Selective attention towards infants in nulliparous women across the menstrual cycle.

Research in women showed that testosterone is associated with decreased selective attention towards infant stimuli, which can be compensated for by oxytocin administration. In theory, caregiving behavior is thought to be mediated by oxytocin. Oxytocin binds to dopaminergic neurons and thus supposedly motivates aspects of caregiving through its influence on dopaminergic transmission. Most previous studies on caregiving behaviors were thereby performed in women under hormonal contraception to avoid hormonal fluctuations. However, recent studies repeatedly demonstrated decisive influences of the hormonal changes across the female menstrual cycle on dopamine-mediated behaviors, suggesting that estradiol acts as dopamine agonist in the follicular phase and progesterone as dopamine antagonist in the luteal phase. In the present study, we investigated selective attention towards infants as one central aspect of caregiving behavior over the natural menstrual cycle and in relation to interindividual differences of estradiol and progesterone. As expected, we found that women with higher estradiol in the follicular phase also showed higher selective attention towards infant faces among adult distractors, whereas the correlation disappeared in the luteal phase. In contrast, progesterone did not correlate with selective attention towards infants. The present findings collectively support the assumption that estradiol may act as dopamine agonist in the follicular phase, thereby supposedly promoting an important aspect of caretaking behavior.

The impact of long-term androgen deprivation therapy on cognitive function and socioeconomic decision making in prostate cancer patients.

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.

Neural substrates of male parochial altruism are modulated by testosterone and behavioral strategy.

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.

Effects of city living on the mesolimbic reward system-An fmri study.

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.

The association between endogenous testosterone level and behavioral flexibility in young men - Evidence from stimulus-outcome reversal learning.

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.

CREB1 Genotype Modulates Adaptive Reward-Based Decisions in Humans.

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.

Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks.

BACKGROUND: Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. METHODS: We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. RESULTS: We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Broca's area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. CONCLUSION: These findings provide evidence for a slightly lower capacity in both WM modalities in females.

Be quick about it. Endogenous estradiol level, menstrual cycle phase and trait impulsiveness predict impulsive choice in the context of reward acquisition.

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.

Dissociating pathomechanisms of depression with fMRI: bottom-up or top-down dysfunctions of the reward system.

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.

Influence of female sex hormones on proactive behavioral and physiological immune parameters.

Women may be more susceptible to infections in the luteal phase, supposedly as a consequence of the hormone progesterone and its immunosuppressive action. While immunosuppression may be important for successful oocyte implantation and pregnancy, it makes women more vulnerable to pathogens. According to theory, to compensate for reduced immunocompetence, women in the luteal phase exhibit proactive behavioral responses, such as disgust and avoidance of disease-associated stimuli, to minimize contagion risk. However, previous studies yielded inconsistent results, and did not account for accompanying proactive immune responses, like the increase of secretory immunoglobin A (sIgA). Here, we assessed the proactive immune response and feelings of disgust associated with disease cues in the comparison of 61 woman with a natural menstrual cycle (31 in the follicular and 30 in the luteal phase) and 20 women taking hormonal contraception (HC). Women rated disease vulnerability and disgust propensity, watched a video displaying people with respiratory symptoms, which was evaluated for its disgust-evoking potential and contagiousness, and provided saliva samples for hormone and sIgA analysis. Women with HC reported a heightened vulnerability to disease compared to naturally cycling women, whereas both the feeling of disgust and the sIgA increase elicited by the disease video were similar across groups, regardless of progesterone. We found a u-shaped relationship between progesterone and baseline sIgA in naturally cycling women, with its nadir during ovulation. Overall, our data do not support a compensatory relationship between the proposed progesterone-induced immunosuppression and heightened disgust or a proactive sIgA response.

The COVID-19 pandemic and changes in social behavior: Protective face masks reduce deliberate social distancing preferences while leaving automatic avoidance behavior unaffected.

Protective face masks were one of the central measures to counteract viral transmission in the COVID-19 pandemic. Prior research indicates that face masks impact various aspects of social cognition, such as emotion recognition and social evaluation. Whether protective masks also influence social avoidance behavior is less clear. Our project assessed direct and indirect measures of social avoidance tendencies towards masked and unmasked faces in two experiments with 311 participants during the first half of 2021. Two interventions were used in half of the participants from each sample (Experiment 1: protective face masks; Experiment 2: a disease prime video) to decrease or increase the salience of the immediate contagion threat. In the direct social avoidance measure, which asked for the deliberate decision to approach or avoid a person in a hypothetical social encounter, participants showed an increased willingness to approach masked as opposed to unmasked faces across experiments. This effect was further related to interindividual differences in pandemic threat perception in both samples. In the indirect measure, which assessed automatic social approach and avoidance tendencies, we neither observed an approach advantage towards masked faces nor an avoidance advantage for unmasked faces. Thus, while the absence of protective face masks may have led to increased deliberate social avoidance during the pandemic, no such effect was observed on automatic regulation of behavior, thus indicating the relative robustness of this latter behavior against changes in superordinate social norms.

SARS-CoV-2 specific sIgA in saliva increases after disease-related video stimulation.

Secretory immunoglobulin A (sIgA) in saliva is the most important immunoglobulin fighting pathogens in the respiratory tract and may thus play a role in preventing SARS-CoV-2 infections. To gain a better understanding of the plasticity in the mucosal antibody, we investigated the proactive change in secretion of salivary SARS-CoV-2-specific sIgA in 45 vaccinated and/or previously infected, generally healthy persons (18 to 35 years, 22 women). Participants were exposed to a disease video displaying humans with several respiratory symptoms typical for COVID-19 in realistic situations of increased contagion risk. The disease video triggered an increase in spike-specific sIgA, which was absent after a similar control video with healthy people. The increase further correlated inversely with revulsion and aversive feelings while watching sick people. In contrast, the receptor binding domain-specific sIgA did not increase after the disease video. This may indicate differential roles of the two salivary antibodies in response to predictors of airborne contagion. The observed plasticity of spike-specific salivary antibody release after visual simulation of enhanced contagion risk suggests a role in immune exclusion.

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.

Testosterone and estradiol affect adolescent reinforcement learning.

During adolescence, gonadal hormones influence brain maturation and behavior. The impact of 17ß-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 17ß-estradiol and testosterone influenced reinforcement learning capacity in a response time adjustment task. Our data showed, that 17ß-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.

Disease-related disgust promotes antibody release in human saliva.

The behavioral immune system (BIS) comprises manifold mechanisms, that may assist the physiological immune system (PIS) in counteracting infection and can even reduce the risk of contagion. Previous studies have found initial evidence for possible interactions between the two systems. However, most of these findings were correlative and have not been replicated. Further, none of these studies examined whether disease stimuli that indicate an enhanced airborne transmission risk may trigger a different immune response in comparison to stimuli that predominantly evoke core disgust. In the present study, we employed a video-priming approach to get further insight in the influence of the perception of disgust- and disease-related stimuli on the rapid physiological immune response, as indicated by changes of secretory immunoglobulin A (S-IgA) in saliva. We created three video primers that represented different categories of disgust- and/or disease-associated content. Two of the videos showed disease-related situations that were associated with contagious respiratory virus infections, varying in concealment of aerosols. The third video incurred no heightened airborne contagion risk, but comprised situations that are known to elicit core disgust, such as rotten foods, decaying animal carcasses, or cockroaches. A fourth video acted as control showing landscape impressions. The different video primers varied in their contagion risk and disgust-evoking potential. Given the role of S-IgA in the mucosal immune defense, we expected differences in the S-IgA response between the two videos indicating a heightened airborne contagion risk and the core disgust video, with the highest S-IgA to occur after the aerosol video. For this, we used the data of 107 healthy participants in a between-subjects design with the four video primers. We found a significant increase of S-IgA in response to both the disease- and the disgust-related videos, which correlated positively with the perceived contagion risk of the displayed situations. Nevertheless, there was no significant difference in the increase between the three disease- and disgust-related videos. We also found that people with a high contamination disgust produced less S-IgA in such situations, which is a hint for a compensating relationship between the BIS and PIS. Our observations suggest that the mere visual perception of videos showing realistic situations of an increased contagion risk can elicit a heightened release of salivary antibodies.

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."

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 power of imagination--how anticipatory mental imagery alters perceptual processing of fearful facial expressions.

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.

Daytime and season do not affect reinforcement learning capacity in a response time adjustment task.

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.

Dopamine multilocus genetic profiles predict sex differences in reactivity of the human reward system.

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.