Differences In Human Brain Research Articles

Integrated analysis of robust sex-biased gene signatures in human brain

BackgroundSexual dimorphism is highly prominent in mammals with many physiological and behavioral differences between male and female form of the species. Accordingly, the fundamental social and cultural stratification factors for humans is sex. The sex differences are thought to emerge from a combination of genetic and environmental factors. It distinguishes individuals most prominently on the reproductive traits, but also affects many of the other related traits and manifest in different disease susceptibilities and treatment responses across sexes. Sex differences in brain have raised a lot of controversy due to small and sometimes contradictory sex-specific effects. Many studies have been published to identify sex-biased genes in one or several brain regions, but the assessment of the robustness of these studies is missing. We therefore collected huge amount of publicly available transcriptomic data to first estimate whether consistent sex differences exist and further explore their likely origin and functional significance.Results and conclusionIn order to systematically characterise sex-specific differences across human brain regions, we collected transcription profiles for more than 16,000 samples from 46 datasets across 11 brain regions. By systematic integration of the data from multiple studies, we identified robust transcription level differences in human brain across to identify male-biased and female-biased genes in each brain region. Firstly, both male and female-biased genes were highly conserved across primates and showed a high overlap with sex-biased genes in other species. Female-biased genes were enriched for neuron-associated processes while male-biased genes were enriched for membranes and nuclear structures. Male-biased genes were enriched on the Y chromosome while female-biased genes were enriched on the X chromosome, which included X chromosome inactivation escapees explaining the origins of some sex differences. Male-biased genes were enriched for mitotic processes while female-biased genes were enriched for synaptic membrane and lumen. Finally, sex-biased genes were enriched for drug-targets and more female-biased genes were affected by adverse drug reactions than male-biased genes. In summary, by building a comprehensive resource of sex differences across human brain regions at gene expression level, we explored their likely origin and functional significance. We have also developed a web resource to make the entire analysis available for the scientific community for further exploration, available at https://joshiapps.cbu.uib.no/SRB_app/

Multimodal Image Analysis of Sexual Dimorphism in Developing Childhood Brain.

It is well known that there exist great differences in human brain anatomy and functions between males and females. With the development of noninvasive neuroimaging techniques, the sex differences in adult human brain have been well studied in some researches. However, the sexual dimorphism of human brain anatomy and functions has not been sufficiently described during the developmental period of early childhood brain when the sex differences emerge in behavior. This study was to identify specific patterns of the sexual dimorphism in developing brain structure of early childhood using multimodal brain image analysis. We have performed a multivariate and data-driven analysis by combining multiple neuroimaging technologies including the 3D T1-weighted structural MR images (sMRI) and diffusion tensor imaging (DTI) in a prospective cohort of 188 children (128 males and 60 females) between the ages of 0 and 15. First, the brain images were segmented into 90 regions of interest (ROIs) based on the AAL template to extract the ROI volume and connectivity features. Then, the individual multimodal imaging biomarkers were identified associated with the sex differences. Finally, the selected features from multi-modality neuroimages were combined using multi-kernel support vector machine for classifications of male or female. The method achieved sex classification accuracy 72% for the children between the ages of 0 and 15. And the volumes of right precuneus and right postcentral were more related to sexual dimorphism of developing brain structure than those of other regions in sMRI (p < 0.002). In DTI, the connections between right middle occipital gyrus and right inferior occipital gyrus, between left superior marginal gyrus and left middle temporal gyrus, and between right triangle inferior frontal gyrus and right putamen are also more relevant to the sexual dimorphism than others (p < 0.005). The brain regions and connections related to the sexual differences were identified with sMRI and DTI in early developing brain structure by using the multimodal image analysis. And these sexually dimorphic patterns of brain may be related to the observed sex differences in developing childhood brain structure and connectivity.

Neuroscience and Sex/Gender: Looking Back and Forward.

Phoenix et al. (1959) reported that treating pregnant guinea pigs with testosterone had enduring effects on the sex-related behavior of their female offspring. Since then, similar enduring effects of early testosterone exposure have been found in other species, including humans, and for other behaviors that show average sex differences. In humans, the affected outcomes include gender identity, sexual orientation, and children's sex-typical play behavior. The evidence linking early testosterone exposure to sex-typed play is particularly robust, and sex-typed play is also influenced by many other factors, including socialization by parents and peers and self-socialization, based on cognitive understanding of gender. In addition to influencing behavior, testosterone and hormones produced from testosterone affect mammalian brain structure. Studies using human autopsy material have found some sex differences in the human brain similar to those seen in other species, and have reported that some brain sex differences correlate with sexual orientation or gender identity, although the causes of these brain/behavior relationships are unclear. Studies that have imaged the living human brain have found only a small number of sex differences, and these differences are generally small in magnitude. In addition, they have not been linked to robust psychological or behavioral sex differences. Future research might benefit from improved imaging technology, and attention to other brain characteristics. In addition, it might usefully explore how different types of factors, such as early testosterone exposure and parental socialization, work together in the developmental system that produces sex/gender differences in human brain and behavior.

Beyond the Low Frequency Fluctuations: Morning and Evening Differences in Human Brain.

Human performance, alertness, and most biological functions express rhythmic fluctuations across a 24-h-period. This phenomenon is believed to originate from differences in both circadian and homeostatic sleep-wake regulatory processes. Interactions between these processes result in time-of-day modulations of behavioral performance as well as brain activity patterns. Although the basic mechanism of the 24-h clock is conserved across evolution, there are interindividual differences in the timing of sleep-wake cycles, subjective alertness and functioning throughout the day. The study of circadian typology differences has increased during the last few years, especially research on extreme chronotypes, which provide a unique way to investigate the effects of sleep-wake regulation on cerebral mechanisms. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on resting-state functional connectivity. Twenty-nine extreme morning- and 34 evening-type participants underwent two fMRI sessions: about 1 h after wake-up time (morning) and about 10 h after wake-up time (evening), scheduled according to their declared habitual sleep-wake pattern on a regular working day. Analysis of obtained neuroimaging data disclosed only an effect of time of day on resting-state functional connectivity; there were different patterns of functional connectivity between morning (MS) and evening (ES) sessions. The results of our study showed no differences between extreme morning-type and evening-type individuals. We demonstrate that circadian and homeostatic influences on the resting-state functional connectivity have a universal character, unaffected by circadian typology.

Gender differences in human brain

Gender differences in human brain

Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants.

Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44–77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.

157. Novel Methods for Assessing Cell-Type Specific Differences in Human Brain

157. Novel Methods for Assessing Cell-Type Specific Differences in Human Brain

Recalled and current gender role behavior, gender identity and sexual orientation in adults with Disorders/Differences of Sex Development

The magnitude of sex differences in human brain and behavior and the respective contributions of biology versus socialization remain a topic of ongoing study in science. The preponderance of evidence attests to the notion that sexual differentiation processes are at least partially hormonally mediated, with high levels of prenatal androgens facilitating male-typed and inhibiting female-typed behaviors. In individuals with Disorders/Differences of Sex Development (DSD), hormonal profiles or sensitivities have been altered due to genetic influences, presumably affecting gender(ed) activity interests as well as gender identity development in a minority of the affected population. While continued postnatal androgen exposure in a number of DSD syndromes has been associated with higher rates of gender dysphoria and gender change, the role of a number of mediating and moderating factors, such as initial gender assignment, syndrome severity and clinical management remains largely unclear. Limited investigations of the associations between these identified influences and gendered development outcomes impede optimization of clinical care. Participants with DSD (n=123), recruited in the context of a Dutch multi-center follow-up audit, were divided in subgroups reflecting prenatal androgen exposure, genital appearance at birth and gender of rearing. Recalled childhood play and playmate preferences, gender identity and sexual orientation were measured with questionnaires and semi-structured interviews. Data were compared to those of control male (n=46) and female participants (n=79). The findings support that (a) prenatal androgen exposure has large effects on (gendered) activity interests, but to a much lesser extent on sexual orientation and that (b) initial gender of rearing remains a better predictor of gender identity contentedness than prenatal androgen exposure, beyond syndrome severity and medical treatment influences. Nonetheless, 3.3% of individuals with DSD in our sample self-reported gender dysphoria from an early age and changed gender, which further underlines the need for thorough long- term follow-up and specific clinical support.

Reward processing and drug addiction: does sex matter?

Reward processing is crucial to our health and wellbeing and dysfunctional brain reward signaling is a component of a number of psychiatric disorders, including major depression and drug addiction. Rewarding behaviors like eating, parenting, nursing, social play, and sexual activity are powerfully preserved in evolution and are essential for survival. All of them gratifying, they represent enjoyable experiences with high reward values and activate the same brain circuits that mediate the positive reinforcing effects of drugs of abuse. In line with preclinical findings and clinical observations, recent imaging studies confirmed that natural (sex, food) and non-natural (drugs of abuse) rewards differently activate male and female brains (Haase et al., 2011; Wetherill et al., 2014) and also that men and women differ in the ability to resist reward-related impulses (Diekhof et al., 2012). The study of sexual morphological differences in human brain has provided evidence of critical effects of gender on brain architecture and morphometry (Giedd et al., 2012; Feis et al., 2013). Male-female differences in human brain anatomy have stimulated research on the difference in onset, prevalence, and symptomatology of many neuropsychiatric illnesses between women and men, including drug addiction (Rando et al., 2013; Tanabe et al., 2013; Ide et al., 2014). Following the official recognition by International Institutions and Funding Research Agencies on the importance of taking into account potential differences between men and women in all of the relevant aspects of health-related research, gender is receiving increasing attention by medical and scientific communities. As a consequence, evaluation of sex and gender (i.e., biological characteristics and socio-political-cultural influences associated with the terms “male” and “female,” respectively) differences in reward processing in general, and in drug addiction in particular, is increasingly being studied. Numerous human behaviors are driven by evolved instincts and urges. We have evolved the capacity to experience considerable pleasure and happiness from several behaviors, among which are eating, drinking, mating, creating protective shelter, and reproducing, all activating an anatomical and neurochemically defined brain circuit commonly referred to as the “pleasure circuit” or “brain reward system.” In both animals and humans, males and females display diverse attitudes and expectancies, process information differently, perceive experience and emotions in different ways and are behaviorally determined by different needs and drives. Reward processing may also differ between male and female population with sexual hormones playing an important, although not exclusive, role. When looking at the most common behavioral features known to favor the development of drug dependence, such as poor impulse control, risk-taking behavior, a heightened reactivity to stress and psychiatric comorbidity, all reveal important differences between men and women. Here I will illustrate the most recent evidence showing sex/gender differences in these and other behavioral traits linked to reward processing and enhancing the vulnerability to drug addiction.

A role for human brain pericytes in neuroinflammation.

BackgroundBrain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events in animal models, potential differences in human brain versus rodent models makes it imperative that we also study these phenomena in human cells and tissue.MethodsPrimary human brain cell cultures were generated from biopsy tissue of patients undergoing surgery for drug-resistant epilepsy. Cells were treated with pro-inflammatory compounds IFNγ, TNFα, IL-1β, and LPS, and chemokines IP-10 and MCP-1 were measured by immunocytochemistry, western blot, and qRT-PCR. Microarray analysis was also performed on late passage cultures treated with vehicle or IFNγ and IL-1β.ResultsEarly passage human brain cell cultures were a mixture of microglia, astrocytes, fibroblasts and pericytes. Later passage cultures contained proliferating fibroblasts and pericytes only. Under basal culture conditions all cell types showed cytoplasmic NFκB indicating that they were in a non-activated state. Expression of IP-10 and MCP-1 were significantly increased in response to pro-inflammatory stimuli. The two chemokines were expressed in mixed cultures as well as cultures of fibroblasts and pericytes only. The expression of IP-10 and MCP-1 were regulated at the mRNA and protein level, and both were secreted into cell culture media. NFκB nuclear translocation was also detected in response to pro-inflammatory cues (except IFNγ) in all cell types. Microarray analysis of brain pericytes also revealed widespread changes in gene expression in response to the combination of IFNγ and IL-1β treatment including interleukins, chemokines, cellular adhesion molecules and much more.ConclusionsAdult human brain cells are sensitive to cytokine challenge. As expected ‘classical’ brain immune cells, such as microglia and astrocytes, responded to cytokine challenge but of even more interest, brain pericytes also responded to such challenge with a rich repertoire of gene expression. Immune activation of brain pericytes may play an important role in communicating inflammatory signals to and within the brain interior and may also be involved in blood brain barrier (BBB) disruption . Targeting brain pericytes, as well as microglia and astrocytes, may provide novel opportunities for reducing brain inflammation and maintaining BBB function and brain homeostasis in human brain disease.

Gender Differences in Human Brain: A Review

Why do men and women think differently? Why do they behave differently in stressed situations? Why do women act more emotionally as compared to men? Why do men and women excel at different types of tasks? Why do boys like to play with cars and trucks and superman? These are the common questions which arise commonly in minds.The human brain is a highly complex organ. Studies of perception, cognition, memory and neural functions have found apparent gender differences. These differences may be attributed to various genetic, hormonal, and environmental factors and do not reflect any overall superiority advantage to either sex. Both sexes are equal in intelligence, but tend to operate differently. Men and women appear to use different parts of the brain to encode memories, sense emotions, recognize faces, solve certain problems and make decisions. Indeed, when men and women of similar intelligence and aptitude perform equally well, their brains appear to go about it differently, as if nature had separate blueprints. Sex differences in the brain may play a role in learning processes, language development, and progression of neurologically- based diseases. Sex differences need to be considered in studying brain structure and function and may raise the possibility of sex-specific treatments for neurological diseases. In this article it is reviewed that how does the brain of a male look and function differently from a female's brain, and what accounts for these differences?