Esther K. Diekhof

Fear is only as deep as the mind allows: a coordinate-based meta-analysis of neuroimaging studies on the regulation of negative affect.

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.

The role of the human ventral striatum and the medial orbitofrontal cortex in the representation of reward magnitude - an activation likelihood estimation meta-analysis of neuroimaging studies of passive reward expectancy and outcome processing.

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.

Functional neuroimaging of reward processing and decision-making: A review of aberrant motivational and affective processing in addiction and mood disorders

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 brains 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.

When Desire Collides with Reason: Functional Interactions between Anteroventral Prefrontal Cortex and Nucleus Accumbens Underlie the Human Ability to Resist Impulsive Desires

Human decisions are guided by “desire” or “reason,” which control actions oriented toward either proximal or long-term goals. Here we used functional magnetic resonance imaging to assess how the human brain mediates the balance between proximal reward desiring and long-term goals, when actions promoting a superordinate goal preclude exploitation of an immediately available reward option. Consistent with the view that the reward system interacts with prefrontal circuits during action control, we found that behavior favoring the long-term goal, but counteracting immediate reward desiring, relied on a negative functional interaction of anteroventral prefrontal cortex (avPFC) with nucleus accumbens (Nacc) and ventral tegmental area. The degree of functional interaction between avPFC and Nacc further predicted behavioral success during pursuit of the distal goal, when confronted with a proximal reward option, and scaled with interindividual differences in trait impulsivity. These findings reveal how the human brain accomplishes voluntary action control guided by “reason,” suggesting that inhibitory avPFC influences Nacc activity during actions requiring a restraint of immediate “desires.”

Impulsive personality and the ability to resist immediate reward: an fMRI study examining interindividual differences in the neural mechanisms underlying self-control.

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.

Testosterone is associated with cooperation during intergroup competition by enhancing parochial altruism

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 prisoners dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, 50 male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subjects 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.

Does Competition Really Bring Out the Worst? Testosterone, Social Distance and Inter-Male Competition Shape Parochial Altruism in Human Males

Parochial altruism, defined as increased ingroup favoritism and heightened outgroup hostility, is a widespread feature of human societies that affects altruistic cooperation and punishment behavior, particularly in intergroup conflicts. Humans tend to protect fellow group members and fight against outsiders, even at substantial costs for themselves. Testosterone modulates responses to competition and social threat, but its exact role in the context of parochial altruism remains controversial. Here, we investigated how testosterone influences altruistic punishment tendencies in the presence of an intergroup competition. Fifty male soccer fans played an ultimatum game (UG), in which they faced anonymous proposers that could either be a fan of the same soccer team (ingroup) or were fans of other teams (outgroups) that differed in the degree of social distance and enmity to the ingroup. The UG was played in two contexts with varying degrees of intergroup rivalry. Our data show that unfair offers were rejected more frequently than fair proposals and the frequency of altruistic punishment increased with increasing social distance to the outgroups. Adding an intergroup competition led to a further escalation of outgroup hostility and reduced punishment of unfair ingroup members. High testosterone levels were associated with a relatively increased ingroup favoritism and also a change towards enhanced outgroup hostility in the intergroup competition. High testosterone concentrations further predicted increased proposer generosity in interactions with the ingroup. Altogether, a significant relation between testosterone and parochial altruism could be demonstrated, but only in the presence of an intergroup competition. In human males, testosterone may promote group coherence in the face of external threat, even against the urge to selfishly maximize personal reward. In that way, our observation refutes the view that testosterone generally promotes antisocial behaviors and aggressive responses, but underlines its rather specific role in the fine-tuning of male social cognition.

Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.

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.

Brain mechanisms associated with background monitoring of the environment for potentially significant sensory events

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.

A neural system for evaluating the behavioural relevance of salient events outside the current focus of attention

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.