the ability to make optimal choices across a range of decision types. We simultaneously recorded the activity of multiple single neurons in the frontal cortex while subjects made choices involving the three aforementioned decision variables. This enabled us to contrast the relative contribution of the anterior cingulate cortex (ACC), the orbito-frontal cortex, and the lateral prefrontal cortex to the decision-making process. Neurons in all three areas encoded value relating to choices involving probability, payoff, or cost manipulations. However, the most significant signals were in the ACC, where neurons encoded multiplexed representations of the three different decision variables. This supports the notion that the ACC is an important component of the neural circuitry underlying optimal decision making.     

Neuronal correlates of reward and loss in Cluster B personality disorders: a functional magnetic resonance imaging study

Decision making is guided by the likely consequences of behavioural choices. Neuronal correlates of financial reward have been described in a number of functional imaging studies in humans. Areas implicated in reward include ventral striatum, dopaminergic midbrain, amygdala and orbitofrontal cortex. Response to loss has not been as extensively studied but may involve prefrontal and medial temporal cortices. It has been proposed that increased sensitivity to reward and reduced sensitivity to punishment underlie some of the psychopathology in impulsive personality disordered individuals. However, few imaging studies using reinforcement tasks have been conducted in this group. In this fMRI study, we investigate the effects of positive (monetary reward) and negative (monetary loss) outcomes on BOLD responses in two target selection tasks. The experimental group comprised eight people with Cluster B (antisocial and borderline) personality disorder, whilst the control group contained fourteen healthy participants. A key finding was the absence of prefrontal responses and reduced BOLD signal in the subcortical reward system in the PD group during positive reinforcement. Impulsivity scores correlated negatively with prefrontal responses in the PD but not the control group during both, reward and loss. Our results suggest dysfunctional responses to rewarding and aversive stimuli in Cluster B personality disordered individuals but do not support the notion of hypersensitivity to reward and hyposensitivity to loss.     

From affective value to decision-making in the prefrontal cortex

Representing the affective value of a reward on a continuous scale may occur separately from making a binary, for example yes vs no, decision about whether to choose the reward. To investigate whether these are separable processes, we used functional magnetic resonance imaging to measure activations produced by pleasant warm, unpleasant cold, and affectively complex combinations of these stimuli applied to the hand. On some trials the affective value was rated on a continuous scale, and on different trials a yes-no decision was made about whether the stimulus should be repeated in future. Decision-making contrasted with just rating the affective stimuli revealed activations in the medial prefrontal cortex area 10, implicating this area in binary decision-making. Activations related to the pleasantness ratings and which were not influenced when a binary decision was made were found in the pregenual cingulate and parts of the orbitofrontal cortex, implicating these regions in the continuous representation of affective value. When a decision was yes vs. no, effects were found in the dorsal cingulate cortex, agranular (anterior) insula and ventral tegmental area, implicating these areas in initiating actions to obtain goals.