Differences In Brain Structure Research Articles

Brain volume metric analysis is correlated with aging changes and sex differences in Thai older adults

Introduction: Normative data on structural brain volume changes with age and sex differences are required as a reference standard for future research and clinical use. Methods: We studied a two-center, metropolitan-based, prospective cohort of adults aged fifty-five years and older who were recruited from community-dwelling settings and outpatient clinics without cognitive impairment at baseline and who were followed up for 2 years. The clinical data, neuropsychological tests, and brain MRI obtained with FreeSurfer software were utilized for quantitative volumetric measurements. Results: A total of 296 participants were recruited at the beginning, with 17 participants (5.8%, excluding 2 subjects with claustrophobia) excluded due to abnormal MRI findings and 27 participants (9.1%) excluded due to MCI/dementia. Among the 250 remaining, 14 patients dropped out or were lost to follow-up, and 35 had MCI or AD converters (14.8%). The remaining 201 subjects with normal cognitive function aged 55-85 years were analyzed for structural brain volume. There were significant correlations between age and brain parameters, including the hippocampus, corpus callosum, thalamus and ventricular volume changes (p value < 0.05). There were significant differences between males and females in total intracranial volume, caudate, temporal lobe, and ventricle volumes in subjects aged 65–74 years, and in total intracranial volume and ventricle volumes in subjects aged 55–64 years (p value < 0.05). Conclusion: Age and sex contributed to differences in brain structure and ventricular volume. These data could be used as a normative reference for clinical interpretation in people up to 85 years old and for understanding the physiological aging-related changes in the brain.

Enlargement of the human prefrontal cortex and brain mentalizing network: anatomically homogenous cross-species brain transformation

To achieve a better understanding of the evolution of the large brain in humans, a comparative analysis of species differences in the brains of extant primate species is crucial, as it allows direct comparisons of the brains. We developed a method to achieve anatomically precise region-to-region homologous brain transformations across species using computational neuroanatomy. Utilizing three-dimensional neuroimaging data from humans (Homo sapiens), chimpanzees (Pan troglodytes), and Japanese macaques (Macaca fuscata), along with the anatomical labels of their respective brains, we aimed to create a cross-species average template brain that preserves neuroanatomical correspondence across species. Homologous transformation of the brain from one species to another can be computed using the cross-species average brain. Applying this transformation to human and chimpanzee brains revealed that, compared to chimpanzees, humans had significantly larger and more expanded prefrontal cortex, middle and posterior temporal gyrus, angular gyrus, precuneus, and cortical areas associated with mentalization. This neuroanatomically homologous brain transformation enables the systematic investigation of the similarities and differences in brain anatomy and structure across different species.

Neuroanatomical and Neurocognitive Differences Between the Executive Functions in Child Sexual Offenders: A Systematic Review.

Studies on executive functions in child sex offenders relate their findings to the presence of pedophilia, but they are not able to distinguish between paraphilia and abuse. It is therefore this lack of a distinction that leads us to complement the existing information. Thus, the purpose of this review is to find all available evidence on the neurocognitive and neuroanatomical differences in executive functions among pedophilic and non-pedophilic child sex offenders, and non-offender pedophiles. The present review, in accordance with the PRISMA statement, ran a systematic search of three databases (Web of Science, Scopus and ProQuest). This search identified 5697 potential articles, but only 16 studies met all the inclusion criteria. Most of the studies were conducted in Europe, using a cross-sectional design with a convenience sample. The results showed alterations in frontal, temporal and parietal structures related to executive functions (e.g., response inhibition) in child sexual offenders, regardless of the presence of pedophilia. In summary, there are differences in brain structure underlying executive functions related to child sexual abuse, but not to pedophilia as such.

Brain structural differences in cocaine use disorder: Insights from multivariate and neurotransmitter analyses

Cocaine use disorder (CUD) is a chronic and relapsing neuropsychiatric disorder characterized by structural and functional brain lesions, posing a significant public health challenge. While the disruptive effects of cocaine on neurotransmitter systems (receptors/transporters) have been well established, the patterns of brain structural abnormalities in CUD and its interaction with other factors remain an ongoing topic of investigation. We employed source-based morphometry (SBM), a multivariate approach on 50 CUD participants and 50 matched healthy controls from the public SUDMEX CONN dataset. This method allowed us to identify co-varying patterns of brain tissue volume differences, and further explore the effect of average cocaine dosage through moderation analysis. Spatial correlation analysis was also performed to examine micro-macro structural consistency between tissue volume variations and chemoarchitectural distribution of dopamine and serotonin. Our SBM analysis findings were consistent with reward-related neuroadaptations in the striato-thalamo-cortical and limbic pathways and also exhibited co-localization with the distribution of dopamine and serotonin systems. The moderation analysis suggested that the average dosage positively strengthens cocaine consumption years' effect on brain structures. By integrating our findings of gray and white matter volume differences and corresponding neurotransmitter profiles, this comprehensive view not only strengthens our understanding of the brain's structural abnormalities in CUD, but also reveals potential mechanisms underlying its development and progression.

Retinal Microperimetry as a Novel Tool for Early Detection of Subclinical Cognitive Dysfunction and Brain Damage in Type 1 Diabetes: A Pilot Study.

Retinal microperimetry (MPR) is a non-invasive method that measures retinal light sensitivity (RS) and gaze fixation stability (GFS). MPR has been described as a marker of cognitive impairment in people with Type 2 diabetes, but it has never been assessed in people with Type 1 diabetes (T1D). Our group described subclinical cognitive alterations, structural brain differences, and increased levels of light chain neurofilament (NfL) in people with T1D and impaired awareness of hypoglycaemia. To measure RS and GFS using MPR in individuals with T1D and evaluate its correlation with neuropsychological assessment, plasma NfL levels and CGM-derived glucometric parameters. to evaluate the possible differences of RS and GFS in people with T1D depending on hypoglycaemia awareness. Pilot observational study, people with T1D without clinical cognitive impairment, moderate-severe retinopathy or glaucoma. MPR was performed with MAIA3. A total of 30 subjects were studied: 40% women, age 58 ± 11 years; T1D duration 31 ± 9 years, mild retinopathy 33%. RS was 27.5 dB (26.1-28.3) and GFS(%) 97.6% (93.5%-99.5%). We found a correlation between RS and memory alteration tests (p = 0.016) and between GFS(%) and a composite of attention and executive neuropsychological tests (p = 0.025). An inverse correlation between GFS and time below range was found. No correlation was found with NfL. This first exploratory study in people with T1D supports the potential utility of MPR as a screening tool for subclinical neurocognitive alterations in this population.

Differing Effects of Alcohol Use on Epigenetic and Brain Age in Adult Children of Parents with Alcohol Use Disorder.

It is known that being the adult child of a parent with an alcohol use disorder (ACoA) can confer a wide variety of increased health and psychological risks, including higher rates of anxiety, depression, and post-traumatic stress disorder symptoms. Additionally, ACoAs are at greater risk of developing alcohol/substance use disorders (AUDs/SUDs) than individuals from families without a history of AUDs. ACoA individuals with risky hazardous alcohol use (n = 14) and those not engaged in hazardous use (n = 14) were compared to a group of healthy controls. We examined structural brain differences and applied machine learning algorithms to predict biological brain and DNA methylation ages to investigate differences and determine any accelerated aging between these groups. Hazardous and non-hazardous ACoA groups had lower predicted brain ages than the healthy control group (n = 100), which may result from neuro-developmental differences between ACoA groups and controls. Within specific brain regions, we observed decreased cortical volume within bilateral pars orbitalis and frontal poles, and the left middle temporal gyrus and entorhinal cortex within the hazardous alcohol ACoA group. When looking at the epigenetic aging data, the hazardous ACoA participants had increased predicted epigenetic age difference scores compared to the control group (n = 34) and the non-hazardous ACoA participant groups. The results demonstrate a decreased brain age in the ACoAs compared to control, concurrent with increased epigenetic age specifically in the hazardous ACoA group, laying the foundation for future research to identify individuals with an increased susceptibility to developing hazardous alcohol use. Together, these results provide a better understanding of the associations between epigenetic factors, brain structure, and alcohol use disorders.

Body dysmorphic disorder.

Body dysmorphic disorder (BDD) is an obsessive-compulsive disorder-related psychiatric condition characterized by an intense preoccupation with perceived physical flaws that are not observable by others. BDD affects ~2% of the adult population but is underdiagnosed, partly owing to limited clinician awareness, and undertreated, partly due to limited access to treatment. Research on the aetiology of BDD is scarce but likely involves an interplay between genetic and environmental factors. A few studies suggest functional and structural brain differences (compared with controls) in the regions involved in visual and emotional processing, although firm conclusions about the pathophysiology of the disorder cannot be made at this stage. Diagnosis requires the presence of repetitive behaviours or mental acts typically aimed at checking, correcting or concealing perceived flaws. The disorder typically has its onset before 18 years of age, with a female preponderance in youth but no major gender disparity in adults. Quality of life is markedly impaired across multiple domains and suicide risk is considerable. Evidence-based treatments include cognitive behavioural therapy and selective serotonin reuptake inhibitors. Future research should focus on understanding the biological and environmental factors that increase the risk of BDD, and on improving access to effective treatments, thereby addressing a critical gap in care for this often misunderstood and overlooked disorder.

An optimized ensemble search approach for classification of higher-level gait disorder using brain magnetic resonance images

Higher-Level Gait Disorder (HLGD) is a type of gait disorder estimated to affect up to 6% of the older population. By definition, its symptoms originate from the higher-level nervous system, yet its association with brain morphology remains unclear. This study hypothesizes that there are patterns in brain morphology linked to HLGD. For the first time in the literature, this work investigates whether deep learning, in the form of convolutional neural networks, can capture patterns in magnetic resonance images to identify individuals affected by HLGD. To handle this new classification task, we propose setting up an ensemble of models. This leverages the benefits of combining classifiers instead of determining which network is the most suitable, developing a new architecture, or customizing an existing one. We introduce a computationally cost-effective search algorithm to find the optimal ensemble by leveraging a cost function of both traditional performance scores and the diversity among the models. Using a unique dataset from a large population-based cohort (VESPR), the ensemble identified by our algorithm demonstrated superior performance compared to single networks, other ensemble fusion techniques, and the best linear radiological measure. This emphasizes the importance of implementing diversity into the cost function. Furthermore, the results indicate significant morphological differences in brain structure between HLGD-affected individuals and controls, motivating research about which areas the networks base their classifications on, to get a better understanding of the pathophysiology of HLGD.

Investigating sex-related differences in brain structure and function in bipolar I disorder using multimodal MRI

BackgroundPast research has highlighted that bipolar I disorder is associated with significant changes in brain structure and function. Notably, the manifestation and progression of bipolar I disorder have been known to differ between males and females. However, the relationship between sex-related differences and bipolar I disorder diagnosis affecting these changes was not fully understood. This study aimed to investigate the sex-by-diagnosis interactions concerning the structural and functional features of the brain in individuals with bipolar I disorder.MethodsBoth structural and functional MRI data were obtained from 105 individuals with bipolar I disorder (36 males and 69 females) and 210 healthy controls (72 males and 138 females). Voxel-wise analyses of gray matter volume and functional connectivity were conducted using a general linear regression model. This model included age, sex, diagnosis, and a sex-by-diagnosis interaction as predictors to explore potential sex-related differences in the brain features of participants with bipolar I disorder.ResultsThe gray matter volume analysis revealed significant sex-by-diagnosis interactions in six brain regions: the left caudate (p < 0.001), left thalamus (p < 0.001), right caudate (p = 0.003), right thalamus (p < 0.001), left anterior cingulate gyrus (p = 0.022), and left middle/posterior cingulate gyrus (p = 0.015). Using these regions as seeds, we detected a significant sex-by-diagnosis interaction in the functional connectivity alteration between the left thalamus and right angular gyrus (p = 0.019).ConclusionsOur findings revealed a noteworthy sex-by-diagnosis interaction, with male individuals with bipolar I disorder displaying larger gray matter volume and altered functional connectivity in the limbic system compared to female individuals with bipolar I disorder and healthy participants. These results hint at potential sex-related differences in the pathophysiology of the limbic system in bipolar I disorder, which may have significant implications for understanding the underlying mechanisms in bipolar I disorder. Our findings could contribute to developing more personalized treatment approaches for individuals with bipolar I disorder.

Neuroanatomy, episodic memory and inhibitory control of Persian-Kurdish simultaneous bilinguals

We assessed simultaneous bilinguals and monolinguals on inhibitory control and episodic memory, and assessed their grey matter volumes in brain regions known to be involved in language processing, executive control and memory. Bilinguals outperformed monolinguals on episodic memory, and performance on the memory and inhibition tasks were correlated, only in the bilingual group. This suggests that the bilingualism-related benefits on memory are related to individual differences in executive control. We found larger grey matter volumes in bilinguals in left pars opercularis and in bilateral SFG, caudate nuclei, and parasubiculum. Episodic memory performance was correlated with volumes of bilateral posterior hippocampi, again only in the bilinguals, again suggesting that bilingualism may be driving this effect. Finally, we found positive structural covariance between the volumes of the bilateral parasubiculum and that of important components of the executive control network. We provide a novel, mechanistic explanation accounting for observed behavioural advantage and brain structural differences: bilingualism may boost the prefrontal cortex-hippocampal neural circuitry commonly underlying both executive control and memory, via cascade and reverberant effects, leading to synergistic benefits in both cognitive domains. This new framework has important implications for protective effects on cognition and brain health in relation to second language learning.

Sex differences in the antinociceptive effect of codeine and its peripheral but not central metabolism in adult mice

Codeine is a natural opiate extracted from opium poppy (Papaver somniferum) and used to alleviate mild to moderate pain. The analgesic effect of this molecule results from its metabolism into morphine which is an agonist of the mu opioid receptor. Morphine's major metabolite morphine-3-glucuronide induces both thermal and mechanical hypersensitivies while codeine-6-glucuronide has been proposed to be antinociceptive. However, sex differences in codeine antinociceptive effect and pharmacokinetics were barely studied. To this purpose, we injected male and female mice with codeine (2.5, 5, 10, 20 and 40 mg/kg) and thermal hypersensitivity was assessed 30 min after injection using the Tail Immersion Test. Moreover, both peripheral and central metabolism of codeine were evaluated respectively in the blood or pain-related brain structures in the central nervous system. The amounts of codeine and its metabolites were quantified using the isotopic dilution method by liquid chromatography coupled to a mass spectrometer. Our results show that codeine induces a greater antinociceptive effect in males than females mice independently of the estrous cycle. Moreover, major sex differences were found in the peripheral metabolism of this molecule, with higher amounts of pronociceptive morphine-3-glucuronide and less antinociceptive codeine-6-glucuronide in females than in males. Concerning the central metabolism of codeine, we did not find significant sex differences in pain-related brain structures. Collectively, these findings support a greater codeine antinociceptive effect in males than females in mice. These sex differences could be influenced by a higher peripheral metabolism of this molecule in female mice rather than central metabolism.

Biological, psychological, and socio-structural underpinnings of dissociative identity disorder

Abstract. Epidemiological studies revealed the prevalence and diverse symptoms of dissociative identity disorder (DID), emphasizing diagnostic complexities. Debates over its etiology, ranging from trauma to fantasy predisposition, highlight the need for ongoing research and varied therapeutic approaches. Neuroimaging has uncovered distinct structural and functional brain differences in DID patients, contributing to our understanding of its neurological basis. Despite therapeutic progress, including behavioral and pharmacological interventions, effectively DID treatments remain challenging. Integrating biological, psychological, and sociocultural perspectives is crucial for advancing DID diagnosis and treatment.

Volumetric Analysis of Motor Cortex and Basal Ganglia in Pediatric Celiac Disease Patients Using volBrain: Implications for Neurological Dysfunction-Preliminary Results.

Celiac disease (CD) is a common immune-mediated, chronic systemic disorder that is treated with a strict, life-long gluten-free diet (GFD). In addition to gastrointestinal manifestations, CD also presents with a variety of extraintestinal symptoms, including significant neurological and neuropsychiatric symptoms. Among these neurological manifestations, motor dysfunctions are particularly notable. The aim of this study is to investigate the potential volumetric differences in brain structures, particularly the motor cortex and basal ganglia, between pediatric CD patients and healthy controls using the volBrain software AssemblyNet version 1.0. This prospective study included pediatric patients with CD who complained of neurological symptoms and were scheduled for brain magnetic resonance imaging (MRI). All children had been previously diagnosed with CD and their adherence to GFD was evaluated using the Biagi score. Brain MRIs were performed on all included patients to obtain volumetry at the onset of the disease. For volumetric and segmentation data, the volBrain software was used. In total, 12 pediatric patients with CD were included, with a median duration of a GFD of 5.3 years at the time of the MRI examination. There were no statistically significant differences between patients compliant with the GFD and those non-compliant in terms of age or duration of GFD. Volumetric analysis revealed deviations in all patients analyzed, which involved either a decrease or increase in the volume of the structures studied. Despite the limited number of patients in this study, the initial findings support previously described neurological manifestations in patients with CD. Newly developed MRI tools have the potential to enable a more detailed analysis of disease progression and its impact on the motor cortex.

Synesthesia is linked to large and extensive differences in brain structure and function as determined by whole-brain biomarkers derived from the HCP (Human Connectome Project) cortical parcellation approach.

There is considerable interest in understanding the developmental origins and health implications of individual differences in brain structure and function. In this pre-registered study we demonstrate that a hidden subgroup within the general population-people with synesthesia (e.g. who "hear" colors)-show a distinctive behavioral phenotype and wide-ranging differences in brain structure and function. We assess the performance of 13 different brain-based biomarkers (structural and functional MRI) for classifying synesthetes against general population samples, using machine learning models. The features in these models were derived from subject-specific parcellations of the cortex using the Human Connectome Project approach. All biomarkers performed above chance with intracortical myelin being a particularly strong predictor that has not been implicated in synesthesia before. Resting state data show widespread changes in the functional connectome (including less hub-based connectivity). These brain-based individual differences within the neurotypical population can be as large as those that differentiate neurotypical from clinical brain states.

Structural MRI findings in the brain related to pain distribution in chronic overlapping pain conditions: An explorative case-control study in females with fibromyalgia, temporomandibular disorder-related chronic pain and pain-free controls.

Few neuroimaging studies have investigated structural brain differences associated with variations in pain distribution. To explore structural differences of the brain in fibromyalgia (FM), temporomandibular disorder pain (TMD) and healthy pain-free controls (CON) using structural and diffusion MRI. A case-control exploratory study with three study groups with different pain distribution were recruited: FM (n = 16; mean age [standard deviation]: 44 [14] years), TMD (n = 17, 39 [14] years) and CON (n = 10, 37 [14] years). Participants were recruited at the University Dental Clinic in Malmö, Sweden. T1-weighted and diffusion MRIs were acquired, clinical and psychosocial measures were obtained. Main outcome measures were subcortical volume, cortical thickness, white matter microstructure and whole brain grey matter intensity. Patients with FM had smaller volume in the right thalamus than patients with TMD (p = .020) and CON (p = .030). The right thalamus volume was negatively correlated to pain intensity (r = -0.37, p = .022) and pain-related disability (r = -0.45, p = .004). The FM group had lower cortical thickness in the right anterior prefrontal cortex than CON (p = .005). Cortical thickness in this area was negatively correlated to pain intensity (r [37] = - 0.48, p = .002). This study suggests that thalamus grey matter alterations are associated with FM and TMD, and that anterior prefrontal cortex grey matter alterations are associated with FM but not TMD. Studies on chronic overlapping pain conditions are needed in relation to possible nociplastic pain mechanisms in the brain and central nervous system.

It Takes Three: Parental Hostility, Brain Morphology, and Child Externalizing Problems in a Parent-Offspring Neuroimaging Trio Design.

Hostility often co-occurs in parents and associates with increased aggression and inattention problems in children. In this population-based cohort of 484 mother-father-child neuroimaging trios, we investigated the degree to which associations of prenatal and childhood parental hostility would be associated with maternal, paternal, and child brain structural differences. Also, we examined whether hippocampal volumes of the parents or child mediate the association of prenatal parental hostility with child externalizing behaviors. Maternal and paternal hostility was assessed with the hostility subscale of the Brief Symptom Inventory at three time points: prenatally at 30 weeks' gestation and when the child was 3 and 10 years old. During adolescence assessment wave (age 14), maternal, paternal, and offspring assessment included a magnetic resonance imaging. Child externalizing problems were assessed with Youth Self-Report Child Behavior Checklist. Our findings suggest that maternal and paternal hostility were each associated with smaller gray matter, white matter, and hippocampal volumes of their own and their partner's brain. Prenatal maternal but not paternal hostility was associated with smaller total gray matter, white matter, and hippocampal volumes in the offspring. The child's hippocampal volumes partially mediated the associations of prenatal parental hostility (latent construct) with adolescent externalizing behavior, even after adjusting for prior child externalizing problems. Moreover, parental psychopathology may have long-lasting neurodevelopmental correlates in children that underlie the intergenerational transmission of behavioral problems. The behavior of family members results from a system of interdependent dyadic relationships over time that associate with specific brain structural differences.

Exploring the Impact of Sex and Gender in Brain Function: Implications and Considerations.

Sex and gender are crucial variables in understanding brain development and disease. Biological sex is determined by genetic and hormonal factors, whereas gender is a multidimensional construct shaped by social and cultural influences. The interplay of these factors contributes to sex-specific susceptibilities and disease progression in psychiatric and neurological disorders. However, sex and gender are often considered as a single variable, which can lead to biased data analysis and interpretation. This commentary aims to analyze how sex and gender influence brain structure and function, with implications for personalized medicine, research, and the development of gender-sensitive clinical guidelines. Findings from various studies employing neuroimaging techniques and animal models are discussed, as well as the impact of biological sex, gender, environmental, cultural, and social factors on brain development, organization, and behavior. Evidence suggests that sex differences in brain structure and function are not only genetically determined but arealso influenced by gender-related experiences and societal contexts. Importantly, discrepancies between male and female brains are reduced in gender-equal societies. Preclinical studies play a pivotal role in determining the influence of biological sex, independent of gender, in different disease models. The findings underscore the need to consider both sex and gender in research and clinical practice to avoid biases and promote equitable health outcomes. Moving forward, we advocate for gender-sensitive approaches to be integrated into brain research and in clinical guidelines to achieve personalized and precision medicine.

More similarity than difference: comparison of within- and between-sex variance in early adolescent brain structure.

Background Adolescent neuroimaging studies of sex differences in the human brain predominantly examine mean differences between males and females. This focus on between-groups differences without probing relative distributions and similarities may contribute to both conflation and overestimation of sex differences and sexual dimorphism in the developing human brain. Methods We aimed to characterize the variance in brain macro- and micro-structure in early adolescence as it pertains to sex at birth using a large sample of 9-11 year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N=7,723). Specifically, for global and regional estimates of gray and white matter volume, cortical thickness, and white matter microstructure (i.e., fractional anisotropy and mean diffusivity), we examined: within- and between-sex variance, overlap between male and female distributions, inhomogeneity of variance via the Fligner-Killeen test, and an analysis of similarities (ANOSIM). For completeness, we examined these sex differences using both uncorrected (raw) brain estimates and residualized brain estimates after using mixed-effects modeling to account for age, pubertal development, socioeconomic status, race, ethnicity, MRI scanner manufacturer, and total brain volume, where applicable. Results The overlap between male and female distributions was universally greater than the difference (overlap coefficient range: 0.585 - 0.985) and the ratio of within-sex and between-sex differences was similar (ANOSIM R range: -0.001 - 0.117). All cortical and subcortical volumes showed significant inhomogeneity of variance, whereas a minority of brain regions showed significant sex differences in variance for cortical thickness, white matter volume, fractional anisotropy, and mean diffusivity. Inhomogeneity of variance was reduced after accounting for other sources of variance. Overlap coefficients were larger and ANOSIM R values were smaller for residualized outcomes, indicating greater within- and smaller between-sex differences once accounting for other covariates. Conclusions Reported sex differences in early adolescent human brain structure may be driven by disparities in variance, rather than binary, sex-based phenotypes. Contrary to the popular view of the brain as sexually dimorphic, we found more similarity than difference between sexes in all global and regional measurements of brain structure examined. This study builds upon previous findings illustrating the importance of considering variance when examining sex differences in brain structure.

Sex Differences in Human Brain Structure at Birth

BackgroundSex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.MethodsHere, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0–28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.ResultsOn average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).ConclusionsOur findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.

A stroke organoids-multiomics platform to study injury mechanism and drug response

Stroke is one of the top causes of death and disability worldwide, and its pathogenesis and mechanism have not been fully elucidated. Several agents have shown protective effects against stroke in animal models; however, few studies have shown obvious effects in clinical practice. This might be due to differences in brain structure and physiological function between humans and rodents. In this study, we established a hypoxic stroke model in human-induced pluripotent stem cell (hiPSC)-derived brain organoids to simulate the hypoxic stroke caused by ischemia. Then, by combining proteomics, single-cell transcriptome analysis, and histopathological analysis, a significant increase of three types of astrocytes was identified and they showed different responses to hypoxic environments; also the main type of astrocyte that cause brain tissue hyperplasia in ischemia brains was identified. In addition, the cortical excitatory neurons had signs of apoptosis and aging after hypoxia both in vivo and in vitro. Most importantly, we identified a possible role of a traditional Chinese medicine formula called DengZhanShengMai capsule in ischemic and hypoxic stroke treatment through regulation of lipid metabolism related biological functions. These results indicate that the combination of brain organoids and multiomics method is helpful for developing a new strategy to direct study stroke, and could provide a promising platform for drug screening of stroke in the future.