Progesterone and contraceptive progestin actions on the brain: A systematic review of animal studies and comparison to human neuroimaging studies.

In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.

Emotion recognition and mood along the menstrual cycle.

Previous studies have demonstrated menstrual cycle dependent changes in the recognition of facial emotional expressions, specifically the expression of fear, anger, sadness or disgust. While some studies demonstrate an improvement of emotion recognition performance during the peri-ovulatory phase, when estradiol levels peak, other studies demonstrate a deterioration of emotion recognition performance during the mid-luteal phase, when progesterone levels peak. It has been hypothesized, that these changes in emotion recognition performance mirror mood changes along the menstrual cycle. In the present study, we investigate, whether changes in emotion recognition performance along the menstrual cycle are mediated by mood changes along the menstrual cycle. In a combined cross-sectional and longitudinal study design, two large samples of women completed an emotion recognition task, as well as several mood questionnaires during their menses, peri-ovulatory or mid-luteal cycle phase. 65 women completed the task thrice, once during each cycle phase, order counterbalanced. In order to control for potential learning effects, a sample of 153 women completed the task only once in one of the three cycle phases. In both samples, results demonstrated no significant changes in emotion recognition performance along the menstrual cycle, irrespective of the performance measure investigated (accuracy, reaction time, frequency of emotion classifications) and irrespective of the emotion displayed. Bayesian statistics provided very strong evidence for the null hypothesis, that emotion recognition does not change along the menstrual cycle. There was also no moderation of emotion recognition changes along the menstrual cycle by mood changes along the menstrual cycle. Mood changes along the menstrual cycle followed the expected pattern with highest positive affect and least premenstrual symptoms around ovulation and lowest positive affect, but strongest premenstrual symptoms during menses. Interestingly, premenstrual symptoms were negatively related to estradiol, suggesting a protective effect of estrogen during the luteal cycle phase against mood worsening during the premenstrual phase.

Neuroimaging the menstrual cycle: A multimodal systematic review.

Increasing evidence indicates that ovarian hormones affect brain structure, chemistry and function of women in their reproductive age, potentially shaping their behavior and mental health. Throughout the reproductive years, estrogens and progesterone levels fluctuate across the menstrual cycle and can modulate neural circuits involved in affective and cognitive processes. Here, we review seventy-seven neuroimaging studies and provide a comprehensive and data-driven evaluation of the accumulating evidence on brain plasticity associated with endogenous ovarian hormone fluctuations in naturally cycling women (n = 1304). The results particularly suggest modulatory effects of ovarian hormones fluctuations on the reactivity and structure of cortico-limbic brain regions. These findings highlight the importance of performing multimodal neuroimaging studies on neural correlates of systematic ovarian hormone fluctuations in naturally cycling women based on careful menstrual cycle staging.

The gonadal response to social stress and its relationship to cortisol.

The cortisol response to social evaluative stress has been well characterized. However, data regarding changes in gonadal hormones after stress are still scarce and inconsistent. The majority of studies have focused on testosterone reactivity to stress in men, while estradiol responses or gonadal stress responses in women have hardly been investigated. Furthermore, it has not been evaluated whether sex hormone reactivity to stress differs between men and women and the relationship between cortisol and gonadal reactivity to stress is still unclear. To address these questions, we re-analyzed saliva samples collected from 37 men and 30 women in their luteal cycle phase before and repeatedly after social-evaluative stress. Both, testosterone and estradiol levels were assessed. In both men and women, testosterone was significantly reduced after stress. Testosterone levels were at their lowest after 20 minutes, but did not return to baseline until 35 minutes after stress. Across the whole sample, estradiol was significantly increased after stress with two separate peaks after 15 and 30 minutes. Follow-up analyses revealed that 41 participants actually responded with a decrease in estradiol levels to stress, with lowest levels after 20 min, while the remaining participants responded with an increase in estradiol levels. These gonadal stress responses appear to be largely independent of the cortisol response to stress. These results demonstrate that the endocrinological stress response is not restricted to the HPA axis and stress responsivity of gonadal hormones is not simply driven by cortisol. Accordingly, the stress responsivity of gonadal hormones and their association to psychological variables is an additional avenue to explore in both men and women.

Impact of menstrual cycle phase and oral contraceptives on sleep and overnight memory consolidation.

Sleep spindles benefit declarative memory consolidation and are considered to be a biological marker for general cognitive abilities. However, the impact of sexual hormones and hormonal oral contraceptives (OCs) on these relationships are less clear. Thus, we here investigated the influence of endogenous progesterone levels of naturally cycling women and women using OCs on nocturnal sleep and overnight memory consolidation. Nineteen healthy women using OCs (MAge  = 21.4, SD = 2.1 years) were compared to 43 healthy women with a natural menstrual cycle (follicular phase: n = 16, MAge  = 21.4, SD = 3.1 years; luteal phase: n = 27, MAge  = 22.5, SD = 3.6 years). Sleep spindle density and salivary progesterone were measured during an adaptation and an experimental night. A word pair association task preceding the experimental night followed by two recalls (pre-sleep and post-sleep) was performed to test declarative memory performance. We found that memory performance improved overnight in all women. Interestingly, women using OCs (characterized by a low endogenous progesterone level but with very potent synthetic progestins) and naturally cycling women during the luteal phase (characterized by a high endogenous progesterone level) had a higher fast sleep spindle density compared to naturally cycling women during the follicular phase (characterized by a low endogenous progesterone level). Furthermore, we observed a positive correlation between endogenous progesterone level and fast spindle density in women during the luteal phase. Results suggest that the use of OCs and the menstrual cycle phase affects sleep spindles and therefore should be considered in further studies investigating sleep spindles and cognitive performance.

Can Cochlear Implantation in Older Adults Reverse Cognitive Decline Due to Hearing Loss?

INTRODUCTION: Older adults with late-onset hearing loss are at risk for cognitive decline. Our study addresses the question of whether cochlear implantation (CI) can counteract this potential influence. We investigated whether cognitive performance in older adults with severe and profound hearing loss improves 12 months after CI to a level comparable to controls with normal hearing, matched for age, sex, and education level. DESIGN: This cohort study was performed at two tertiary referral centers. The study included 29 patients, of age between 60 and 80 years, with adult-onset, severe to profound bilateral sensorineural hearing loss and indication for CI (study group), as well as 29 volunteers with age-adjusted hearing abilities, according to the norm curves of ISO-702 9:2000-01, (control group). Before CI and 12 months after CI, participants completed a neurocognitive test battery including tests of global cognition, verbal and figural episodic memory, and executive functions (attentional control, inhibition, and cognitive flexibility). RESULTS: Twelve months after CI, the performance of the study group improved significantly in global cognition, compared to the situation before CI. Differences in verbal episodic memory, figural episodic memory, and executive function were not significant. Moreover, the improvement of the study group was significantly larger only in global cognition compared to the control group. Noninferiority tests on the cognitive performances of the study group after CI revealed that comparable levels to normal hearing controls were reached only in global cognition, figural episodic memory (immediate recall), and attentional control. The improvement in global cognition was significantly associated with speech recognition 3 months after CI, but not with speech recognition 12 months after CI. CONCLUSION: One year after CI, cognitive deficits in older individuals with adult-onset hearing loss, compared to normal-hearing peers, could only improve some cognitive skills.

Neurobiological mechanisms underlying sex-related differences in stress-related disorders: Effects of neuroactive steroids on the hippocampus.

Men and women differ in their vulnerability to a variety of stress-related illnesses, but the underlying neurobiological mechanisms are not well understood. This is likely due to a comparative dearth of neurobiological studies that assess male and female rodents at the same time, while human neuroimaging studies often don't model sex as a variable of interest. These sex differences are often attributed to the actions of sex hormones, i.e. estrogens, progestogens and androgens. In this review, we summarize the results on sex hormone actions in the hippocampus and seek to bridge the gap between animal models and findings in humans. However, while effects of sex hormones on the hippocampus are largely consistent in animals and humans, methodological differences challenge the comparability of animal and human studies on stress effects. We summarise our current understanding of the neurobiological mechanisms that underlie sex-related differences in behavior and discuss implications for stress-related illnesses.

Cognition in older adults with severe to profound sensorineural hearing loss compared to peers with normal hearing for age.

Objective: Cognitive performance of older adults with severe to profound sensorineural hearing loss and indication for cochlear implantation was evaluated compared to peers with age appropriate hearing.Design: Prospective matched case control study.Study sample: Study group consisted of n = 30 patients aged between 60 and 80 years, with adult onset, severe to profound sensorineural hearing loss on both sides and indication for cochlear implantation. Matched control group consisted of n = 30 peers with age-adjusted hearing abilities, based on age- appropriate norms.Results: Differences in Constructional Praxis and Recall, Trail Making Test A and Stroop were not significant between both groups. However, the differences in Clock Drawing Test, Word Lists and Trail Making Test B were significant. The impairment in TMT B (cognitive flexibility) was mediated via the severity of depressive problems. Cognitive performance was not related to word recognition, the percentage and duration of hearing loss and hearing aid use.Conclusion: Severely hearing-impaired older adults show widespread impairments in cognitive performance.

Psychometric Properties of the Multifaceted Gender-Related Attributes Survey (GERAS).

Since the 1920s, psychologists have sought to assess the sex- and gender-related attributes of men and women, including primarily aspects of personality and focusing on positive characteristics. In this paper, we introduce a new questionnaire for assessing gender-related attributes with a broader approach than provided by previous ones. Therefore, the questionnaire includes (a) not only personality traits but also cognitions and interests and (b) not only positive but also negative and neutral characteristics. Two independent datasets were acquired (Study 1: N = 1,466; Study 2: N = 471) for development and psychometric analyses. Factor analysis confirmed a hierarchical structure with two separate dimensions of masculinity and femininity overarching the multiple first-order domains of personality, cognition, and interests. Analyses of reliability and convergence with other gender identity and personality scales revealed sufficient values. The new instrument discriminated between the biological sexes and was related to the gender quotas in participants' occupations and social environments, thus providing evidence for criterion-related validity. Therefore, we propose the Gender-Related Attributes Survey (GERAS) as a useful tool for objectively assessing gender-related attributes across multiple facets in gender and sex-difference research.

Sex hormones and number processing. Progesterone and testosterone relate to hemispheric asymmetries during number comparison.

Like many visual stimuli, multi-digit numbers are of a hierarchical nature, with whole number magnitudes depending on individual digit magnitudes. Accordingly, multi-digit numbers can be processed in a holistic (whole number magnitudes) or decomposed manner (digit magnitudes). The compatibility effect during number comparison serves as an indicator of decomposed processing. It is characterized by impaired performance for items where the larger number contains the smaller unit-digit. We were recently able to demonstrate, that the compatibility effect indeed depends on an individual's tendency to process visual hierarchical stimuli on a global or local level. Accordingly, factors affecting global-local processing, should also affect number magnitude processing, i.e. the compatibility effect. Among these factors are hemispheric asymmetries, sex differences and sex hormones (estradiol, progesterone, testosterone). In the present study 39 men and 37 naturally cycling women in their luteal cycle phase completed a number comparison task with stimuli randomly presented to the left and right hemifield. As in previous studies, we observed a larger compatibility effect in the right hemifield (left hemisphere) than in the left hemifield (right hemisphere) and in men than in women. However, this is the first study to evaluate the effects of sex hormones on hemispheric asymmetries during number comparison. We found progesterone to relate to increased hemispheric asymmetries in men, but decreased hemispheric asymmetries in women. Additionally, testosterone was negatively related to hemispheric asymmetries in women's compatibility effect in reaction times. These results add to the growing evidence that sex hormones relate to hemispheric asymmetries in cognitive functions.

Sex differences in verbal fluency: the role of strategies and instructions.

Sex differences in verbal fluency performance and strategies are highly controversial, nevertheless suggesting a slight female advantage at least for phonemic fluency. A tendency of increased clustering of words into phonemic and semantic subcategories in men and increased switching between those categories in women has been suggested. In spatial tasks, it has been demonstrated that changes in instructions favoring a certain cognitive strategy can alter sex differences in performance. Such an approach has, however, not been attempted previously with verbal tasks. In the present investigation, 19 women in their luteal cycle phase and 23 men performed a phonemic and a semantic fluency task with three different instructions, one neutral, one emphasizing the clustering, and one emphasizing the switching of words. While under neutral instructions no sex differences were observed in verbal fluency performance and strategies, sex differences in switching and overall performance were observed in semantic fluency with an instruction requiring a switching strategy. Furthermore, correlation analyses suggested that the importance of strategies for overall performance differed between women and men. While only switching, but not clustering was related to overall verbal fluency performance in all tasks under all instructions, this relationship was driven by women in the phonemic task, but by men in the semantic task. These results highlight the importance of a consistent methodology in sex difference research. Slight variations in instructions may in part explain inconsistencies regarding sex differences in verbal fluency between previous studies.

Behavioural evidence for sex differences in the overlap between subtraction and multiplication.

The present study aims to identify factors that may influence the dissociability of number magnitude processing and arithmetic fact retrieval at the behavioural level. To that end, we assessed both subtraction and multiplication performance in a within-subject approach and evaluated the interdependence of unit-decade integration measures on the one hand as well as sex differences in the interdependence of performance measures on the other hand. We found that subtraction items requiring borrowing (e.g. 53-29 = 24, 3 < 9) are more error prone than subtraction items not requiring borrowing (e.g. 59-23 = 34, 9 > 3), thereby demonstrating a borrowing effect, which has been suggested as a measure of unit-decade integration in subtraction. Furthermore, we observed that multiplication items with decade-consistent distractors (e.g. 6 × 4 = 28 instead of 24) are more error prone that multiplication items with decade-inconsistent distractors (e.g. 6 × 4 = 30 instead of 24), thereby demonstrating a decade-consistency effect, which has been suggested as a measure of unit-decade integration in simple multiplication. However, the borrowing effect in subtraction was not correlated with the effect of decade consistency in simple multiplication in either men or women. This indicates that unit-decade integration arises from different systems in subtraction and multiplication. Nevertheless, men outperformed women not only in subtraction, but also in multiplication. Furthermore, subtraction and multiplication performance on correct solution probes were correlated in women, but unrelated in men. Thus, the view of differential systems for number magnitude processing and arithmetic fact retrieval may not be universal across sexes.

Switching between forest and trees: opposite relationship of progesterone and testosterone to global-local processing.

Sex differences in attentional selection of global and local components of stimuli have been hypothesized to underlie sex differences in cognitive strategy choice. A Navon figure paradigm was employed in 32 men, 41 naturally cycling women (22 follicular, 19 luteal) and 19 users of oral contraceptives (OCs) containing first to third generation progestins in their active pill phase. Participants were first asked to detect targets at any level (divided attention) and then at either the global or the local level only (focused attention). In the focused attention condition, luteal women showed reduced global advantage (i.e. faster responses to global vs. local targets) compared to men, follicular women and OC users. Accordingly, global advantage during the focused attention condition related significantly positively to testosterone levels and significantly negatively to progesterone, but not estradiol levels in a multiple regression model including all naturally cycling women and men. Interference (i.e. delayed rejection of stimuli displaying targets at the non-attended level) was significantly enhanced in OC users as compared to naturally cycling women and related positively to testosterone levels in all naturally cycling women and men. Remarkably, when analyzed separately for each group, the relationship of testosterone to global advantage and interference was reversed in women during their luteal phase as opposed to men and women during their follicular phase. As global processing is lateralized to the right and local processing to the left hemisphere, we speculate that these effects stem from a testosterone-mediated enhancement of right-hemisphere functioning as well as progesterone-mediated inter-hemispheric decoupling.

Reproducible stability of verbal and spatial functions along the menstrual cycle.

Recent studies have reported brain changes in response to ovarian hormonal fluctuations along the menstrual cycle. However, it remains unclear, whether these brain changes are of an adaptive nature or whether they are linked to changes in behavior along the menstrual cycle, particularly with respect to cognitive performance. To address this knowledge gap, we report results from 3 well-powered behavioral studies with different task designs, leveraging the advantages of each design type. In all three studies we assessed whether verbal or spatial performance (i) differed between cycle phases, (ii) were related to estradiol and / or progesterone levels and (iii) were moderated by individual hormone sensitivity as estimated by premenstrual symptoms. Overall, results of all three studies point towards a null effect of menstrual cycle phase and - to a lesser extent - ovarian hormones on verbal and spatial performance and provided no evidence for a moderation of this effect by individual hormone sensitivity. We conclude that there is substantial consistency in verbal and spatial performance across the menstrual cycle, and that future studies of intra-individual variation are needed.

Effects of evening smartphone use on sleep and declarative memory consolidation in male adolescents and young adults.

Exposure to short-wavelength light before bedtime is known to disrupt nocturnal melatonin secretion and can impair subsequent sleep. However, while it has been demonstrated that older adults are less affected by short-wavelength light, there is limited research exploring differences between adolescents and young adults. Furthermore, it remains unclear whether the effects of evening short-wavelength light on sleep architecture extend to sleep-related processes, such as declarative memory consolidation. Here, we recorded polysomnography from 33 male adolescents (15.42 ± 0.97 years) and 35 male young adults (21.51 ± 2.06 years) in a within-subject design during three different nights to investigate the impact of reading for 90 min either on a smartphone with or without a blue-light filter or from a printed book. We measured subjective sleepiness, melatonin secretion, sleep physiology and sleep-dependent memory consolidation. While subjective sleepiness remained unaffected, we observed a significant melatonin attenuation effect in both age groups immediately after reading on the smartphone without a blue-light filter. Interestingly, adolescents fully recovered from the melatonin attenuation in the following 50 min before bedtime, whereas adults still, at bedtime, exhibited significantly reduced melatonin levels. Sleep-dependent memory consolidation and the coupling between sleep spindles and slow oscillations were not affected by short-wavelength light in both age groups. Nevertheless, adults showed a reduction in N3 sleep during the first night quarter. In summary, avoiding smartphone use in the last hour before bedtime is advisable for adolescents and young adults to prevent sleep disturbances. Our research empirically supports general sleep hygiene advice and can inform future recommendations regarding the use of smartphones and other screen-based devices before bedtime.

Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal.

Importance: Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation. Objective: To evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs. Design, Setting, and Participants: This case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria. Exposure: COC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses. Main Outcomes and Measures: Negative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed. Results: A total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause. Conclusions and Relevance: In this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.

Hormonal contraceptive exposure relates to changes in resting state functional connectivity of anterior cingulate cortex and amygdala.

Introduction: Hormonal contraceptives (HCs), nowadays one of the most used contraceptive methods, downregulate endogenous ovarian hormones, which have multiple plastic effects in the adult brain. HCs usually contain a synthetic estrogen, ethinyl-estradiol, and a synthetic progestin, which can be classified as androgenic or anti-androgenic, depending on their interaction with androgen receptors. Both the anterior cingulate cortex (ACC) and the amygdala express steroid receptors and have shown differential functionality depending on the hormonal status of the participant and the use of HC. In this work, we investigated for the first time the relationship between ACC and amygdala resting state functional connectivity (rs-FC) and HC use duration, while controlling for progestin androgenicity. Methods: A total of 231 healthy young women participated in five different magnetic resonance imaging studies and were included in the final analysis. The relation between HC use duration and (i) gray matter volume, (ii) fractional amplitude of low-frequency fluctuations, and (iii) seed-based connectivity during resting state in the amygdalae and ACC was investigated in this large sample of women. Results: In general, rs-FC of the amygdalae with frontal areas, and between the ACC and temporoparietal areas, decreased the longer the HC exposure and independently of the progestin's androgenicity. The type of HC's progestin did show a differential effect in the gray matter volume of left ACC and the connectivity between bilateral ACC and the right inferior frontal gyrus.

Hormonal contraception & face processing: Examining face gender, androgenicity & treatment duration.

Previous cross-sectional studies observed differences between users and non-users of combined oral contraceptives (COCs) in both the structure and function of the fusiform face area (FFA) related to face processing. For the present study 120 female participants performed high-resolution structural, as well as functional scans at rest, during face encoding and face recognition. Participants were either never-users of COCs (26), current first-time users of androgenic (29) or anti-androgenic COCs (23) or previous users of androgenic (21) or anti-androgenic COCs (21). Results suggest that associations between COC-use and face processing are modulated by androgenicity, but do not persist beyond the duration of COC use. The majority of findings concern the connectivity of the left FFA to the left supramarginal gyrus (SMG), which is a key region in cognitive empathy. While connectivity in anti-androgenic COC users differs from never users irrespective of the duration of COC use already at rest, connectivity in androgenic COC users decreases with longer duration of use during face recognition. Furthermore, longer duration of androgenic COC use was related to reduced identification accuracy, as well as increased connectivity of the left FFA to the right orbitofrontal cortex. Accordingly, the FFA and SMG emerge as promising ROIs for future randomized controlled trials on the effects of COC use on face processing.

Triple network model of brain connectivity changes related to adverse mood effects in an oral contraceptive placebo-controlled trial.

Combined oral contraceptives (COC) are among the most commonly used contraceptive methods worldwide, and mood side effects are the major reason for discontinuation of treatment. We here investigate the directed connectivity patterns associated with the mood side effects of an androgenic COC in a double-blind randomized, placebo-controlled trial in women with a history of affective COC side effects (n = 34). We used spectral dynamic causal modeling on a triple network model consisting of the default mode network (DMN), salience network (SN) and executive control network (ECN). Within this framework, we assessed the treatment-related changes in directed connectivity associated with adverse mood side effects. Overall, during COC use, we found a pattern of enhanced connectivity within the DMN and decreased connectivity within the ECN. The dorsal anterior cingulate cortex (SN) mediates an increased recruitment of the DMN by the ECN during treatment. Mood lability was the most prominent COC-induced symptom and also arose as the side effect most consistently related to connectivity changes. Connections that were related to increased mood lability showed increased connectivity during COC treatment, while connections that were related to decreased mood lability showed decreased connectivity during COC treatment. Among these, the connections with the highest effect size could also predict the participants' treatment group above chance.

Hearing loss, depression, and cognition in younger and older adult CI candidates.

Background and Aim: Hearing loss in old age is associated with cognitive decline and with depression. Our study aimed to investigate the relationship between hearing loss, cognitive decline, and secondary depressive symptoms in a sample of younger and older cochlear implant candidates with profound to severe hearing loss. Methods: This study is part of a larger cohort study designated to provide information on baseline data before CI. Sixty-one cochlear implant candidates with hearing loss from adulthood onwards (>18 years) were enrolled in this study. All had symmetrical sensorineural hearing loss in both ears (four-frequency hearing threshold difference of no more than 20 dB, PTA). Individuals with primary affective disorders, psychosis, below-average intelligence, poor German language skills, visual impairment, and a medical diagnosis with potential impact on cognition (e.g., neurodegenerative diseases,) were excluded. Four-frequency hearing thresholds (dB, PTA, better ear) were collected. Using the Abbreviated Profile of Hearing Aid Benefit, we assessed subjective hearing in noise. Clinical and subclinical depressive symptoms were assessed with the Beck Depression Inventory (BDI II). Cognitive status was assessed with a neurocognitive test battery. Results: Our findings revealed a significant negative association between subjective hearing in noise (APHAB subscale "Background Noise") and BDII. However, we did not observe any link between hearing thresholds, depression, and cognition. Additionally, no differences emerged between younger (25-54 years) and older subjects (55-75 years). Unexpectedly, further unplanned analyses unveiled correlations between subjective hearing in quiet environments (APHAB) and cognitive performance [phonemic fluency (Regensburg Word Fluency), cognitive flexibility (TMTB), and nonverbal episodic memory (Nonverbal Learning Test), as well as subjective hearing of aversive/loud sounds (APHAB)], cognitive performance [semantic word fluency (RWT), and inhibition (Go/Nogo) and depression]. Duration of hearing loss and speech recognition at quiet (Freiburg Monosyllables) were not related to depression and cognitive performance. Conclusion: Impact of hearing loss on mood and cognition appears to be independent, suggesting a relationship with distinct aspects of hearing loss. These results underscore the importance of considering not only conventional audiometric measures like hearing thresholds but also variables related to hearing abilities during verbal communication in everyday life, both in quiet and noisy settings.