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Diamond is a potential host material for laser applications due to its exceptional thermal properties, ultrawide bandgap, and color centers, which promise gain across the visible spectrum. More recently, coherent laser methods offer improved sensitivity for magnetometry. However, diamond fabrication is difficult in comparison to other crystalline matrices, and many optical loss channels are not yet understood. Here, we demonstrate a continuous-wave laser threshold as a function of the pump intensity on nitrogen-vacancy (NV) color centers. To achieve this, we constructed a laser cavity with both an NV diamond medium and an intracavity antireflection-coated diode laser. This dual-medium approach compensates intrinsic losses of the cavity by providing a fixed additional gain below threshold of the diode laser. We observe a continuous-wave laser threshold of the laser system and linewidth narrowing with increasing green pump power on the NV centers. Our results are a major development toward coherent approaches to magnetometry.

Differences in brain size between the sexes are consistently reported. However, the consequences of this anatomical difference on sex differences in intrinsic brain function remain unclear. In the current study, we investigate whether sex differences in intrinsic cortical functional organization may be associated with differences in cortical morphometry, namely different measures of brain size, microstructure, and the geodesic distance of connectivity profiles. For this, we compute a low dimensional representation of functional cortical organization, the sensory-association axis, and identify widespread sex differences. Contrary to our expectations, sex differences in functional organization do not appear to be systematically associated with differences in total surface area, microstructural organization, or geodesic distance, despite these morphometric properties being per se associated with functional organization and differing between sexes. Instead, functional sex differences in the sensory-association axis are associated with differences in functional connectivity profiles and network topology. Collectively, our findings suggest that sex differences in functional cortical organization extend beyond sex differences in cortical morphometry., (© 2024. The Author(s).)

Determining sex-bias in brain structure is of great societal interest to improve diagnostics and treatment of brain-related disorders. So far, studies on sex-bias in brain structure predominantly focus on macro-scale measures, and often ignore factors determining this bias. Here we study sex-bias in cortical and hippocampal microstructure in relation to sex hormones. Investigating quantitative intracortical profiling in-vivo using the T1w/T2w ratio in 1093 healthy females and males of the cross-sectional Human Connectome Project young adult sample, we find that regional cortical and hippocampal microstructure differs between males and females and that the effect size of this sex-bias varies depending on self-reported hormonal status in females. Microstructural sex-bias and expression of sex hormone genes, based on an independent post-mortem sample, are spatially coupled. Lastly, sex-bias is most pronounced in paralimbic areas, with low laminar complexity, which are predicted to be most plastic based on their cytoarchitectural properties. Albeit correlative, our study underscores the importance of incorporating sex hormone variables into the investigation of brain structure and plasticity., (© 2024. The Author(s).)

The female reproductive years are characterized by fluctuations in ovarian hormones across the menstrual cycle, which have the potential to modulate neurophysiological and behavioral dynamics. Menstrually-related mood disorders (MRMDs) comprise cognitive-affective or somatic symptoms that are thought to be triggered by the rapid fluctuations in ovarian hormones in the luteal phase of the menstrual cycle. MRMDs include premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and premenstrual exacerbation (PME) of other psychiatric disorders. Electroencephalography (EEG) non-invasively records in vivo synchronous activity from populations of neurons with high temporal resolution. The present overview sought to systematically review the current state of task-related and resting-state EEG investigations on MRMDs. Preliminary evidence indicates lower alpha asymmetry at rest being associated with MRMDs, while one study points to the effect being luteal-phase specific. Moreover, higher luteal spontaneous frontal brain activity (slow/fast wave ratio as measured by the delta/beta power ratio) has been observed in persons with MRMDs, while sleep architecture results point to potential circadian rhythm disturbances. In this review, we discuss the quality of study designs as well as future perspectives and challenges of supplementing the diagnostic and scientific toolbox for MRMDs with EEG., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Premenstrual dysphoric disorder (PMDD) disrupts the lives of millions of people each month. The timing of symptoms suggests that hormonal fluctuations play a role in the pathogenesis. Here, we tested whether a heightened sensitivity of the serotonin system to menstrual cycle phase underlies PMDD, assessing the relationship of serotonin transporter (5-HTT) changes with symptom severity across the menstrual cycle., Methods: In this longitudinal case-control study, we acquired 118 [ 11 C]DASB positron emission tomography scans measuring 5-HTT nondisplaceable binding potential (BP ND ) in 30 patients with PMDD and 29 controls during 2 menstrual cycle phases (periovulatory, premenstrual). The primary outcome was midbrain and prefrontal cortex 5-HTT BP ND . We tested whether BP ND changes correlated with depressed mood., Results: Linear mixed effects modeling (significant group × time × region interaction) showed a mean increase of 18% in midbrain 5-HTT BP ND (mean [SD] periovulatory = 1.64 [0.40], premenstrual = 1.93 [0.40], delta = 0.29 [0.47]: t 29  = -3.43, p = .0002) in patients with PMDD, whereas controls displayed a mean 10% decrease in midbrain 5-HTT BP ND (periovulatory = 1.65 [0.24] > premenstrual = 1.49 [0.41], delta = -0.17 [0.33]: t 28  = -2.73, p = .01). In patients, increased midbrain 5-HTT BP ND correlated with depressive symptom severity (R 2  = 0.41, p < .0015) across the menstrual cycle., Conclusions: These data suggest cycle-specific dynamics with increased central serotonergic uptake followed by extracellular serotonin loss underlying the premenstrual onset of depressed mood in patients with PMDD. These neurochemical findings argue for systematic testing of pre-symptom-onset dosing of selective serotonin reuptake inhibitors or nonpharmacological strategies to augment extracellular serotonin in people with PMDD., (Copyright © 2023. Published by Elsevier Inc.)

Multiorgan imaging unveils the intertwined nature of the human heart and brain.

Tyrosine (tyr), the precursor of the neurotransmitter dopamine, is known to modulate cognitive functions including executive attention. Tyr supplementation is suggested to influence dopamine-modulated cognitive performance. However, results are inconclusive regarding the presence or strength and also the direction of the association between tyr and cognitive function. This pre-registered cross-sectional analysis investigates whether diet-associated serum tyr relates to executive attention performance, and whether this relationship is moderated by differences in white matter microstructure. 59 healthy, overweight, young to middle-aged adults (20 female sex/gender group, 28.3 ± 6.6 years, BMI: 27.3 ± 1.5 kg/m 2 ) drawn from a longitudinal study reported dietary habits, donated blood and completed diffusion-weighted brain magnetic resonance imaging and the attention network test. Main analyses were performed using linear regressions and non-parametric voxel-wise inference testing. Confirmatory analyses did neither support an association between dietary and serum tyr nor a relationship between relative serum tyr/large neutral amino acids (LNAA) levels or white matter microstructure and executive attention performance. However, exploratory analyses revealed higher tyr intake, higher serum tyr and better executive attention performance in the male sex/gender group. In addition, older age was associated with higher dietary tyr intake and lower fractional anisotropy in a widespread cluster across the brain. Finally, a positive association between relative serum tyr/LNAA level and executive attention performance was found in the male sex/gender group when accounting for age effects. Our analysis advances the field of dopamine-modulated cognitive functions by revealing sex/gender and age differences which might be diet-related. Longitudinal or intervention studies and larger sample sizes are needed to provide more reliable evidence for links between tyr and executive attention., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebo-controlled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beinhölzl, Molloy, Zsido, Richter, Piecha, Zheleva, Scharrer, Regenthal, Villringer, Okon-Singer and Sacher.)

Importance: Language development builds on speech perception, with early disruptions increasing the risk for later language difficulties. Although a major postpartum depressive episode is associated with language development, this association has not been investigated among infants of mothers experiencing a depressed mood at subclinical levels after birth, even though such a mood is frequently present in the first weeks after birth. Understanding whether subclinical depressed maternal mood after birth is associated with early language development is important given opportunities of coping strategies for subclinical depressed mood., Objective: To examine whether depressed maternal mood at subclinical levels 2 months after birth is associated with infant speech perception trajectories from ages 2 to 6.5 months., Design, Setting, and Participants: In this longitudinal cohort study conducted between January 1, 2018, and October 31, 2019, 46 healthy, monolingual German mother-infant dyads were tested. The sample was recruited from the infants database of the Max Planck Institute for Human Cognitive and Brain Sciences. Initial statistical analysis was performed between January 1 and March 31, 2021; the moderation analysis (results reported herein) was conducted between July 1 and July 31, 2022., Exposures: Mothers reported postpartum mood via the German version of the Edinburgh Postnatal Depression Scale (higher scores indicated higher levels of depressed mood, with a cutoff of 13 points indicating a high probability of clinical depression) when their infants were 2 months old., Main Outcomes and Measures: Electrophysiological correlates of infant speech perception (mismatch response to speech stimuli) were tested when the infants were aged 2 months (initial assessment) and 6.5 months (follow-up)., Results: A total of 46 mothers (mean [SD] age, 32.1 [3.8] years) and their 2-month-old children (mean [SD] age, 9.6 [1.2] weeks; 23 girls and 23 boys) participated at the initial assessment, and 36 mothers (mean [SD] age, 32.2 [4.1] years) and their then 6.5-month-old children (mean [SD] age, 28.4 [1.5 weeks; 18 girls and 18 boys) participated at follow-up. Moderation analyses revealed that more depressed maternal subclinical postpartum mood (mean [SD] Edinburgh Postnatal Depression Scale score, 4.8 [3.6]) was associated with weaker longitudinal changes of infants' electrophysiological brain responses to syllable pitch speech information from ages 2 to 6.5 months (coefficient: 0.68; 95% CI, 0.03-1.33; P = .04)., Conclusions and Relevance: The results of this cohort study suggest that infant speech perception trajectories are correlated with subclinical depressed mood in postpartum mothers. This finding lays the groundwork for future research on early support for caregivers experiencing depressed mood to have a positive association with children's language development.

Fluctuating ovarian hormones have been shown to affect decision-making processes in women. While emerging evidence suggests effects of endogenous ovarian hormones such as estradiol and progesterone on value-based decision-making in women, the impact of exogenous synthetic hormones, as in most oral contraceptives, is not clear. In a between-subjects design, we assessed measures of value-based decision-making in three groups of women aged 18 to 29 years, during (1) active oral contraceptive intake (N = 22), (2) the early follicular phase of the natural menstrual cycle (N = 20), and (3) the periovulatory phase of the natural menstrual cycle (N = 20). Estradiol, progesterone, testosterone, and sex-hormone binding globulin levels were assessed in all groups via blood samples. We used a test battery which measured different facets of value-based decision-making: delay discounting, risk-aversion, risk-seeking, and loss aversion. While hormonal levels did show the expected patterns for the three groups, there were no differences in value-based decision-making parameters. Consequently, Bayes factors showed conclusive evidence in support of the null hypothesis. We conclude that women on oral contraceptives show no differences in value-based decision-making compared to the early follicular and periovulatory natural menstrual cycle phases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JB declared a past collaboration with one of the authors BD to the handling editor., (Copyright © 2022 Lewis, Kimmig, Kroemer, Pooseh, Smolka, Sacher and Derntl.)

Neural health relies on cortical excitation-inhibition balance (EIB). Previous research suggests a link between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear. Thus, in a randomized double-blind study, we administered a clinically relevant dose of 20 mg escitalopram for 7 days (time when steady state is achieved) in 59 healthy women (28 escitalopram, 31 placebo) on oral contraceptives. We acquired resting-state electroencephalography data at baseline, after a single dose, and at steady state. We assessed 1/f slope of the power spectrum as a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram-intake was associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after a single dose of escitalopram was associated with 1/f slope at steady state. Higher plasma escitalopram levels at a single dose were associated with better maintenance of these EIB changes throughout the drug administration week. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the lens through which we map the human brain by testing an interventional psychopharmacological design in a clearly defined endocrinological state., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Although previous studies report an association between Premenstrual Dysphoric Disorder (PMDD) and suicidal ideation, most studies have only established a provisional and retrospective diagnosis of PMDD fundamentally invalidating the diagnosis. Therefore, the aim of this study was to describe the prevalence and to explore correlates of current suicidal ideation in the late luteal phase in women with prospectively assessed and confirmed PMDD., Methods: Participants were 110 women who attended the pre-randomization baseline visit of two randomized placebo-controlled clinical trials between January 15, 2017 and October 19, 2019. PMDD was diagnosed prospectively in line with DSM-5 criteria. Current suicidal ideation was measured by the MADRS-S in the late luteal phase. Descriptive statistics were presented and logistic regression analyses were carried out to explore the association between psychosocial and health characteristics and current suicidal ideation, presenting unadjusted odds ratios (OR) and 95% confidence intervals (CI)., Results: Current suicidal ideation was reported by nearly 40% of women with confirmed PMDD (n = 43, 39.1%). Previous psychological treatment for PMDD and higher depressive symptoms in the late luteal phase were positively associated with current suicidal ideation (OR 5.63, 95% CI 1.07-29.49, and OR 1.17, 95% CI 1.10-1.25, respectively), whereas higher ratings of self-rated health were associated with lower odds ratios for current suicidal ideation (OR 0.98, 95% CI 0.96-0.99)., Conclusions: A substantial proportion of women with confirmed PMDD report current suicidal ideation in the late luteal phase. Results point to a need for better awareness and screening of suicidal ideation in women with PMDD., (© 2022. The Author(s).)

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design. We assessed task-modulated functional connectivity with a psycho-physiological interaction (PPI) analysis in the thalamus, putamen, cerebellum, dorsal premotor, primary motor, supplementary motor, and dorsolateral prefrontal cortices. Comparing an implicit sequence learning condition to a control learning condition, we observed decreased connectivity between the thalamus and bilateral motor regions after 7 days of escitalopram intake. Additionally, we observed a negative correlation between plasma escitalopram levels and PPI connectivity changes, with higher escitalopram levels being associated with greater thalamo-cortico decreases. Our results suggest that escitalopram enhances network-level processing efficiency during sequence motor learning, despite no changes in behaviour. Future studies in more diverse samples, however, with quantitative imaging of neurochemical markers of excitation and inhibition, are necessary to further assess neural responses to escitalopram., (© 2021. The Author(s).)

The contribution of selective serotonin reuptake inhibitors to motor learning by inducing motor cortical plasticity remains controversial given diverse findings from positive preclinical data to negative findings in recent clinical trials. To empirically address this translational disparity, we use functional magnetic resonance imaging in a double-blind, randomized controlled study to assess whether 20 mg escitalopram improves sequence-specific motor performance and modulates cortical motor response in 64 healthy female participants. We found decreased left premotor cortex responses during sequence-specific learning performance comparing single dose and steady escitalopram state. Escitalopram plasma levels negatively correlated with the premotor cortex response. We did not find evidence in support of improved motor performance after a week of escitalopram intake. These findings do not support the conclusion that one week escitalopram intake increases motor performance but could reflect early adaptive plasticity with improved neural processing underlying similar task performance when steady peripheral escitalopram levels are reached.

Molecular gases are highly relevant in healthcare, production control, safety, and environmental monitoring. They often appear in small concentrations. The measurement of trace gases has increasingly become a key technique in those domains. Quartz-enhanced photoacoustic spectroscopy (QEPAS) is a suitable method that can provide the required low detection limits in such applications at comparatively low cost and small size. For mobile implementation, the size of an entire sensor unit matters. In this paper, we present a QEPAS sensor that fits into a standard butterfly package, its characterization, and its application on C H 4 and C O 2 .

Background: Selective serotonin reuptake inhibitors (SSRIs) show acute effects on the neural processes associated with negative affective bias in healthy people and people with depression. However, whether and how SSRIs also affect reward and punishment processing on a similarly rapid time scale remains unclear., Methods: We investigated the effects of an acute and clinically relevant dose (20 mg) of the SSRI escitalopram on brain response during reward and punishment processing in 19 healthy participants. In a doubleblind, placebo-controlled study using functional MRI, participants performed a well-established monetary reward task at 3 time points: at baseline; after receiving placebo or escitalopram; and after receiving placebo or escitalopram following an 8-week washout period., Results: Acute escitalopram administration reduced blood-oxygen-level-dependent (BOLD) response during punishment feedback in the right thalamus (family-wise error corrected [FWE] p = 0.013 at peak level) and the right caudate head (pFWE = 0.011 at peak level) compared to placebo. We did not detect any significant BOLD changes during reward feedback., Limitations: We included only healthy participants, so interpretation of findings are limited to the healthy human brain and require future testing in patient populations. The paradigm we used was based on monetary stimuli, and results may not be generalizable to other forms of reward., Conclusion: Our findings extend theories of rapid SSRI action on the neural processing of rewarding and aversive stimuli and suggest a specific and acute effect of escitalopram in the punishment neurocircuitry., Competing Interests: E. Forbes declares an honorarium for editorial activities for the Association for Psychological Science; paid consultancy for DSMB, Durham VA (sponsor), Otsuka (funder); an honorarium for mentoring activities as part of Research Centre, Brown University; research funding from the National Institutes of Health; and an honorarium for a grant review from the National Institutes of Health, all outside the published work. No other competing interests declared., (© 2021 CMA Joule Inc. or its licensors.)

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., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Social cognition, in particular mindreading, enables the understanding of another individual's feelings, intentions, desires, and mental states. The Reading the Mind in the Eyes Test (RMET) captures the ability to identify mental states from gaze. We investigated RMET accuracy in the context of age and cognition across the whole adult age-range (19-79 years) in a very large population-based sample ( N = 1,603) with linear regression models accounting for cognitive abilities, neurological diseases, and psychiatric disorders. Higher age predicted lower RMET performance in women and men, suggesting difficulties to infer mental states from gaze at older age. Effects remained stable when taking other cognitive abilities and psychiatric disorders or neurological diseases into account. Our results show that RMET performance as a measure of social cognition declines with increasing age., (Copyright © 2020 Kynast, Quinque, Polyakova, Luck, Riedel-Heller, Baron-Cohen, Hinz, Witte, Sacher, Villringer and Schroeter.)

The peripartum period offers a unique opportunity to improve our understanding of how dramatic fluctuations in endogenous ovarian hormones affect the human brain and behavior. This notwithstanding, peripartum depression remains an underdiagnosed and undertreated disorder. Here, we review recent neuroimaging findings with respect to the neuroplastic changes in the maternal brain during pregnancy and the postpartum period. We seek to provide an overview of multimodal neuroimaging designs of current peripartum depression models of hormone withdrawal, changes in monoaminergic signaling, and maladaptive neuroplasticity, which likely lead to the development of a condition that puts the lives of mother and infant at risk. We discuss the need to effectively integrate the available information on psychosocial and neurobiological risk factors contributing to individual vulnerability. Finally, we propose a systematic approach to neuroimaging the peripartum brain that acknowledges important co-morbidities and variation in disease onset., (Copyright © 2020. Published by Elsevier Inc.)

Background: Atomoxetine and escitalopram are potent and selective drugs approved for noradrenergic or serotonergic modulation of neuronal networks in attention-deficit hyperactivity disorder (ADHD) or depression, respectively. High-performance liquid chromatography (HPLC) methods still play an important role in the therapeutic drug monitoring (TDM) of psychopharmacological drugs, and coupled with tandem mass spectrometry are the gold standard for the quantification of drugs in biological matrices, but not available everywhere. The aim of this work was to develop and validate a HPLC method for neuroscientific studies using atomoxetine or escitalopram as a test drug., Materials and Methods: A HPLC method from routine TDM determination of atomoxetine or citalopram in plasma was adapted and validated for use in neuroscientific research. Using photo diode array detection with UV absorption at 205 nm, the variation of internal standard within one chromatographic method enables separate drug monitoring for concentration-controlled explorative studies in healthy humans and patients with Parkinson's disease., Results: The method described here was found to be linear in the range of 0.002 - 1.4 mg/L for atomoxetine and 0.0012 - 0.197 mg/L for escitalopram, with overall mean intra-day and inter-day imprecision and accuracy bias < 10% for both drugs. The method was successfully applied in concentration-controlled neuroimaging studies in populations of healthy humans and patients with Parkinson's disease., Conclusion: A simple, sensitive, robust HPLC method capable of monitoring escitalopram and atomoxetine is presented and validated, as a useful tool for drug monitoring and the study of pharmacokinetics in neuroscientific study applications.

Competing Interests: The author is an independent consultant for clinical trials and has been involved with the development of Phages4All.

Background: Alexithymia is a personality trait characterized by difficulties identifying and describing feelings, an externally oriented style of thinking, and a reduced inclination to imagination. Previous research has shown deficits in the recognition of emotional facial expressions in alexithymia and reductions of brain responsivity to emotional stimuli. Using an affective priming paradigm, we investigated automatic perception of facial emotions as a function of alexithymia at the behavioral and neural level. In addition to self-report scales, we applied an interview to assess alexithymic tendencies., Results: During 3 T fMRI scanning, 49 healthy individuals judged valence of neutral faces preceded by briefly shown happy, angry, fearful, and neutral facial expressions. Alexithymia was assessed using the 20-Item Toronto Alexithymia Scale (TAS-20), the Bermond-Vorst Alexithymia Questionnaire (BVAQ) and the Toronto Structured Interview for Alexithymia (TSIA). As expected, only negative correlations were found between alexithymic features and affective priming. The global level of self-reported alexithymia (as assessed by the TAS-20 and the BVAQ) was found to be related to less affective priming owing to angry faces. At the facet level, difficulties identifying feelings, difficulties analyzing feelings, and impoverished fantasy (as measured by the BVAQ) were correlated with reduced affective priming due to angry faces. Difficulties identifying feelings (BVAQ) correlated also with reduced affective priming due to fearful faces and reduced imagination (TSIA) was related to decreased affective priming due to happy faces. There was only one significant correlation between alexithymia dimensions and automatic brain response to masked facial emotions: TAS-20 alexithymia correlated with heightened brain response to masked happy faces in superior and medial frontal areas., Conclusions: Our behavioral results provide evidence that alexithymic features are related in particular to less sensitivity for covert facial expressions of anger. The perceptual alterations could reflect impaired automatic recognition or integration of social anger signals into judgemental processes and might contribute to the problems in interpersonal relationships associated with alexithymia. Our findings suggest that self-report measures of alexithymia may have an advantage over interview-based tests as research tools in the field of emotion perception at least in samples of healthy individuals characterized by rather low levels of alexithymia.

Increasing evidence suggests that endogenous sex steroid changes affect human brain functional connectivity, which could be obtained by resting-state fMRI (RS-fMRI). Nevertheless, RS studies on the menstrual cycle (MC) are underrepresented and yield inconsistent results. We attribute these inconsistencies to the use of various methods in exploratory approaches and small sample sizes. Hormonal fluctuations along the MC likely elicit subtle changes that, however, may still have profound impact on network dynamics when affecting key brain nodes. To address these issues, we propose a ROI-based multimodal analysis approach focusing on areas of high functional relevance to adequately capture these changes. To that end, sixty naturally cycling women underwent RS-fMRI in three different cycle phases and we performed the following analyses: (1) group-independent component analyses to identify intrinsic connectivity networks, (2) eigenvector centrality (EC) as a measure of centrality in the global connectivity hierarchy, (3) amplitude of low-frequency fluctuations (ALFF) as a measure of oscillatory activity and (4) seed-based analyses to investigate functional connectivity from the ROIs. For (2)-(4), we applied a hypothesis-driven ROI approach in the hippocampus, caudate and putamen. In the luteal phase, we found (1) decreased intrinsic connectivity of the right angular gyrus with the default mode network, (2) heightened EC for the hippocampus, and (3) increased ALFF for the caudate. Furthermore, we observed (4) stronger putamen-thalamic connectivity during the luteal phase and stronger fronto-striatal connectivity during the pre-ovulatory phase. This hormonal modulation of connectivity dynamics may underlie behavioural, emotional and sensorimotor changes along the MC.

Purpose of Review: We review recent research investigating the relationship of hormonal contraceptives and mood with a focus on relevant underlying mechanisms, such as emotion recognition and reactivity, reward processing, and stress response., Recent Findings: Adverse effects of hormonal contraceptives (HCs) on mood seem most consistent in women with a history of depressive symptoms and/or previous negative experience with HC-intake. Current evidence supports a negativity bias in emotion recognition and reactivity in HC-users, although inconsistent to some extent. Some data, however, do indicate a trend towards a blunted reward response and a potential dysregulation of the stress response in some HC-users. HC-effects on psychological and neurophysiological mechanisms underlying mood are likely context-dependent. We provide suggestions on how to address some of the contributing factors to this variability in future studies, such as HC-dose, timing, administration-mode, and individual risk. A better understanding of how and when HCs affect mood is critical to provide adequate contraceptive choices to women worldwide.

Social Signal Transduction Theory of Depression is a biologically plausible, multi-level theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental adversity with internal biological processes that drive depression pathogenesis, maintenance, and recurrence. Central to this theory is the hypothesis that interpersonal stressors involving social threat (e.g., social conflict, evaluation, rejection, isolation, and exclusion) upregulate inflammatory processes that can induce several depressive symptoms, including sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. The original article describing this formulation (Psychol Bull 140:774-815, 2014) addressed critical questions involving depression onset and recurrence, as well as why depression is strongly predicted by early life stress and comorbid with anxiety disorders and certain physical disease conditions, such as asthma, rheumatoid arthritis, chronic pain, and cardiovascular disease. Here, we extend the theory to help explain sex differences in depression prevalence, which is a defining feature of this disorder. Central to this extension is research demonstrating that ovarian hormone fluctuations modulate women's susceptibility to stress, brain structure and function, and inflammatory activity and reactivity. These effects are evident at multiple levels and are highly context-dependent, varying as a function of several factors including sex, age, reproductive state, endogenous versus exogenous hormones, and hormone administration mode and dose. Together, these effects help explain why women are at greater risk for developing inflammation-related depressed mood and other neuropsychiatric, neurodevelopmental, and neurodegenerative disorders during the reproductive years, especially for those already at heightened risk for depression or in the midst of a hormonal transition period.

Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition ( p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group.

The food addiction model suggests neurobiological similarities between substance-related and addictive disorders and obesity. While structural brain differences have been consistently reported in these conditions, little is known about the neuroanatomical correlates of food addiction. We therefore aimed to determine whether symptoms of food addiction related to body mass index (BMI), personality, and brain structure in a large population-based sample. Participants of the LIFE-Adult study (n = 625; 20-59 years old, 45% women) answered the Yale Food Addiction Scale (YFAS) and further personality measures, underwent anthropometric assessments and high-resolution 3T-neuroimaging. A higher YFAS symptom score correlated with higher BMI, eating behavior traits, neuroticism, and stress. Higher BMI predicted significantly lower thickness of (pre)frontal, temporal and occipital cortex and increased volume of left nucleus accumbens. In a whole-brain analysis, YFAS symptom score was not associated with significant differences in cortical thickness or subcortical gray matter volumes. A hypothesis-driven Bayes factor analysis suggested a small, additional contribution of YFAS symptom score to lower right lateral orbitofrontal cortex thickness over the effect of BMI. Our study indicates that symptoms of food addiction do not account for the major part of the structural brain differences associated with BMI in the general population. Yet, symptoms of food addiction might explain additional variance in orbitofrontal cortex, a hub area of the reward network. Longitudinal studies implementing both anatomical and functional MRI could further disentangle the neural mechanisms of addictive eating behaviors., (© 2019 Wiley Periodicals, Inc.)

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m 2 ), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance.

Importance: Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss., Objectives: To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure., Design, Setting, and Participants: Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 2018., Exposures: Serum estradiol levels from fasting blood and visceral adipose tissue volume from T1-weighted magnetic resonance imaging (MRI)., Main Outcomes and Measures: Brain network covariance (individual loading on structural network derived from T1-weighted MRI) and memory performance (composite score from the Consortium to Establish a Registry for Alzheimer Disease [CERAD] verbal episodic memory test on learning [score range, 0-30], recall [score range, 0-10], and recognition [score range, 0-20])., Results: Final analyses included data from 473 women (mean [SD] age, 50.10 [15.63] years) and 501 men (mean [SD] age, 51.24 [15.67] years). Visceral adipose tissue was associated with an exacerbation of the negative association of aging with network covariance for women (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P = .001) and men (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P < .001). Estradiol level was associated with a reduction in the negative association of VAT with network covariance in women (interaction term β = 0.63; 95% bias-corrected bootstrap CI, 0.14-1.12; P = .01), with no significant association in men. In the female midlife subgroup (age range, 35-55 years, when menopause transition occurs), low estradiol levels were associated with lower memory network covariance (Cohen d = 0.61; t80 = 2.76; P = .007) and worse memory performance (Cohen d = 0.63; t76 = 2.76; P = .007)., Conclusions and Relevance: This study reports a novel association between VAT, estradiol, and structural brain networks as a potential mechanism underlying cognitive decline in women. These findings appear to highlight the need for sex-specific strategies, including VAT and hormonal screening during midlife, to support healthy cognitive aging.

Resistance to asparaginase, an antileukemic enzyme that depletes asparagine, is a common clinical problem. Using a genome-wide CRISPR/Cas9 screen, we found a synthetic lethal interaction between Wnt pathway activation and asparaginase in acute leukemias resistant to this enzyme. Wnt pathway activation induced asparaginase sensitivity in distinct treatment-resistant subtypes of acute leukemia, but not in normal hematopoietic progenitors. Sensitization to asparaginase was mediated by Wnt-dependent stabilization of proteins (Wnt/STOP), which inhibits glycogen synthase kinase 3 (GSK3)-dependent protein ubiquitination and proteasomal degradation, a catabolic source of asparagine. Inhibiting the alpha isoform of GSK3 phenocopied this effect, and pharmacologic GSK3α inhibition profoundly sensitized drug-resistant leukemias to asparaginase. Our findings provide a molecular rationale for activation of Wnt/STOP signaling to improve the therapeutic index of asparaginase., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The MIR wavelength regime promises better gas detection possibilities than the NIR or the visible region because of the higher absorbencies simulated by HITRAN. In the MIR region are many important absorption lines of significant gases, which are relevant in healthcare, production supervision, and safety and environmental monitoring. One of those gases is methane. CH4 shows significant variations in absorbance with a maximum at 3.3 μm, which results in low detection limits in the range of low ppm. Interband-cascade- and quantum-cascade-based lasers emit at higher wavelengths, where the absorbencies of methane are higher. The comparison is done by analyzing the performance of two spectroscopy applications: tunable diode laser absorption spectroscopy and quartz-enhanced photoacoustic spectroscopy.

We present a publicly available dataset of 227 healthy participants comprising a young (N=153, 25.1±3.1 years, range 20-35 years, 45 female) and an elderly group (N=74, 67.6±4.7 years, range 59-77 years, 37 female) acquired cross-sectionally in Leipzig, Germany, between 2013 and 2015 to study mind-body-emotion interactions. During a two-day assessment, participants completed MRI at 3 Tesla (resting-state fMRI, quantitative T1 (MP2RAGE), T2-weighted, FLAIR, SWI/QSM, DWI) and a 62-channel EEG experiment at rest. During task-free resting-state fMRI, cardiovascular measures (blood pressure, heart rate, pulse, respiration) were continuously acquired. Anthropometrics, blood samples, and urine drug tests were obtained. Psychiatric symptoms were identified with Standardized Clinical Interview for DSM IV (SCID-I), Hamilton Depression Scale, and Borderline Symptoms List. Psychological assessment comprised 6 cognitive tests as well as 21 questionnaires related to emotional behavior, personality traits and tendencies, eating behavior, and addictive behavior. We provide information on study design, methods, and details of the data. This dataset is part of the larger MPI Leipzig Mind-Brain-Body database.

We report here the complete genome sequence of Campylobacter jejuni strain 12567, a member of a C. jejuni livestock-associated clade that expresses glycoconjugates associated with improved gastrointestinal tract persistence., (Copyright © 2018 Sacher et al.)

Bacteriophage therapy can potentially reduce Campylobacter jejuni numbers in livestock, but it requires a detailed understanding of phage-host interactions. C. jejuni strains readily infected by certain phages are designated as phage-propagating strains. Here, we report the complete genome sequences of three such strains, NCTC 12660, NCTC 12661, and NCTC 12664., (Copyright © 2018 Sacher et al.)

The measurement of trace gases has increasingly become a key technique in healthcare and other medical applications. Quartz-enhanced photoacoustic spectroscopy (QEPAS) is a suitable method that can provide the required characteristics in such applications for a comparatively low cost and small size. The quantitative detection and a low detection limit are also required by applications. In this paper, we present new results on sensing biomedically relevant gases using the on-beam QEPAS technique with some newly developed tunable high-power single-mode laser diodes based on GaSb material. The data processing and detection limit determination are done by a field programmable gate array device, as well as an automatic measurement of the resonance frequency.

During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis., (© 2018 Mangal et al.)

Ovarian hormones, particularly oestrogen and progesterone, undergo major fluctuations across the female lifespan. These hormone transition periods, such as the transition from pregnancy to postpartum, as well as the transition into menopause (perimenopause), are also known to be times of elevated susceptibility to depression. This study reviews how these transition periods likely influence neurochemical changes in the brain that result in disease vulnerability. While there are known associations between oestrogen/progesterone and different monoaminergic systems, the interactions and their potential implications for mood disorders are relatively unknown. Positron Emission Tomography (PET) allows for the in-vivo quantification of such neurochemical changes, and, thus, can provide valuable insight into how both subtle and dramatic shifts in hormones contribute to the elevated rates of depression during pre-menstrual, post-partum, and perimenopausal periods in a woman's life. As one better understands how to address the challenges of PET studies involving highly vulnerable populations, such as women who have recently given birth, one will gain the insight necessary to design and individualize treatment and therapy. Understanding the precise time-line in younger women when dramatic fluctuations in the hormonal milieu may contribute to brain changes may present a powerful opportunity to intervene before a vulnerable state develops into a diseased state in later life.

The wavelength, λ, range of 1.8  μm≤λ≤3.5  μm contains strong spectral absorption lines of many gases used in health, industry, safety, and medicine and whose sensitive and quantitative detection is desirable. However, the performance of InP diode lasers markedly deteriorates beyond λ∼2  μm. In this paper we present new results on developing tunable high power single mode laser diodes based on the GaSb material system with emission in the wavelength range of 1.8  μm≤λ≤2.2  μm.

Brain-derived neurotrophic factor (BDNF), an important neural growth factor, has gained growing interest in neuroscience, but many influencing physiological and analytical aspects still remain unclear. In this study we assessed the impact of storage time at room temperature, repeated freeze/thaw cycles, and storage at -80 °C up to 6 months on serum and ethylenediaminetetraacetic acid (EDTA)-plasma BDNF. Furthermore, we assessed correlations of serum and plasma BDNF concentrations in two independent sets of samples. Coefficients of variations (CVs) for serum BDNF concentrations were significantly lower than CVs of plasma concentrations ( n = 245, p = 0.006). Mean serum and plasma concentrations at all analyzed time points remained within the acceptable change limit of the inter-assay precision as declared by the manufacturer. Serum and plasma BDNF concentrations correlated positively in both sets of samples and at all analyzed time points of the stability assessment ( r = 0.455 to r s = 0.596; p < 0.004). In summary, when considering the acceptable change limit, BDNF was stable in serum and in EDTA-plasma up to 6 months. Due to a higher reliability, we suggest favoring serum over EDTA-plasma for future experiments assessing peripheral BDNF concentrations., Competing Interests: The authors declare no conflict of interest.

Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.

Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting-state fMRI data in 25 young (mean age 24.8 ± 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 ± 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Neuron-specific enolase (NSE) has been suggested as a prognostic biomarker for neuronal alterations resulting from conditions such as traumatic brain injury (TBI), neurodegenerative disease, or cardiac arrest. To validate serum NSE (sNSE) as a brain-specific biomarker, we related it to functional brain imaging data in 38 healthy adults to create a physiological framework for future studies in neuropsychiatric diseases. sNSE was measured by monoclonal two-site immunoluminometric assays, and functional connectivity was investigated with resting-state functional magnetic resonance imaging (rfMRI). To identify neural hubs most essentially related to sNSE, we applied graph theory approaches, namely, the new data-driven and parameter-free approach, eigenvector centrality mapping. sNSE and eigenvector centrality were negatively correlated in the female cerebellum, without any effects in male subjects. In cerebellar cortex, NSE expression was significantly higher than whole-brain expression as investigated in the whole brain and whole genome-wide atlas of the Allen Institute for Brain Sciences (Seattle, WA). Our study shows a specific linkage between the neuronal marker protein, sNSE, and cerebellar connectivity as measured with rfMRI in the female human brain, although this finding shall be proven in future studies including more subjects. Results suggest that the inclusion of sNSE in the analysis of imaging data is a useful approach to obtain more-specific information on the neuronal mechanisms that underlie functional connectivity at rest. Establishing such a baseline resting-state pattern that is tied to a neuronal serum marker opens new perspectives in the characterization of neuropsychiatric disorders as disconnective syndromes or nexopathies, in particular, resulting from TBI, neurodegenerative disease, or cardiac arrest, in the future.

It is unclear whether reflective awareness of emotions is related to extent and intensity of implicit affective reactions. This study is the first to investigate automatic brain reactivity to emotional stimuli as a function of trait emotional awareness. To assess emotional awareness the Levels of Emotional Awareness Scale (LEAS) was administered. During scanning, masked happy, angry, fearful and neutral facial expressions were presented to 46 healthy subjects, who had to rate the fit between artificial and emotional words. The rating procedure allowed assessment of shifts in implicit affectivity due to emotion faces. Trait emotional awareness was associated with increased activation in the primary somatosensory cortex, inferior parietal lobule, anterior cingulate gyrus, middle frontal and cerebellar areas, thalamus, putamen and amygdala in response to masked happy faces. LEAS correlated positively with shifts in implicit affect caused by masked happy faces. According to our findings, people with high emotional awareness show stronger affective reactivity and more activation in brain areas involved in emotion processing and simulation during the perception of masked happy facial expression than people with low emotional awareness. High emotional awareness appears to be characterized by an enhanced positive affective resonance to others at an automatic processing level., (© The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC) mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal Resting-state functional Magnetic Resonance Imaging (rs-fMRI) design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.

Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.

Postpartum depression (PPD) has a prevalence rate of 13% and a similarly high proportion of women report a subclinical state of one or more major depressive episode symptoms. The aim was to investigate whether monoamine oxidase-A (MAO-A) VT, an index of MAO-A density, is increased in the prefrontal and anterior cingulate cortex (PFC and ACC), during PPD or when a PPD spectrum symptom, greater predisposition to crying, is present. MAO-A is an enzyme that increases in density after estrogen decline, and has several functions including creating oxidative stress, influencing apoptosis and monoamine metabolism. Fifty-seven women were recruited including 15 first-onset, antidepressant naive, PPD subjects, 12 postpartum healthy who cry due to sad mood, 15 asymptomatic postpartum healthy women, and 15 healthy women not recently pregnant. Each underwent [(11)C]-harmine positron emission tomography scanning to measure MAO-A VT. Both PPD and greater predisposition to crying were associated with greater MAO-A VT in the PFC and ACC (multivariate analysis of variance (MANOVA), group effect, F21,135=1.856; p=0.019; mean combined region elevation 21% and 14% in PPD and crying groups, respectively, relative to postpartum asymptomatic). Greater MAO-A VT in the PFC and ACC represents a new biomarker in PPD, and the PPD symptom of predisposition to crying. Novel strategies for preventing PPD (and some PPD symptoms) may be possible by avoiding environmental conditions that elevate MAO-A level and enhancing conditions that normalize MAO-A level. These findings also argue for clinical trials in PPD with the newer, well-tolerated MAO-A inhibitor antidepressants.

Bacteriophage receptor-binding proteins (RBPs) confer host specificity. We previously identified a putative RBP (Gp047) from the campylobacter lytic phage NCTC 12673 and demonstrated that Gp047 has a broader host range than its parent phage. While NCTC 12673 recognizes the capsular polysaccharide (CPS) of a limited number of Campylobacter jejuni isolates, Gp047 binds to a majority of C. jejuni and related Campylobacter coli strains. In this study, we demonstrate that Gp047 also binds to acapsular mutants, suggesting that unlike the parent phage, CPS is not the receptor for Gp047. Affinity chromatography and far-western analyses of C. jejuni lysates using Gp047 followed by mass spectrometry indicated that Gp047 binds to the major flagellin protein, FlaA. Because C. jejuni flagellin is extensively glycosylated, we investigated this binding specificity further and demonstrate that Gp047 only recognizes flagellin decorated with acetamidino-modified pseudaminic acid. This binding activity is localized to the C-terminal quarter of the protein and both wild-type and coccoid forms of C. jejuni are recognized. In addition, Gp047 treatment agglutinates vegetative cells and reduces their motility. Because Gp047 is highly conserved among all campylobacter phages sequenced to date, it is likely that this protein plays an important role in the phage life cycle., (© 2014 John Wiley & Sons Ltd.)

The ability to recognize subtle facial expressions can be valuable in social interaction to infer emotions and intentions of others. Research has shown that the personality trait of alexithymia is linked to difficulties labeling facial expressions especially when these are presented with temporal constraints. The present study investigates the neural mechanisms underlying this deficit. 50 young healthy volunteers had to label briefly presented (≤100ms) emotional (happy, angry, fearful) facial expressions masked by a neutral expression while undergoing functional magnetic resonance imaging (fMRI). A multi-method approach (20-Item Toronto Alexithymia Scale and Toronto Structured Interview for Alexithymia) was administered to assess alexithymic tendencies. Behavioral results point to a global deficit of alexithymic individuals in labeling brief facial expressions. Alexithymia was related to decreased response of the ventral striatum to negative facial expressions. Moreover, alexithymia was associated with lowered activation in frontal, temporal and occipital cortices. Our data suggest that alexithymic individuals have difficulties in creating appropriate representations of the emotional state of other persons under temporal constraints. These deficiencies could lead to problems in labeling other people׳s facial emotions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)