Search

Sex differences in the neural processing of decision-making are of high interest as they may have pronounced effects on reward- and addiction-related processes. In these, the neurotransmitter dopamine plays a central role by modulating the responsiveness of the reward circuitry. The present functional magnetic resonance imaging study aimed to explore sex and dopamine transmission interactions in decision-making. 172 subjects (111 women) performed a behavioral self-control task assessing reward-related activation during acceptance and rejection of conditioned rewards. Participants were genotyped for six key genetic polymorphisms in the dopamine system that have previously been associated with individual differences in reward sensitivity or dopaminergic transmission in the human striatum, such as rs7118900 (dopamine receptor D2 (DRD2) Taq1A), rs1554929 (DRD2 C957T), rs907094 (DARPP-32), rs12364283 (DRD2), rs6278 (DRD2), and rs107656 (DRD2). The selected polymorphisms were combined in a so-called multilocus genetic composite (MGC) score reflecting the additive effect of different alleles conferring relative increased dopamine transmission in every individual. We successfully demonstrated that reward-related activation in the ventral striatum and ventral tegmental area (VTA) was significantly modulated by biologically informed MGC profiles and sex. When comparing men and women with low MGC profiles that may indicate lower dopamine transmission, only women displayed a reduced down-regulation of activation in the mesolimbic system during reward rejection and additionally, a significant non-linear u-shape relationship between MGC score and VTA activation. Taken together, by integrating neuroimaging and genetics, the present findings contribute to a better understanding of the effects of sex differences on the human brain.

Seasonal and circadian rhythms have a broad impact on physiological aspects, such as dopamine neurotransmission, and may be involved in the etiology of mood disorders. Considering this, studies on the influence of season and daytime on cognitive function are rare. The present study aimed to assess the impact of seasonal and diurnal effects on the ability to maximize reward outcomes by optimizing response times adaptively. For this purpose, a reward-based learning task that required an adaptation of response time to either a fast or a slow response was used. Eighty German participants (mean age ± SD = 21.86 ± 1.89 years, 41 women) were examined twice, in the morning and in the evening. Half of the participants were tested during the summer, while the other half performed the test in the winter. No impact of daytime, season or of the external factors photoperiodicity and temperature on reinforcement learning could be found. However, a generally slower response speed in the morning compared to the evening appeared. Previously conducted tasks could not display behavioral differences in both times of season and daytime, although neurophysiological findings suggest it.

During adolescence, gonadal hormones influence brain maturation and behavior. The impact of 17β-estradiol and testosterone on reinforcement learning was previously investigated in adults, but studies with adolescents are rare. We tested 89 German male and female adolescents (mean age ± sd = 14.7 ± 1.9 years) to determine the extent 17β-estradiol and testosterone influenced reinforcement learning capacity in a response time adjustment task. Our data showed, that 17β-estradiol correlated with an enhanced ability to speed up responses for reward in both sexes, while the ability to wait for higher reward correlated with testosterone primary in males. This suggests that individual differences in reinforcement learning may be associated with variations in these hormones during adolescence, which may shift the balance between a more reward- and an avoidance-oriented learning style.

Empirical evidence suggests that sex hormones modulate behavior associated with parental caretaking (Gettler et al. 2011; Kuzawa et al. 2010). In women, endogenous testosterone seems to be negatively correlated with selective attention towards infant faces (Holtfrerich et al. 2016). To investigate this interrelation, this study uses a computer based odd-one-out paradigm consisting of infant and adult human portraits in a transgender population. The subjects (male-to-female and female-to-male) are tested before the first hormone administration and at six months under therapy to verify whether the altered hormonal milieu causes a change in the attentional processing of infant faces. References: Gettler, Lee T.; McDade, Thomas W.; Feranil, Alan B.; Kuzawa, Christopher W. (2011): Longitudinal evidence that fatherhood decreases testosterone in human males. In: Proceedings of the National Academy of Sciences of the United States of America 108 (39), S. 16194–16199. DOI: 10.1073/pnas.1105403108. Holtfrerich, Sarah K. C.; Schwarz, Katharina A.; Sprenger, Christian; Reimers, Luise; Diekhof, Esther K. (2016): Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces. In: PloS one 11 (11), e0166617. DOI: 10.1371/journal.pone.0166617. Kuzawa, Christopher W.; Gettler, Lee T.; Huang, Yuan-yen; McDade, Thomas W. (2010): Mothers have lower testosterone than non-mothers: evidence from the Philippines. In: Hormones and behavior 57 (4-5), S. 441–447. DOI: 10.1016/j.yhbeh.2010.01.014.

Objective Androgen deprivation therapy (ADT) enhances survival of advanced prostate cancer patients and is therefore used as a concomitant therapy. However, ADT has been reported to cause negative side effects on cognition and emotional processing. So far, research referred to the effects of short-term treatment. Since the brain may adapt to androgen deprivation, we were especially interested in the long-term effects of ADT on cognitive and socioeconomic decision making. Methods Participants underwent a battery of tests that have been associated with testosterone. We compared the results of three matched test groups: (1) prostate cancer patients with ADT up to 20 years, (2) prostate cancer controls without treatment and (3) healthy controls. We further measured the morning testosterone content in participants' saliva. Results Testosterone concentration was positively associated with visuospatial performance across and within the test groups. Patients with long-term ADT showed an overall decline in cognitive performance. Compared with untreated patients, ADT was also associated with a reduced intergroup bias during socioeconomic decision making, which was in line with previous observations in young men suggesting that testosterone may promote ingroup favoritism. Finally, depression scores were increased in ADT, while quality of life was negatively associated with the treatment. Conclusion These findings conform to results made after short-term treatment. ADT promotes negative side effects on cognitive function. We also show for the first time that testosterone deprivation may affect socioeconomic decision making. Nevertheless, it should be emphasized that these effects cannot outweigh the previously described advantages of ADT in the treatment of prostate cancer.

This review is intended to summarize the literature on the modulation of the human reward system by estradiol. It will integrate previous neuroimaging findings in current rodent models, which suggest a dopamine-agonistic effect of physiological estradiol that may increase reward sensitivity in females. In human research, most neuroimaging studies have addressed menstrual cycle-related differences in reward-related brain activation and behaviors by comparing phases of high versus low estradiol availability. Few studies have also used pharmacological intervention to induce different hormonal states for comparisons of high and low estradiol, while others have also assessed the correlations between brain activation and state-related estradiol to infer causality. Since most human samples were small (n

Sex differences in the neural processing of decision-making are of high interest as they may have pronounced effects on reward- and addiction-related processes. In these, the neurotransmitter dopamine plays a central role by modulating the responsiveness of the reward circuitry. The present functional magnetic resonance imaging study aimed to explore sex and dopamine transmission interactions in decision-making. 172 subjects (111 women) performed a behavioral self-control task assessing reward-related activation during acceptance and rejection of conditioned rewards. Participants were genotyped for six key genetic polymorphisms in the dopamine system that have previously been associated with individual differences in reward sensitivity or dopaminergic transmission in the human striatum, such as rs7118900 (dopamine receptor D2 (DRD2) Taq1A), rs1554929 (DRD2 C957T), rs907094 (DARPP-32), rs12364283 (DRD2), rs6278 (DRD2), and rs107656 (DRD2). The selected polymorphisms were combined in a so-called multilocus genetic composite (MGC) score reflecting the additive effect of different alleles conferring relative increased dopamine transmission in every individual. We successfully demonstrated that reward-related activation in the ventral striatum and ventral tegmental area (VTA) was significantly modulated by biologically informed MGC profiles and sex. When comparing men and women with low MGC profiles that may indicate lower dopamine transmission, only women displayed a reduced down-regulation of activation in the mesolimbic system during reward rejection and additionally, a significant non-linear u-shape relationship between MGC score and VTA activation. Taken together, by integrating neuroimaging and genetics, the present findings contribute to a better understanding of the effects of sex differences on the human brain.

Stereotypes are abundant in everyday life – and whereas their influence on cognitive and motor performance is well documented, a causal role in pain processing is still elusive. Nevertheless, previous studies have implicated gender-related stereotype effects in pain perception as potential mediators partly accounting for sex effects on pain. An influence of stereotypes on pain seems indeed likely as pain measures have proven especially susceptible to expectancy effects such as placebo effects. However, so far empirical approaches to stereotype effects on pain are correlational rather than experimental. In this study, we aimed at documenting gender-related stereotypes on pain perception and processing by actively manipulating the participants’ awareness of common stereotypical expectations. We discovered that gender-related stereotypes can significantly modulate pain perception which was mirrored by activity levels in pain-associated brain areas.

Testosterone plays a key role in shaping human social behavior. Recent findings have linked testosterone to altruistic behavior in economic decision tasks depending on group membership and intergroup competition. The preferential treatment of ingroup members, while aggression and discrimination is directed towards outgroup members, has been referred to as parochial altruism. Here we investigated in two consecutive studies, whether testosterone is associated with parochial altruism depending on individual tendency for costly punishment. In the first study, 61 men performed a single-shot ultimatum game (UG) in a minimal group context, in which they interacted with members of an ingroup and an outgroup. In the second study, 34 men performed a single-shot UG in a more realistic group context, in which they responded to the proposals of supporters of six political parties during the German election year 2017. Political parties varied in their social distance to the participants’ favorite party as indicated by an individual ranking, which resulted in one ingroup (rank 1) and five outgroups of varying social distance (rank 6 referred to as the most distant outgroup). Participants also performed a cued recall task, in which they had to decide whether they had already encountered a face during the UG (old-new decision). In both studies, results showed a parochial pattern with higher rejection rates of outgroup than ingroup offers. Interestingly, higher salivary testosterone was associated with higher rejection rates related to unfair offers by the most distant outgroup, yet only in the group of self-oriented subjects (pro-selfs). Further, only the pro-selfs showed a memory advantage for unfair interaction partners in study 2, especially if those were ingroup members. The present findings suggest that the latent intergroup bias during decision-making, that was particularly visible in pro-selfs, may be related to endogenous testosterone. In line with previous evidence that already indicated a role of testosterone in shaping male parochial altruism in male soccer fans, these data underscore the general yet rather subtle role of testosterone also in other social settings.

Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18-31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the 'Desire-Reason Dilemma' paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1.

Nurturing behavior may be critically influenced by the interplay of different hormones. The neuropeptide oxytocin is known to promote maternal behavior and its reduction has been associated with postpartum depression risk and child neglect. Contrariwise, the observed decrease in testosterone level during early parenthood may benefit caretaking behavior, whereas increased testosterone may reduce attention to infants. Here we used functional magnetic resonance imaging to investigate the interactive influence of testosterone and oxytocin on selective attention to and neural processing of the baby schema (BS). 57 nulliparous women performed a target detection task with human faces with varying degree of BS following double-blinded placebo-controlled oxytocin administration in a between-subjects design. Our results support the idea that oxytocin enhances attention to the BS. Oxytocin had a positive effect on activation of the inferior frontal junction during identification of infant targets with a high degree of BS that were presented among adult distractors. Further, activation of the putamen was positively correlated with selective attention to the BS, but only in women with high endogenous testosterone who received oxytocin. These findings provide initial evidence for the neural mechanism by which oxytocin may counteract the negative effects of testosterone in the modulation of nurturing behavior.

The most anterior portion of prefrontal cortex (aPFC), more specifically Brodman Area 10 (BA10), has been implicated in 'branching operations', or the ability to perform tasks related to one goal, while keeping in working memory information related to a secondary goal. Such findings have been based on fMRI recordings under complex behavioral paradigms that compare 'branching' tasks with tasks where one goal is pursued at a time, but are limited by their complete reliance on verbal working memory and by small sample sizes. Here, we test the specificity of BA 10 to branching in similar behavioral paradigms but with a larger sample and in two different conditions involving verbal and visual working memory respectively. We find that BA 10 and other frontal and parietal brain areas are activated in all tasks, with an extent and level of significance increasing with the complexity of the task. We conclude that the activation of BA 10 is not specific to branching as previously hypothesized, but is related to the level of complexity of working memory performance. For further insight into the specific role of anterior portions of the frontal cortex we highlight the importance of simple control tasks with gradual and incremental increase in complexity.

This article is part of a Special Issue "Estradiol and Cognition". Variations in the steroid hormone 17ß-estradiol (E2) may promote intra-individual differences in reward seeking behavior and temporal decision-making (Reimers et al., 2014; Front. Neurosci. 8: 401). Yet, in humans the exact role of E2 in impulsive choice still needs to be determined. The present study assessed the effect of a cycle-dependent rise in endogenous E2 on temporal response adaptation across the follicular phase (FP). For this purpose a reward acquisition paradigm was employed that is sensitive to hormone-induced changes in central dopamine (DA) level. The present data show that women acted more impulsively in the early as opposed to the late FP. Early follicular E2 further correlated with an increased capacity to speed up for reward maximization, while simultaneously the ability to wait for higher reward was compromised. This correlation was most pronounced in women with low trait impulsiveness. In contrast, E2 and optimized response speed failed to correlate in women with high trait impulsiveness and in the late FP, despite a generally higher E2 level. Collectively, these findings support the theory that E2 may act as an endogenous DA agonist. The fact that the hormone-behavior relationship was restricted to women with low trait impulsiveness and thus supposedly lower central DA level provides indirect support for this idea. Yet, choices became relatively less impulsive in the state of heightened E2 (i.e., in the late FP), suggesting that the relationship between E2 and impulsive choice may not be linear, but might resemble an inverted U-function.

Cyclic AMP response element-binding protein (CREB) contributes to adaptation of mesocorticolimbic networks by modulating activity-regulated transcription and plasticity in neurons. Activity or expression changes of CREB in the nucleus accumbens (NAc) and orbital frontal cortex (OFC) interact with behavioral changes during reward-motivated learning. However, these findings from animal models have not been evaluated in humans. We tested whether CREB1 genotypes affect reward-motivated decisions and related brain activation, using BOLD fMRI in 224 young and healthy participants. More specifically, participants needed to adapt their decision to either pursue or resist immediate rewards to optimize the reward outcome. We found significant CREB1 genotype effects on choices to pursue increases of the reward outcome and on BOLD signal in the NAc, OFC, insula cortex, cingulate gyrus, hippocampus, amygdala, and precuneus during these decisions in comparison with those decisions avoiding total reward loss. Our results suggest that CREB1 genotype effects in these regions could contribute to individual differences in reward- and associative memory-based decision-making.

Hormone by genotype interactions have been widely ignored by cognitive neuroscience. Yet, the dependence of cognitive performance on both baseline dopamine (DA) and current 17ß-estradiol (E2) level argues for their combined effect also in the context of reinforcement learning. Here, we assessed how the interaction between the natural rise of E2 in the late follicular phase (FP) and the 40 base-pair variable number tandem repeat polymorphism of the dopamine transporter (DAT1) affects reinforcement learning capacity. 30 women with a regular menstrual cycle performed a probabilistic feedback learning task twice during the early and late FP. In addition, 39 women, who took hormonal contraceptives (HC) to suppress natural ovulation, were tested during the “pill break” and the intake phase of HC. The present data show that DAT1-genotype may interact with transient hormonal state, but only in women with a natural menstrual cycle. We found that carriers of the 9-repeat allele (9RP) experienced a significant decrease in the ability to avoid punishment from early to late FP. Neither homozygote subjects of the 10RP allele, nor subjects from the HC group showed a change in behavior between phases. These data are consistent with neurobiological studies that found that rising E2 may reverse DA transporter function and could enhance DA efflux, which would in turn reduce punishment sensitivity particularly in subjects with a higher transporter density to begin with. Taken together, the present results, although based on a small sample, add to the growing understanding of the complex interplay between different physiological modulators of dopaminergic transmission. They may not only point out the necessity to control for hormonal state in behavioral genetic research, but may offer new starting points for studies in clinical settings.

Based on higher prevalence rates of several mental disorders for city dwellers, psychosocial stress effects of urban living have been proposed as an environmental risk factor contributing to the development of mental disorders. Recently, it was shown that amygdala activation differs between city dwellers and rural residents in response to a cognitive-social stressor. Besides its influence on the amygdala, chronic stress also affects mesocorticolimbic brain regions involved in reward processing, and stress-related dysregulation of the mesocorticolimbic dopamine system is thought to contribute to onset and manifestation of psychiatric disorders. Here, we investigated differences in reward systems functioning in 147 healthy subjects living either in cities or in less urban areas by means of functional magnetic resonance imaging during performance of the desire-reason-dilemma paradigm, which permits a targeted investigation of bottom-up activation and top-down regulation of the reward circuit. Compared with subjects from less urban areas, city dwellers showed an altered activation and modulation capability of the midbrain (VTA) dopamine system. City dwellers also revealed increased responses in other brain regions involved in reward processing and in the regulation of stress and emotions, such as amygdala, orbitofrontal, and pregenual anterior cingulate cortex. These results provide further evidence for effects of an urban environment on the mesolimbic dopamine system and the limbic system which may increase the risk to develop mental disorders. Hum Brain Mapp 38:3444-3453, 2017. © 2017 Wiley Periodicals, Inc.

Parochial altruism refers to ingroup favoritism and outgroup hostility and has recently been linked to testosterone. Here, we investigated the neurobiological mechanism of parochial altruism in male soccer fans playing the ultimatum game (UG) against ingroup and outgroup members (i.e., fans of the favorite or of a rivalling team) using functional magnetic resonance imaging. Our results suggest that individual differences in altruistic tendency influence the tendency for parochialism. While altruistic subjects rejected unfair offers independent of team membership, the more self-oriented 'pro-selfs' displayed a stronger ingroup bias and rejected outgroup offers more often. However, during a second session that introduced a team competition the altruists adapted to this parochial pattern. Behavioral strategy was further characterized by dissociable and context-dependent correlations between endogenous testosterone and neural responses in the anterior insula and the ventromedial prefrontal cortex. In sum, the present findings indicate that parochial altruism is shaped by individual differences in testosterone and behavioral strategy. In that way the results are in line with evolutionary theories of both individual and group selection.

Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicated patients diagnosed with bipolar I disorder, euthymic to mildly depressed, and sixteen matched healthy controls performed the 'desire-reason dilemma' (DRD) paradigm demanding rejection of priorly conditioned reward stimuli to successfully pursue a superordinate goal. Both groups exhibited significant activations in reward-related brain regions, particularly in the mesolimbic reward system. However, bipolar patients showed reduced neural responses of the ventral striatum (vStr) when exploiting a reward stimulus, and exhibited a decreased suppression of the reward-related activation of the mesolimbic reward system while having to reject immediate reward in favor of the long-term goal. Further, functional interaction between the anteroventral prefrontal cortex and the vStr in the 'DRD' was significantly impaired in the bipolar group. These findings provide evidence for a reduced responsivity of the vStr to reward stimuli in BD, possibly related to clinical features like anhedonia. The disturbed top-down control of mesolimbic reward signals by prefrontal brain regions in BD can be interpreted in terms of a disease-related enhanced impulsivity, a trait marker of BD.

The capacity to flexibly adapt responding to unexpected changes in the environment is crucial for survival. Several neurotransmitters have been implicated in stimulus-outcome reversal learning. Yet, it remains an open question whether inter-individual differences in the neuroactive hormone testosterone may also be related to this type of behavioral flexibility. In this study we assessed the association between endogenous testosterone level and reversal learning in young healthy men. We used an observer reversal learning task, in which subjects viewed computer-based decisions between two stimuli, of which one was currently rewarded while the other one was punished. Contingencies reversed unpredictably every 5-9 trials. Subjects had to indicate the current outcome association before the actual outcome was revealed. In the trial following an unexpected reversal either the same stimulus from the reversal (experienced reversal), or its alternative, for which the reversal had not yet been shown (inferred reversal), could be chosen by the computer, and subjects had to adapt responding accordingly. We found that testosterone predicted better post-reversal performance. This correlation was strongest in the more difficult inferred reversal condition, particularly in impulsive individuals. Collectively, these data support the view that endogenous testosterone may enhance behavioral flexibility in men, particularly when working memory demand is high and subjects have to update several stimulus-outcome contingencies at the same time. It remains to be further elucidated whether this testosterone effect was achieved through an interaction with dopaminergic transmission or through direct interplay with androgen receptors in the brain regions implicated in reversal learning.

The ability to resist immediate rewards is crucial for lifetime success and individual well‐being. Using functional magnetic resonance imaging, we assessed the association between trait impulsivity and the neural underpinnings of the ability to control immediate reward desiring. Low and high extreme impulsivity groups were compared with regard to their behavioral performance and brain activation in situations, in which they had to forego immediate rewards with varying value to achieve a superordinate long‐term goal. We found that highly impulsive (HI) individuals, who successfully compensated for their lack in behavioral self‐control, engaged two complementary brain mechanisms when choosing actions in favor of a long‐term goal, but at the expense of an immediate reward. First, self‐controlled decisions led to a general attenuation of reward‐related activation in the nucleus accumbens, which was accompanied by an increased inverse connectivity with the anteroventral prefrontal cortex. Second, HI subjects controlled their desire for increasingly valuable, but suboptimal rewards through a linear reduction of activation in the ventromedial prefrontal cortex (VMPFC). This was achieved by an increased inverse coupling between the VMPFC and the ventral striatum. Importantly, the neural mechanisms observed in the HI group differed from those in extremely controlled individuals, despite similar behavioral performance. Collectively, these results suggest trait‐specific neural mechanisms that allow HI individuals to control their desire for immediate reward. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

Humans have the ability to control negative affect and perceived fear. Nevertheless, it is still unclear whether this affect regulation capacity relies on a common neural mechanism in different experimental domains. Here, we sought to identify commonalities in regulatory brain activation in the domains of fear extinction, placebo, and cognitive emotion regulation. Using coordinate-based activation-likelihood estimation meta-analysis we intended to elucidate concordant hyperactivations and the associated deactivations in the three experimental domains, when human subjects successfully diminished negative affect. Our data show that only one region in the ventromedial prefrontal cortex (VMPFC) controlled negative affective responses and reduced the degree of subjectively perceived unpleasantness independent of the experimental domain. This down-regulation of negative affect was further accompanied by a concordant reduction of activation in the left amygdala. Finally, the soothing effect of placebo treatments and cognitive reappraisal strategies, but not extinction retrieval, was specifically accompanied by a coherent hyperactivation in the anterior cingulate and the insular cortex. Collectively, our data strongly imply that the human VMPFC may represent a domain-general controller of perceived fear and aversiveness that modulates negative affective responses in phylogenetically older structures of the emotion processing system. In addition, higher-level regulation strategies may further engage complementary neural resources to effectively deal with the emotion-eliciting events.

Expectancies strongly shape our perception of the world and preconceptions about stimulus characteristics can even bias the sensory system for illusory percepts. Here we assessed with functional magnetic resonance imaging how anticipatory mental imagery of a mildly fearful face created a predictive bias that proactively altered perception of highly fearful faces and generated the "illusion" of reduced fearfulness. We found that anticipatory activation of the fusiform gyrus (FG) was modulated by the fearfulness of the imagined face. Further during anticipatory imagery, regulatory influences from the lateral and ventromedial prefrontal cortex on the FG primed the perceptual system for a subsequent misperception. This was achieved by increasing perceptual activation in higher-order brain regions for the evaluation of affective valence and contextual framing, while at the same time restricting bottom-up arousal and attention to fearful expressions. Anticipatory mental imagery may thus represent an effective antecedent strategy through which emotional perception can be significantly altered.

Adaptive behaviour requires that organisms continuously monitor the environment for potentially significant information and evaluate whether currently unattended stimuli afford a behavioural change. Here we used event-related functional magnetic resonance imaging in humans to assess the neural mechanisms underlying the evaluation of and rapid behavioural adjustments to salient stimuli occurring outside the current focus of (feature) attention. While subjects performed a task-switching paradigm in which they had to respond to either the colour or the shape of visual stimuli, occasionally deviant stimuli were presented that differed from the remaining stimuli with respect to the currently unattended feature. By systematically varying the frequency and the behavioural relevance of these perceptual deviations, we obtained a context-sensitive modulation of neural activity in a frontoparietal network including the posterior orbitofrontal cortex, the anterior cingulate cortex and the temporoparietal junction area, which may underlie a specific role in the adaptive guidance of behaviour in a changing environment. Together these brain regions may ensure that the relevance of a sudden environmental change is rapidly evaluated and implemented in appropriate action selection.

Background monitoring is a necessary prerequisite to detect unexpected changes in the environment, while being involved in a primary task. Here, we used fMRI to investigate the neural mechanisms that underlie adaptive goal-directed behavior in a cued task switching paradigm during real response conflict or, more generally, when expectations on the repetitive features of the environment were violated. Unexpected changes in sensory stimulus attributes in the currently unattended stimulus dimension thereby led to activations in a bilateral network comprising inferior lateral frontal, intraparietal, and posterior medial frontal brain regions, independent of whether these attributes elicited a factual response conflict or not. This fronto-parietal network may thus play an important role in adaptive responding to potentially significant events outside the current focus of attention.

The adequate integration of reward- and decision-related information provided by the environment is critical for behavioral success and subjective well being in everyday life. Functional neuroimaging research has already presented a comprehensive picture on affective and motivational processing in the healthy human brain and has recently also turned its interest to the assessment of impaired brain function in psychiatric patients. This article presents an overview on neuroimaging studies dealing with reward processing and decision-making by combining most recent findings from fundamental and clinical research. It provides an outline on the neural mechanisms guiding context-adequate reward processing and decision-making processes in the healthy brain, and also addresses pathophysiological alterations in the brain's reward system that have been observed in substance abuse and mood disorders, two highly prevalent classes of psychiatric disorders. The overall goal is to critically evaluate the specificity of neurophysiological alterations identified in these psychiatric disorders and associated symptoms, and to make suggestions concerning future research.

Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.

The steroid hormone testosterone is widely associated with negative behavioral effects, such as aggression or dominance. However, recent studies applying economic exchange tasks revealed conflicting results. While some point to a prosocial effect of testosterone by increasing altruistic behavior, others report that testosterone promotes antisocial tendencies. Taking into account additional factors such as parochial altruism (i.e., ingroup favoritism and outgroup hostility) might help to explain this contradiction. First evidence for a link between testosterone and parochial altruism comes from recently reported data of male soccer fans playing the ultimatum game. In this study high levels of endogenous testosterone predicted increased altruistic punishment during outgroup interactions and at the same time heightened ingroup generosity. Here, we report findings of another experimental task, the prisoner’s dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, fifty male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subject’s own favorite team (ingroup) or fans of other teams (outgroups). Our results show that high testosterone levels were associated with increased ingroup cooperation during intergroup competition. In addition, subjects displaying a high degree of parochialism during intergroup competition had significantly higher levels of testosterone than subjects who did not differentiate much between the different groups. In sum, the present data demonstrate that the behavioral effects of testosterone are not limited to aggressive and selfish tendencies but may imply prosocial aspects depending on the context. By this means, our results support the previously reported findings on testosterone-dependent intergroup bias and indicate that this social hormone might be an important factor driving parochial altruism.

The ability to learn from errors or the positive outcomes of one's actions has been connected to a differential functionality of the mesolimbic dopamine system. Variations in dopaminergic transmission and D2-receptor (DRD2) density in the striatum may thereby incline the individual to be either more reward- or punishment-sensitive. The steroid hormones estradiol (E2) and progesterone (PROG) are known to modulate dopaminergic tone. While E2 may enhance dopaminergic release and reduces DRD2, PROG may oppose these effects and attenuates dopaminergic responses. In women, marked changes in the concentration of these hormones occur across the menstrual cycle. Hence, the aim of this study was to assess whether reinforcement learning is modulated by menstrual cycle phase. Fifteen female subjects underwent fMRI while performing a probabilistic feedback learning task twice during their menstrual cycle--once in a phase dominated by E2 (late follicular phase), and a second time in the presence of high PROG (mid luteal phase).The goal of the learning task was to select the more frequently rewarded symbols from 3 symbol pairs, which was enforced by probabilistic feedback. A behavioral post-test examined learning performance and the tendency towards reward or punishment sensitivity (i.e., preference to choose the most often rewarded symbol 'A' or to avoid the least often rewarded symbol 'B', respectively). We found that individual reward sensitivity was enhanced in the follicular relative to the luteal phase, while the ability to learn from negative feedback was compromised. In contrast, during the luteal phase this behavior was reversed and women showed an enhanced punishment learning bias. On the neural level, activation of the dorsal anterior cingulate cortex and adjacent rostral cingulate zone (dACC/RCZ) was decreased when subjects received negative feedback in the follicular relative to the luteal phase. Additionally, in the luteal phase an enhanced ability to learn from negative feedback was accompanied by a stronger signal in the dACC/RCZ in response to negative feedback. These findings provide initial evidence for intra-individual differences in reward and punishment sensitivity due to naturally occurring hormonal changes across the menstrual cycle.

Schizophrenia is characterized by substantial dysfunctions of reward processing, leading to detrimental consequences for decision-making. The neurotransmitter dopamine is responsible for the transmission of reward signals and also known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), sixteen medicated patients with schizophrenia and sixteen healthy controls performed the 'desire-reason dilemma' (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Both patients and controls showed significant activations in the mesolimbic reward system. In patients with schizophrenia, however, we found a significant hyperactivation of the left ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide evidence for an increased ventral striatal activation to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia.

Dopamine (DA) plays a major role in reinforcement learning with increases promoting reward sensitivity (Go learning) while decreases facilitate the avoidance of negative outcomes (NoGo learning). This is also reflected in adaptations of response time: higher levels of DA enhance speeding up to get a reward, whereas lower levels favor slowing down. The steroid hormones estradiol and progesterone have been shown to modulate dopaminergic tone. Here, we tested fourteen women twice during their menstrual cycle, during the follicular (FP) and the luteal phase (LP), applying functional magnetic resonance imaging while they performed a feedback learning task. Subsequent behavioral testing assessed response time preferences with a clock task, in which subjects had to explore the optimal response time (RT) to maximize reward. In the FP subjects displayed a greater learning-related change of their RT than during the LP, when they were required to slow down. Final RTs in the slow condition were also predicted by feedback-related brain activation, but only in the FP. Increased activation of the inferior frontal junction and rostral cingulate zone was thereby predictive of slower and thus better adapted final RTs. Conversely, final RT was faster and less optimal for reward maximization if activation in the ventromedial prefrontal cortex was enhanced. These findings show that hormonal shifts across the menstrual cycle affect adaptation of response speed during reward acquisition with higher RT adjustment in the FP in the condition that requires slowing down. Since high estradiol levels during the FP increase synaptic DA levels, this conforms well to our hypothesis that estradiol supports Go learning at the expense of NoGo learning. Brain-behavior correlations further indicated that the compensatory capacity to counteract the follicular Go bias may be linked to the ability to more effectively monitor action outcomes and suppress bottom-up reward desiring during feedback processing.

Depression is a debilitating psychiatric disorder characterized among other aspects by the inability to properly experience or respond to reward. However, it remains unclear whether patients with depression present impaired reward system due to abnormal modulatory mechanisms. We investigated the activation of the nucleus accumbens (NAcc), a crucial region involved in reward processing, with functional magnetic resonance imaging using the desire-reason-dilemma paradigm. This task allows tracking the activity of the NAcc during the acceptance or the rejection of previously conditioned reward stimuli. Patients were assigned into subgroups of lower (LA) or higher (HA) NAcc activation according to beta weights. LA patients presented significant hypoactivation in the ventral tegmental area in addition to bilateral ventral striatum, confirming impairments in the bottom-up input to the NAcc. Conversely, HA patients presented significant hyperactivation in prefrontal areas such as the rostral anterior cingulate cortex and the anterior ventral prefrontal cortex in addition to bilateral ventral striatum, suggesting disturbances in the top-down regulation of the NAcc. Demographic and clinical differences explaining the abnormal co-activations of midbrain and prefrontal regions were not identified. Therefore, we provide evidence for dysfunctional bottom-up processing in one potential neurobiological subtype of depression (LA) and dysfunctional top-down modulation in another subtype (HA). We suggest that the midbrain and prefrontal regions are more specific pathophysiological substrates for each depression subtype. Above all, our results encourage the segregation of patients by similar dysfunctional mechanisms of the dopaminergic system, which would finally contribute to disentangle more specific pathogeneses and guide the development of more personalized targets for future therapies.

There is ample evidence of gender differences in neural processes and behavior. Differences in reward-related behaviors have been linked to either temporary or permanent organizational influences of gonadal hormones on the mesolimbic dopamine system and reward-related activation. Still, little is known about the association between biological gender and the neural underpinnings of the ability to resist reward-related impulses. Here we assessed with functional magnetic resonance imaging which neural processes enable men and women to successfully control their desire for immediate reward when this is required by a higher-order goal (i.e., during a ‘desire-reason dilemma’; Diekhof and Gruber, 2010 ). Thirty-two participants (16 females) were closely matched for age, personality characteristics (e.g., novelty seeking) and behavioral performance in the ‘desire-reason task’. On the neural level, men and women showed similarities in the general response of the nucleus accumbens and of the ventral tegmental area to predictors of immediate reward, but they differed in additional brain mechanisms that enabled self-controlled decisions against the preference for immediate reward. Firstly, men exhibited a stronger reduction of activation in the ventral pallidum, putamen, temporal pole and pregenual anterior cingulate cortex during the ‘desire-reason dilemma’. Secondly, connectivity analyses revealed a significant change in the direction of the connectivity between anteroventral prefrontal cortex and nucleus accumbens during decisions counteracting the reward-related impulse when comparing men and women. Together, these findings support the view of a sexual dimorphism that manifested in the recruitment of gender-specific neural resources during the successful deployment of self-control.

Obesity is one of the most pressing issues in modern medicine. Previous studies indicated that food images activate distinct brain areas such as the nucleus accumbens (Nacc), ventral tegmental Area (VTA), and the OFC. We used fMRI to examine the effect of food images vs. images of non-food objects on self-control and reward processing in the hungry and satiated state. Nineteen healthy adults (9 f) performed a desire-reason paradigm (Diekhof & Gruber 2010) and were scanned in hungry (> 12 hours) and satiated state. Corresponding to previous studies we found bilateral activation of Nacc and VTA when subjects gained immediate reward from conditioned stimuli. However, at a threshold of p

Reward maximization is a core motivation of every organism. In humans, several brain regions have been implicated in the representation of reward magnitude. Still, it is unclear whether identical brain regions consistently play a role in reward prediction and its consumption. In this study we used coordinate-based ALE meta-analysis to determine the individual roles of the ventral striatum (vSTR) and the medial orbitofrontal cortex (mOFC/VMPFC) in the representation of reward in general and of reward magnitude in particular. Specifically, we wanted to assess commonalities and differences in regional brain activation during the passive anticipation and consumption of rewards. Two independent meta-analyses of neuroimaging data from the past decade revealed a general role for the vSTR in reward anticipation and consumption. This was the case particularly when the consumed rewards occurred unexpectedly or were uncertain. In contrast, for the mOFC/VMPFC the present meta-analytic data suggested a rather specific function in reward consumption as opposed to passive anticipation. Importantly, when considering only coordinates that compared different reward magnitudes, the same parts of the vSTR and the mOFC/VMPFC showed concordant responses across studies, although areas of coherence were regionally more confined. These meta-analytic data suggest that the vSTR may be involved in both prediction and consumption of salient rewards, and may also be sensitive to different reward magnitudes, while the mOFC/VMPFC may rather process the magnitude during reward receipt. Collectively, our meta-analytic data conform with the notion that these two brain regions may subserve different roles in processing of reward magnitude.