scholarly journals Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

2022 ◽  
Author(s):  
Carla Sanchis-Segura ◽  
Naiara Aguirre ◽  
Álvaro Javier Cruz-Gómez ◽  
Sonia Félix ◽  
Cristina Forn
Keyword(s):  
Sex Differences ◽  
Gray Matter Volume ◽  
Group Differences ◽  
Intracranial Volume ◽  
Brain Areas ◽  
High Classification Accuracy ◽  
Detailed Assessment ◽  
Functional Features ◽  
Males And Females ◽  
The Brain

Abstract Previous studies have shown that machine-learning (ML) algorithms can “predict” sex based on brain anatomical/ functional features. The high classification accuracy achieved by ML algorithms is often interpreted as revealing large differences between the brains of males and females and as confirming the existence of “male/female brains”. However, classification and estimation are quite different concepts, and using classification metrics as surrogate estimates of between-group differences results in major statistical and interpretative distortions. The present study illustrates these distortions and provides a novel and detailed assessment of multivariate sex differences in gray matter volume (GMVOL) that does not rely on classification metrics. Moreover, modeling and clustering techniques and analyses of similarities (ANOSIM) were used to identify the brain areas that contribute the most to these multivariate differences, and to empirically assess whether they assemble into two sex-typical profiles. Results revealed that multivariate sex differences in GMVOL: 1) are “large” if not adjusted for total intracranial volume (TIV) variation, but “small” when controlling for this variable; 2) differ in size between individuals and also depends on the ML algorithm used for their calculation 3) do not stem from two sex-typical profiles, and so describing them in terms of “male/female brains” is misleading.

scholarly journals Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

2021 ◽  
Author(s):  
Carla Sanchis-Segura ◽  
Naiara Aguirre ◽  
Álvaro Javier Cruz-Gómez ◽  
Sonia Félix ◽  
Cristina Forn
Keyword(s):  
Sex Differences ◽  
Gray Matter Volume ◽  
Group Differences ◽  
Intracranial Volume ◽  
Brain Areas ◽  
High Classification Accuracy ◽  
Detailed Assessment ◽  
Functional Features ◽  
Males And Females ◽  
The Brain

Abstract Previous studies have shown that machine-learning (ML) algorithms can “predict” sex based on brain anatomical/ functional features. The high classification accuracy achieved by ML algorithms is often interpreted as revealing large differences between the brains of males and females and as confirming the existence of “male/female brains”. However, classification and estimation are quite different concepts, and using classification metrics as surrogate estimates of between-group differences results in major statistical and interpretative distortions. The present study illustrates these distortions and provides a novel and detailed assessment of multivariate sex differences in gray matter volume (GMVOL) that does not rely on classification metrics. Moreover, modeling and clustering techniques and analyses of similarities (ANOSIM) were used to identify the brain areas that contribute the most to these multivariate differences, and to empirically assess whether they assemble into two sex-typical profiles. Results revealed that multivariate sex differences in GMVOL: 1) are “large” if not adjusted for total intracranial volume (TIV) variation, but “small” when controlling for this variable; 2) differ in size between individuals and also depends on the ML algorithm used for their calculation 3) do not stem from two sex-typical profiles, and so describing them in terms of “male/female brains” is misleading.

scholarly journals Sex differences in neural and behavioral signatures of cooperation revealed by fNIRS hyperscanning

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joseph M. Baker ◽  
Ning Liu ◽  
Xu Cui ◽  
Pascal Vrticka ◽  
Manish Saggar ◽  
...  
Keyword(s):  
Sex Differences ◽  
Temporal Cortex ◽  
Neural Correlates ◽  
Behavioral Signatures ◽  
Computer Based ◽  
Males And Females ◽  
Brain And Behavior ◽  
The Right ◽  
And Behavior ◽  
The Brain

Abstract Researchers from multiple fields have sought to understand how sex moderates human social behavior. While over 50 years of research has revealed differences in cooperation behavior of males and females, the underlying neural correlates of these sex differences have not been explained. A missing and fundamental element of this puzzle is an understanding of how the sex composition of an interacting dyad influences the brain and behavior during cooperation. Using fNIRS-based hyperscanning in 111 same- and mixed-sex dyads, we identified significant behavioral and neural sex-related differences in association with a computer-based cooperation task. Dyads containing at least one male demonstrated significantly higher behavioral performance than female/female dyads. Individual males and females showed significant activation in the right frontopolar and right inferior prefrontal cortices, although this activation was greater in females compared to males. Female/female dyad’s exhibited significant inter-brain coherence within the right temporal cortex, while significant coherence in male/male dyads occurred in the right inferior prefrontal cortex. Significant coherence was not observed in mixed-sex dyads. Finally, for same-sex dyads only, task-related inter-brain coherence was positively correlated with cooperation task performance. Our results highlight multiple important and previously undetected influences of sex on concurrent neural and behavioral signatures of cooperation.

scholarly journals Multifaceted origins of sex differences in the brain

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150106 ◽  
Author(s):  
Margaret M. McCarthy
Keyword(s):  
Sex Differences ◽  
State Of The Art ◽  
Human Subjects ◽  
Special Issue ◽  
Molecular Analyses ◽  
The Past ◽  
Current State ◽  
Biological Variable ◽  
Males And Females ◽  
The Brain

Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

scholarly journals Sex in the brain: hormones and sex differences

2016 ◽  
Vol 18 (4) ◽  
pp. 373-383 ◽  
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Genetic Factors ◽  
Motor Coordination ◽  
Brain Regions ◽  
New Era ◽  
Brain Functions ◽  
Opioid Sensitivity ◽  
Males And Females ◽  
The Brain

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

scholarly journals Species variation in the degree of sex differences in brain and behaviour related to birdsong: adaptations and constraints

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150117 ◽  
Author(s):  
Gregory F. Ball
Keyword(s):  
Sex Differences ◽  
Neural Circuit ◽  
Species Variation ◽  
Song System ◽  
System A ◽  
Song Control System ◽  
Males And Females ◽  
Song Control ◽  
Area X ◽  
The Brain

The song-control system, a neural circuit that controls the learning and production of birdsong, provided the first example in vertebrates of prominent macro-morphological sex differences in the brain. Forebrain nuclei HVC, robust nucleus of the arcopallium (RA) and area X all exhibit prominent male-biased sex differences in volume in zebra finches and canaries. Subsequent studies compared species that exhibited different degrees of a sex difference in song behaviour and revealed an overall positive correlation between male biases in song behaviour and male biases in the volume of the song nuclei. However, several exceptions have been described in which male biases in HVC and RA are observed even though song behaviour is equal or even female-biased. Other phenotypic measures exhibit lability in both sexes. In the duetting plain-tailed wren ( Pheugopedius euophrys ), males and females have auditory cells in the song system that are tuned to the joint song the two sexes produce rather than just male or female components. These findings suggest that there may be constraints on the adaptive response of the song system to ecological conditions as assessed by nucleus volume but that other critical variables regulating song can respond so that each sex can modify its song behaviour as needed.

scholarly journals Effects of Meditation on Structural Changes of the Brain in Patients With Mild Cognitive Impairment or Alzheimer’s Disease Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Madhukar Dwivedi ◽  
Neha Dubey ◽  
Aditya Jain Pansari ◽  
Raju Surampudi Bapi ◽  
Meghoranjani Das ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cortical Thickness ◽  
Gray Matter ◽  
Gray Matter Volume ◽  
Brain Areas ◽  
Hippocampal Subfields ◽  
Matter Volume ◽  
The Right ◽  
The Brain

Previous cross-sectional studies reported positive effects of meditation on the brain areas related to attention and executive function in the healthy elderly population. Effects of long-term regular meditation in persons with mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD) have rarely been studied. In this study, we explored changes in cortical thickness and gray matter volume in meditation-naïve persons with MCI or mild AD after long-term meditation intervention. MCI or mild AD patients underwent detailed clinical and neuropsychological assessment and were assigned into meditation or non-meditation groups. High resolution T1-weighted magnetic resonance images (MRI) were acquired at baseline and after 6 months. Longitudinal symmetrized percentage changes (SPC) in cortical thickness and gray matter volume were estimated. Left caudal middle frontal, left rostral middle frontal, left superior parietal, right lateral orbitofrontal, and right superior frontal cortices showed changes in both cortical thickness and gray matter volume; the left paracentral cortex showed changes in cortical thickness; the left lateral occipital, left superior frontal, left banks of the superior temporal sulcus (bankssts), and left medial orbitofrontal cortices showed changes in gray matter volume. All these areas exhibited significantly higher SPC values in meditators as compared to non-meditators. Conversely, the left lateral occipital, and right posterior cingulate cortices showed significantly lower SPC values for cortical thickness in the meditators. In hippocampal subfields analysis, we observed significantly higher SPC in gray matter volume of the left CA1, molecular layer HP, and CA3 with a trend for increased gray matter volume in most other areas. No significant changes were found for the hippocampal subfields in the right hemisphere. Analysis of the subcortical structures revealed significantly increased volume in the right thalamus in the meditation group. The results of the study point out that long-term meditation practice in persons with MCI or mild AD leads to salutary changes in cortical thickness and gray matter volumes. Most of these changes were observed in the brain areas related to executive control and memory that are prominently at risk in neurodegenerative diseases.

scholarly journals S159. SUBCORTICAL GRAY MATTER VOLUME IS ASSOCIATED WITH SCHIZOPHRENIA AND WITH BOTH ITS FAMILIAL AND CLINICAL RISK

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S96-S97
Author(s):  
Roberta Passiatore ◽  
Linda A Antonucci ◽  
Leonardo Fazio ◽  
Barbara Gelao ◽  
Andrea Falsetti ◽  
...  
Keyword(s):  
Gray Matter ◽  
Gray Matter Volume ◽  
Familial Risk ◽  
Structural Features ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Group Differences ◽  
Intracranial Volume ◽  
Significant Group ◽  
Clinical Risk

Abstract Background Patients with schizophrenia (SCZ) show lower volumetric estimates of gray matter (GM) than healthy controls (HC). Similar results have been reported in healthy siblings of patients (SIB). However, it is unclear whether this phenotype is also present in individuals at clinical high-risk (CHR), characterized by sub-threshold symptoms and loss of functioning. We hypothesized that GM volumetric differences are associated with both familial and clinical risk for schizophrenia Methods We processed the T1-weighted MRI scans acquired at 3 Tesla of 544 HC, 63 SIB, 20 CHR and 120 SCZ using CAT12. We used ANCOVA to assess group differences (HC vs. CHR vs. SIB vs. SCZ), with linear and quadratic age, gender and total intracranial volume as nuisance covariates. We assessed the reproducibility of our case/control findings in an independent sample of 127 HC and 36 SCZ. Group differences were tested post hoc through Fisher’s test. Results We found significant group effects in the bilateral thalamus, bilateral hippocampus and anterior cingulate (FWE<0.05). Specifically, SCZ presented the lowest GM volume in these regions compared to the other three groups, with SIB and CHR’s GM estimates intermediate between HC and SCZ (p<0.05). The associations with schizophrenia were replicated in the independent validation sample. Discussion Individuals with familial or clinical risk for schizophrenia have lower GM estimates in the same brain regions. These findings, suggest that these structural features are not only associated with familial risk for schizophrenia but that they are also associated with its sub-threshold symptoms.

scholarly journals Sex differences in gray and white matter structure in age-matched unrelated males and females and opposite-sex siblings.

2013 ◽  
Vol 6 ◽  
pp. 7-21 ◽  
Author(s):  
Anouk Den Braber ◽  
Dennis Van ‘t Ent ◽  
Diederick Stoffers ◽  
Klaus Linkenkaer-Hansen ◽  
Dorret I. Boomsma ◽  
...  
Keyword(s):  
Sex Differences ◽  
White Matter ◽  
Family Background ◽  
Gray Matter Volume ◽  
Brain Volumes ◽  
Men And Women ◽  
Matter Volume ◽  
Opposite Sex ◽  
Males And Females ◽  
Global Brain

Apart from the general finding of larger global brain volumes in men, neuroimaging studies that compared brain structure between men and women have yielded some inconsistencies with regard to regional differences. One confound when comparing men and women may be differences in their genetic and or family background. A design that addresses such confounds compares brain structures between brothers and sisters, who share their genetic and family background.In the present study, we aimed to contribute to the existing literature on structural brain sex differences by comparing regional gray and white matter volume, using voxel based morphometry (VBM); and white matter microstructure, using tract-based spatial statistics (TBSS), between 40 unrelated males and females, and contrasting the results with those obtained in a group of 47 opposite-sex siblings, including 42 dizygotic opposite-sex (DOS) twin pairs.”Our results showed that men had larger global brain volumes as well as higher mean fractional anisotropy across the brain and showed regionally enlarged gray matter volume and higher fractional anisotropy in, or surrounding, subcortical structures (hypothalamus, thalamus, putamen and globus pallidus and rostral midbrain). Increased gray matter volume in women was restricted to areas of the cortex, including inferior temporal, insular, cingulate, precentral and frontal/prefrontal regions.These sex differences were generally consistent between the unrelated male-female pairs and the opposite-sex sibling pairs. Therefore, we conclude that these sex differences are not the result of confounding differences in genetic or family background and that the etiology of these sex differences merits further investigation.

scholarly journals Sex differences in hippocampal cytokines after systemic immune challenge

2018 ◽  
Author(s):  
Ian C. Speirs ◽  
Natalie C. Tronson
Keyword(s):  
Sex Differences ◽  
Neural Function ◽  
Immune Challenge ◽  
Systemic Injection ◽  
Gm Csf ◽  
Cytokine Activation ◽  
Inflammatory State ◽  
Males And Females ◽  
Cytokine Networks ◽  
The Brain

ABSTRACTIllness or injury causes an inflammatory state consisting of activation of immune cells and increased production of cytokines in the periphery and in the brain, resulting changes in physiological processes, behavior, and cognition. The immune and neuroimmune response consist of a tightly controlled activation and resolution of cytokine networks, the precise patterns of which are determined, in part, by the immune stimulus. Importantly, the pattern of cytokines, rather than the presence of any individual cytokine, determines the functional outcome of immune signaling. In this project, we hypothesized that given sex differences in behavioral responses to immune challenge, the patterns of cytokine activation induced in the hippocampus after a systemic immune challenge differ between males and females. We examined 32 cytokines in the hippocampus and periphery of male and female mice 2, 6, 24, 48, and 168 hours after an acute systemic injection of lipopolysaccharides (LPS; 250μg/kg). All animals showed resolution of the neuroimmune response 168 hours after immune challenge Males and females differed in the specific cytokines activated in the hippocampus, the magnitude of elevation, and the timecourse of activation and resolution of neuroimmune signaling. Briefly, male-specific elevations included IFNγ, CSF1 (M-CSF) and CSF2 (GM-CSF), and the regulatory cytokine IL-10, whereas female-specific activation included the IL-2 family and the regulatory IL-4. Females showed rapid elevation and resolution of the hippocampal immune response, with cytokine levels peaking at 2 and 6 hours after immune challenge. In contrast, males showed slower and more persistent activation, with peaks at 6-24 hours. These findings demonstrate that sex differences in neuroimmune response are not limited to the intensity of the cytokine response, but more importantly differs in the cytokine networks activated. These findings suggest that delineating the broad, sex-specific patterns of cytokine activity in the brain is critical for understanding of the role of neuroimmune signaling in neural function.

scholarly journals Establishing a link between sex-related differences in the structural connectome and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150111 ◽  
Author(s):  
Birkan Tunç ◽  
Berkan Solmaz ◽  
Drew Parker ◽  
Theodore D. Satterthwaite ◽  
Mark A. Elliott ◽  
...  
Keyword(s):  
Sex Differences ◽  
Brain Structure ◽  
Research Effort ◽  
Structural Connectivity ◽  
Human Mind ◽  
Brain Network ◽  
Attention And Memory ◽  
Behavioural Patterns ◽  
Males And Females ◽  
The Brain

Recent years have witnessed an increased attention to studies of sex differences, partly because such differences offer important considerations for personalized medicine. While the presence of sex differences in human behaviour is well documented, our knowledge of their anatomical foundations in the brain is still relatively limited. As a natural gateway to fathom the human mind and behaviour, studies concentrating on the human brain network constitute an important segment of the research effort to investigate sex differences. Using a large sample of healthy young individuals, each assessed with diffusion MRI and a computerized neurocognitive battery, we conducted a comprehensive set of experiments examining sex-related differences in the meso-scale structures of the human connectome and elucidated how these differences may relate to sex differences at the level of behaviour. Our results suggest that behavioural sex differences, which indicate complementarity of males and females, are accompanied by related differences in brain structure across development. When using subnetworks that are defined over functional and behavioural domains, we observed increased structural connectivity related to the motor, sensory and executive function subnetworks in males. In females, subnetworks associated with social motivation, attention and memory tasks had higher connectivity. Males showed higher modularity compared to females, with females having higher inter-modular connectivity. Applying multivariate analysis, we showed an increasing separation between males and females in the course of development, not only in behavioural patterns but also in brain structure. We also showed that these behavioural and structural patterns correlate with each other, establishing a reliable link between brain and behaviour.

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