Attenuation of Typical Sex Differences in 800 Adults with Autism vs. 3,900 Controls

Sex differences have been reported in autistic traits and systemizing (male advantage), and empathizing (female advantage) among typically developing individuals. In individuals with autism, these cognitive-behavioural profiles correspond to predictions from the “extreme male brain” (EMB) theory of autism (extreme scores on autistic traits and systemizing, below average on empathizing). Sex differences within autism, however, have been under-investigated. Here we show in 811 adults (454 females) with autism and 3,906 age-matched typical control adults (2,562 females) who completed the Empathy Quotient (EQ), the Systemizing Quotient-Revised (SQ-R), and the Autism Spectrum Quotient (AQ), that typical females on average scored higher on the EQ, typical males scored higher on the SQ-R and AQ, and both males and females with autism showed a shift toward the extreme of the “male profile” on these measures and in the distribution of “brain types” (the discrepancy between standardized EQ and SQ-R scores). Further, normative sex differences are attenuated but not abolished in adults with autism. The findings provide strong support for the EMB theory of autism, and highlight differences between males and females with autism.     

A behavioral comparison of male and female adults with high functioning autism spectrum conditions

Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males.     

Constraints on the coevolution of contemporary human males and females

Because autosomal genes in sexually reproducing organisms spend on average half their time in each sex, and because the traits that they influence encounter different selection pressures in males and females, the evolutionary responses of one sex are constrained by processes occurring in the other sex. Although intralocus sexual conflict can restrict sexes from reaching their phenotypic optima, no direct evidence currently supports its operation in humans. Here, we show that the pattern of multivariate selection acting on human height, weight, blood pressure and glucose, total cholesterol, and age at first birth differs significantly between males and females, and that the angles between male and female linear (77.8 ± 20.5°) and nonlinear (99.1 ± 25.9°) selection gradients were closer to orthogonal than zero, confirming the presence of sexually antagonistic selection. We also found evidence for intralocus sexual conflict demonstrated by significant changes in the predicted male and female responses to selection of individual traits when cross-sex genetic covariances were included and a significant reduction in the angle between male- and female-predicted responses when cross-sex covariances were included (16.9 ± 15.7°), compared with when they were excluded (87.9 ± 31.6°). We conclude that intralocus sexual conflict constrains the joint evolutionary responses of the two sexes in a contemporary human population.     

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

Background

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods

Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.

Results

There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.

Discussion

Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.     

Sexuality and Gender Role in Autism Spectrum Disorder: A Case Control Study

The ‘extreme male brain theory of autism’ describes an extreme male pattern of cognitive traits defined as strong systemising abilities paired with empathising weaknesses in autism spectrum disorder. However, beyond these cognitive traits, clinical observations have suggested an ambiguous gender-typed pattern regarding several sexually dimorphic traits.The aim of the present study was to investigate if patterns of non-cognitive sexually dimorphic traits differed between the autism spectrum disorder and control groups. Fifty adults with autism spectrum disorder and intelligence within the normal range, and 53 neurotypical controls responded to questions on gender role, self-perceived gender typicality and gender identity, as well as sexuality. Measures used were a Swedish modification of the Bem Sex Role Inventory and questions on sexuality and gender designed for the purpose of this study. Our results showed that one common gender role emerged in the autism spectrum disorder group. Masculinity (e.g. assertiveness, leadership and competitiveness) was weaker in the autism spectrum disorder group than in the controls, across men and women. Self-perceived gender typicality did not differ between the groups but tomboyism and bisexuality were overrepresented amongst women with autism spectrum disorder. Lower libido was reported amongst both male and female participants with autism spectrum disorder compared with controls. We conclude that the extreme male patterns of cognitive functions in the autistic brain do not seem to extend to gender role and sexuality. A gender-atypical pattern for these types of characteristics is suggested in autism spectrum disorder.     

Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People

This study assesses Autism-Spectrum Quotient (AQ) scores in a ‘big data’ sample collected through the UK Channel 4 television website, following the broadcasting of a medical education program. We examine correlations between the AQ and age, sex, occupation, and UK geographic region in 450,394 individuals. We predicted that age and geography would not be correlated with AQ, whilst sex and occupation would have a correlation. Mean AQ for the total sample score was m = 19.83 (SD = 8.71), slightly higher than a previous systematic review of 6,900 individuals in a non-clinical sample (mean of means = 16.94) This likely reflects that this big-data sample includes individuals with autism who in the systematic review score much higher (mean of means = 35.19). As predicted, sex and occupation differences were observed: on average, males (m = 21.55, SD = 8.82) scored higher than females (m = 18.95; SD = 8.52), and individuals working in a STEM career (m = 21.92, SD = 8.92) scored higher than individuals non-STEM careers (m = 18.92, SD = 8.48). Also as predicted, age and geographic region were not meaningfully correlated with AQ. These results support previous findings relating to sex and STEM careers in the largest set of individuals for which AQ scores have been reported and suggest the AQ is a useful self-report measure of autistic traits.     

The “Reading the Mind in the Eyes” Test: Complete Absence of Typical Sex Difference in ~400 Men and Women with Autism

The “Reading the Mind in the Eyes” test (Eyes test) is an advanced test of theory of mind. Typical sex difference has been reported (i.e., female advantage). Individuals with autism show more difficulty than do typically developing individuals, yet it remains unclear how this is modulated by sex, as females with autism have been under-represented. Here in a large, non-male-biased sample we test for the effects of sex, diagnosis, and their interaction. The Eyes test (revised version) was administered online to 395 adults with autism (178 males, 217 females) and 320 control adults (152 males, 168 females). Two-way ANOVA showed a significant sex-by-diagnosis interaction in total correct score (F(1,711) = 5.090, p = 0.024, η_p ² = 0.007) arising from a significant sex difference between control males and females (p < 0.001, Cohen’s d = 0.47), and an absence of a sex difference between males and females with autism (p = 0.907, d = 0.01); significant case-control differences were observed across sexes, with effect sizes of d = 0.35 in males and d = 0.69 in females. Group-difference patterns fit with the extreme-male-brain (EMB) theory predictions. Eyes test-Empathy Quotient and Eyes test-Autism Spectrum Quotient correlations were significant only in females with autism (r = 0.35, r = -0.32, respectively), but not in the other 3 groups. Support vector machine (SVM) classification based on response pattern across all 36 items classified autism diagnosis with a relatively higher accuracy for females (72.2%) than males (65.8%). Nevertheless, an SVM model trained within one sex generalized equally well when applied to the other sex. Performance on the Eyes test is a sex-independent phenotypic characteristic of adults with autism, reflecting sex-common social difficulties, and provides support for the EMB theory predictions for both males and females. Performance of females with autism differed from same-sex controls more than did that of males with autism. Females with autism also showed stronger coherence between self-reported dispositional traits and Eyes test performance than all other groups.     

Heart Rate Responses to Autonomic Challenges in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is accompanied by structural alterations and dysfunction in central autonomic regulatory regions, which may impair dynamic and static cardiovascular regulation, and contribute to other syndrome pathologies. Characterizing cardiovascular responses to autonomic challenges may provide insights into central nervous system impairments, including contributions by sex, since structural alterations are enhanced in OSA females over males. The objective was to assess heart rate responses in OSA versus healthy control subjects to autonomic challenges, and, separately, characterize female and male patterns. We studied 94 subjects, including 37 newly-diagnosed, untreated OSA patients (6 female, age mean±std: 52.1±8.1 years; 31 male aged 54.3±8.4 years), and 57 healthy control subjects (20 female, 50.5±8.1 years; 37 male, 45.6±9.2 years). We measured instantaneous heart rate with pulse oximetry during cold pressor, hand grip, and Valsalva maneuver challenges. All challenges elicited significant heart rate differences between OSA and control groups during and after challenges (repeated measures ANOVA, p<0.05). In post-hoc analyses, OSA females showed greater impairments than OSA males, which included: for cold pressor, lower initial increase (OSA vs. control: 9.5 vs. 7.3 bpm in females, 7.6 vs. 3.7 bpm in males), OSA delay to initial peak (2.5 s females/0.9 s males), slower mid-challenge rate-of-increase (OSA vs. control: −0.11 vs. 0.09 bpm/s in females, 0.03 vs. 0.06 bpm/s in males); for hand grip, lower initial peak (OSA vs. control: 2.6 vs. 4.6 bpm in females, 5.3 vs. 6.0 bpm in males); for Valsalva maneuver, lower Valsalva ratio (OSA vs. control: 1.14 vs. 1.30 in females, 1.29 vs. 1.34 in males), and OSA delay during phase II (0.68 s females/1.31 s males). Heart rate responses showed lower amplitude, delayed onset, and slower rate changes in OSA patients over healthy controls, and impairments may be more pronounced in females. The dysfunctions may reflect central injury in the syndrome, and suggest autonomic deficiencies that may contribute to further tissue and functional pathologies.     

Functional Network Endophenotypes Unravel the Effects of Apolipoprotein E Epsilon 4 in Middle-Aged Adults

Apolipoprotein E-ε4 (APOE-ε4) accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN), executive control (ECN) and salience (SN) networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc) in these networks. Resting-state functional connectivity MRI (R-fMRI) was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.     

Abnormal brain default-mode network functional connectivity in drug addicts

Background

The default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention and self-monitoring. As the anterior cingulate cortex and hippocampus are impaired in drug addiction and meanwhile are parts of the DMN, the present study examined addiction-related alteration of functional connectivity of the DMN.

Methodology

Resting-state functional magnetic resonance imaging data of chronic heroin users (14 males, age: 30.1±5.3 years, range from 22 to 39 years) and non-addicted controls (13 males, age: 29.8±7.2 years, range from 20 to 39 years) were investigated with independent component analysis to address their functional connectivity of the DMN.

Principal Findings

Compared with controls, heroin users showed increased functional connectivity in right hippocampus and decreased functional connectivity in right dorsal anterior cingulate cortex and left caudate in the DMN.

Conclusions

These findings suggest drug addicts'' abnormal functional organization of the DMN, and are discussed as addiction-related abnormally increased memory processing but diminished cognitive control related to attention and self-monitoring, which may underlie the hypersensitivity toward drug related cues but weakened strength of cognitive control in the state of addiction.     

Cognition in Males and Females with Autism: Similarities and Differences

The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. This lack of attention to females could hide variability due to sex that may explain some of the heterogeneity within ASC. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC (n = 128 adults; n = 32 per group). In the mentalizing and facial emotion perception domain, males and females with ASC showed similar deficits compared to neurotypical controls. However, in attention to detail and dexterity involving executive function, although males with ASC showed poorer performance relative to neurotypical males, females with ASC performed comparably to neurotypical females. We conclude that performance in the social-cognitive domain is equally impaired in male and female adults with ASC. However, in specific non-social cognitive domains, performance within ASC depends on sex. This suggests that in specific domains, cognitive profiles in ASC are modulated by sex.     

Gender Differences of Brain Glucose Metabolic Networks Revealed by FDG-PET: Evidence from a Large Cohort of 400 Young Adults

Background

Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample.

Materials and Methods

FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25∼45 years, mean age±SD: 40.9±3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders.

Results

Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study.

Conclusion

This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.     

Density-Dependent Natal Dispersal Patterns in a Leopard Population Recovering from Over-Harvest

Natal dispersal enables population connectivity, gene flow and metapopulation dynamics. In polygynous mammals, dispersal is typically male-biased. Classically, the ‘mate competition’, ‘resource competition’ and ‘resident fitness’ hypotheses predict density-dependent dispersal patterns, while the ‘inbreeding avoidance’ hypothesis posits density-independent dispersal. In a leopard (Panthera pardus) population recovering from over-harvest, we investigated the effect of sex, population density and prey biomass, on age of natal dispersal, distance dispersed, probability of emigration and dispersal success. Over an 11-year period, we tracked 35 subadult leopards using VHF and GPS telemetry. Subadult leopards initiated dispersal at 13.6 ± 0.4 months. Age at commencement of dispersal was positively density-dependent. Although males (11.0 ± 2.5 km) generally dispersed further than females (2.7 ± 0.4 km), some males exhibited opportunistic philopatry when the population was below capacity. All 13 females were philopatric, while 12 of 22 males emigrated. Male dispersal distance and emigration probability followed a quadratic relationship with population density, whereas female dispersal distance was inversely density-dependent. Eight of 12 known-fate females and 5 of 12 known-fate male leopards were successful in settling. Dispersal success did not vary with population density, prey biomass, and for males, neither between dispersal strategies (philopatry vs. emigration). Females formed matrilineal kin clusters, supporting the resident fitness hypothesis. Conversely, mate competition appeared the main driver for male leopard dispersal. We demonstrate that dispersal patterns changed over time, i.e. as the leopard population density increased. We conclude that conservation interventions that facilitated local demographic recovery in the study area also restored dispersal patterns disrupted by unsustainable harvesting, and that this indirectly improved connectivity among leopard populations over a larger landscape.     

Heat Stress Impedes Development and Lowers Fecundity of the Brown Planthopper Nilaparvata lugens (St?l)

This study investigated the effects of sub-lethal high temperatures on the development and reproduction of the brown plant hopper Nilaparvata lugens (Stål). When first instar nymphs were exposed at their ULT₅₀ (41.8°C) mean development time to adult was increased in both males and females, from 15.2±0.3 and 18.2±0.3 days respectively in the control to 18.7±0.2 and 19±0.2 days in the treated insects. These differences in development arising from heat stress experienced in the first instar nymph did not persist into the adult stage (adult longevity of 23.5±1.1 and 24.4±1.1 days for treated males and females compared with 25.7±1.0 and 20.6±1.1 days in the control groups), although untreated males lived longer than untreated females. Total mean longevity was increased from 38.8±0.1 to 43.4±1.0 days in treated females, but male longevity was not affected (40.9±0.9 and 42.2±1.1 days respectively). When male and female first instar nymphs were exposed at their ULT₅₀ of 41.8°C and allowed to mate on reaching adult, mean fecundity was reduced from 403.8±13.7 to 128.0±16.6 eggs per female in the treated insects. Following exposure of adult insects at their equivalent ULT₅₀ (42.5°C), the three mating combinations of treated male x treated female, treated male x untreated female, and untreated male x treated female produced 169.3±14.7, 249.6±21.3 and 233.4±17.2 eggs per female respectively, all significantly lower than the control. Exposure of nymphs and adults at their respective ULT₅₀ temperatures also significantly extended the time required for their progeny to complete egg development for all mating combinations compared with control. Overall, sub-lethal heat stress inhibited nymphal development, lowered fecundity and extended egg development time.     

Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load

Background

Recent functional MRI (fMRI) studies have demonstrated that there is an intrinsically organized default mode network (DMN) in the resting brain, primarily made up of the posterior cingulate cortex (PCC) and the medial prefrontal cortex (MPFC). Several previous studies have found that the DMN is minimally disturbed during different resting-state conditions with limited cognitive demand. However, this conclusion was drawn from the visual inspection of the functional connectivity patterns within the DMN and no statistical comparison was performed.

Methodology/Principal Findings

Four resting-state fMRI sessions were acquired: 1) eyes-closed (EC) (used to generate the DMN mask); 2) EC; 3) eyes-open with no fixation (EO); and 4) eyes-open with a fixation (EO-F). The 2–4 sessions were counterbalanced across participants (n = 20, 10 males). We examined the statistical differences in both functional connectivity and regional amplitude of low frequency fluctuation (ALFF) within the DMN among the 2–4 resting-state conditions (i.e., EC, EO, and EO-F). Although the connectivity patterns of the DMN were visually similar across these three different conditions, we observed significantly higher functional connectivity and ALFF in both the EO and the EO-F conditions as compared to the EC condition. In addition, the first and second resting EC conditions showed significant differences within the DMN, suggesting an order effect on the DMN activity.

Conclusions/Significance

Our findings of the higher DMN connectivity and regional spontaneous activities in the resting state with the eyes open suggest that the participants might have more non-specific or non-goal-directed visual information gathering and evaluation, and mind wandering or daydreaming during the resting state with the eyes open as compared to that with the eyes closed, thus providing insights into the understanding of unconstrained mental activity within the DMN. Our results also suggest that it should be cautious when choosing the type of a resting condition and designating the order of the resting condition in multiple scanning sessions in experimental design.     

Catechol-O-Methyltransferase Val158Met Polymorphism Modulates Gray Matter Volume and Functional Connectivity of the Default Mode Network

The effect of catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV) differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype × gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC) with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC) compared with Met carriers; decreased GMV in the medial superior frontal gyrus (mSFG) was found only in male Val/Val subjects. The rsFC analysis revealed that both the PCC and mSFG were functionally correlated with brain regions of the default mode network (DMN). Both of these regions showed decreased rsFCs with different parts of the frontopolar cortex of the DMN in Val/Val individuals than Met carriers. Our findings suggest that the COMT Val158Met polymorphism modulates both the structure and functional connectivity within the DMN and that gender interactions should be considered in studies of the effect of this genetic variant, especially those involving prefrontal morphology.     

Global Brain Blood-Oxygen Level Responses to Autonomic Challenges in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD) signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr), and 20 female (age 50.5±8.1 yrs) and 37 male (age 45.6±9.2 yrs) healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip), but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05). OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error) at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex-specific brain injury in the syndrome.     

Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss

The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting–state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network.     

Effect of Orthostasis on Endothelial Function: A Gender Comparative Study

As the vascular endothelium has multiple functions, including regulation of vascular tone, it may play a role in the pathophysiology of orthostatic intolerance. We investigated the effect of orthostasis on endothelial function using EndoPAT®, a non-invasive and user-independent method, and across gender. As sex steroid hormones are known to affect endothelial function, this study examined the potential effect of these hormones on the endothelial response to orthostasis by including females at different phases of the menstrual cycle (follicular and luteal—where the hormone balance differs), and females taking an oral contraceptive. A total of 31 subjects took part in this study (11 males, 11 females having normal menstrual cycles and 9 females taking oral contraceptive). Each subject made two visits for testing; in the case of females having normal menstrual cycles the first session was conducted either 1–7 (follicular) or 14–21 days (luteal) after the start of menstruation, and the second session two weeks later, i.e., during the other phase, respectively. Endothelial function was assessed at baseline and following a 20-min orthostatic challenge (active standing). The EndoPAT® index increased from 1.71 ± 0.09 (mean ± SEM) at baseline to 2.07 ± 0.09 following orthostasis in females (p<0.001). In males, the index increased from 1.60 ± 0.08 to 1.94 ± 0.13 following orthostasis (p<0.001). There were no significant differences, however, in the endothelial response to orthostasis between females and males, menstrual cycle phases and the usage of oral contraceptive. Our results suggest an increased vasodilatatory endothelial response following orthostasis in both females and males. The effect of gender and sex hormones on the endothelial response to orthostasis appears limited. Further studies are needed to determine the potential role of this post orthostasis endothelial response in the pathophysiology of orthostatic intolerance.     

Social Cognition,the Male Brain and the Autism Spectrum

Behavioral studies have shown that, at a population level, women perform better on tests of social cognition and empathy than men. Furthermore Autism Spectrum Disorders (ASDs), which are characterized by impairments in social functioning and empathy, occur more commonly in males than females. These findings have led to the hypothesis that differences in the functioning of the social brain between males and females contribute to the greater vulnerability of males to ASD and the suggestion that ASD may represent an extreme form of the male brain. Here we sought to investigate this hypothesis by determining: (i) whether males and females differ in social brain function, and (ii) whether any sex differences in social brain function are exaggerated in individuals with ASD. Using fMRI we show that males and females differ markedly in social brain function when making social decisions from faces (compared to simple sex judgements) especially when making decisions of an affective nature, with the greatest sex differences in social brain activation being in the inferior frontal cortex (IFC). We also demonstrate that this difference is exaggerated in individuals with ASD, who show an extreme male pattern of IFC function. These results show that males and females differ significantly in social brain function and support the view that sex differences in the social brain contribute to the greater vulnerability of males to ASDs.