The levonorgestrel-releasing intrauterine device is related to early emotional reactivity: An ERP study.

Despite the evidence of altered emotion processing in oral contraceptive (OC) users, the impact of hormonal intrauterine devices (IUD) on emotional processing remains unexplored. Our study aimed to investigate how behavioural performance and event-related potentials (ERPs) linked with emotion reactivity and its regulation are associated with hormonal profiles of women using different types of hormonal contraception and naturally cycling women. Women using OCs (n = 25), hormonal IUDs (n = 33), and naturally cycling women in their early follicular (NCF, n = 33) or mid-luteal (NCL, n = 28) phase of the menstrual cycle were instructed to view emotional pictures (neutral, low and high negativity) and use cognitive reappraisal to up- or down-regulate negative emotions, while their electroencephalogram was recorded. Participants rated perceived negativity after each picture and their emotional arousal throughout the task. Saliva samples were collected to assess levels of 17ß-estradiol, progesterone, and testosterone. As expected, emotional arousal increased throughout the task and correlated positively with perceived negativity. Perceived negativity and the amplitudes of the middle (N2/P3) and later (LPP) latency ERP components increased with increasing stimuli negativity. Emotion regulation modulated perceived negativity and the amplitudes of very late ERP components (parietal and frontal LPP). Moreover, IUD-users showed a higher negative amplitude of the frontal N2 in comparison to all three other groups, with the most consistent differences during up-regulation. Finally, testosterone correlated positively with the N2 peak in IUD-users and NCL women. Overall, our findings suggest that IUD-use and testosterone might be related to altered preconscious processing during the emotion regulation task requiring attention to the stimulus. The study underscores the need for additional research into how different hormonal contraceptives are linked to socio-emotional functioning.

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.

The Human Affectome.

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective phenomena can collectively be considered algorithms that either adjust based on the human comfort zone (affective concerns) or monitor those adaptive processes (affective features). This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope the Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis.

Worldwide, over 150 million adolescent and adult women use oral contraceptives (OC). An association between OC-use and the emergence of symptoms of mental disorders has been suggested. This systematic review and meta-analysis provide an overview of published research regarding symptoms of mental disorders in association with OC-use, factoring the influence of OC types, age of first-use, duration of OC-intake, and previous diagnoses of mental disorders. A systematic literature search was conducted between June-July 2022. 22 studies were included. While most found no significant OC-use effects on mental symptoms, some hinted at OCs as a potential risk. The existing evidence regarding the potential link between progestin-only OC-use and an elevated risk of mental symptoms in comparison to combined OC-use remains inconclusive. However, due to emerging indications suggesting that the formulation of OC might play a role in mental health outcomes, this topic warrants further investigation. Moreover, indications of an increased risk for depressive symptoms in adolescent OC-users should be noted. Hence, while general population effects seem unlikely, they cannot be completely disregarded. The decision on OC-use should depend on the patient's medical history and should be re-evaluated regularly.

Sex matters for the enhancement of cognitive training with transcranial direct current stimulation (tDCS).

BACKGROUND: Transcranial direct current stimulation (tDCS) can influence brain network activity and associated cognitive and behavioural functions. In addition to the extensive variety in stimulation parameters, numerous biological factors drive these effects, however these are yet poorly understood. Here, we investigate one of the major biological factors by focusing on sex-dependent effects of tDCS on a challenging cognitive control task (adaptive paced auditory serial addition task [PASAT]) in healthy humans. METHODS: This sex-specific re-analysis was performed on data of 163 subjects who underwent a 2-week cognitive control training (6 sessions in total). Subjects received either verum (anodal/cathodal) or sham tDCS. Electrodes were placed over the left or right dorsolateral prefrontal cortex and the respective contralateral deltoid muscle. Cognitive control was measured as performance in the PASAT and was analysed in respect to stimulation conditions (sham, anodal, cathodal) and sex. RESULTS: Regardless of stimulation condition, performance gains between the sexes were higher in females compared to males (p = 0.0038). Female's performance during anodal tDCS exceeded male's (p = 0.0070), yet no effects were found for cathodal or sham tDCS. Moreover, in females we found a superior effect for anodal tDCS over sham stimulation (fanodal: p = 0.0354; fcathodal: p = 0.6181), but no such effect in males (manodal: p = 0.6882; mcathodal: p = 0.4822). CONCLUSIONS: This study highlights the relevance of biological sex for the effects of tDCS on cognitive training. Thus, an increased attention to biological sex is advisable in future brain stimulation research to highlight and in consequence better understand potentially underlying sex-specific mechanisms. Considering biological sex will further advance customisation and individualisation of tDCS interventions. Trial registration ClinicalTrials.gov, NCT04108663.

In previous studies, brain stimulation techniques like transcranial direct current stimulation (tDCS) have been shown to support cognitive trainings. However, these effects are rather small and vary between people. A key factor of variability is the biological sex. Hence, in this study we were interested in whether the effects of tDCS differ between females and males. To answer this research question, we analysed the data of 163 human subjects who underwent a 2-week cognitive control training program, which incorporates a challenging cognitive task (the adaptive paced auditory serial addition task [PASAT]). During the PASAT, subjects have to solve a stressful calculation exercise. Concurrently to solving this task, the subjects received either real (further divided into anodal [= enhancing] and cathodal [= inhibiting]) or placebo tDCS. We found that females had greater performance gains in the task than males, regardless of the type of tDCS they received. Furthermore, females performed particularly well when they received anodal tDCS, but there were no significant effects for cathodal or placebo tDCS. For males, we did not find any significant benefits of tDCS. These findings highlight the importance of considering biological sex in future brain stimulation research and suggest that biological sex is an important component to consider when studying the effects of tDCS. By paying more attention to this factor, researchers can better understand how tDCS works and develop more effective and personalised interventions.

Interrelated effects of age and parenthood on whole-brain controllability: protective effects of parenthood in mothers.

Background: Controllability is a measure of the brain's ability to orchestrate neural activity which can be quantified in terms of properties of the brain's network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to long-lasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging. Methods: In a sample of 814 healthy individuals (aged 33.9 ± 12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability). Results and conclusion: In nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers.

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.

Accurate sex prediction of cisgender and transgender individuals without brain size bias.

The increasing use of machine learning approaches on neuroimaging data comes with the important concern of confounding variables which might lead to biased predictions and in turn spurious conclusions about the relationship between the features and the target. A prominent example is the brain size difference between women and men. This difference in total intracranial volume (TIV) can cause bias when employing machine learning approaches for the investigation of sex differences in brain morphology. A TIV-biased model will not capture qualitative sex differences in brain organization but rather learn to classify an individual's sex based on brain size differences, thus leading to spurious and misleading conclusions, for example when comparing brain morphology between cisgender- and transgender individuals. In this study, TIV bias in sex classification models applied to cis- and transgender individuals was systematically investigated by controlling for TIV either through featurewise confound removal or by matching the training samples for TIV. Our results provide strong evidence that models not biased by TIV can classify the sex of both cis- and transgender individuals with high accuracy, highlighting the importance of appropriate modeling to avoid bias in automated decision making.

The impact of emotional stimuli on response inhibition in an inpatient and day-hospital patient psychosomatic cohort.

Objectives: To correctly recognize and respond to your counterpart's emotion is essential for a successful get-together. To ensure this, emotional processes and inhibitory control are linked and interact with each other. However, this interaction can be altered in several mental disorders. In a group of psychosomatic patients, we investigated possible differences in the response inhibition between neutral and emotional stimuli and whether a psychosomatic inpatient and day-hospital patient treatment influences response inhibition profiles. Methods: One hundred and one patients, diagnosed with different psychiatric diagnoses (77 women, 41.43 ± 13.13 years), completed an emotional stop-signal task (ESST) and an impulsive behavior scale upon admission in an inpatient and day-hospital patient treatment on a psychosomatic ward (T0) and at discharge (T1). Patients with depressive disorders completed the test again after 1 year (follow-up measurement T2, n = 22). Emotional stimuli were angry and neutral faces. Stop-signal reaction time (SSRT) and stop-signal delay (SSD) were calculated as the main behavioral parameters. Results: We found a significantly higher SSRT for neutral than angry faces at both admission (8.538 ms, p < 0.001) and discharge (11.142 ms, p < 0.001), with a matching higher SSD for angry than neutral faces at both timepoints (T0: 8.360 ms, p < 0.001, T1: (6.950 ms, p < 0.001). The SSRT for angry faces significantly decreased after treatment (-8.485 ms, p = 0.0110). For neutral faces, the decrease failed to reach significance (-5.881 ms, p = 0.250). A significant decrease in SSRT for neutral faces in patients with depressive disorders was found 1 year after discharge compared with admission (-19.040 ms, p = 0.0380). Conclusion: Our data demonstrate a decreased response inhibition for neutral compared with emotional stimuli and an improved response inhibition for angry faces after discharge in a psychosomatic inpatient and day-hospital patient cohort. Additionally, patients with depressive disorders displayed a significantly better response inhibition for neutral faces 1 year after discharge compared with the baseline measurement. With this study, we provide more evidence for altered emotional response inhibition in different mental disorders and a hint that psychosomatic inpatient and day-hospital patient treatment may help to normalize it, even if the effects remained small and it needs further research to prove causality.

Inhibitory control towards angry stimuli in patients with binge eating disorder: a pilot study.

BACKGROUND: Emotion regulation theories and the negative urgency concept assume that negative mood increases binge eating. Negative emotions are considered as a trigger for binge eating, while binge eating itself is regarded as an impulsive behavior and should thus be increased within the negative urgency concept. Anger might be a specific negative emotion triggering binge eating in patients with binge eating disorder (BED). We investigated how inhibitory control as one main factor of impulsivity is influenced by anger stimuli in patients with BED and two control groups. METHODS: We compared patients with BED (N = 20) with normal-weight healthy control participants (NW-CG, N = 20) and BMI-matched overweight and obese control participants (BMI-CG, N = 18). We used the emotional Stop Signal task (eSST) to investigate inhibitory control, where we presented angry facial expressions in comparison with neutral facial expressions as emotional stimuli. RESULTS: All participants showed decreased inhibitory control in the angry versus neutral condition, i.e., a faster Stop Signal Reaction Time and a lower percentage of correct reactions. However, no significant group differences emerged in terms of performance. Performance in the eSST did not correlate with negative urgency, disorder- or emotion-related characteristics. CONCLUSIONS: The current pilot study does not deliver evidence for decreased inhibitory control towards angry stimuli in patients with BED, as we detected a general and not disorder-related effect in all participants that might represent the conjunction of inhibitory control and anger. A direct mood induction technique might have led to different results. Further research in healthy and clinical groups is needed.

Several theories suggest that binge eating episodes are often appearing in negative mood and anger is one specific emotion that might commonly trigger binge eating. The aim of this study was to investigate inhibitory control under anger in patients with binge eating disorder (BED). Inhibitory control is a specific component of impulsivity and further studies suggest that inhibitory control deficits are related to binge eating. We compared patients with BED with normal-weight participants and overweight or obese participants as control groups in a specific inhibitory control task, where faces with angry or neutral expressions were presented and participants should stop, i.e. inhibit their reactions. All participants had more inhibitory control deficits when they viewed angry faces in comparison with neutral expressions, and patients with BED did not differ from the participants of the two control groups. Thus, all participants react on anger with increased impulsivity indicating that patients with BED seem to have no specific deficit in this regard. As this was a pilot study, further studies should investigate the interplay of several emotions and impulsivity in healthy and clinical groups.

Women compared with men work harder for small rewards.

In cost-benefit decision-making, women and men often show different trade-offs. However, surprisingly little is known about sex differences in instrumental tasks, where physical effort is exerted to gain rewards. To this end, we tested 81 individuals (47 women) with an effort allocation task, where participants had to repeatedly press a button to collect food and money tokens. We analyzed the motivational phases of invigoration and effort maintenance with varying reward magnitude, difficulty, and reward type. Whereas women and men did not differ in invigoration, we found that women showed higher effort maintenance as well as higher subjective wanting and exertion ratings for small rewards compared with men. Notably, men increased their effort more than women for higher rewards to match women's levels of performance. Crucially, we found no sex differences depending on reward type or difficulty, indicating that sex differences were specific to the encoding of the magnitude of benefits, not costs. To summarize, women exerted higher physical effort for small rewards, which corresponded with an elevated subjective value in women compared with men. Therefore, sex differences in perceived reward magnitude may contribute to differential behavioral preferences highlighting the potential of cost-benefit decision-making to provide insights about potential mechanisms.

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.

Accurate machine learning prediction of sexual orientation based on brain morphology and intrinsic functional connectivity.

BACKGROUND: Sexual orientation in humans represents a multilevel construct that is grounded in both neurobiological and environmental factors. OBJECTIVE: Here, we bring to bear a machine learning approach to predict sexual orientation from gray matter volumes (GMVs) or resting-state functional connectivity (RSFC) in a cohort of 45 heterosexual and 41 homosexual participants. METHODS: In both brain assessments, we used penalized logistic regression models and nonparametric permutation. RESULTS: We found an average accuracy of 62% (±6.72) for predicting sexual orientation based on GMV and an average predictive accuracy of 92% (±9.89) using RSFC. Regions in the precentral gyrus, precuneus and the prefrontal cortex were significantly informative for distinguishing heterosexual from homosexual participants in both the GMV and RSFC settings. CONCLUSIONS: These results indicate that, aside from self-reports, RSFC offers neurobiological information valuable for highly accurate prediction of sexual orientation. We demonstrate for the first time that sexual orientation is reflected in specific patterns of RSFC, which enable personalized, brain-based predictions of this highly complex human trait. While these results are preliminary, our neurobiologically based prediction framework illustrates the great value and potential of RSFC for revealing biologically meaningful and generalizable predictive patterns in the human brain.

Sex-dependent multimodal response profiles to psychosocial stress.

INTRODUCTION: Sex differences in stress reactions are often reported in the literature. However, the sex-dependent interplay of different facets of stress is still not fully understood. Particularly in neuroimaging research, studies on large samples combining different indicators of stress remain scarce. MATERIALS AND METHODS: In a functional magnetic resonance imaging study, a sample of 140 healthy participants (67 females using oral contraceptives) underwent a standardized stress induction protocol, the ScanSTRESS. During the experiment, salivary cortisol and subjective ratings were obtained at multiple time points and heart rate was recorded. RESULTS: Sex differences emerged in different facets of the stress response:Women reacted with enhanced subjective feelings of stress and increases in heart rate, while men showed more pronounced neural activation in stress-related brain regions such as the inferior frontal gyrus and insula. Subjective feelings of stress and (para) hippocampal activity were negatively related in women,whereas a slightly positive association was observed in men. DISCUSSION: These results provide further insight in the sex-specific stress response patterns. Moreover, they emphasize the role of the hippocampus in the regulation of the stress response. This paves the way for the identification of sex-dependent vulnerability factors that can, in the future, be implemented in the prevention and treatment of stress-related disorders.

Lower affective empathy in oral contraceptive users: a cross-sectional fMRI study.

Evidence accumulates that oral contraceptive (OC) use modulates various socio-affective behaviors, including empathic abilities. Endogenous and synthetic sex hormones, such as estrogens and progestogens, bind to receptor sites in brain regions (i.e. frontal, limbic, and cerebellar) involved in socio-affective processing. Therefore, the aim of this study was to investigate the role of OC use in empathy. In a cross-sectional functional magnetic resonance imaging study, women in different hormonal states, including OC use (n = 46) or being naturally cycling in the early follicular (fNC: n = 37) or peri-ovulatory phase (oNC: n = 28), performed a visual, sentence-based empathy task. Behaviorally, OC users had lower empathy ratings than oNC women. Congruently, whole-brain analysis revealed significantly larger task-related activation of several brain regions, including the left dorsomedial prefrontal gyrus (dmPFG), left precentral gyrus, and left temporoparietal junction in oNC compared to OC women. In OC users, the activity of the left dmPFG and precentral gyrus was negatively associated with behavioral and self-reported affective empathy. Furthermore, empathy-related region-of-interest analysis indicated negative associations of brain activation with synthetic hormone levels in OC women. Overall, this multimodal, cross-sectional investigation of empathy suggests a role of OC intake in especially affective empathy and highlights the importance of including synthetic hormone levels in OC-related analyses.

Weak associations between personality and contraceptive choice.

Prospective randomized controlled trials on hormonal contraceptive (HC) effects on the brain are rare due to a number of methodological challenges. Thus, much of the evidence on HC effects on the brain comes from cross-sectional studies comparing HC-users to non-users. In interpreting these findings, it is of importance to be aware of potential confounds associated with women's contraceptive choices. Previous studies have discussed age, education, social status, sexual orientation, relationship status, and tolerability of HC. Given the current trend toward a reduction in HC use and increased skepticism toward HC it seems relevant to also identify variables associated with women's attitudes toward HC and whether they may represent confounds for neuroscientific studies. In the present study, we investigated whether women's personality characteristics were associated with their choice to use or not use HC in the present, past and future and the type of HC chosen. 1,391 females aged 18-45 years participated in an online survey including the HEXACO-60 personality questionnaire, as well as two different measures of gender role, and provided information about their current and previous contraceptive status, as well as experiences with and attitudes toward contraceptive use. We compared (i) current, previous and never-users of HC, (ii) prospective users of HC to women who opposed future HC use, and (iii) current users of IUDs to current users of oral contraceptives. Results revealed that associations between personality and the decision to use or not use HC were negligible, while differences in personality were observed corresponding to contraceptive type. Current users of IUDs showed higher agreeableness and extraversion compared to current users of oral contraceptives. The results suggest that personality is more strongly associated to the choice of contraceptive type rather than the choice between hormonal and non-hormonal options.

Imaging the human brain on oral contraceptives: A review of structural imaging methods and implications for future research goals.

Worldwide over 150 million women use oral contraceptives (OCs), which are the most prescribed form of contraception in both the United States and in European countries. Sex hormones, such as estradiol and progesterone, are important endogenous hormones known for shaping the brain across the life span. Synthetic hormones, which are present in OCs, interfere with the natural hormonal balance by reducing the endogenous hormone levels. Little is known how this affects the brain, especially during the most vulnerable times of brain maturation. Here, we review studies that investigate differences in brain gray and white matter in women using OCs in comparison to naturally cycling women. We focus on two neuroimaging methods used to quantify structural gray and white matter changes, namely structural MRI and diffusion MRI. Finally, we discuss the potential of these imaging techniques to advance knowledge about the effects of OCs on the brain and wellbeing in women.