Robustness of sex-differences in functional connectivity over time in middle-aged marmosets
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ABSTRACT:
SUBMITTER: Nephew B
PROVIDER: S-EPMC7538565 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundFrailty is a clinical syndrome described as reduced physiological reserve and increased vulnerability. Typically examined in older adults, recent work shows frailty occurs in middle-aged individuals and is associated with increased mortality. Previous investigation of global transcriptome changes in a middle-aged cohort from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study demonstrated inflammatory genes and pathways were significantly altered by frailty status and race. Transcriptome differences in frailty by sex remain unclear. We sought to discover novel genes and pathways associated with sex and frailty in a diverse middle-aged cohort using RNA-Sequencing.MethodsDifferential gene expression and pathway analyses were performed in peripheral blood mononuclear cells for 1) frail females (FRAF, n = 4) vs non-frail females (NORF, n = 4), 2) frail males (FRAM, n = 4) vs non-frail males (NORM, n = 4), 3) FRAM vs FRAF, and 4) NORM vs NORF. We evaluated exclusive significant genes and pathways, as well as overlaps, between the comparison groups.ResultsOver 80% of the significant genes exclusive to FRAF vs NORF, FRAM vs NORM, and FRAM vs FRAF, respectively, were novel and associated with various biological functions. Pathways exclusive to FRAF vs NORF were associated with reduced inflammation, while FRAM vs NORM exclusive pathways were related to aberrant musculoskeletal physiology. Pathways exclusive to FRAM vs FRAF were associated with reduced cell cycle regulation and activated catabolism and Coronavirus pathogenesis.ConclusionsOur results indicate sex-specific transcriptional changes occur in middle-aged frailty, enhancing knowledge on frailty progression and potential therapeutic targets to prevent frailty.
| S-EPMC9361278 | biostudies-literature
Project description:INTRODUCTION:The influence of sex on the prevalence and clinical manifestations of functional dyspepsia (FD) has recently been a topic of increasing interest. However, brain MRI pathology based on sexual dimorphism in FD has not yet been investigated. The amygdala, which plays a vital role in processing gastrointestinal signals, may be associated with the sex-related pathophysiology of FD. METHODS:We investigated the resting-state functional connectivity (rsFC) of amygdala subregions in patients with FD and healthy subjects as well as the sex differences between male and female FD patients. RESULTS:The results showed that FD patients manifested altered rsFC in the basolateral amygdala (BLA) and centromedial amygdala subregions compared with HS and that female FD patients showed increased BLA rsFC with the insula (INS) and decreased BLA rsFC with the medial prefrontal cortex and dorsal lateral prefrontal cortex compared with male FD patients and female HS. DISCUSSION:Our findings suggest that FD females tend to have more severe dysfunction of cognitive-affective processing among the brain regions associated with the salience network, central executive network, and default mode network.
| S-EPMC6613861 | biostudies-other
Project description:Sex-related differences in brain and behavior are apparent across the life course, but the exact set of processes that guide their emergence in utero remains a topic of vigorous scientific inquiry. Here, we evaluate sex and gestational age (GA)-related change in functional connectivity (FC) within and between brain wide networks. Using resting-state functional magnetic resonance imaging we examined FC in 118 human fetuses between 25.9 and 39.6 weeks GA (70 male; 48 female). Infomap was applied to the functional connectome to identify discrete prenatal brain networks in utero. A consensus procedure produced an optimal model comprised of 16 distinct fetal neural networks distributed throughout the cortex and subcortical regions. We used enrichment analysis to assess network-level clustering of strong FC-GA correlations separately in each sex group, and to identify network pairs exhibiting distinct patterns of GA-related change in FC between males and females. We discovered both within and between network FC-GA associations that varied with sex. Specifically, associations between GA and posterior cingulate-temporal pole and fronto-cerebellar FC were observed in females only, whereas the association between GA and increased intracerebellar FC was stronger in males. These observations confirm that sexual dimorphism in functional brain systems emerges during human gestation.
| S-EPMC6944279 | biostudies-literature
Project description:The existence of "sex phenotype" in migraine is a long-standing scientific question. Fluctuations of female sex hormones contribute to migraine attacks, and women also have enhanced brain activity during emotional processing and their functional brain networks seem to be more vulnerable to migraine-induced disruption compared to men. Periaqueductal grey matter (PAG) is a core region of pain processing and modulation networks with possible sex-related implications in migraine. In our study, sex differences of PAG functional resting-state connectivity were investigated in the interictal state in 32 episodic migraines without aura patients (16 women and 16 men). A significant main effect of sex was detected in PAG connectivity with postcentral, precentral, and inferior parietal gyri, and further differences were found between right PAG and visual areas (superior occipital gyrus, calcarine, and cuneus), supplementary motor area, and mid-cingulum connectivity. In all cases, PAG functional connectivity was stronger in female migraineurs compared to males. However, higher average pain intensity of migraine attacks correlated with stronger connectivity of PAG and middle temporal, superior occipital, and parietal gyri in male migraineurs compared to females. Migraine-related disability is also associated with PAG connectivity but without sex differences. Our results indicate that sex differences in PAG connectivity with brain regions involved in sensory and emotional aspects of pain might contribute to the "sex-phenotype" in migraine. The stronger functional connectivity between PAG and pain processing areas may be a sign of increased excitability of pain pathways even in resting-state in females compared to male migraineurs, which could contribute to female vulnerability for migraine. However, pain intensity experienced by male migraineurs correlated with increased connectivity between PAG and regions involved in the subjective experience of pain and pain-related unpleasantness. The demonstrated sex differences of PAG functional connectivity may support the notion that the female and male brain is differently affected by migraine.
| S-EPMC8915645 | biostudies-literature
Project description:BackgroundFemales may have a higher risk of dementia than males. It is not clear if sex differences in Alzheimer's disease (AD) neuropathology explain the higher risk of dementia in females. Sex differences in AD neuropathology might begin in middle age, decades before the sex differences in dementia are apparent.ObjectiveTo examine sex differences in in vivo AD neuropathology in late middle age.MethodsWe conducted a cross-sectional comparison of AD biomarkers among 266 Hispanic males and females (mean age: 64.0; 71.8% females) without dementia. Amyloid burden was measured as global standardized uptake value ratio (SUVR) with18F-Florbetaben positron emission tomography (PET). Neurodegeneration was ascertained as cortical thickness in AD signature areas using brain magnetic resonance imaging. Tau burden was measured as tau SUVR in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 in 75 of the 266 participants.ResultsFemales had higher amyloid SUVR and tau SUVR in the middle/inferior temporal gyri than males. However, females had higher cortical thickness than males and performed better in a test of verbal memory despite having higher AD neuropathology burden.ConclusionHigher amyloid and tau in females compared to males in late middle-age may explain the reported higher dementia risk in elderly females compared to males. Longitudinal follow-up is necessary to examine whether higher amyloid and tau burden in late middle age is followed by increased neurodegeneration and cognitive decline in females as compared with males.
| S-EPMC7656318 | biostudies-literature
Project description:Non-linear relations of brain amyloid beta (A?) with task- based functional connectivity (tbFC) measured with functional magnetic resonance imaging (fMRI) have been reported in late middle age. Our objective was to examine the association between brain A? and resting-state functional connectivity (rsFC) in late middle-aged adults. Global brain A? burden was ascertained with 18F-Florbetaben Positron Emission Tomography (PET); rsFC was ascertained on 3T Magnetic Resonance Imaging (MRI) among 333 late middle-aged Hispanics adults without dementia in four major brain functional connectivity networks: default mode network (DMN), fronto-parietal control network (FPC), salience network (SAL) and dorsal attention network (DAN). We examined the relationship of global brain A? with rsFC using multivariable linear regression adjusted for age, sex, education, and APOE-?4 genotype. We quantified the non-linear associations both with quadratic terms and by categorizing A? into three groups: low A?, intermediate A?, and positive A?. We found no significant linear or non-linear associations between A?, measured either continuously or categorically, with rsFC in the examined networks. Our null findings may be explained by the younger age of our participants in whom amyloid burden is relatively low. It is also possible that the recently reported non-linear relationship is exclusive to task fMRI and not rsfMRI.
| S-EPMC7573129 | biostudies-literature
Project description:Numerous lines of evidence have shown that cognitive processes engaged during response inhibition tasks are associated with structure and functional integration of regions within fronto-parietal networks. However, while prior studies have started to characterize how intrinsic connectivity during resting state differs between boys and girls, comparatively less is known about how functional connectivity differs between males and females when brain function is exogenously driven by the processing demands of typical Go/No-Go tasks that assess both response inhibition and error processing. The purpose of this study was to characterize adolescent sex differences and possible changes in sexually dimorphic regional functional connectivity across adolescent development in both cortical and subcortical brain connectivity elicited during a visual Go/No-Go task. A total of 130 healthy adolescents (ages 12-25 years) performed a Go/No-Go task during functional magnetic resonance imaging. High model-order group independent component analysis was used to characterize whole-brain network functional connectivity during response inhibition and then a univariate technique used to evaluate differences related to sex and age. As predicted and similar to previously described findings from non-task-driven resting state connectivity studies, functional connectivity sex differences were observed in several subcortical regions, including the amygdala, caudate, thalamus, and cortical regions, including inferior frontal gyrus engaged most strongly during successful response inhibition and/or error processing. Importantly, adolescent boys and girls exhibited different normative profiles of age-related changes in several default mode networks of regions and anterior cingulate cortex. These results suggest that cortical-subcortical functional networks supporting response inhibition operate differently between sexes during adolescence.
| S-EPMC8259338 | biostudies-literature
Project description:During adolescence, considerable social and biological changes occur that interact with functional brain maturation, some of which are sex-specific. The amygdala is one brain area that has displayed sexual dimorphism, specifically in socio-affective (superficial amygdala [SFA]), stress (centromedial amygdala [CMA]), and learning and memory (basolateral amygdala [BLA]) processing. The amygdala has also been implicated in mood and anxiety disorders which display sex-specific features, most prominently observed during adolescence. Using functional magnetic resonance imaging (fMRI), the present study examined the interaction of age and sex on resting state functional connectivity (RSFC) of amygdala sub-regions, BLA and SFA, in a sample of healthy adolescents between the ages 10 and 16 years (n = 122, 71 boys). Whole-brain, voxel-wise partial correlation analyses were conducted to determine RSFC of bilateral BLA and SFA seed regions, created using the Eickhoff-Zilles maximum probability maps based on cytoarchitectonic mapping and FMRIB's Integrated Registration and Segmentation Tool (FIRST). Monte Carlo simulation was implemented to correct for multiple comparisons (threshold of 53 contiguous voxels with a z-value ≥ 2.25). Results indicated that with increasing age, there was a corresponding decrease in RSFC between both amygdala sub-regions and parieto-occipital cortices, with a concurrent increase in RSFC with medial prefrontal cortex (mPFC). Specifically, boys and girls demonstrated increased coupling of mPFC and left and right SFA with age, respectively; however, neither sex showed increased connectivity between mPFC and BLA, which could indicate relative immaturity of fronto-limbic networks that is similar across sex. A dissociation in connectivity between BLA- and SFA-parieto-occipital RSFC emerged, in which girls had weaker negative RSFC between SFA and parieto-occipital regions and boys had weaker negative RSFC of BLA and parieto-occipital regions with increased age, both standing in contrast to adult patterns of amygdala sub-regional RSFC. The present findings suggest relative immaturity of amygdala sub-regional RSFC with parieto-occipital cortices during adolescence, with unique patterns in both sexes that may support memory and socio-affective processing in boys and girls, respectively. Understanding the underlying normative functional architecture of brain networks associated with the amygdala during adolescence may better inform future research of the neural features associated with increased risk for internalizing psychopathology.
| S-EPMC4461484 | biostudies-literature
Project description:Longitudinal studies are essential to understand healthy and pathological neurocognitive aging such as Alzheimer's Disease, but longitudinal designs are rare in both humans and non-human primate models of aging because of the difficulty of tracking cognitive change in long-lived primates. Common marmosets (Callithrix jacchus) are uniquely suited for aging studies due to their naturally short lifespan (10-12 years), sophisticated cognitive and social abilities and Alzheimer Disease-like neuropathology. We report the first longitudinal study of cognitive aging in marmosets (N = 28) as they transitioned from middle- (∼5 years) to old age (∼9 years). We characterized aging trajectories using reversal learning with different stimuli each year. Marmosets initially improved on cognitive performance due to practice, but worsened in the final year, suggesting the onset of age-related decline. Cognitive impairment emerged earlier in females than males and was more prominent for discrimination than for reversal learning. Sex differences in cognitive aging could not be explained by differences in motivation or motor abilities, which improved or remained stable across aging. Likewise, males and females did not differ in aging trajectories of overall behavior or reactivity to a social stressor, with the exception of a progressive decline in the initiation of social behavior in females. Patterns of cognitive aging were highly variable across marmosets of both sexes, suggesting the potential for pathological aging for some individuals. Future work will link individual cognitive trajectories to neuropathology in order to better understand the relationships between neuropathologic burden and vulnerability to age-related cognitive decline in each sex.
| S-EPMC8841951 | biostudies-literature
Project description:BackgroundCerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time.MethodsA total of 4943 participants (mean age = 64.6 ± 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used.ResultsA smaller total brain volume (β = -0.107, 95% CI -0.192 to -0.022), larger white matter hyperintensities volume (β = 0.047, 95% CI 0.010-0.084), presence of cortical infarcts (β = 0.194, 95% CI 0.047-0.341), and higher MD levels (β = 0.060, 95% CI 0.022-0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (β = -0.091, 95% CI -0.167 to -0.015) and presence of cortical infarcts (β = 0.168, 95% CI 0.022-0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages.ConclusionsNeuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.
| S-EPMC10388307 | biostudies-literature