'That Time of the Month' - Investigating the Influence of the Menstrual Cycle and Oral Contraceptives on the Brain Using Magnetic Resonance Imaging.

The stereotypic and oversimplified relationship between female sex hormones and undesirable behavior dates to the earliest days of human society, as already the ancient Greek word for the uterus, "hystera" indicated an aversive connection. Remaining and evolving throughout the centuries, transcending across cultures and various aspects of everyday life, its perception was only recently reframed. Contemporarily, the complex interaction of hormonal phases (i. e., the menstrual cycle), hormonal medication (i. e., oral contraceptives), women's psychological well-being, and behavior is the subject of multifaceted and more reflected discussions. A driving force of this ongoing paradigm shift was the introduction of this highly interesting and important topic into the realm of scientific research. This refers to neuroscientific research as it enables a multimodal approach combining aspects of physiology, medicine, and psychology. Here a growing body of literature points towards significant alterations of both brain function, such as lateralization of cognitive functions, and structure, such as gray matter concentrations, due to fluctuations and changes in hormonal levels. This especially concerns female sex hormones. However, the more research is conducted within this field, the less reliable these observations and derived insights appear. This may be due to two particular factors: measurement inconsistencies and diverse hormonal phases accompanied by interindividual differences. The first factor refers to the prominent unreliability of one of the primarily utilized neuroscientific research instruments: functional magnetic resonance imaging (fMRI). This unreliability is seemingly present in paradigms and analyses, and their interplay, and is additionally affected by the second factor. In more detail, hormonal phases and levels further influence neuroscientific results obtained through fMRI as outcomes vary drastically across different cycle phases and medication. This resulting vast uncertainty thus tremendously hinders the further advancement of our understanding of how female sex hormones might alter brain structure and function and, ultimately, behavior.This review summarizes parts of the current state of research and outlines the essential requirements to further investigate and understand the female brain's underlying physiological and anatomical features.

The German research consortium for the study of bipolar disorder (BipoLife): a magnetic resonance imaging study protocol.

BACKGROUND: Bipolar disorder is one of the most severe mental disorders. Its chronic course is associated with high rates of morbidity and mortality, a high risk of suicide and poor social and occupational outcomes. Despite the great advances over the last decades in understanding mental disorders, the mechanisms underlying bipolar disorder at the neural network level still remain elusive. This has severe consequences for clinical practice, for instance by inadequate diagnoses or delayed treatments. The German research consortium BipoLife aims to shed light on the mechanisms underlying bipolar disorders. It was established in 2015 and incorporates ten university hospitals across Germany. Its research projects focus in particular on individuals at high risk of bipolar disorder, young patients in the early stages of the disease and patients with an unstable highly relapsing course and/or with acute suicidal ideation. METHODS: Functional and structural magnetic resonance imaging (MRI) data was acquired across nine sites within three different studies. Obtaining neuroimaging data in a multicenter setting requires among others the harmonization of the acquisition protocol, the standardization of paradigms and the implementation of regular quality control procedures. The present article outlines the MRI imaging protocols, the acquisition parameters, the imaging paradigms, the neuroimaging quality assessment procedures and the number of recruited subjects. DISCUSSION: The careful implementation of a MRI study protocol as well as the adherence to well-defined quality assessment procedures is one key benchmark in the evaluation of the overall quality of large-scale multicenter imaging studies. This article contributes to the BipoLife project by outlining the rationale and the design of the MRI study protocol. It helps to set the necessary standards for follow-up analyses and provides the technical details for an in-depth understanding of follow-up publications.

Prospective pilot study to identify psychological factors influencing peri-operative pain in total knee arthroplasty (TKA).

PURPOSE: Up to 20% of total knee arthroplasty (TKA) patients remain dissatisfied, with chronic pain as the most frequently named cause. A pilot study was conducted to assess the progression of peri-operative pain intensity and the parallel development of different psychological factors and coping strategies, as well as correlations indicating potential inter-relationships. METHODS: Pain, psychological impairment [FESV BE], and coping strategies [FESV BW] were assessed before and after TKA [days - 5 to 31]. Patients were stratified according to the presence or absence of peri-operative pain improvement [decreasing pain: Group 1 [69%; n = 36]; persisting pain: group 2 [31%; n = 16]]. Group 2 was additionally tested with the Toronto Alexithymia Scale [TAS] and Screening for Somatoform Disorders [SOMS]. RESULTS: Pain intensity in group 1 decreased from significantly higher pre-operative levels to significantly lower values at 31 days post-operatively, whereas group 2 did not show significant changes. Concurrently, the psychological impairment parameter anxiety (AN) significantly decreased and the pain coping parameter relaxation significantly increased in group 1, but not in group 2. Whereas pre-operative pain was positively and significantly correlated with AN throughout time in group 2, it was negatively correlated with relaxation at day 29 in group 1. Concerning TAS and SOMS, considerable percentages of the participants in group 2 (37.5% and 68.75%, respectively) showed values > 50% of those in normal controls. CONCLUSIONS: Parallel (or anti-parallel) and partially correlated developments of pain improvement and parameters of psychological impairment or coping strategies after TKA suggest a pre-operative screening with tools like the FESV BE and BW or TAS and SOMS questionnaires in order to classify individuals for peri-operative mental training.

LAB-QA2GO: A Free, Easy-to-Use Toolbox for the Quality Assessment of Magnetic Resonance Imaging Data.

Image characteristics of magnetic resonance imaging (MRI) data (e.g., signal-to-noise ratio, SNR) may change over the course of a study. To monitor these changes a quality assurance (QA) protocol is necessary. QA can be realized both by performing regular phantom measurements and by controlling the human MRI datasets (e.g., noise detection in structural or movement parameters in functional datasets). Several QA tools for the assessment of MRI data quality have been developed. Many of them are freely available. This allows in principle the flexible set-up of a QA protocol specifically adapted to the aims of one's own study. However, setup and maintenance of these tools takes substantial time, in particular since the installation and operation often require a fair amount of technical knowledge. In this article we present a light-weighted virtual machine, named LAB-QA2GO, which provides scripts for fully automated QA analyses of phantom and human datasets. This virtual machine is ready for analysis by starting it the first time. With minimal configuration in the guided web-interface the first analysis can start within 10 min, while adapting to local phantoms and needs is easily possible. The usability and scope of LAB-QA2GO is illustrated using a data set from the QA protocol of our lab. With LAB-QA2GO we hope to provide an easy-to-use toolbox that is able to calculate QA statistics without high effort.

Longitudinal brain volume changes in major depressive disorder.

Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years. The Cat12 toolbox was used to analyze longitudinal data (p < 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; > 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.

The Marburg-Münster Affective Disorders Cohort Study (MACS): A quality assurance protocol for MR neuroimaging data.

Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses. We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data. We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are most pronounced in the bilateral basal ganglia, thalamus, and posterior regions. Using DTI data, we also show that fractional anisotropy (FA) differs between sites in almost all regions assessed. When pooling data from multiple centers, our data show that it is a necessity to account not only for inter-site differences but also for hardware and software changes of the scanning equipment. Also, the strong dependence of the QA statistics on the reliable placement of the MRI phantom shows that the use of a phantom holder is recommended to reduce the variance of the QA statistics and thus to increase the probability of detecting potential scanner malfunctions.

Comparison of fMRI paradigms assessing visuospatial processing: Robustness and reproducibility.

The development of brain imaging techniques, in particular functional magnetic resonance imaging (fMRI), made it possible to non-invasively study the hemispheric lateralization of cognitive brain functions in large cohorts. Comprehensive models of hemispheric lateralization are, however, still missing and should not only account for the hemispheric specialization of individual brain functions, but also for the interactions among different lateralized cognitive processes (e.g., language and visuospatial processing). This calls for robust and reliable paradigms to study hemispheric lateralization for various cognitive functions. While numerous reliable imaging paradigms have been developed for language, which represents the most prominent left-lateralized brain function, the reliability of imaging paradigms investigating typically right-lateralized brain functions, such as visuospatial processing, has received comparatively less attention. In the present study, we aimed to establish an fMRI paradigm that robustly and reliably identifies right-hemispheric activation evoked by visuospatial processing in individual subjects. In a first study, we therefore compared three frequently used paradigms for assessing visuospatial processing and evaluated their utility to robustly detect right-lateralized brain activity on a single-subject level. In a second study, we then assessed the test-retest reliability of the so-called Landmark task-the paradigm that yielded the most robust results in study 1. At the single-voxel level, we found poor reliability of the brain activation underlying visuospatial attention. This suggests that poor signal-to-noise ratios can become a limiting factor for test-retest reliability. This represents a common detriment of fMRI paradigms investigating visuospatial attention in general and therefore highlights the need for careful considerations of both the possibilities and limitations of the respective fMRI paradigm-in particular, when being interested in effects at the single-voxel level. Notably, however, when focusing on the reliability of measures of hemispheric lateralization (which was the main goal of study 2), we show that hemispheric dominance (quantified by the lateralization index, LI, with |LI| >0.4) of the evoked activation could be robustly determined in more than 62% and, if considering only two categories (i.e., left, right), in more than 93% of our subjects. Furthermore, the reliability of the lateralization strength (LI) was "fair" to "good". In conclusion, our results suggest that the degree of right-hemispheric dominance during visuospatial processing can be reliably determined using the Landmark task, both at the group and single-subject level, while at the same time stressing the need for future refinements of experimental paradigms and more sophisticated fMRI data acquisition techniques.

Mindfulness meditation regulates anterior insula activity during empathy for social pain.

Mindfulness has been shown to reduce stress, promote health, and well-being, as well as to increase compassionate behavior toward others. It reduces distress to one's own painful experiences, going along with altered neural responses, by enhancing self-regulatory processes and decreasing emotional reactivity. In order to investigate if mindfulness similarly reduces distress and neural activations associated with empathy for others' socially painful experiences, which might in the following more strongly motivate prosocial behavior, the present study compared trait, and state effects of long-term mindfulness meditation (LTM) practice. To do so we acquired behavioral data and neural activity measures using functional magnetic resonance imaging (fMRI) during an empathy for social pain task while manipulating the meditation state between two groups of LTM practitioners that were matched with a control group. The results show increased activations of the anterior insula (AI) and anterior cingulate cortex (ACC) as well as the medial prefrontal cortex and temporal pole when sharing others' social suffering, both in LTM practitioners and controls. However, in LTM practitioners, who practiced mindfulness meditation just prior to observing others' social pain, left AI activation was lower and the strength of AI activation following the mindfulness meditation was negatively associated with trait compassion in LTM practitioners. The findings suggest that current mindfulness meditation could provide an adaptive mechanism in coping with distress due to the empathic sharing of others' suffering, thereby possibly enabling compassionate behavior. Hum Brain Mapp 38:4034-4046, 2017. © 2017 Wiley Periodicals, Inc.

Ascending Aortic Disease is Associated with Earlier Menopause and Shorter Reproductive Life Span.

OBJECTIVES: The incidence of cardiovascular morbidity and mortality in premenopausal women is comparatively low, but increases sharply after menopause. The principal aim of this study was to determine whether women with ascending aortic disease (AAD) have a different reproductive history from that of an age-matched control group. METHODS: In this retrospective study, women who had undergone ascending aortic aneurysm (AscAA) repair between 2000 and 2010 were asked to complete a questionnaire concerning risk factors and reproductive history. Data from 142 women with AAD were evaluated, and a subgroup (n = 64) with AscAA ≥5 cm was analyzed and compared to an age-matched random control group without known aortic diseases. RESULTS: Almost all women were menopausal at the time of the questionnaire (98.4% vs. 90.6%, AscAA ≥5 cm subcohort vs. control, p = 0.12) and all subjects presented with a comparable age of menarche (13.7 ± 2.6 years vs. 14.2 ± 1.8 years, AscAA ≥5 cm subcohort vs. control, log-rank 0.04, p = 0.84). However, mean menopausal age was significantly lower in the case subcohort than in controls (48.1 ± 4.8 years vs. 50.6 ± 5.8 years, AscAA ≥5 cm subcohort vs. control, log-rank 8.35, p = 0.004), and reproductive life span was correspondingly shorter (34.2 ± 5.2 years vs. 36.2 ± 5.7 years, p = 0.04). Furthermore, hypertension was more prevalent in women with AscAA ≥5 cm compared to controls (89.1% vs. 61.9%, AscAA ≥5 cm subcohort vs. control, p < 0.001). CONCLUSION: Women who experience menopause at an earlier age than the regional mean could profit from screening for cardiovascular disease in general and particularly for AAD. Screening would enable early aneurysm detection and could, therefore, reduce morbidity and mortality.

Effects of Long-Term Mindfulness Meditation on Brain's White Matter Microstructure and its Aging.

Although research on the effects of mindfulness meditation (MM) is increasing, still very little has been done to address its influence on the white matter (WM) of the brain. We hypothesized that the practice of MM might affect the WM microstructure adjacent to five brain regions of interest associated with mindfulness. Diffusion tensor imaging was employed on samples of meditators and non-meditators (n = 64) in order to investigate the effects of MM on group difference and aging. Tract-Based Spatial Statistics was used to estimate the fractional anisotrophy of the WM connected to the thalamus, insula, amygdala, hippocampus, and anterior cingulate cortex. The subsequent generalized linear model analysis revealed group differences and a group-by-age interaction in all five selected regions. These data provide preliminary indications that the practice of MM might result in WM connectivity change and might provide evidence on its ability to help diminish age-related WM degeneration in key regions which participate in processes of mindfulness.

MRI phantoms - are there alternatives to agar?

The suitability of different gelling agents as MRI phantoms was evaluated in terms of homogeneity, gel stability and reproducibility. Time and effort for preparation were also taken into account. The relaxation times of various gel compositions were estimated. Carbomer-980 and Carbopol-974P were determined to be promising novel phantom materials. These gelling agents are readily available, inexpensive and easy to handle given that thermal treatment is not required. Furthermore, the viscoelasticity of their polymer network is pH-dependent. With such characteristics, it was even possible to embed sensitive objects and retrieve them after testing. This was demonstrated with a fiber phantom for Diffusion Weighted MRI applications. Since Carbomer-980 and Carbopol-974P are non-hazardous, they are also suitable for multimodal setups (e.g., MRI as well as ultrasonic imaging).