Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome.

The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer's disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (mIns). The NA+/mIns co-transporter is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain mIns was previously associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain mIns is increased earlier in development. The aim of this study was to estimate mIns concentration levels and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr)] in the developing brain in DS and aged-matched controls. We used in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n = 12) and age-matched controls (n = 26) scanned just after birth (36-45 weeks postmenstrual age). Moreover, we used Mass Spectrometry in early (10-20 weeks post conception) ex vivo fetal brain tissue samples from DS (n = 14) and control (n = 30) cases. Relative to [Cho] and [Cr], we report elevated ratios of [mIns] in vivo in the basal ganglia/thalamus, in neonates with DS, when compared to age-matched typically developing controls. Glycine concentration ratios [Gly]/[Cr] and [Cho]/[Cr] also appear elevated. We observed elevated [mIns] in the ex vivo fetal cortical brain tissue in DS compared with controls. In conclusion, a higher level of brain mIns was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.

Precision, Applicability, and Economic Implications: A Comparison of Alternative Biodiversity Offset Indexes.

The rates of ecosystem degradation and biodiversity loss are alarming and current conservation efforts are not sufficient to stop them. The need for new tools is urgent. One approach is biodiversity offsetting: a developer causing habitat degradation provides an improvement in biodiversity so that the lost ecological value is compensated for. Accurate and ecologically meaningful measurement of losses and estimation of gains are essential in reaching the no net loss goal or any other desired outcome of biodiversity offsetting. The chosen calculation method strongly influences biodiversity outcomes. We compare a multiplicative method, which is based on a habitat condition index developed for measuring the state of ecosystems in Finland to two alternative approaches for building a calculation method: an additive function and a simpler matrix tool. We examine the different logic of each method by comparing the resulting trade ratios and examine the costs of offsetting for developers, which allows us to compare the cost-effectiveness of different types of offsets. The results show that the outcomes of the calculation methods differ in many aspects. The matrix approach is not able to consider small changes in the ecological state. The additive method gives always higher biodiversity values compared to the multiplicative method. The multiplicative method tends to require larger trade ratios than the additive method when trade ratios are larger than one. Using scoring intervals instead of using continuous components may increase the difference between the methods. In addition, the calculation methods have differences in dealing with the issue of substitutability.

Reforming a pre-existing biodiversity conservation scheme: Promoting climate co-benefits by a carbon payment.

Protecting forests provides potential synergies for both biodiversity conservation and climate change mitigation. Payments for ecosystem services (PES) schemes are commonly used to promote biodiversity conservation in private forests, and including carbon as another target may be a cost-efficient way to promote both goals. We analyse a hypothetical reform on a forest biodiversity PES scheme by supplementing it with a carbon payment paid to landowners for also providing carbon benefits. With a site selection model, we examine how the proposed scheme could promote biodiversity and carbon values, and what level of the carbon payment would provide the highest synergy gains. We found that introducing the payment promotes both targets, but there is a temporal trade-off between selecting sites with high carbon storage or sites with good sequestration potential. The highest synergy gains are obtained in most cases by a second-best payment level of 10-20 € tCO2-1.

Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment.

Down Syndrome (DS) is the most frequent genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. At present, the relationship between structural brain morphology and the spectrum of cognitive phenotypes in DS, is not well understood. This study aimed to quantify the development of the fetal and neonatal brain in DS participants, with and without a congenital cardiac defect compared with a control population using dedicated, optimised and motion-corrected in vivo magnetic resonance imaging (MRI). We detected deviations in development and altered regional brain growth in the fetus with DS from 21 weeks' gestation, when compared to age-matched controls. Reduced cerebellar volume was apparent in the second trimester with significant alteration in cortical growth becoming evident during the third trimester. Developmental abnormalities in the cortex and cerebellum are likely substrates for later neurocognitive impairment, and ongoing studies will allow us to confirm the role of antenatal MRI as an early biomarker for subsequent cognitive ability in DS. In the era of rapidly developing technologies, we believe that the results of this study will assist counselling for prospective parents.

Emerging functional connectivity differences in newborn infants vulnerable to autism spectrum disorders.

Studies in animal models of autism spectrum disorders (ASD) suggest atypical early neural activity is a core vulnerability mechanism which alters functional connectivity and predisposes to dysmaturation of neural circuits. However, underlying biological changes associated to ASD in humans remain unclear. Results from functional connectivity studies of individuals diagnosed with ASD are highly heterogeneous, in part because of complex life-long secondary and/or compensatory events. To minimize these confounds and examine primary vulnerability mechanisms, we need to investigate very early brain development. Here, we tested the hypothesis that brain functional connectivity is altered in neonates who are vulnerable to this condition due to a family history of ASD. We acquired high temporal resolution multiband resting state functional magnetic resonance imaging (fMRI) in newborn infants with and without a first-degree relative with ASD. Differences in local functional connectivity were quantified using regional homogeneity (ReHo) analysis and long-range connectivity was assessed using distance correlation analysis. Neonates who have a first-degree relative with ASD had significantly higher ReHo within multiple resting state networks in comparison to age matched controls; there were no differences in long range connectivity. Atypical local functional activity may constitute a biomarker of vulnerability, that might precede disruptions in long range connectivity reported in older individuals diagnosed with ASD.

Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder.

Importance: What is inherited or acquired in neurodevelopmental conditions such as autism spectrum disorder (ASD) is not a fixed outcome, but instead is a vulnerability to a spectrum of traits, especially social difficulties. Identifying the biological mechanisms associated with vulnerability requires looking as early in life as possible, before the brain is shaped by postnatal mechanisms and/or the experiences of living with these traits. Animal studies suggest that susceptibility to neurodevelopmental disorders arises when genetic and/or environmental risks for these conditions alter patterns of synchronous brain activity in the perinatal period, but this has never been examined in human neonates. Objective: To assess whether alternation of functional maturation of social brain circuits is associated with a family history of ASD in newborns. Design, Setting, and Participants: In this cohort study of 36 neonates with and without a family history of ASD, neonates underwent magnetic resonance imaging at St Thomas Hospital in London, England, using a dedicated neonatal brain imaging system between June 23, 2015, and August 1, 2018. Neonates with a first-degree relative with ASD (R+) and therefore vulnerable to autistic traits and neonates without a family history (R-) were recruited for the study. Synchronous neural activity in brain regions linked to social function was compared. Main Outcomes and Measures: Regions responsible for social function were selected with reference to a published meta-analysis and the level of synchronous activity within each region was used as a measure of local functional connectivity in a regional homogeneity analysis. Group differences, controlling for sex, age at birth, age at scan, and group × age interactions, were examined. Results: The final data set consisted of 18 R+ infants (13 male; median [range] postmenstrual age at scan, 42.93 [40.00-44.86] weeks) and 18 R- infants (13 male; median [range] postmenstrual age at scan, 42.50 [39.29-44.58] weeks). Neonates who were R+ had significantly higher levels of synchronous activity in the right posterior fusiform (t = 2.48; P = .04) and left parietal cortices (t = 3.96; P = .04). In addition, there was a significant group × age interaction within the anterior segment of the left insula (t = 3.03; P = .04) and cingulate cortices (right anterior: t = 3.00; P = .03; left anterior: t = 2.81; P = .03; right posterior: t = 2.77; P = .03; left posterior: t = 2.55; P = .03). In R+ infants, levels of synchronous activity decreased over 39 to 45 weeks' postmenstrual age, whereas synchronous activity levels increased in R- infants over the same period. Conclusions and Relevance: Synchronous activity is required during maturation of functionally connected networks. This study found that in newborn humans, having a first-degree relative with ASD was associated with higher levels of local functional connectivity and dysmaturation of interconnected regions responsible for processing higher-order social information.

Father-infant interactions and infant regional brain volumes: A cross-sectional MRI study.

Fathers play a crucial role in their children's socio-emotional and cognitive development. A plausible intermediate phenotype underlying this association is father's impact on infant brain. However, research on the association between paternal caregiving and child brain biology is scarce, particularly during infancy. Thus, we used magnetic resonance imaging (MRI) to investigate the relationship between observed father-infant interactions, specifically paternal sensitivity, and regional brain volumes in a community sample of 3-to-6-month-old infants (N = 28). We controlled for maternal sensitivity and examined the moderating role of infant communication on this relationship. T2-weighted MR images were acquired from infants during natural sleep. Higher levels of paternal sensitivity were associated with smaller cerebellar volumes in infants with high communication levels. In contrast, paternal sensitivity was not associated with subcortical grey matter volumes in the whole sample, and this was similar in infants with both high and low communication levels. This preliminary study provides the first evidence for an association between father-child interactions and variation in infant brain anatomy.