Cortical gyrification in women and men and the (missing) link to prenatal androgens.

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex-specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex-wise absolute mean curvature-a common estimate for cortical gyrification-in individuals with CAH (33 women and 20 men) and pair-wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH-by-sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly-the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women.

The neuroanatomy of pregnancy and postpartum.

Pregnancy and giving birth are exceptional states in a woman's life for many reasons. While the effects of pregnancy and childbirth on the female body are obvious, less is known about their impact on the female brain, especially in humans. The scientific literature is still sparse but we have identified 12 longitudinal neuroimaging studies conducted in women whose brains were scanned before pregnancy, during pregnancy, and/or after giving birth. This review summarizes and discusses the reported neuroanatomical changes during pregnancy, postpartum, and beyond. Some studies suggest that pregnancy is mainly associated with tissue decreases, and a few studies suggest that this tissue loss is mostly permanent. In contrast, the majority of studies seems to indicate that the postpartum period is accompanied by substantial tissue increases throughout the entire brain. Future research is clearly warranted to replicate and extend the current findings, while addressing various limitations and shortcomings of existing studies.

Aberrant callosal morphology in ex-smokers.

BACKGROUND: Cigarette smoking is associated with widespread structural alterations in both brain hemispheres as well as of the corpus callosum (i.e., the brain's main interhemispheric white matter pathway). While similar hemispheric alterations have also been reported in ex-smokers, no study has yet examined the corpus callosum in ex-smokers. METHODS: We compared callosal morphology in a sample of 107 ex-smokers (57 males/50 females) and 193 non-smokers (73 males/120 females), aged between 42 and 97 years. More specifically, we measured the total callosal area as well as seven callosal subregions using the Witelson parcellation scheme. RESULTS: At uncorrected levels, we detected significantly smaller callosal areas in ex-smokers than in non-smokers within the posterior midbody, genu, and isthmus (albeit the latter only on a trend level). When applying corrections for multiple comparisons, only the effect within the posterior midbody remained significant. CONCLUSIONS: Our findings suggest a weaker interhemispheric connectivity in ex-smokers compared to non-smokers, specifically between frontal and temporal areas.

Progesterone - Friend or foe?

Estradiol is the "prototypic" sex hormone of women. Yet, women have another sex hormone, which is often disregarded: Progesterone. The goal of this article is to provide a comprehensive review on progesterone, and its metabolite allopregnanolone, emphasizing three key areas: biological properties, main functions, and effects on mood in women. Recent years of intensive research on progesterone and allopregnanolone have paved the way for new treatment of postpartum depression. However, treatment for premenstrual syndrome and premenstrual dysphoric disorder as well as contraception that women can use without risking mental health problems are still needed. As far as progesterone is concerned, we might be dealing with a two-edged sword: while its metabolite allopregnanolone has been proven useful for treatment of PPD, it may trigger negative symptoms in women with PMS and PMDD. Overall, our current knowledge on the beneficial and harmful effects of progesterone is limited and further research is imperative.

The impact of aging on the subregions of the fusiform gyrus in healthy older adults.

The fusiform gyrus is known to decrease in size with increasing age. However, reported findings are inconsistent and existing studies differ in terms of the cohorts examined and/or the methods applied. Here, we analyzed age-related links in four distinct subregions of the fusiform gyrus through integrating imaging-based intensity information with microscopically defined cytoarchitectonic probabilities. In addition to age effects we investigated sex effects as well as age-by-sex interactions in a relatively large sample of 468 healthy subjects (272 females/196 males) covering a broad age range (42-97 years). We observed significant negative correlations between age and all four subregions of the fusiform gyrus indicating volume decreases over time, albeit with subregion-specific trajectories. Additionally, we observed significant negative quadratic associations with age for some subregions, suggesting an accelerating volume loss over time. These findings may serve as a frame of reference for future cross-sectional as well as longitudinal studies, not only for normative samples but also potentially for clinical conditions that present with abnormal atrophy of the fusiform gyrus. We did not detect any significant sex differences or sex-by-age interactions, suggesting that the size of the fusiform gyrus is similar in male and female brains and that age-related atrophy follows a similar trajectory in both men and women.

Significant increases of the amygdala between immediate and late postpartum: Pronounced effects within the superficial subregion.

Research exploring the underlying neuroanatomical correlates of early motherhood seems to suggest that the period after giving birth is marked by tissue increases in the mother's brain. While some studies point to the amygdala as one of the areas undergoing postpartum changes, existing analyses did not discriminate between the different subregions of this functionally heterogeneous structure. Thus, to further extend this understudied field of research and to better understand the potential role of the amygdala when transitioning to motherhood, we applied an advanced region-of-interest technique that enabled us to analyze the amygdala as a whole as well as its different subareas, specifically the left and right centromedian (CM), laterobasal (LB), and superficial (SF) regions. Comparing the brains of 14 healthy women between immediate postpartum (within 1-2 days of childbirth) and late postpartum (at 4-6 weeks after childbirth), we revealed increases of the amygdala. However, effects manifested differentially across subareas, with particularly strong effects for the SF region, moderate effects for the CM region, and no effects for the LB region. These findings might reflect region-specific adaptations of the mother's brain tuning into the distinct and ever-changing needs of a newborn, either as a cause for it or as a consequence thereof.

Diminished Age-Related Decline of the Amygdala in Long-Term Meditation Practitioners.

OBJECTIVE: A growing body of scientific evidence suggests that meditation may slow brain aging. The amygdala-a heterogenous brain region known to decrease in volume with increasing age-seems to be involved in meditation and affected by meditation. Thus, we hypothesized that the age-related decline of the amygdala is diminished in meditation practitioners. METHODS: We investigated whether correlations between age and gray matter volumes of the amygdala are significantly reduced in 50 long-term meditators compared with 50 sex- and age-matched healthy controls. Both the meditator and control groups included 44% women. The age of the participants ranged between 24 and 77 years, with mean (standard deviation) ages of 50.4 (±11.8) years in meditators and 51.4 (±12.8) years in controls. In addition to studying the amygdala as a whole, we investigated its centromedial, laterobasal, and superficial subregions using a well-validated approach combining imaging-based signal intensities and cytoarchitectonically defined probabilities. RESULTS: We detected significant group-by-age interactions for the whole amygdala and for its subregions. Follow-up analyses indicated negative age-related correlations in both meditators and controls (the older the participants, the smaller the volumes) but with significantly steeper aging trajectories in controls. CONCLUSIONS: Altogether, these findings suggest that the age-related volume loss of the amygdala is less pronounced in long-term meditators. This effect was particularly evident for the laterobasal subregion, which has been functionally linked to aspects of self-focused reflection.

The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group.

BACKGROUND: In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings. AIM: To examine the neurobiology of transgender persons in a large sample. METHODS: Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed. OUTCOMES: Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness. RESULTS: Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. CLINICAL TRANSLATION: The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies. STRENGTHS AND LIMITATIONS: While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites. CONCLUSION: Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype. Mueller SC, Guillamon A, Zubiaurre-Elorza L, et al. The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group. J Sex Med 2021;18:1122-1129.

Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case-control study.

Hippocampal brain regions are strongly implicated in Niemann Pick type C disease (NPC), but little is known regarding distinct subregions of the hippocampal complex and whether these are equally or differentially affected. To address this gap, we compared volumes of five hippocampal subfields between NPC and healthy individuals using MRI. To this end, 9 adult-onset NPC cases and 9 age- and gender-matched controls underwent a 3 T T1-weighted MRI scan. Gray matter volumes of the cornu ammonis (CA1, CA2 and CA3), dentate gyrus (DG), subiculum, entorhinal cortex and hippocampal-amygdalar transition area were calculated by integrating MRI-based image intensities with microscopically defined cytoarchitectonic probabilities. Compared to healthy controls, NPC patients showed smaller volumes of the CA1-3 and DG regions bilaterally, with the greatest difference localized to the left DG (Cohen's d = 1.993, p = 0.008). No significant associations were shown between hippocampal subfield volumes and key clinical features of NPC, including disease duration, symptom severity and psychosis. The pattern of hippocampal subregional atrophy in NPC differs from those seen in other dementias, which may indicate unique cytoarchitectural vulnerabilities in this earlier-onset disorder. Future MRI studies of hippocampal subfields may clarify its potential as a biomarker of neurodegeneration in NPC.

The Link between Estradiol and Neuroplasticity in Transgender Women after Gender-Affirming Surgery: A Bimodal Hypothesis.

For transgender individuals, gender-affirming surgery (GAS) and cross-sex hormone therapy (CSHT) are part of the gender transition process. Scientific evidence supporting the maintenance of CSHT after GAS-related gonadectomy is accumulating. However, few data are available on the impact of CSHT on the brain structure following hypogonadism. Thus, we aimed to investigate links between estradiol and brain cortical thickness (CTh) and cognition in 18 post-gonadectomy transgender women using a longitudinal design. For this purpose, the participants underwent a voluntary period of CSHT washout of at least 30 days, followed by estradiol re-institution for 60 days. High-resolution T1-weighted brain images, hormonal measures, working and verbal memory were collected at 2 time points: on the last day of the washout (t1) and on the last day of the 2-month CSHT period (t2). Between these 2 time points, CTh increased within the left precentral gyrus and right precuneus but decreased within the right lateral occipital cortex. However, these findings did not survive corrections of multiple comparisons. Nevertheless, there was a significant negative correlation between changes in estradiol levels and changes in CTh. This effect was evident in the left superior frontal gyrus, the left middle temporal gyrus, the right precuneus, the right superior temporal gyrus, and the right pars opercularis. Although there was an improvement in verbal memory following hypogonadism correction, we did not observe a significant relationship between changes in memory scores and CTh. Altogether, these findings suggest that there is a link between estradiol and CTh.

Age but no sex effects on subareas of the amygdala.

The amygdala, an anatomical composite of several nuclei that have been grouped anatomically and functionally into three major subareas, has been reported to decrease in size with increasing age and to differ in size between male and female brains. However, findings are rather inconsistent across existing studies, possibly reflecting differences in the cohorts examined or the approaches chosen to define and measure the dimensions of the amygdala. Here, we investigated possible effects of age and sex on the amygdala as well as age-by-sex interactions in 100 healthy subjects (50 men/50 women) aged 18-69 years. For this purpose, we enhanced conventional imaging-based information with microscopically defined cytoarchitectonic probabilities to discriminate between different subareas. We observed significant negative correlations between age and all subareas of the amygdala indicating decreases over time, but with subarea-specific trajectories. In addition, we detected a significant quadratic association with age for the left superficial subarea suggesting an accelerating volume loss over time. Such regional information may serve as a frame of reference in future studies, not only for normative samples but also potentially for clinical populations known to present with an atypical atrophy of the amygdala. There were no sex differences and no interactions between sex and age, suggesting that the size of the amygdala is similar in male and female brains (at least when properly accounting for total intracranial volume) and that its age-related decline follows a similar trajectory in both sexes.

Sex differences in associations between spatial ability and corpus callosum morphology.

Rotating mental representations of objects is accompanied by widespread bilateral brain activations. Thus, interhemispheric communication channels may play a relevant part when engaging in mental rotation tasks. Indeed, links between mental rotation and dimensions of the corpus callosum-the brain's main commissure system-have been reported. However, existing findings are sparse and inconsistent across studies. Here we set out to further characterize the nature of any such links, including their exact location across the corpus callosum. For this purpose, we applied an advanced image analysis approach assessing callosal thickness at 100 equidistant points in a sample of 38 healthy adults (19 men, 19 women), aged between 22 and 45 years. We detected a sex interaction, with significant structure-performance relationships in women, but not in men. Specifically, better mental rotation performance was linked to a thicker female corpus callosum within regions of the callosal splenium, posterior midbody, and anterior third. These findings may suggest sex differences in problem solving strategies where in women, more than in men, stronger interhemispheric connectivity-especially between occipitoparietal, frontal, and prefrontal regions-is associated with improved task performance. © 2018 Wiley Periodicals, Inc.

Altered gray matter volumes in language-associated regions in children with developmental language disorder and speech sound disorder.

Developmental language disorder (DLD) and speech sound disorder (SSD) are common, and although scientific evidence for structural and functional alterations in DLD/SSD is accumulating, current neuroimaging studies provide an incongruent picture. Here, we hypothesized that children affected by DLD and SSD present with gray matter (or gray matter asymmetry) aberrations in brain areas associated with language processing compared to typically developing (TD) children. To assess this hypothesis, we enhanced MRI-based information with microscopically defined cytoarchitectonic probabilities of Broca's area (BA 45, BA 44) as well as an auditory area (TE 3.0). We detected a larger rightward gray matter asymmetry in BA 45 in children with DLD (n = 13) and with SSD (n = 18) compared to TD children (n = 18), albeit only on a trend level. Interestingly though, we observed significantly larger gray matter volumes in right BA 45 in DLD compared to SSD children (and also compared to TD children).

The impact of aging on subregions of the hippocampal complex in healthy adults.

The hippocampal complex, an anatomical composite of several subregions, is known to decrease in size with increasing age. However, studies investigating which subregions are particularly prone to age-related tissue loss revealed conflicting findings. Possible reasons for such inconsistencies may reflect differences between studies in terms of the cohorts examined or techniques applied to define and measure hippocampal subregions. In the present study, we enhanced conventional MR-based information with microscopically defined cytoarchitectonic probabilities to investigate aging effects on the hippocampal complex in a carefully selected sample of 96 healthy subjects (48 males/48 females) aged 18-69 years. We observed significant negative correlations between age and volumes of the cornu ammonis, fascia dentata, subiculum, and hippocampal-amygdaloid transition area, but not the entorhinal cortex. The estimated age-related annual atrophy rates were most pronounced in the left and right subiculum with -0.23% and -0.22%, respectively. These findings suggest age-related atrophy of the hippocampal complex overall, but with differential effects in its subregions. If confirmed in future studies, such region-specific information may prove useful for the assessment of diseases and disorders known to modulate age-related hippocampal volume loss.

Sexual dimorphism of Broca's region: More gray matter in female brains in Brodmann areas 44 and 45.

Although a sexual dimorphism in brain structure is generally well established, evidence for sex differences in Brodmann areas (BA) 44 and 45 is inconclusive. This may be due to the difficulty of accurately defining BA 44 and BA 45 in magnetic resonance images, given that these regions are variable in their location and extent and that they do not match well with macroanatomic landmarks. Here we set out to test for possible sex differences in the local gray matter of BA 44/45 by integrating imaging-based signal intensities with cytoarchitectonically defined tissue probabilities in a sample of 50 male and 50 female subjects. In addition to testing for sex differences with respect to left- and right-hemispheric measures of BA 44/45, we also assessed possible sex differences in BA 44/45 asymmetry. Our analyses revealed significantly larger gray matter volumes in females compared with males for BA 44 and BA 45 bilaterally. However, there was a lack of significant sex differences in BA 44/45 asymmetry. These results corroborate reports of a language-related female superiority, particularly with respect to verbal fluency and verbal memory tasks. © 2016 Wiley Periodicals, Inc.

Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life.

Why size matters: differences in brain volume account for apparent sex differences in callosal anatomy: the sexual dimorphism of the corpus callosum.

Numerous studies have demonstrated a sexual dimorphism of the human corpus callosum. However, the question remains if sex differences in brain size, which typically is larger in men than in women, or biological sex per se account for the apparent sex differences in callosal morphology. Comparing callosal dimensions between men and women matched for overall brain size may clarify the true contribution of biological sex, as any observed group difference should indicate pure sex effects. We thus examined callosal morphology in 24 male and 24 female brains carefully matched for overall size. In addition, we selected 24 extremely large male brains and 24 extremely small female brains to explore if observed sex effects might vary depending on the degree to which male and female groups differed in brain size. Using the individual T1-weighted brain images (n=96), we delineated the corpus callosum at midline and applied a well-validated surface-based mesh-modeling approach to compare callosal thickness at 100 equidistant points between groups determined by brain size and sex. The corpus callosum was always thicker in men than in women. However, this callosal sex difference was strongly determined by the cerebral sex difference overall. That is, the larger the discrepancy in brain size between men and women, the more pronounced the sex difference in callosal thickness, with hardly any callosal differences remaining between brain-size matched men and women. Altogether, these findings suggest that individual differences in brain size account for apparent sex differences in the anatomy of the corpus callosum.

Approximation of bone mineral density and subcutaneous adiposity using T1-weighted images of the human head.

Bones and brain are intricately connected and scientific interest in their interaction is growing. This has become particularly evident in the framework of clinical applications for various medical conditions, such as obesity and osteoporosis. The adverse effects of obesity on brain health have long been recognised, but few brain imaging studies provide sophisticated body composition measures. Here we propose to extract the following bone- and adiposity-related measures from T1-weighted MR images of the head: an approximation of skull bone mineral density (BMD), skull bone thickness, and two approximations of subcutaneous fat (i.e., the intensity and thickness of soft non-brain head tissue). The measures pertaining to skull BMD, skull bone thickness, and intensi-ty-based adiposity proxy proved to be reliable ( r =.93/.83/.74, p <.001) and valid, with high correlations to DXA-de-rived head BMD values (rho=.70, p <.001) and MRI-derived abdominal subcutaneous adipose volume (rho=.62, p <.001). Thickness-based adiposity proxy had only a low retest reliability ( r =.58, p <.001).The outcomes of this study constitute an important step towards extracting relevant non-brain features from available brain scans.

Corpus callosum morphology and relationships to illness phenotypes in individuals with anorexia nervosa.

Anorexia nervosa is an often-severe psychiatric illness characterized by significantly low body weight, fear of gaining weight, and distorted body image. Multiple neuroimaging studies have shown abnormalities in cortical morphology, mostly associated with the starvation state. Investigations of white matter, while more limited in number, have suggested global and regional volume reductions, as well as abnormal diffusivity in multiple regions including the corpus callosum. Yet, no study has specifically examined thickness of the corpus callosum, a large white matter tract instrumental in the inter-hemispheric integration of sensory, motor, and cognitive information. We analyzed MRI data from 48 adolescents and adults with anorexia nervosa and 50 healthy controls, all girls/women, to compare corpus callosum thickness and examined relationships with body mass index (BMI), illness duration, and eating disorder symptoms (controlling for BMI). There were no significant group differences in corpus callosum thickness. In the anorexia nervosa group, severity of body shape concerns was significantly, positively correlated with callosal thickness in the rostrum, genu, rostral body, isthmus, and splenium. In addition, there were significant positive correlations between eating disorder-related obsessions and compulsions and thickness of the anterior midbody, rostral body, and splenium. There were no significant associations between callosal thickness and BMI or illness duration. In sum, those with AN with worse concerns about bodily appearance and worse eating disorder-related obsessive thought patterns and compulsive behaviours have regionally thicker corpus callosum, independent of current weight status. These findings provide important neurobiological links to key, specific eating disorder behavioural phenotypes.

Decoding gender dimorphism of the human brain using multimodal anatomical and diffusion MRI data.

The female brain contains a larger proportion of gray matter tissue, while the male brain comprises more white matter. Findings like these have sparked increasing interest in studying dimorphism of the human brain: the general effect of gender on aspects of brain architecture. To date, the vast majority of imaging studies is based on unimodal MR images and typically limited to a small set of either gray or white matter regions-of-interest. The morphological content of magnetic resonance (MR) images, however, strongly depends on the underlying contrast mechanism. Consequently, in order to fully capture gender-specific morphological differences in distinct brain tissues, it might prove crucial to consider multiple imaging modalities simultaneously. This study introduces a novel approach to perform such multimodal classification incorporating the relative strengths of each modality-specific physical aperture to tissue properties. To illustrate our approach, we analyzed multimodal MR images (T(1)-, T(2)-, and diffusion-weighted) from 121 subjects (67 females) using a linear support vector machine with a mass-univariate feature selection procedure. We demonstrate that the combination of different imaging modalities yields a significantly higher balanced classification accuracy (96%) than any one modality by itself (83%-88%). Our results do not only confirm previous morphometric findings; crucially, they also shed new light on the most discriminative features in gray-matter volume and microstructure in cortical and subcortical areas. Specifically, we find that gender disparities are primarily distributed along brain networks thought to be involved in social cognition, reward-based learning, decision-making, and visual-spatial skills.