Impact of aging on frontostriatal reward processing

Healthy aging is associated with a progressive decline across a range of cognitive functions. An important factor underlying this decline may be the age‐related impairment in stimulus–reward processing. Several studies have investigated age‐related effects, but compared young versus old subjects. This is the first study to investigate the effect of aging on brain activation during reward processing within a continuous segment of the adult life span. We scanned 49 healthy adults aged 40–70 years, using functional MRI. We adopted a simple reward task, which allowed separate evaluation of neural responses to reward anticipation and receipt. The effect of reward on performance accuracy and speed was not related to age, indicating that all subjects could perform the task correctly. We identified a whole‐brain significant age‐related decline of ventral striatum activation during reward anticipation as compared to neutral anticipation. Importantly, the specificity of this finding was underscored by the observation that there was no general decline in activation during anticipation. Activation in the ventral striatum increased with age during reward receipt as compared to receiving neutral outcome. Finally, activation in the ventromedial prefrontal cortex during outcome was not affected by age. Our data demonstrate that the typical shift in striatal activation from reward receipt to reward anticipation in young adults disappears with healthy aging. These changes are consistent the well‐ocumented age‐related decline of striatal dopamine availability, and may provide a stepping stone for further research of age‐related neurodegenerative diseases. Hum Brain Mapp 36:2305–2317, 2015. © 2015 Wiley Periodicals, Inc.     

Distinct neural correlates of the preference‐related valuation of supraliminally and subliminally presented faces

Recent neuroimaging studies have investigated the neural substrates involved in the valuation of supraliminally presented targets and the subsequent preference decisions. However, the neural mechanisms of the valuation of subliminally presented targets, which can guide subsequent preference decisions, remain to be explored. In the present study, we determined whether the neural systems associated with the valuation of supraliminally presented faces are involved in the valuation of subliminally presented faces. The subjects were supraliminally and subliminally presented with faces during functional magnetic resonance imaging (fMRI). Following fMRI, the subjects were presented with pairs of faces and were asked to choose which face they preferred. We analyzed brain activation by back‐sorting the fMRI data according to the subjects' choices. The present study yielded two main findings. First, the ventral striatum and the ventromedial prefrontal cortex predict preferences only for supraliminally presented faces. Second, the dorsomedial prefrontal cortex may predict preferences for subliminally presented faces. These findings indicate that neural correlates of the preference‐related valuation of faces are dissociable, contingent upon whether the subjects consciously perceive the faces. Hum Brain Mapp 36:2865–2877, 2015. © 2015 Wiley Periodicals, Inc.     

Distinct neural responses to conscious versus unconscious monetary reward cues

Human reward pursuit is often assumed to involve conscious processing of reward information. However, recent research revealed that reward cues enhance cognitive performance even when perceived without awareness. Building on this discovery, the present functional MRI study tested two hypotheses using a rewarded mental‐rotation task. First, we examined whether subliminal rewards engage the ventral striatum (VS), an area implicated in reward anticipation. Second, we examined differences in neural responses to supraliminal versus subliminal rewards. Results indicated that supraliminal, but not subliminal, high‐value reward cues engaged brain areas involved in reward processing (VS) and task performance (supplementary motor area, motor cortex, and superior temporal gyrus). This pattern of findings is striking given that subliminal rewards improved performance to the same extent as supraliminal rewards. So, the neural substrates of conscious versus unconscious reward pursuit are vastly different—but despite their differences, conscious and unconscious reward pursuit may still produce the same behavioral outcomes. Hum Brain Mapp 35:5578–5586, 2014. © 2014 Wiley Periodicals, Inc .     

Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder

Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and non-social reward anticipation and outcomes were examined in individuals with ASD (n = 16), SAD (n = 15) and a control group (n = 19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD.     

Adaptive neural reward processing during anticipation and receipt of monetary rewards in mindfulness meditators

Reward seeking is ubiquitous and adaptive in humans. But excessive reward seeking behavior, such as chasing monetary rewards, may lead to diminished subjective well-being. This study examined whether individuals trained in mindfulness meditation show neural evidence of lower susceptibility to monetary rewards. Seventy-eight participants (34 meditators, 44 matched controls) completed the monetary incentive delay task while undergoing functional magnetic resonance imaging. The groups performed equally on the task, but meditators showed lower neural activations in the caudate nucleus during reward anticipation, and elevated bilateral posterior insula activation during reward anticipation. Meditators also evidenced reduced activations in the ventromedial prefrontal cortex during reward receipt compared with controls. Connectivity parameters between the right caudate and bilateral anterior insula were attenuated in meditators during incentive anticipation. In summary, brain regions involved in reward processing—both during reward anticipation and receipt of reward—responded differently in mindfulness meditators than in nonmeditators, indicating that the former are less susceptible to monetary incentives.     

Empathic neural responses to others' pain depend on monetary reward

Human empathy is not merely a resonance with others' physical condition, but is modulated by social factors. Using functional magnetic resonance imaging, the present study demonstrated an increased brain empathic response to others in pain when they received no rather than a large reward, with increments of the ACC, aMCC, insula and postcentral gyrus in the pain matrix and temporoparietal junction. Thus, pain target's financial situation modulated brain empathic responses in the pain matrix based on an understanding of the situation pain target faces.     

Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning

In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment.     

Anticipation of monetary and social reward differently activates mesolimbic brain structures in men and women

Motivation for goal-directed behaviour largely depends on the expected value of the anticipated reward. The aim of the present study was to examine how different levels of reward value are coded in the brain for two common forms of human reward: money and social approval. To account for gender differences 16 male and 16 female participants performed an incentive delay task expecting to win either money or positive social feedback. fMRI recording during the anticipation phase revealed proportional activation of neural structures constituting the human reward system for increasing levels of reward, independent of incentive type. However, in men activation in the prospect of monetary rewards encompassed a wide network of mesolimbic brain regions compared to only limited activation for social rewards. In contrast, in women, anticipation of either incentive type activated identical brain regions. Our findings represent an important step towards a better understanding of motivated behaviour by taking into account individual differences in reward valuation.     

Differential patterns of nucleus accumbens activation during anticipation of monetary and social reward in young and older adults

Recent studies have reported inconsistent results regarding the loss of reward sensitivity in the aging brain. Although such an age effect might be due to a decline of physiological processes, it may also be a consequence of age-related changes in motivational preference for different rewards. Here, we examined whether the age effects on neural correlates of reward anticipation are modulated by the type of expected reward. Functional magnetic resonance images were acquired in 24 older (60–78 years) and 24 young participants (20–28 years) while they performed an incentive delay task offering monetary or social rewards. Anticipation of either reward type recruited brain structures associated with reward, including the nucleus accumbens (NAcc). Region of interest analysis revealed an interaction effect of reward type and age group in the right NAcc: enhanced activation to cues of social reward was detected in the older subsample while enhanced activation to cues of monetary reward was detected in the younger subsample. Our results suggest that neural sensitivity to reward-predicting cues does not generally decrease with age. Rather, neural responses in the NAcc appear to be modulated by the type of reward, presumably reflecting age-related changes in motivational value attributed to different types of reward.     

Enhanced striatal and prefrontal activity is associated with individual differences in nonreinforced preference change for faces

Developing effective preference modification paradigms is crucial to improve the quality of life in a wide range of behaviors. The cue‐approach training (CAT) paradigm has been introduced as an effective tool to modify preferences lasting months, without external reinforcements, using the mere association of images with a cue and a speeded button response. In the current work for the first time, we used fMRI with faces as stimuli in the CAT paradigm, focusing on face‐selective brain regions. We found a behavioral change effect of CAT with faces immediately and 1‐month after training, however face‐selective regions were not indicative of behavioral change and thus preference change is less likely to rely on face processing brain regions. Nevertheless, we found that during training, fMRI activations in the ventral striatum were correlated with individual preference change. We also found a correlation between preference change and activations in the ventromedial prefrontal cortex during the binary choice phase. Functional connectivity among striatum, prefrontal regions, and high‐level visual regions was also related to individual preference change. Our work sheds new light on the involvement of neural mechanisms in the process of valuation. This could lead to development of novel real‐world interventions.     

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.     

Self-Controlled Choice Arises from Dynamic Prefrontal Signals That Enable Future Anticipation

Self-control allows humans the patience necessary to maximize reward attainment in the future. Yet it remains elusive when and how the preference to self-controlled choice is formed. We measured brain activity while female and male humans performed an intertemporal choice task in which they first received delayed real liquid rewards (forced-choice trial), and then made a choice between the reward options based on the experiences (free-choice trial). We found that, while subjects were awaiting an upcoming reward in the forced-choice trial, the anterior prefrontal cortex (aPFC) tracked a dynamic signal reflecting the pleasure of anticipating the future reward. Importantly, this prefrontal signal was specifically observed in self-controlled individuals, and moreover, interregional negative coupling between the prefrontal region and the ventral striatum (VS) became stronger in those individuals. During consumption of the liquid rewards, reduced ventral striatal activity predicted self-controlled choices in the subsequent free-choice trials. These results suggest that a well-coordinated prefrontal-striatal mechanism during the reward experience shapes preferences regarding the future self-controlled choice.SIGNIFICANCE STATEMENT Anticipating future desirable events is a critical mental function that guides self-controlled behavior in humans. When and how are the self-controlled choices formed in the brain? We monitored brain activity while humans awaited a real liquid reward that became available in tens of seconds. We found that the frontal polar cortex tracked temporally evolving signals reflecting the pleasure of anticipating the future reward, which was enhanced in self-controlled individuals. Our results highlight the contribution of the fronto-polar cortex to the formation of self-controlled preferences, and further suggest that future prospect in the prefrontal cortex (PFC) plays an important role in shaping future choice behavior.     

Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction.     

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.     

Effect of brain structure and function on reward anticipation in children and adults with attention deficit hyperactivity disorder combined subtype

Attention deficit hyperactivity disorder (ADHD) is associated with decreased ventral-striatal responsiveness during reward anticipation. However, previous research mostly focused on adults with heterogeneous ADHD subtype and divers drug treatment status while studies in children with ADHD are sparse. Moreover, it remains unclear to what degree ADHD is characterized by a delay of normal brain structure or function maturation. We therefore attempt to determine whether results from structural and functional magnetic resonance imaging (fMRI) are associated with childhood and adult ADHD combined subtype (ADHD-CT). This study used fMRI to compare VS structure and function of 30 participants with ADHD-CT (16 adults, 14 children) and 30 controls (20 adults, 10 children), using a monetary incentive delay task. Joint analyses of structural and functional imaging data were conducted with Biological Parametric Mapping. Reward anticipation elicited decreased ventral-striatal responsiveness in adults but not in children with ADHD-CT. Children and adults with ADHD showed reduced ventral-striatal volume. Taking these gray matter differences into account, the results remained the same. These results suggest that decreased ventral-striatal responsiveness during reward anticipation is present in adults but not in children with ADHD-CT, irrespective of structural characteristics. The question arises whether ventral-striatal hypoactivity is an ADHD correlate that develops during the course of illness.     

Differential reward responses during competition against in- and out-of-network others

Social interactions occur within a variety of different contexts––cooperative/competitive––and often involve members of our social network. Here, we investigated whether social network modulated the value placed on positive outcomes during a competitive context. Eighteen human participants played a simple card-guessing game with three different competitors: a close friend (in-network), a confederate (out-of-network) and a random number generator (non-social condition) while undergoing functional magnetic resonance imaging. Neuroimaging results at the time of outcome receipt demonstrated a significant main effect of competitor across multiple regions of medial prefrontal cortex, with Blood Oxygen Level Dependent (BOLD) responses strongest when competing against one’s friend compared with all other conditions. Striatal BOLD responses demonstrated a more general sensitivity to positive compared with negative monetary outcomes, which an exploratory analysis revealed to be stronger when interacting with social, compared with non-social, competitors. Interestingly, a Granger causality analysis indicated directed influences sent from an medial prefrontal cortex (mPFC) region, which shows social network differentiation of outcomes, and the ventral striatum bilaterally. Our results suggest that when competing against others of varying degrees of social network, mPFC differentially values these outcomes, perhaps treating in-network outcomes as more informative, leaving the striatum to more general value computations.     

Emotional imagery: Assessing pleasure and arousal in the brain's reward circuitry

Research on emotional perception and learning indicates appetitive cues engage nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), whereas amygdala activity is modulated by the emotional intensity of appetitive and aversive cues. This study sought to determine patterns of functional activation and connectivity among these regions during narrative emotional imagery. Using event‐related fMRI, we investigate activation of these structures when participants vividly imagine pleasant, neutral, and unpleasant scenes. Results indicate that pleasant imagery selectively activates NAc and mPFC, whereas amygdala activation was enhanced during both pleasant and unpleasant imagery. NAc and mPFC activity were each correlated with the rated pleasure of the imagined scenes, while amygdala activity was correlated with rated emotional arousal. Functional connectivity of NAc and mPFC was evident throughout imagery, regardless of hedonic content, while correlated activation of the amygdala with NAc and mPFC was specific to imagining pleasant scenes. These findings provide strong evidence that pleasurable text‐driven imagery engages a core appetitive circuit, including NAc, mPFC, and the amygdala. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Pramipexole modulates the neural network of reward anticipation

Pramipexole is widely prescribed to treat Parkinson's disease. It has been found to cause impulse control disorders such as pathological gambling. To examine how pramipexole modulates the network of reward anticipation, we carried out a pharmacological functional magnetic resonance imaging study with a double-blind, within-subject design. During the anticipation of monetary rewards, pramipexole increased the activity of the nucleus accumbens (NAcc), enhanced the interaction between the NAcc and the anterior insula, but weakened the interaction between the NAcc and the prefrontal cortex. These results suggest that pramipexole may exaggerate incentive and affective responses to possible rewards, but reduce the top-down control of impulses, leading to an increase in impulsive behaviors. This imbalance between the prefrontal-striatum connectivity and the insula-striatum connectivity may represent the neural mechanism of pathological gambling caused by pramipexole.