Neural processing of reward and punishment in young people at increased familial risk of depression

Background Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. Methods We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16–21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. Results We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Conclusions Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior.

Through Jewish eyes: polemical literature and the medieval papacy

Although the medieval papacy's stance towards the Jews is a well-established area of research, Jewish ideas about the papacy remain a surprisingly underdeveloped historical topic. This article explores such ideas through the genre of polemic and disputational literature. Jewish writers were keen to ensure the safety of their communities in western Europe and grateful for statements of papal protection. They fully acknowledged that popes had always played and would continue to play an important role in safeguarding their well-being and determining their future. Yet although contemporary and later writers often valued papal protection more highly than that of monarchs, emperors or clergy, they also knew that it had its carefully circumscribed limits. Furthermore, although they were respectful of the papacy's power, both spiritual and temporal, they were dismissive of the scriptural and theological formulations on which Christian claims for apostolic authority rested and highly critical of Christian beliefs about the papacy, in particular that of apostolic succession. Jewish ideas about both individual popes and the medieval papacy as an institution are therefore nuanced and complex; they deserve rigorous and wide-ranging investigation and it is hoped that this article will contribute to their better understanding.

Sex differences in reward-related decision processing under stress

Recent research indicates gender differences in the impact of stress on decision behavior, but little is known about the brain mechanisms involved in these gender-specific stress effects. The current study used functional magnetic resonance imaging (fMRI) to determine whether induced stress resulted in gender-specific patterns of brain activation during a decision task involving monetary reward. Specifically, we manipulated physiological stress levels using a cold pressor task, prior to a risky decision making task. Healthy men (n = 24, 12 stressed) and women (n = 23, 11 stressed) completed the decision task after either cold pressor stress or a control task during the period of cortisol response to the cold pressor. Gender differences in behavior were present in stressed participants but not controls, such that stress led to greater reward collection and faster decision speed in males but less reward collection and slower decision speed in females. A gender-by-stress interaction was observed for the dorsal striatum and anterior insula. With cold stress, activation in these regions was increased in males but decreased in females. The findings of this study indicate that the impact of stress on reward-related decision processing differs depending on gender.

Neural basis of the undermining effect of monetary reward on intrinsic motivation

Contrary to the widespread belief that people are positively motivated by reward incentives, some studies have shown that performance-based extrinsic reward can actually undermine a person's intrinsic motivation to engage in a task. This “undermining effect” has timely practical implications, given the burgeoning of performance-based incentive systems in contemporary society. It also presents a theoretical challenge for economic and reinforcement learning theories, which tend to assume that monetary incentives monotonically increase motivation. Despite the practical and theoretical importance of this provocative phenomenon, however, little is known about its neural basis. Herein we induced the behavioral undermining effect using a newly developed task, and we tracked its neural correlates using functional MRI. Our results show that performance-based monetary reward indeed undermines intrinsic motivation, as assessed by the number of voluntary engagements in the task. We found that activity in the anterior striatum and the prefrontal areas decreased along with this behavioral undermining effect. These findings suggest that the corticobasal ganglia valuation system underlies the undermining effect through the integration of extrinsic reward value and intrinsic task value.

Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events

Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward. (PsycINFO Database Record (c) 2013 APA, all rights reserved)(journal abstract)

Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal rTMS in major depression

Background Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain’s emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. Methods Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. Results Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. Conclusions The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

Opposing neural effects of naltrexone on food reward and aversion: implications for the treatment of obesity

Rationale: Opioid antagonism reduces the consumption of palatable foods in humans but the neural substrates implicated in these effects are less well understood. Objectives: The aim of the present study was to examine the effects of the opioid antagonist, naltrexone, on neural response to rewarding and aversive sight and taste stimuli. Methods: We used functional magnetic resonance imaging (fMRI) to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 20 healthy volunteers who received a single oral dose of naltrexone (50 mg) and placebo in a double-blind, repeated-measures cross-over, design. Results: Relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula. Conclusions: These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit formation such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake with opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli. These results support further investigation of opioid treatments in obesity.

Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers

Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. The anti-obesity drug and cannabinoid type 1 receptor (CB(1)) antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use and was recently withdrawn from the market because of these adverse effects. Using a functional magnetic resonance imaging (fMRI) model of reward we hypothesized that rimonabant would impair reward processing. Twenty-two healthy participants were randomly allocated to receive rimonabant (20 mg), or placebo, for 7 d in a double-blind, parallel group design. We used fMRI to measure the neural response to rewarding (sight and/or flavour of chocolate) and aversive (sight of mouldy strawberries and/or an unpleasant strawberry taste) stimuli on the final day of drug treatment. Rimonabant reduced the neural response to chocolate stimuli in key reward areas such as the ventral striatum and the orbitofrontal cortex. Rimonabant also decreased neural responses to the aversive stimulus condition in the caudate nucleus and ventral striatum, but increased lateral orbitofrontal activations to the aversive sight and taste of strawberry condition. Our findings are the first to show that the anti-obesity drug rimonabant inhibits the neural processing of rewarding food stimuli in humans. This plausibly underlies its ability to promote weight loss, but may also indicate a mechanism for inducing anhedonia which could lead to the increased risk of depressive symptomatology seen in clinical use. fMRI may be a useful method of screening novel agents for unwanted effects on reward and associated clinical adverse reactions.

Neural representation of reward in recovered depressed patients

These findings support the view that abnormal neural responses to reward may be an endophenotype for depression and a potential target for intervention and prevention strategies.

Expected value, reward outcome, and temporal difference error representations in a probabilistic decision task

In probabilistic decision tasks, an expected value (EV) of a choice is calculated, and after the choice has been made, this can be updated based on a temporal difference (TD) prediction error between the EV and the reward magnitude (RM) obtained. The EV is measured as the probability of obtaining a reward x RM. To understand the contribution of different brain areas to these decision-making processes, functional magnetic resonance imaging activations related to EV versus RM (or outcome) were measured in a probabilistic decision task. Activations in the medial orbitofrontal cortex were correlated with both RM and with EV and confirmed in a conjunction analysis to extend toward the pregenual cingulate cortex. From these representations, TD reward prediction errors could be produced. Activations in areas that receive from the orbitofrontal cortex including the ventral striatum, midbrain, and inferior frontal gyrus were correlated with the TD error. Activations in the anterior insula were correlated negatively with EV, occurring when low reward outcomes were expected, and also with the uncertainty of the reward, implicating this region in basic and crucial decision-making parameters, low expected outcomes, and uncertainty.

How reward and emotional stimuli induce different reactions across the menstrual cycle

Despite widespread belief that moods are affected by the menstrual cycle, researchers on emotion and reward have not paid much attention to the menstrual cycle until recently. However, recent research has revealed different reactions to emotional stimuli and to rewarding stimuli across the different phases of the menstrual cycle. The current paper reviews the emerging literature on how ovarian hormone fluctuation during the menstrual cycle modulates reactions to emotional stimuli and to reward. Behavioral and neuroimaging studies in humans suggest that estrogen and progesterone have opposing influences. That is, it appears that estrogen enhances reactions to reward, but progesterone counters the facilitative effects of estrogen and decreases reactions to rewards. In contrast, reactions to emotionally arousing stimuli (particularly negative stimuli) appear to be decreased by estrogen but enhanced by progesterone. Potential factors that can modulate the effects of the ovarian hormones (e.g., an inverse quadratic function of hormones’ effects; the structural changes of the hippocampus across the menstrual cycle) are also discussed.