Validation of the Awareness Atlas-a new measure of the manifestation of consciousness.

Consciousness has intrigued philosophers and scholars for millennia and has been the topic of considerable scientific investigation in recent decades. Despite its importance, there is no unifying definition of the term, nor are there widely accepted measures of consciousness. Indeed, it is likely that consciousness-by its very nature-eludes measurement. It is, however, possible to measure how consciousness manifests as a lived experience. Yet here, too, holistic measures are lacking. This investigation describes the development and validation of the Awareness Atlas, a measure of the manifestation of consciousness. The scale was informed by heart-based contemplative practices and the resulting lived experience with a focus on the impacts of manifestation of consciousness on daily life. Four hundred forty-nine individuals from the USA, Canada, India, and Europe participated in psychometric testing of the scale. Exploratory and confirmatory factor analyses were used for validation, demonstrating excellent validity in measuring manifestation of consciousness. The final model fit exceeded all required thresholds, indicating an excellent fitted model with a single dimensionality to measure the manifestation of consciousness comprised of four subscales: Relationship to Others; Listening to the Heart; Connection with Higher Self; and Acceptance and Letting Go. Number of years meditating and practicing Heartfulness meditation were positively related to the total and subscale scores. Test-retest reliability was excellent for the total scale, and good to excellent for the four subscales. Findings demonstrate that the Awareness Atlas is a well-constructed tool that will be useful in examining changes in manifestation of consciousness with various experiences (e.g., meditation, life-altering conditions).

Increased Resting-State Functional Connectivity in Patients With Autoimmune Addison Disease.

CONTEXT: Individuals with autoimmune Addison disease (AAD) take replacement medication for the lack of adrenal-derived glucocorticoid (GC) and mineralocorticoid hormones from diagnosis. The brain is highly sensitive to these hormones, but the consequence of having AAD for brain health has not been widely addressed. OBJECTIVE: The present study compared resting-state functional connectivity (rs-fc) of the brain between individuals with AAD and healthy controls. METHODS: Fifty-seven patients with AAD (33 female) and 69 healthy controls (39 female), aged 19 to 43 years were scanned with 3-T magnetic resonance imaging (MRI). RESULTS: Independent component and subsequent dual regression analyses revealed that individuals with AAD had stronger rs-fc compared to controls in 3 networks: the bilateral orbitofrontal cortex (OFC), the left medial visual and left posterior default mode network. A higher GC replacement dose was associated with stronger rs-fc in a small part of the left OFC in patients. We did not find any clear associations between rs-fc and executive functions or mental fatigue. CONCLUSION: Our results suggest that having AAD affects the baseline functional organization of the brain and that current treatment strategies of AAD may be one risk factor.

An update on the long-term outcomes of prenatal dexamethasone treatment in congenital adrenal hyperplasia.

First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in girls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up research is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DEX may avoid unnecessary treatment and improve treatment safety.

Brain activity during visuospatial working memory in congenital adrenal hyperplasia.

CONTEXT: Patients with congenital adrenal hyperplasia (CAH) require life-long replacement of cortisol. Problems with cognitive function, especially working memory, have previously been identified, but the long-term effects of this disease on brain function are unknown. OBJECTIVE: We investigate brain activity during working memory in CAH compared to controls. DESIGN, SETTING, AND PARTICIPANTS: Twenty-nine individuals with CAH (17 females) and 40 healthy controls (24 females), 16-33 years, from a single research institute, underwent functional magnetic resonance imaging while doing a verbal and visuospatial working memory task. RESULTS: Individuals with CAH responded faster on the verbal task. Although we found no differences in BOLD response over the whole group, there were significant interactions with sex: CAH males had increased activity in the bilateral lateral superior occipital cortex, left supramarginal and angular gyri, left precuneus, left posterior cingulate cortex and bilateral cerebellum during decoding of the visuospatial task, while females showed decreased activity in these regions. CONCLUSIONS: Long-term cortisol imbalances do not seem to have a major impact on the functional brain responses during working memory in CAH. However, activity of the left dorsal visual stream in particular might be affected depending on sex. As the task employed may have been relatively easy, larger studies using more complex tasks are needed to further investigate this.

Brain structure in autoimmune Addison's disease.

Long-term disturbances in cortisol levels might affect brain structure in individuals with autoimmune Addison's disease (AAD). This study investigated gray and white matter brain structure in a cohort of young adults with AAD. T1- and diffusion-weighted images were acquired for 52 individuals with AAD and 70 healthy controls, aged 19-43 years, using magnetic resonance imaging. Groups were compared on cortical thickness, surface area, cortical gray matter volume, subcortical volume (FreeSurfer), and white matter microstructure (FSL tract-based spatial statistics). Individuals with AAD had 4.3% smaller total brain volume. Correcting for head size, we did not find any regional structural differences, apart from reduced volume of the right superior parietal cortex in males with AAD. Within the patient group, a higher glucocorticoid (GC) replacement dose was associated with smaller total brain volume and smaller volume of the left lingual gyrus, left rostral anterior cingulate cortex, and right supramarginal gyrus. With the exception of smaller total brain volume and potential sensitivity of the parietal cortex to GC disturbances in men, brain structure seems relatively unaffected in young adults with AAD. However, the association between GC replacement dose and reduced brain volume may be reason for concern and requires follow-up study.

First Trimester Dexamethasone Treatment Is Not Associated With Alteration in Resting-state Connectivity at Adolescent or Adult Age.

CONTEXT: Prenatal treatment with dexamethasone (DEX) has been used to prevent virilization in females at risk of congenital adrenal hyperplasia (CAH). Both affected and unaffected girls, as well boys, are treated until the genotype and sex of the fetus is known (gestational weeks 10-12). After that, only affected girls are treated until term. Exposure to a high synthetic glucocorticoid dosage may alter the developmental trajectory of the brain, with alterations in resting-state functional connectivity of the brain at adult age. OBJECTIVE: To investigate resting-state functional connectivity in subjects at risk of having CAH, exposed to DEX treatment during the first trimester of fetal life, both in the whole brain and in 3 regions of interest (amygdala, hippocampus, and superior frontal gyrus). DESIGN, SETTING, AND PARTICIPANTS: Eighteen participants (8 females) at risk of having CAH, exposed to DEX treatment, and 38 controls (24 females), age range 16 to 26 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. We used 2 different approaches: an exploratory whole-brain analysis and seed-based analysis. For seed-based analysis, we chose 3 different brain regions (amygdala, hippocampus, and superior frontal gyrus) based on our previous findings and literature evidence. RESULTS: We did not observe any differences in functional connectivity during rest, either in the whole brain nor in seed-based connectivity analyses at this adolescent and young adult age. CONCLUSIONS: Our results are reassuring; however, future studies on larger samples and with more sensitive methodologies are needed to confirm these findings.

Changes in resting-state functional connectivity in patients with congenital adrenal hyperplasia.

CONTEXT: Patients with congenital adrenal hyperplasia (CAH) are treated with life-long glucocorticoid (GC) replacement therapy. Negative effects on cognition, brain structure and function during working memory tasks have been identified. To date, no studies on functional connectivity during rest have been performed in patients with CAH. OBJECTIVE: To investigate resting-state functional connectivity in patients with CAH compared with healthy untreated controls and the association between functional connectivity in the precuneus and disease severity, dose of GC and working memory (WM). DESIGN, SETTING AND PARTICIPANTS: Thirty-one patients with CAH (18 females) and 38 healthy controls (24 females), aged 16-33 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. RESULTS: Patients with CAH showed increased functional connectivity in the precuneus compared with controls. Post-hoc tests within the precuneus showed that only patients with simple virilising CAH had stronger connectivity compared to controls. Further, while both patients with salt-wasting and simple virilising CAH performed worse on a WM task compared to controls, functional connectivity in the precuneus was not associated with executive function performance. CONCLUSION: Patients with CAH demonstrated altered functional connectivity during rest in the precuneus. Such a change may reflect a functional reorganisation in response to the CAH disease. The change in functional connectivity may depend on the severity of CAH.

Heartfulness Meditation: A Yogic and Neuroscientific Perspective.

Today, as research into the contemplative sciences is being widely referenced, the research community would benefit from an understanding of the Heartfulness method of meditation. Heartfulness offers an in-depth experiential practice focused on the evolution of human consciousness using the ancient technique of Pranahuti (yogic Transmission) during Meditation, in combination with the more active mental practice of "Cleaning." Both are enabled by initiation into the Heartfulness practices. These unique features distinguish Heartfulness from other paths that have been described in the scientific literature thus far. In this introductory paper, we present the Heartfulness practices, the philosophy upon which the practices are based, and we reflect on the putative mechanisms through which Heartfulness could exert its effects on the human body and mind in the light of scientific research that has been done in other meditation systems. We conclude with suggestions for future research on the Heartfulness way of meditation.

Young adult Swedish patients with autoimmune Addison's disease report difficulties with executive functions in daily life despite overall good cognitive performance.

OBJECTIVES: Sub-optimal replacement of glucocorticoids (GC) in autoimmune Addison's disease (AAD) may affect cognitive functioning. The present study therefore sought to investigate cognitive performance and self-reported problems with executive functions in a cohort of young adult patients with AAD. DESIGN AND METHODS: 67 patients with AAD (39 females), mean age 32 yrs. (range 19-41), and 80 control participants (43 females), mean age 29 yrs. (range 19-43), completed neuropsychological tests estimating verbal and non-verbal intellectual ability, learning, memory and executive functioning, in addition to self-report scales assessing problems with executive functions, fatigue and symptoms of anxiety and depression. RESULTS: Patients performed within the average range on all cognitive tests compared to population norms. However, female AAD patients reported more problems than controls with both hot (emotion regulation) and cold (cognitive regulation) executive functions in daily life. Moreover, experienced problems with executive functions in both male and female patients were associated with increased mental fatigue and lower GC replacement doses. CONCLUSIONS: Despite average performance in neuropsychological tests by both sexes, young adult female patients with AAD experience problems with executive functions in daily life. Coping with mental fatigue and optimization of pharmacotherapy may be important factors to be addressed in order to provide timely support for patients. Future research is needed to further determine other risk factors for experiencing executive function impairments in AAD.

First Trimester DEX Treatment Is Not Associated with Altered Brain Activity During Working Memory Performance in Adults.

CONTEXT: Prenatal dexamethasone (DEX) treatment is sometimes used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in female fetuses with CAH. In boys and in fetuses not having CAH, there is no benefit of early DEX treatment and the risks of this therapy must be thoroughly investigated. High doses of prenatal glucocorticoid might alter the developmental trajectory of the brain into adulthood, even for CAH unaffected subjects treated with DEX for a short term during the first trimester. OBJECTIVE: The present study investigated brain activation during working memory performance in DEX-treated subjects compared with controls. DESIGN, SETTING, AND PARTICIPANTS: We tested 18 participants who were exposed to DEX during the first trimester of fetal life but did not have CAH (8 females; mean age 20.78 [standard deviation (SD), 2.67] years) and 40 control participants (24 females; mean age 20.53 [SD, 2.64]) from a single research institute. Participants underwent functional magnetic resonance imaging on a 3T scanner during a verbal and visuospatial working memory task. RESULTS: We did not observe any differences in brain activity during working memory performance. However, DEX-treated subjects responded faster during the experimental condition of the verbal WM task. CONCLUSIONS: First trimester DEX treatment did not seem to result in altered working memory-related brain activity at adult age. Our findings contribute to the risk-benefit assessment of prenatal DEX treatment in the context of CAH.

First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age.

CONTEXT: Prenatal treatment of human disease is rare. Dexamethasone (DEX) is used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in an affected female fetus. The safety and long-term consequences of prenatal DEX exposure on the brain are largely unknown. OBJECTIVE: We investigate whether first-trimester prenatal DEX treatment is associated with alterations in brain structure at adult age, and if these alterations are associated with DNA methylation, mood, and cognitive abilities. DESIGN, SETTING, AND PARTICIPANTS: T1-weighted and diffusion-weighted imaging scans, from a single research institute, are compared between 19 (9 women) first-trimester DEX-treated individuals, at risk of CAH but not having CAH, and 43 (26 women) controls (age range, 16.0-26.4 years). RESULTS: DEX-treated participants showed bilateral enlargement of the amygdala, increased surface area and volume of the left superior frontal gyrus, and widespread increased radial, mean, and axial diffusivity of white matter, in particular in the superior longitudinal fasciculi and corticospinal tracts. In the DEX-treated group, increased mean and radial diffusivity correlated with increased methylation of the promotor region of the FKBP5 gene. There were no group differences in cognition or in scales assessing depression or anxiety, and the relationship between brain structure and cognition did not differ between DEX-treated and controls. CONCLUSIONS: First-trimester prenatal DEX treatment is associated with structural alterations of the brain at adult age, with an accompanying change in gene methylation. The findings add to the safety concerns of prenatal DEX treatment in the context of CAH.

The social brain in female autism: a structural imaging study of twins.

A female advantage in social cognition (SoC) might contribute to women's underrepresentation in autism spectrum disorder (ASD). The latter could be underpinned by sex differences in social brain structure. This study investigated the relationship between structural social brain networks and SoC in females and males in relation to ASD and autistic traits in twins. We used a co-twin design in 77 twin pairs (39 female) aged 12.5 to 31.0 years. Twin pairs were discordant or concordant for ASD or autistic traits, discordant or concordant for other neurodevelopmental disorders or concordant for neurotypical development. They underwent structural magnetic resonance imaging and were assessed for SoC using the naturalistic Movie for the Assessment of Social Cognition. Autistic traits predicted reduced SoC capacities predominantly in male twins, despite a comparable extent of autistic traits in each sex, although the association between SoC and autistic traits did not differ significantly between the sexes. Consistently, within-pair associations between SoC and social brain structure revealed that lower SoC ability was associated with increased cortical thickness of several brain regions, particularly in males. Our findings confirm the notion that sex differences in SoC in association with ASD are underpinned by sex differences in brain structure.

Sex differences in brain structure: a twin study on restricted and repetitive behaviors in twin pairs with and without autism.

Background: Females with autism spectrum disorder have been reported to exhibit fewer and less severe restricted and repetitive behaviors and interests compared to males. This difference might indicate sex-specific alterations of brain networks involved in autism symptom domains, especially within cortico-striatal and sensory integration networks. This study used a well-controlled twin design to examine sex differences in brain anatomy in relation to repetitive behaviors. Methods: In 75 twin pairs (n = 150, 62 females, 88 males) enriched for autism spectrum disorder (n = 32), and other neurodevelopmental disorders (n = 32), we explored the association of restricted and repetitive behaviors and interests-operationalized by the Autism Diagnostic Interview-Revised (C domain) and the Social Responsiveness Scale-2 (Restricted Interests and Repetitive Behavior subscale)-with cortical volume, surface area and thickness of neocortical, sub-cortical, and cerebellar networks. Results: Co-twin control analyses revealed within-pair associations between RRBI symptoms and increased thickness of the right intraparietal sulcus and reduced volume of the right orbital gyrus in females only, even though the mean number of RRBIs did not differ between the sexes. In a sub-sample of ASD-discordant pairs, increased thickness in association with RRBIs was found exclusively in females in the orbitofrontal regions, superior frontal gyrus, and intraparietal sulcus, while in males RRBIs tended to be associated with increased volume of the bilateral pallidum. Limitations: However, due to a small sample size and the small difference in RRBI symptoms within pairs, the results of this exploratory study need to be interpreted with caution. Conclusions: Our findings suggest that structural alterations of fronto-parietal networks in association with RRBIs are found mostly in females, while striatal networks are more affected in males. These results endorse the importance of investigating sex differences in the neurobiology of autism symptoms, and indicate different etiological pathways underlying restricted and repetitive behaviors and interests in females and males.

Altered Gray Matter Structure and White Matter Microstructure in Patients with Congenital Adrenal Hyperplasia: Relevance for Working Memory Performance.

Congenital adrenal hyperplasia (CAH) has been associated with brain structure alterations, but systematic studies are lacking. We explore brain morphology in 37 (21 female) CAH patients and 43 (26 female) healthy controls, aged 16-33 years, using structural magnetic resonance imaging to estimate cortical thickness, surface area, volume, subcortical volumes, and white matter (WM) microstructure. We also report data on a small cohort of patients (n = 8) with CAH, who received prenatal dexamethasone (DEX). Patients with CAH had reduced whole brain volume (4.23%) and altered structure of the prefrontal, parietal, and superior occipital cortex. Patients had reduced mean FA, and reduced RD and MD, but not after correcting for brain volume. The observed regions are hubs of the visuospatial working memory and default mode (DMN) networks. Thickness of the left superior parietal and middle frontal gyri was associated with visuospatial working memory performance, and patients with CAH performed worse on this task. Prenatal treatment with DEX affected brain structures in the parietal and occipital cortex, but studies in larger cohorts are needed. In conclusion, our study suggests that CAH is associated with brain structure alterations, especially in the working memory network, which might underlie the cognitive outcome observed in patients.

Sex Differences Along the Autism Continuum: A Twin Study of Brain Structure.

Females might possess protective mechanisms regarding autism spectrum disorder (ASD) and require a higher detrimental load, including structural brain alterations, before developing clinically relevant levels of autistic traits. This study examines sex differences in structural brain morphology in autism and autistic traits using a within-twin pair approach. Twin design inherently controls for shared confounders and enables the study of gene-independent neuroanatomical variation. N = 148 twins (62 females) from 49 monozygotic and 25 dizygotic same-sex pairs were included. Participants were distributed along the whole continuum of autism including twin pairs discordant and concordant for clinical ASD. Regional brain volume, surface area, and cortical thickness were computed. Within-twin pair increases in autistic traits were related to decreases in cortical volume and surface area of temporal and frontal regions specifically in female twin pairs, in particular regions involved in social communication, while only two regions were associated with autistic traits in males. The same pattern was detected in the monozygotic twin pairs only. Thus, non-shared environmental factors seem to impact female more than male cerebral architecture associated with autistic traits. Our results are in line with the hypothesis of a female protective effect in autism and highlights the need to study ASD in females separately from males.

2D:4D Ratio in Neurodevelopmental Disorders: A Twin Study.

The second to fourth digit (2D:4D) ratio is of interest in autism spectrum disorder (ASD). Studies on the relationship of this ratio with other neurodevelopmental disorders (NDDs) are lacking. Investigating the association between the ratio and NDDs in twins can provide insight into genetic and/or environmental factors driving the ratio. Hand images were collected in N = 238 twins with NDDs or typical development from 70 monozygotic and 49 dizygotic pairs to examine ratios and their associations to DSM-5 defined categorical NDDs, autistic traits, zygosity, and sex. There were small associations for males between the ratios and any NDD and ADHD diagnoses. Males had lower ratios than females. Future studies exploring the ratio alongside physical anomalies could provide etiological insight into NDDs.