Sex differences in cortisol levels in depression: A systematic review and meta-analysis.

Higher prevalence of depression in females might be associated with sex-specific cortisol levels. Evidence exists that cortisol levels differ between healthy females and males, however a sex-specific association in depression has not been systematically assessed. Thus, the current study quantifies the existing literature on different cortisol parameters, i.e., basal cortisol, hair cortisol, cortisol awakening response (CAR), and cortisol stress reactivity comparing depressed females and males as well as sex-specific comparisons with healthy controls. Following an extensive literature research, fifty original articles were included. Depressed females had significantly higher hair cortisol, higher CAR, and lower cortisol stress reactivity compared to depressed males. In comparison with sex-matched controls, female patients had significantly higher evening basal cortisol, higher CAR and lower cortisol stress reactivity, and male patients had significantly higher general, morning and evening basal cortisol. Overall, sex as a fundamental driver of cortisol levels in depression needs to be taken into account.

Association of levonorgestrel intrauterine devices with stress reactivity, mental health, quality of life and sexual functioning: A systematic review.

Levonorgestrel-intrauterine-devices (LNG-IUD) are one of the most used contraceptive methods worldwide. While several reviews exist on how LNG-IUDs impact physiology and gynaecological functions, this systematic review focuses on stress, mental health, quality of life, sexual functioning, and effects on brain architecture. While data on stress is scarce, results on mental health are ambiguous. More consistently, LNG-IUD use seems to improve quality of life and sexual functioning. No studies highlighting the consequences of LNG-IUD use on the brain were found. The reviewed studies are characterized by a substantial variation in approaches, participant groups, and study quality. More high-quality research assessing the effects of LNG-IUD on mental health, including response to stressors and brain function and structure, is needed to identify women vulnerable to adverse effects of LNG-IUD, also in comparison to oral contraceptives, and to empower women to make more informed choices concerning hormonal contraception.

Functional parcellation of human and macaque striatum reveals human-specific connectivity in the dorsal caudate.

A wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders.

The human body odor compound androstadienone increases neural conflict coupled to higher behavioral costs during an emotional Stroop task.

The androgen derivative androstadienone (AND) is a substance found in human sweat and thus may act as human chemosignal. With the current experiment, we aimed to explore in which way AND affects interference processing during an emotional Stroop task which used human faces as target and emotional words as distractor stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to unravel the neural mechanism of AND-action. Based on previous accounts we expected AND to increase neural activation in areas commonly implicated in evaluation of emotional face processing and to change neural activation in brain regions linked to interference processing. For this aim, a total of 80 healthy individuals (oral contraceptive users, luteal women, men) were tested twice on two consecutive days with an emotional Stroop task using fMRI. Our results suggest that AND increases interference processing in brain areas that are heavily recruited during emotional conflict. At the same time, correlation analyses revealed that this neural interference processing was paralleled by higher behavioral costs (response times) with higher interference related brain activation under AND. Furthermore, AND elicited higher activation in regions implicated in emotional face processing including right fusiform gyrus, inferior frontal gyrus and dorsomedial cortex. In this connection, neural activation was not coupled to behavioral outcome. Furthermore, despite previous accounts of increased hypothalamic activation under AND, we were not able to replicate this finding and discuss possible reasons for this discrepancy. To conclude, AND increased interference processing in regions heavily recruited during emotional conflict which was coupled to higher costs in resolving emotional conflicts with stronger interference-related brain activation under AND. At the moment it remains unclear whether these effects are due to changes in conflict detection or resolution. However, evidence most consistently suggests that AND does not draw attention to the most potent socio-emotional information (human faces) but rather highlights representations of emotional words.

Sex differences in the functional connectivity of the amygdalae in association with cortisol.

Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal-occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required.

Psychosocial versus physiological stress - Meta-analyses on deactivations and activations of the neural correlates of stress reactions.

Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended.

Sex differences in cognitive regulation of psychosocial achievement stress: brain and behavior.

Although cognitive regulation of emotion has been extensively examined, there is a lack of studies assessing cognitive regulation in stressful achievement situations. This study used functional magnetic resonance imaging in 23 females and 20 males to investigate cognitive downregulation of negative, stressful sensations during a frequently used psychosocial stress task. Additionally, subjective responses, cognitive regulation strategies, salivary cortisol, and skin conductance response were assessed. Subjective response supported the experimental manipulation by showing higher anger and negative affect ratings after stress regulation than after the mere exposure to stress. On a neural level, right middle frontal gyrus (MFG) and right superior temporal gyrus (STG) were more strongly activated during regulation than nonregulation, whereas the hippocampus was less activated during regulation. Sex differences were evident: after regulation females expressed higher subjective stress ratings than males, and these ratings were associated with right hippocampal activation. In the nonregulation block, females showed greater activation of the left amygdala and the right STG during stress than males while males recruited the putamen more robustly in this condition. Thus, cognitive regulation of stressful achievement situations seems to induce additional stress, to recruit regions implicated in attention integration and working memory and to deactivate memory retrieval. Stress itself is associated with greater activation of limbic as well as attention areas in females than males. Additionally, activation of the memory system during cognitive regulation of stress is associated with greater perceived stress in females. Sex differences in cognitive regulation strategies merit further investigation that can guide sex sensitive interventions for stress-associated disorders.

Estradiol modulates changes in effective connectivity in emotion regulation networks.

Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So far, the neural underpinnings of the effect of E2 on emotional experience have been investigated using task-based functional magnetic resonance imaging (fMRI) and functional connectivity. In the present study, we examined whether the intrinsic network dynamics at rest (i.e., directed effective connectivity) related to emotion regulation are (1) modulated by E2 levels and (2) linked to behavioral emotion regulation ability. Hence, 29 naturally cycling women participated in two resting-state fMRI scans in their early follicular phase after being administered a placebo or an E2 valerate, respectively. Emotion regulation ability was assessed using a standard emotion regulation task in which participants were asked to down-regulate their emotions in response to negative images. The regions of two functionally predefined neural networks related to emotional down-regulation and reactivity were used to investigate effective connectivity at rest using spectral dynamic causal modelling. We found that E2, compared to placebo, resulted in changes in effective connectivity in both networks. In the regulation network, prefrontal regions showed distinct connectivity in the E2 compared to the placebo condition, while mixed results evolved in the emotional reactivity network. Stepwise regressions revealed that in the E2 condition a connection from the parietal to the prefrontal cortex predicted regulation ability. Our results demonstrate that E2 levels influence effective connectivity in networks underlying emotion regulation and emotional reactivity. Thus, E2 and its potential modification via hormonal administration may play a supporting role in the treatment of mental disorders that show a dysregulation of emotions.

Cognitive Stress Regulation in Schizophrenia Patients and Healthy Individuals: Brain and Behavior.

Stress is an important factor in the development, triggering, and maintenance of psychotic symptoms. Still, little is known about the neural correlates of cognitively regulating stressful events in schizophrenia. The current study aimed at investigating the cognitive down-regulation of negative, stressful reactions during a neuroimaging psychosocial stress paradigm (non-regulated stress versus cognitively regulated stress). In a randomized, repeated-measures within-subject design, we assessed subjective reactions and neural activation in schizophrenia patients (SZP) and matched healthy controls in a neuroimaging psychosocial stress paradigm. In general, SZP exhibited an increased anticipation of stress compared to controls (p = 0.020). During non-regulated stress, SZP showed increased negative affect (p = 0.033) and stronger activation of the left parietal operculum/posterior insula (p < 0.001) and right inferior frontal gyrus/anterior insula (p = 0.005) than controls. Contrarily, stress regulation compared to non-regulated stress led to increased subjective reactions in controls (p = 0.003) but less deactivation in SZP in the ventral anterior cingulate cortex (p = 0.027). Our data demonstrate stronger reactions to and anticipation of stress in patients and difficulties with cognitive stress regulation in both groups. Considering the strong association between mental health and stress, the investigation of cognitive regulation in individuals vulnerable to stress, including SZP, has crucial implications for improving stress intervention trainings.

Stressor-Specific Sex Differences in Amygdala-Frontal Cortex Networks.

Females and males differ in stress reactivity, coping, and the prevalence rates of stress-related disorders. According to a neurocognitive framework of stress coping, the functional connectivity between the amygdala and frontal regions (including the dorsolateral prefrontal cortex (dlPFC), ventral anterior cingulate cortex (vACC), and medial prefrontal cortex (mPFC)) plays a key role in how people deal with stress. In the current study, we investigated the effects of sex and stressor type in a within-subject counterbalanced design on the resting-state functional connectivity (rsFC) of the amygdala and these frontal regions in 77 healthy participants (40 females). Both stressor types led to changes in subjective ratings, with decreasing positive affect and increasing negative affect and anger. Females showed higher amygdala-vACC and amygdala-mPFC rsFC for social exclusion than for achievement stress, and compared to males. Whereas a higher amygdala-vACC rsFC indicates the activation of emotion processing and coping, a higher amygdala-mPFC rsFC indicates feelings of reward and social gain, highlighting the positive effects of social affiliation. Thus, for females, feeling socially affiliated might be more fundamental than for males. Our data indicate interactions of sex and stressor in amygdala-frontal coupling, which translationally contributes to a better understanding of the sex differences in prevalence rates and stress coping.

Testosterone and the Amygdala's Functional Connectivity in Women and Men.

The amygdala contains androgen receptors and is involved in various affective and social functions. An interaction between testosterone and the amygdala's functioning is likely. We investigated the amygdala's resting-state functional connectivity (rsFC) network in association with testosterone in 94 healthy young adult women and men (final data available for analysis from 42 women and 39 men). Across the whole sample, testosterone was positively associated with the rsFC between the right amygdala and the right middle occipital gyrus, and it further predicted lower agreeableness scores. Significant sex differences appeared for testosterone and the functional connectivity between the right amygdala and the right superior frontal gyrus (SFG), showing higher testosterone levels with lower connectivity in women. Sex further predicted the openness and agreeableness scores. Our results show that testosterone modulates the rsFC between brain areas involved in affective processing and executive functions. The data indicate that the cognitive control of the amygdala via the frontal cortex is dependent on the testosterone levels in a sex-specific manner. Testosterone seems to express sex-specific patterns (1) in networks processing affect and cognition, and (2) in the frontal down-regulation of the amygdala. The sex-specific coupling between the amygdala and the frontal cortex in interaction with the hormone levels may drive sex-specific differences in a variety of behavioral phenomena that are further associated with psychiatric illnesses that show sex-specific prevalence rates.

Pregnancy and brain architecture: Associations with hormones, cognition and affect.

Sex hormones such as estradiol (E2) have long-lasting influence on brain architecture. Recent studies indicate further structural changes during hormonal transition periods including pregnancy, when women experience the greatest increase in sex hormone levels across their life span. In the present study, three groups of women (n = 44) with different levels of E2 underwent structural magnetic resonance imaging: (1) first-time pregnant women (n = 13, 'extreme E2 group'); (2), nulliparous, naturally cycling women who received 12 mg of E2 valerate (n = 16, 'high E2 group'); and (3) nulliparous, naturally cycling women receiving a placebo and hence low E2 (n = 15, 'low E2 group'). Blood samples were taken to assess hormonal levels. Moreover, parameters for cognition, emotion regulation and affect were assessed. On the neuronal level, the extreme E2 compared to the high E2 group showed a reduced gray matter volume in the left putamen. However, no significant differences were found between the low vs. high E2 groups, nor between the low E2 and extreme E2 groups. Cognitive performance was reduced in the extreme E2 group, although a positive affect was increased compared to the high E2 and low E2 groups. Furthermore, regression analyses revealed several associations between cognition, subjective measures of affect, emotion regulation and gray matter volume. A volume reduction of the left putamen during pregnancy further supports the notion that the female brain is shaped by hormonal transition phases, possibly preparing women for their future roles (e.g., pregnant women for their role as mothers).

Estradiol administration modulates neural emotion regulation.

Variations of sex hormones during the menstrual cycle can lead to changes in emotion processing. The ability to successfully regulate one's emotions is associated with better social abilities and mental health. While women show better performance in fear extinction learning under high estradiol (E2) compared to women under low E2 levels, little is known about the effect of E2 on emotion regulation. We explored whether E2 modulates emotion regulation in a functional magnetic resonance imaging paradigm and administered E2 valerate to 32 young naturally cycling women during their early follicular phase in a double-blind, placebo-controlled within-subject design. This standardized experimental control allowed us to explore the specific effect of E2 on emotion regulation while controlling for other hormones varying throughout the menstrual cycle. Behaviorally, no difference between conditions appeared. However, on the neural level, E2 administration was associated with lower activation in the right lingual- and left calcarine gyrus, right orbitofrontal cortex and left hippocampus relative to placebo. With respect to the main effect of down-regulation higher activation of the right superior frontal gyrus and left dorsomedial prefrontal cortex was seen; which is in accordance to previous literature. An interaction between drug condition and emotion regulation appeared for the left inferior frontal gyrus extending into the middle frontal gyrus indicating lower activation during down-regulation in the E2 condition than the placebo condition. On the behavioral level, women reported less negative affect in the E2 condition. The results fit well to a previously described psychoneuroendocrinological model in which E2 plays an important modulatory role on emotional processes and risk factors of mental health in women.

Neurobiological substrates of the positive formal thought disorder in schizophrenia revealed by seed connectome-based predictive modeling.

Formal thought disorder (FTD) is a core symptom cluster of schizophrenia, but its neurobiological substrates remain poorly understood. Here we collected resting-state fMRI data from 276 subjects at seven sites and employed machine-learning to investigate the neurobiological correlates of FTD along positive and negative symptom dimensions in schizophrenia. Three a priori, meta-analytically defined FTD-related brain regions were used as seeds to generate whole-brain resting-state functional connectivity (rsFC) maps, which were then compared between schizophrenia patients and controls. A repeated cross-validation procedure was realized within the patient group to identify clusters whose rsFC patterns to the seeds were repeatedly observed as significantly associated with specific FTD dimensions. These repeatedly identified clusters (i.e., robust clusters) were functionally characterized and the rsFC patterns were used for predictive modeling to investigate predictive capacities for individual FTD dimensional-scores. Compared with controls, differential rsFC was found in patients in fronto-temporo-thalamic regions. Our cross-validation procedure revealed significant clusters only when assessing the seed-to-whole-brain rsFC patterns associated with positive-FTD. RsFC patterns of three fronto-temporal clusters, associated with higher-order cognitive processes (e.g., executive functions), specifically predicted individual positive-FTD scores (p = 0.005), but not other positive symptoms, and the PANSS general psychopathology subscale (p > 0.05). The prediction of positive-FTD was moreover generalized to an independent dataset (p = 0.013). Our study has identified neurobiological correlates of positive FTD in schizophrenia in a network associated with higher-order cognitive functions, suggesting a dysexecutive contribution to FTD in schizophrenia. We regard our findings as robust, as they allow a prediction of individual-level symptom severity.

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture.

BACKGROUND: Despite the marked interindividual variability in the clinical presentation of schizophrenia, the extent to which individual dimensions of psychopathology relate to the functional variability in brain networks among patients remains unclear. Here, we address this question using network-based predictive modeling of individual psychopathology along 4 data-driven symptom dimensions. Follow-up analyses assess the molecular underpinnings of predictive networks by relating them to neurotransmitter-receptor distribution patterns. METHODS: We investigated resting-state functional magnetic resonance imaging data from 147 patients with schizophrenia recruited at 7 sites. Individual expression along negative, positive, affective, and cognitive symptom dimensions was predicted using a relevance vector machine based on functional connectivity within 17 meta-analytic task networks following repeated 10-fold cross-validation and leave-one-site-out analyses. Results were validated in an independent sample. Networks robustly predicting individual symptom dimensions were spatially correlated with density maps of 9 receptors/transporters from prior molecular imaging in healthy populations. RESULTS: Tenfold and leave-one-site-out analyses revealed 5 predictive network-symptom associations. Connectivity within theory of mind, cognitive reappraisal, and mirror neuron networks predicted negative, positive, and affective symptom dimensions, respectively. Cognitive dimension was predicted by theory of mind and socioaffective default networks. Importantly, these predictions generalized to the independent sample. Intriguingly, these two networks were positively associated with D1 receptor and serotonin reuptake transporter densities as well as dopamine synthesis capacity. CONCLUSIONS: We revealed a robust association between intrinsic functional connectivity within networks for socioaffective processes and the cognitive dimension of psychopathology. By investigating the molecular architecture, this work links dopaminergic and serotonergic systems with the functional topography of brain networks underlying cognitive symptoms in schizophrenia.

Do I feel or do I know? Neuroimaging meta-analyses on the multiple facets of empathy.

Empathy is a multidimensional construct including affective and cognitive components while maintaining the distinction between one-self and others. Our meta-analyses focused on shared and distinct networks underlying cognitive (taking somebody else's perspective in emotional/painful situations) and affective (self-referentially feeling somebody else's emotions/pain) empathy for various states including painful and emotional situations. Furthermore, a comparison with direct pain experience was carried out. For cognitive empathy, consistent activation in the anterior dorsal medial frontal gyrus (dmPFG) and the supramarginal gyrus (SMG) occurred. For affective empathy, convergent activation of the posterior dmPFG and the inferior frontal gyrus (IFG) was found. Consistent activation of the anterior insula (AI), the anterior dmPFG and the SMG was observed for empathy for pain, while convergent recruitment of the temporo-parietal junction, precuneus, posterior dmPFG, and the IFG was revealed in the meta-analysis across empathy for emotion experiments. The AI and the dmPFG/mid-cingulate cortex (MCC) showed overlapping as well as distinct neural activation for pain processing and empathy for pain. Taken together, we were able to show difference in the meta-analytic networks across cognitive and affective empathy as well as for pain and empathy processing. Based on the current results, distinct functions along the midline structures of the brain during empathy processing are apparent. Our data are lending further support for a multidimensional concept of empathy.

Neurobiological Divergence of the Positive and Negative Schizophrenia Subtypes Identified on a New Factor Structure of Psychopathology Using Non-negative Factorization: An International Machine Learning Study.

BACKGROUND: Disentangling psychopathological heterogeneity in schizophrenia is challenging, and previous results remain inconclusive. We employed advanced machine learning to identify a stable and generalizable factorization of the Positive and Negative Syndrome Scale and used it to identify psychopathological subtypes as well as their neurobiological differentiations. METHODS: Positive and Negative Syndrome Scale data from the Pharmacotherapy Monitoring and Outcome Survey cohort (1545 patients; 586 followed up after 1.35 ± 0.70 years) were used for learning the factor structure by an orthonormal projective non-negative factorization. An international sample, pooled from 9 medical centers across Europe, the United States, and Asia (490 patients), was used for validation. Patients were clustered into psychopathological subtypes based on the identified factor structure, and the neurobiological divergence between the subtypes was assessed by classification analysis on functional magnetic resonance imaging connectivity patterns. RESULTS: A 4-factor structure representing negative, positive, affective, and cognitive symptoms was identified as the most stable and generalizable representation of psychopathology. It showed higher internal consistency than the original Positive and Negative Syndrome Scale subscales and previously proposed factor models. Based on this representation, the positive-negative dichotomy was confirmed as the (only) robust psychopathological subtypes, and these subtypes were longitudinally stable in about 80% of the repeatedly assessed patients. Finally, the individual subtype could be predicted with good accuracy from functional connectivity profiles of the ventromedial frontal cortex, temporoparietal junction, and precuneus. CONCLUSIONS: Machine learning applied to multisite data with cross-validation yielded a factorization generalizable across populations and medical systems. Together with subtyping and the demonstrated ability to predict subtype membership from neuroimaging data, this work further disentangles the heterogeneity in schizophrenia.

Exploring the fMRI based neural correlates of the dot probe task and its modulation by sex and body odor.

The dot probe task implicitly cues attention via emotional information, an effect which is especially pronounced for threat-related cues. However, several questions remain unexplored. The first one is whether chemosignals like the androgen-derivative androstadienone can influence such attentional biases. Second, few studies have addressed sex differences regarding attentional biases. Finally, the neural correlates of these potential behavioral effects based on functional magnetic resonance imaging (fMRI) are not known. In two experiments we aimed to answer these questions. A total of 159 healthy individuals (58 oral-contraceptive-users, 42 luteal women, 59 men) were tested. In experiment 1 (behavioral study) we examined attentional biases behaviorally, while in experiment 2 (fMRI study) the dot probe task was complemented by fMRI. Our results provide robust evidence that in healthy participants fearful but not angry or happy faces lead to a strong general attentional bias. Elucidating the neural basis of this effects points to an early processing advantage in bilateral thalamus for valid compared to invalid cued fear. However, this finding was limited to those participants with the strongest attentional biases and was not linked to behavioral measures. Furthermore, no consistent sex or group differences existed neither did the putative human chemosignal androstadienone reliably modulate attentional biases or change neural processing.

Imaging the up's and down's of emotion regulation in lifetime depression.

Reappraisal is a particularly effective strategy for influencing emotional experiences, specifically for reducing the impact of negative stimuli. Although depression has repeatedly been linked to dysfunctional behavioral and neural emotion regulation, prefrontal and amygdala engagement seems to vary with clinical characteristics and the specific regulation strategy used. Whereas previous neuroimaging research has focused on down-regulating reactions to emotionally evocative scenes, the current study compared up- and down-regulation in response to angry facial expressions in patients with depression and healthy individuals. During the initial viewing of faces, patients with depression showed hypoactivation particularly in areas implicated in emotion generation, i.e., amygdala, insula and putamen. In contrast, up-regulating negative emotions yielded stronger recruitment of core face processing areas and posterior medial frontal cortex in patients than in controls. However, group differences did not extend to resting-state functional connectivity. Recurrent depression was inversely associated with amygdala activation specifically during down-regulation, but differences in medication status may limit the current findings. Despite a pattern of reduced neural emotional reactivity in mainly medicated patients, their 'successful' recruitment of the regulation network for up-regulation might point toward an effective use of reappraisal when increasing negative emotions. Future studies need to address how patients might benefit from transferring this ability to adaptive goals, such as improving interpersonal emotion regulation.

Differential Resting-State Connectivity Patterns of the Right Anterior and Posterior Dorsolateral Prefrontal Cortices (DLPFC) in Schizophrenia.

In schizophrenia (SCZ), dysfunction of the dorsolateral prefrontal cortex (DLPFC) has been linked to the deficits in executive functions and attention. It has been suggested that, instead of considering the right DLPFC as a cohesive functional entity, it can be divided into two parts (anterior and posterior) based on its whole-brain connectivity patterns. Given these two subregions' differential association with cognitive processes, we investigated the functional connectivity (FC) profile of both subregions through resting-state data to determine whether they are differentially affected in SCZ. Resting-state magnetic resonance imaging (MRI) scans were obtained from 120 patients and 172 healthy controls (HC) at 6 different MRI sites. The results showed differential FC patterns for the anterior and posterior parts of the right executive control-related DLPFC in SCZ with the parietal, the temporal and the cerebellar regions, along with a convergent reduction of connectivity with the striatum and the occipital cortex. An increased psychopathology level was linked to a higher difference in posterior vs. anterior FC for the left IFG/anterior insula, regions involved in higher-order cognitive processes. In sum, the current analysis demonstrated that even between two neighboring clusters connectivity could be differentially disrupted in SCZ. Lacking the necessary anatomical specificity, such notions may in fact be detrimental to a proper understanding of SCZ pathophysiology.