Early orbitofrontal hyperactivation in obsessive-compulsive disorder

Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects. However, it is unclear whether OFC activation is dysfunctional at an early stage in patients with OCD. We investigated early electrical OFC activation evoked by reward and punishment feedback in a visual probabilistic object reversal task (pORT). Patients with OCD (n=23) and healthy controls (n=27), matched for gender, age and educational level, performed the pORT during a 29-channel electroencephalographic recording. Low resolution brain electromagnetic tomography was applied to localize orbitofrontal sources of neuronal activity at 80 to 200 ms post-stimulus. Group comparison showed significantly higher orbitofrontal activation in OCD patients at 100-120 ms after the reward stimulus. No group differences were found with respect to OFC activation in response to punishment stimuli and in task performance. Results substantiate dysfunctional OFC activity at a very early stage in the processing of reward stimuli in patients with OCD. Our results provide support for the assumption that the OFC plays a more active role in the processing of visual stimuli as previously supposed. As orbitofrontal hyperactivation following rewarding feedback occurred as early as 100 ms after receipt of the visual stimulus in patients with OCD, and as we did not find any OFC dysfunction following negative feedback, our findings may point towards a specific early disturbance of reward processing in OCD. This finding might have implications for cognitive behavioural therapy of this disorder.     

Influence of ventral tegmental area input on cortico‐subcortical networks underlying action control and decision making

It is argued that the mesolimbic system has a more general function in processing all salient events, including and extending beyond rewards. Saliency was defined as an event that is unexpected due to its frequency of occurrence and elicits an attentional‐behavioral switch. Using functional magnetic resonance imaging (fMRI), signals were measured in response to the modulation of salience of rewarding and nonrewarding events during a reward‐based decision making task, the so called desire‐reason dilemma paradigm (DRD). Replicating previous findings, both frequent and infrequent, and therefore salient, reward stimuli elicited reliable activation of the ventral tegmental area (VTA) and ventral striatum (vStr). When immediate reward desiring contradicted the superordinate task‐goal, we found an increased activation of the VTA and vStr when the salient reward stimuli were presented compared to the nonsalient reward stimuli, indicating a boosting of activation in these brain regions. Furthermore, we found a significantly increased functional connectivity between the VTA and vStr, confirming the boosting of vStr activation via VTA input. Moreover, saliency per se without a reward association led to an increased activation of brain regions in the mesolimbic reward system as well as the orbitofrontal cortex (OFC), inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC). Finally, findings uncovered multiple increased functional interactions between cortical saliency‐processing brain areas and the VTA and vStr underlying detection and processing of salient events and adaptive decision making.     

Beauty in a smile: the role of medial orbitofrontal cortex in facial attractiveness

The attractiveness of a face is a highly salient social signal, influencing mate choice and other social judgements. In this study, we used event-related functional magnetic resonance imaging (fMRI) to investigate brain regions that respond to attractive faces which manifested either a neutral or mildly happy face expression. Attractive faces produced activation of medial orbitofrontal cortex (OFC), a region involved in representing stimulus-reward value. Responses in this region were further enhanced by a smiling facial expression, suggesting that the reward value of an attractive face as indexed by medial OFC activity is modulated by a perceiver directed smile.     

Medial orbitofrontal cortex codes relative rather than absolute value of financial rewards in humans

Functional imaging studies in recent years have confirmed the involvement of orbitofrontal cortex (OFC) in human reward processing and have suggested that OFC responses are context-dependent. A seminal electrophysiological experiment in primates taught animals to associate abstract visual stimuli with differently valuable food rewards. Subsequently, pairs of these learned abstract stimuli were presented and firing of OFC neurons to the medium-value stimulus was measured. OFC firing was shown to depend on the relative value context. In this study, we developed a human analogue of this paradigm and scanned subjects using functional magnetic resonance imaging. The analysis compared neuronal responses to two superficially identical events, which differed only in terms of the preceding context. Medial OFC response to the same perceptual stimulus was greater when the stimulus predicted the more valuable of two rewards than when it predicted the less valuable. Additional responses were observed in other components of reward circuitry, the amygdala and ventral striatum. The central finding is consistent with the primate results and suggests that OFC neurons code relative rather than absolute reward value. Amygdala and striatal involvement in coding reward value is also consistent with recent functional imaging data. By using a simpler and less confounded paradigm than many functional imaging studies, we are able to demonstrate that relative financial reward value per se is coded in distinct subregions of an extended reward and decision-making network.     

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas

Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.     

Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder

Mood abnormalities related to major depressive disorder (MDD) seem to result from disturbances in pathways connecting the fronto-limbic and subcortical, both regions known to be involved in the processing of emotional information. Using functional magnetic resonance imaging (fMRI), we measured neural responses to viewing images of sad, angry and neutral faces in 21 patients with MDD and 15 healthy controls. When shown pictures of sad faces, patients with MDD relative controls showed decreased activations bilaterally in the dorsolateral prefrontal cortex, inferior orbitofrontal cortex (OFC), medial OFC, caudate, and hippocampus. We also found significant group differences under the angry face condition, bilaterally, in the inferior OFC and medial OFC areas. Our findings indicate that decreased activations in the fronto-limbic and subcortical regions in response to affectively negative stimuli may be associated with pathophysiology of MDD.     

Development of alcohol-associated cues and cue-induced brain activation in alcoholics.

The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.     

Brain systems for assessing facial attractiveness

Attractiveness is a facial attribute that shapes human affiliative behaviours. In a previous study we reported a linear response to facial attractiveness in orbitofrontal cortex (OFC), a region involved in reward processing. There are strong theoretical grounds for the hypothesis that coding stimulus reward value also involves the amygdala. The aim of the present investigation is to address whether the amygdala is also sensitive to reward value in faces, indexed as facial attractiveness. We hypothesized that contrary to the linear effects reported previously in OFC, the amygdala would show a non-linear effect of attractiveness by responding to both high and low attractive faces relative to middle attractive faces. Such a non-linear response would explain previous failures to report an amygdala response to attractiveness. Human subjects underwent fMRI while they were presented with faces that varied in facial attractiveness where the task was either to rate faces for facial attractiveness or for age. Consistent with our hypothesis, right amygdala showed a predicted non-linear response profile with greater responses to highly attractive and unattractive faces compared to middle-ranked faces, independent of task. Distinct patterns of activity were seen across different regions of OFC, with some sectors showing linear effects of attractiveness, others exhibiting a non-linear response profile and still others demonstrating activation only during age judgments. Significant effects were also seen in medial prefrontal and paracingulate cortices, posterior OFC, insula, and superior temporal sulcus during explicit attractiveness judgments. The non-linear response profile of the amygdala is consistent with a role in sensing the value of social stimuli, a function that may also involve specific sectors of the OFC.     

Neuronal correlates and serotonergic modulation of behavioural inhibition and reward in healthy and antisocial individuals

Individuals with antisocial personality disorder (ASPD) are impulsive and show impairment in reinforcement processing. There is increasing evidence for a neurobiological basis of psychopathy, which shares some of the characteristics of ASPD, but research on the neuronal correlates of neuropsychological processes in ASPD remains limited. Furthermore, no research has examined the effects of serotonergic manipulation on brain activations in antisocial groups. In this study, 25 male participants with ASPD (mean age 42.1) and 32 male control participants (mean age 30.5; 25 participants providing usable scans) were randomly allocated to receive the 5-HT_2C-agonist mCPP or placebo. Participants were scanned using functional magnetic resonance imaging (fMRI) during a behavioural inhibition (Go/NoGo) and a reward task. In comparison to healthy controls the ASPD group showed reduced task related activations in the dorsolateral prefrontal cortex (DLPFC) but increased signal in the pre/subgenual anterior cingulate cortex (ACC) in the Go/No-Go task and increased activation in OFC in the reward task. mCPP modulated brain responses in both tasks in the whole group. Interactions between group and drug occured in bilateral OFC, caudate and ventral pallidum during the reward task but no significant interactions were found in the Go/No-Go task. This suggests that ASPD involves altered serotonin modulation of reward, but not motor inhibition pathways. These findings suggest that ASPD involves altered DLPFC, ACC and OFC function. Altered serotonergic modulation of reward pathways seen in the ASPD group raises the possibility that targeting serotonin systems may be therapeutic.     

The neural coding of expected and unexpected monetary performance outcomes: dissociations between active and observational learning

Successful adaptation to the environment requires the learning of stimulus-response-outcome associations. Such associations can be learned actively by trial and error or by observing the behaviour and accompanying outcomes in other persons. The present study investigated similarities and differences in the neural mechanisms of active and observational learning from monetary feedback using functional magnetic resonance imaging. Two groups of 15 subjects each - active and observational learners - participated in the experiment. On every trial, active learners chose between two stimuli and received monetary feedback. Each observational learner observed the choices and outcomes of one active learner. Learning performance as assessed via active test trials without feedback was comparable between groups. Different activation patterns were observed for the processing of unexpected vs. expected monetary feedback in active and observational learners, particularly for positive outcomes. Activity for unexpected vs. expected reward was stronger in the right striatum in active learning, while activity in the hippocampus was bilaterally enhanced in observational and reduced in active learning. Modulation of activity by prediction error (PE) magnitude was observed in the right putamen in both types of learning, whereas PE related activations in the right anterior caudate nucleus and in the medial orbitofrontal cortex were stronger for active learning. The striatum and orbitofrontal cortex thus appear to link reward stimuli to own behavioural reactions and are less strongly involved when the behavioural outcome refers to another person's action. Alternative explanations such as differences in reward value between active and observational learning are also discussed.     

Ventrolateral prefrontal cortex and the effects of task demand context on facial affect appraisal in schizophrenia

Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.     

Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task

An important function of the prefrontal cortex (PFC) is the control of goal-directed behaviour. This requires information as to whether actions were successful in obtaining desired outcomes such as rewards. While lesion studies implicate a particular PFC region, the orbitofrontal cortex (OFC), in reward processing, neurons encoding reward have been reported in both the OFC and the dorsolateral prefrontal cortex (DLPFC). To compare and contrast their roles, we recorded simultaneously from both areas while two rhesus monkeys (Macaca mulatta) performed a reward preference task. The monkeys had to choose between pictures associated with different amounts of a juice reward. Neuronal activity in both areas reflected the reward amount. However, neurons in the DLPFC encoded both the reward amount and the monkeys' forthcoming response, while neurons in the OFC more often encoded the reward amount alone. Further, reward selectivity arose more rapidly in the OFC than the DLPFC. These results are consistent with reward information entering the PFC via the OFC, where it is passed to the DLPFC and used to control behaviour.     

Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing

Liu J, Blond BN, van Dyck LI, Spencer L, Wang F, Blumberg HP. Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing.
Bipolar Disord 2012: 14: 432–441. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Convergent evidence supports limbic, anterior paralimbic, and prefrontal cortex (PFC) abnormalities in emotional processing in bipolar disorder (BD) and suggests that some abnormalities are mood‐state dependent and others persist into euthymia. However, few studies have assessed elevated, depressed, and euthymic mood states while individuals processed emotional stimuli of varying valence to investigate trait‐ and state‐related neural system responses. Here, regional brain responses to positive, negative, and neutral emotional stimuli were assessed in individuals with BD during elevated, depressed, and euthymic mood states. Methods: One hundred and thirty‐four subjects participated in functional magnetic resonance imaging scanning while processing faces depicting happy, fearful, and neutral expressions: 76 with BD (18 in elevated mood states, 19 depressed, 39 euthymic) and 58 healthy comparison (HC) individuals. Analyses were performed for BD trait‐ and mood state‐related features. Results: Ventral anterior cingulate cortex (VACC), orbitofrontal cortex (OFC), and ventral striatum responses to happy and neutral faces were decreased in the BD group, compared to the HC group, and were not influenced by mood state. Elevated mood states were associated with decreased right rostral PFC activation to fearful and neutral faces, and depression was associated with increased left OFC activation to fearful faces. Conclusions: The findings suggest that abnormal VACC, OFC, and ventral striatum responses to happy and neutral stimuli are trait features of BD. Acute mood states may be associated with additional lateralized abnormalities of diminished right rostral PFC responses to fearful and neutral stimuli in elevated states and increased left OFC responses to fearful stimuli in depressed states.     

Prefrontal cortical response to emotional faces in individuals with major depressive disorder in remission

Abnormalities in the response of the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to negative emotional stimuli have been reported in acutely depressed patients. However, there is a paucity of studies conducted in unmedicated individuals with major depressive disorder in remission (rMDD) to assess whether these are trait abnormalities. To address this issue, 19 medication-free rMDD individuals and 20 healthy comparison (HC) participants were scanned using functional magnetic resonance imaging while performing an implicit emotion processing task in which they labeled the gender of faces depicting negative (fearful), positive (happy) and neutral facial expressions. The rMDD and HC groups were compared using a region-of-interest approach for two contrasts: fear vs. neutral and happy vs. neutral. Relative to HC, rMDD showed reduced activation in left OFC and DLPFC to fearful (vs. neutral) faces. Right DLPFC activation to fearful (vs. neutral) faces in the rMDD group showed a significant positive correlation with duration of euthymia. The findings support deficits in left OFC and DLPFC responses to negative emotional stimuli during euthymic periods of MDD, which may reflect trait markers of the illness or a 'scar' due to previous depression. Recovery may also be associated with compensatory increases in right DLPFC functioning.     

Distinct orbitofrontal regions encode stimulus and choice valuation

The weak axiom of revealed preferences suggests that the value of an object can be understood through the simple examination of choices. Although this axiom has driven economic theory, the assumption of equation between value and choice is often violated. fMRI was used to decouple the processes associated with evaluating stimuli from evaluating one's actions. Whereas activity in left posterior areas of the orbitofrontal cortex (OFC) was associated with processing the objective value of stimuli, activity in medial anterior areas of the OFC was associated with accepting high value gambles and rejecting low value gambles; that is, making correct decisions. These data demonstrate that distinct areas of the OFC provide dissociated representations for use in adaptive decision-making and suggest an important processing distinction between the concepts of good/bad and right/wrong.     

The human orbitofrontal cortex monitors outcomes even when no reward is at stake

The orbitofrontal cortex (OFC) processes the occurrence or omission of anticipated rewards, but clinical evidence suggests that it might serve as a generic outcome monitoring system, independent of tangible reward. In this positron emission tomography (PET) study, normal human subjects performed a series of tasks in which they simply had to predict behind which one of two colored rectangles a drawing of an object was hidden. While all tasks involved anticipation in that they had an expectation phase between the subject's prediction and the presentation of the outcome, they varied with regards to the uncertainty of outcome. No comment on the correctness of the prediction, no record of ongoing performance, and no reward, not even a score, was provided. Nonetheless, we found strong activation of the OFC: in comparison with a baseline task, the left anterior medial OFC showed activation in all conditions, indicating a basic role in anticipation; the left posterior OFC was activated in all tasks with some uncertainty of outcome, suggesting a role in the monitoring of outcomes; the right medial OFC showed activation exclusively during guessing. The data indicate a generic role of the human OFC, with some topical specificity, in the generation of hypotheses and processing of outcomes, independent of the presence of explicit reward.     

Long- and short-range reward expectancy in the primate orbitofrontal cortex

The orbitofrontal cortex (OFC) is important in motivation and emotion. We previously reported reward expectancy-related delay activities during a delayed reaction time task in primate OFC neurons. To further investigate the significance of the OFC in motivational operations, we examined pre-instruction, baseline activities of OFC neurons in relation to reward expectancy during the delayed reaction time task. In this task, an instruction cue indicated whether reward would be present or absent in the trial. Each set of four consecutive trials constituted one block within which three different kinds of rewards and one trial with no reward were given in a fixed order that differed from the monkey's reward preference. We identified two types of OFC neurons with reward expectancy-related pre-instruction activities: Step-type neurons showed stepwise changes (increase or decrease) in pre-instruction activity toward the trial with a particular outcome, which usually was the most or least attractive within a block; Pref-type neurons showed pre-instruction activity changes according to the monkey's preference for each trial's outcome. We propose that Step-type and Pref-type neurons are related to long-range and short-range reward expectancies of a particular outcome, respectively. The OFC is considered to play important roles in goal-directed behaviour by adjusting the motivational level toward a certain (current or future) outcome of a particular motivational significance based on the two kinds of reward expectancy processes. Impairments in goal-directed behaviour by OFC patients may be caused by a lack of long-range expectancy or by a deficit in compromising between short-range and long-range expectancies.     

Differential representation of Pavlovian–instrumental transfer by prefrontal cortex subregions and striatum

Environmental cues that once predicted reward can restore extinguished behavior directed toward that reward. This process may be modeled by the Pavlovian–instrumental transfer (PIT) paradigm where a previously learned Pavlovian conditioned stimulus (CS) elicits a representation of the reward associated with that CS, prompts motivation toward the absent reward, and triggers an instrumental action. We recorded in the medial and orbital prefrontal cortex (mPFC and OFC) and dorsal striatum (DS) of freely moving rats during PIT and found that a Pavlovian CS, as compared with neutral or no stimuli, amplified the phasic neuronal responses to instrumental nosepokes ('transfer' event). In mPFC and OFC, but not the DS, representation of the transfer event correlated with the strength of PIT behavior. Neurons in all three regions showed CS-selective amplification of Pavlovian approaches toward the reward delivery site. Whereas striatal neurons represented transfer and approach behavior through mostly segregated neuronal subsets, overlapping subsets represented these events in the mPFC and OFC. These findings suggest that parallel phasic activation of mPFC and OFC neuronal subsets participates in the transfer from Pavlovian incentives to instrumental actions.     

Selective prefrontal serotonin depletion impairs acquisition of a detour-reaching task

We have recently shown that serotonin in the primate orbitofrontal cortex (OFC) contributes to the flexible control of behaviour. 5,7-dihydroxytryptamine-induced 5-HT depletions of OFC impair performance on a serial reversal discrimination task [Clarke et al. (2004)Science, 304, 878-880]. The deficit is characterized by perseverative responding to the previously rewarded stimulus, a deficit similar to that seen following lesions of the intrinsic neurones of the OFC [Dias et al. (1996)Nature, 380, 69-72]. The effect is neurochemically selective as dopaminergic lesions of the OFC, induced by 6-hydroxydopamine, have no effect [Clarke et al. (2006)Cerebral Cortex]. In order to test for the generality of the effect of serotonin on orbitofrontal processing and, in particular, its effects on flexible behaviour, the present study investigated the effects of serotonin depletions of OFC on performance of another task dependent upon an intact OFC, the detour-reaching task [Wallis et al. (2001)European Journal of Neuroscience, 13, 1797-1808]. Successful performance of this task requires inhibition of the animal's prepotent response tendency to reach directly along its line of sight to the reward. Compared with sham-operated controls, we found that lesioned monkeys made significantly more barrier reaches directly along their line of sight to the visible reward during task acquisition. This finding provides further support for the role of prefrontal serotonin in inhibitory control processes specifically in tasks sensitive to OFC dysfunction.     

Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

Nusslock R, Almeida JRC, Forbes EE, Versace A, Frank E, LaBarbara EJ, Klein CR, Phillips ML. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults. Bipolar Disord 2012: 14: 249–260. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar disorder may be characterized by a hypersensitivity to reward‐relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward‐processing and approach‐related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods: Twenty‐one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card‐guessing paradigm designed to examine reward‐related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results: Region‐of‐interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right‐sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward relative to healthy controls (p < 0.05, corrected). Whole‐brain analyses indicated that bipolar disorder, relative to healthy, participants also displayed elevated left‐lateral OFC (BA 47) activity during reward anticipation (p < 0.05, corrected). Conclusions: Elevated ventral striatal and OFC activity during reward anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward‐relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward‐related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness.