Learning the Vector Coding of Egocentric Boundary Cells from Visual Data.

The use of spatial maps to navigate through the world requires a complex ongoing transformation of egocentric views of the environment into position within the allocentric map. Recent research has discovered neurons in retrosplenial cortex and other structures that could mediate the transformation from egocentric views to allocentric views. These egocentric boundary cells respond to the egocentric direction and distance of barriers relative to an animal's point of view. This egocentric coding based on the visual features of barriers would seem to require complex dynamics of cortical interactions. However, computational models presented here show that egocentric boundary cells can be generated with a remarkably simple synaptic learning rule that forms a sparse representation of visual input as an animal explores the environment. Simulation of this simple sparse synaptic modification generates a population of egocentric boundary cells with distributions of direction and distance coding that strikingly resemble those observed within the retrosplenial cortex. Furthermore, some egocentric boundary cells learnt by the model can still function in new environments without retraining. This provides a framework for understanding the properties of neuronal populations in the retrosplenial cortex that may be essential for interfacing egocentric sensory information with allocentric spatial maps of the world formed by neurons in downstream areas, including the grid cells in entorhinal cortex and place cells in the hippocampus.SIGNIFICANCE STATEMENT The computational model presented here demonstrates that the recently discovered egocentric boundary cells in retrosplenial cortex can be generated with a remarkably simple synaptic learning rule that forms a sparse representation of visual input as an animal explores the environment. Additionally, our model generates a population of egocentric boundary cells with distributions of direction and distance coding that strikingly resemble those observed within the retrosplenial cortex. This transformation between sensory input and egocentric representation in the navigational system could have implications for the way in which egocentric and allocentric representations interface in other brain areas.

Multi-shell connectome DWI-based graph theory measures for the prediction of temporal lobe epilepsy and cognition.

Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome that empirically represents a network disorder, which makes graph theory (GT) a practical approach to understand it. Multi-shell diffusion-weighted imaging (DWI) was obtained from 89 TLE and 50 controls. GT measures extracted from harmonized DWI matrices were used as factors in a support vector machine (SVM) analysis to discriminate between groups, and in a k-means algorithm to find intrinsic structural phenotypes within TLE. SVM was able to predict group membership (mean accuracy = 0.70, area under the curve (AUC) = 0.747, Brier score (BS) = 0.264) using 10-fold cross-validation. In addition, k-means clustering identified 2 TLE clusters: 1 similar to controls, and 1 dissimilar. Clusters were significantly different in their distribution of cognitive phenotypes, with the Dissimilar cluster containing the majority of TLE with cognitive impairment (χ2 = 6.641, P = 0.036). In addition, cluster membership showed significant correlations between GT measures and clinical variables. Given that SVM classification seemed driven by the Dissimilar cluster, SVM analysis was repeated to classify Dissimilar versus Similar + Controls with a mean accuracy of 0.91 (AUC = 0.957, BS = 0.189). Altogether, the pattern of results shows that GT measures based on connectome DWI could be significant factors in the search for clinical and neurobehavioral biomarkers in TLE.

Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.

How we get a grip: Microstructural neural correlates of manual grip strength in children.

Maximal grip strength is associated with a variety of health-related outcome measures and thus may be reflective of the efficiency of foundational brain-body communication. Non-human primate models of grip strength strongly implicate the cortical lateral grasping network, but little is known about the translatability of these models to human children. Further, it is unclear how supplementary networks that provide proprioceptive information and cerebellar-based motor command modification are associated with maximal grip strength. Therefore, this study employed high resolution, multi-shell diffusion and quantitative T1 imaging to examine how variations in lateral grasping, proprioception input, and cortico-cerebellar modification network white matter microstructure are associated with variations in grip strength across 70 children. Results indicated that stronger grip strength was associated with higher lateral grasping and proprioception input network fractional anisotropy and R1, indirect measures consistent with stronger microstructural coherence and increased myelination. No relationships were found in the cerebellar modification network. These results provide a neurobiological mechanism of grip behavior in children which suggests that increased myelination of cortical sensory and motor pathways is associated with stronger grip. This neurobiological mechanism may be a signature of pediatric neuro-motor behavior more broadly as evidenced by the previously demonstrated relationships between grip strength and behavioral outcome measures across a variety of clinical and non-clinical populations.

Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Gated transformations from egocentric to allocentric reference frames involving retrosplenial cortex, entorhinal cortex, and hippocampus.

This paper reviews the recent experimental finding that neurons in behaving rodents show egocentric coding of the environment in a number of structures associated with the hippocampus. Many animals generating behavior on the basis of sensory input must deal with the transformation of coordinates from the egocentric position of sensory input relative to the animal, into an allocentric framework concerning the position of multiple goals and objects relative to each other in the environment. Neurons in retrosplenial cortex show egocentric coding of the position of boundaries in relation to an animal. These neuronal responses are discussed in relation to existing models of the transformation from egocentric to allocentric coordinates using gain fields and a new model proposing transformations of phase coding that differ from current models. The same type of transformations could allow hierarchical representations of complex scenes. The responses in rodents are also discussed in comparison to work on coordinate transformations in humans and non-human primates.

Association of neighborhood deprivation with white matter connectome abnormalities in temporal lobe epilepsy.

OBJECTIVE: Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census-based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. METHODS: Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI-defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion-weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold-free network-based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross-sectional area (CSA) indicates reduced white matter integrity. RESULTS: Sex- and age-adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network-based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. SIGNIFICANCE: Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage-brain integrity relationship may serve to inform care, management, and policy for patients.

White matter microstructure predicts individual differences in infant fear (But not anger and sadness).

We examine neural correlates of discrete expressions of negative emotionality in infants to determine whether the microstructure of white matter tracts at 1 month of age foreshadows the expression of specific negative emotions later in infancy. Infants (n = 103) underwent neuroimaging at 1-month, and mothers reported on infant fear, sadness, and anger at 6, 12, and 18 months using the Infant Behavior Questionnaire-Revised. Levels and developmental change in fear, sadness, and anger were estimated from mother reports. Relations between MRI and infant emotion indicated that 1-month white matter microstructure was differentially associated with level and change in infant fear, but not anger or sadness, in the left stria terminalis (p < 0.05, corrected), a tract that connects frontal and tempo-parietal regions and has been implicated in emerging psychopathology in adults. More relaxed constraints on significance (p < 0.10, corrected) revealed that fear was associated with lower white matter microstructure bilaterally in the inferior portion of the stria terminalis and regions within the sagittal stratum. Results suggest the neurobehavioral uniqueness of fear as early as 1 month of age in regions that are associated with potential longer-term outcomes. This work highlights the early neural precursors of fearfulness, adding to literature explaining the psychobiological accounts of affective development. HIGHLIGHTS: Expressions of infant fear and anger, but not sadness, increase from 6 to 18 months of age. Early neural architecture in the stria terminalis is related to higher initial levels and increasing fear in infancy. After accounting for fear, anger and sadness do not appear to be associated with differences in early white matter microstructure. This work identifies early neural precursors of fearfulness as early as 1-month of age.

Effects of anesthesia exposure on postnatal maturation of white matter in rhesus monkeys.

There is increasing concern about the potential effects of anesthesia exposure on the developing brain. The effects of relatively brief anesthesia exposures used repeatedly to acquire serial magnetic resonance imaging scans could be examined prospectively in rhesus macaques. We analyzed magnetic resonance diffusion tensor imaging (DTI) of 32 rhesus macaques (14 females, 18 males) aged 2 weeks to 36 months to assess postnatal white matter (WM) maturation. We investigated the longitudinal relationships between each DTI property and anesthesia exposure, taking age, sex, and weight of the monkeys into consideration. Quantification of anesthesia exposure was normalized to account for variation in exposures. Segmented linear regression with two knots provided the best model for quantifying WM DTI properties across brain development as well as the summative effect of anesthesia exposure. The resulting model revealed statistically significant age and anesthesia effects in most WM tracts. Our analysis indicated there were major effects on WM associated with low levels of anesthesia even when repeated as few as three times. Fractional anisotropy values were reduced across several WM tracts in the brain, indicating that anesthesia exposure may delay WM maturation, and highlight the potential clinical concerns with even a few exposures in young children.

Longitudinal assessment of early-life white matter development with quantitative relaxometry in nonhuman primates.

Alterations in white matter (WM) development are associated with many neuropsychiatric and neurodevelopmental disorders. Most MRI studies examining WM development employ diffusion tensor imaging (DTI), which relies on estimating diffusion patterns of water molecules as a reflection of WM microstructure. Quantitative relaxometry, an alternative method for characterizing WM microstructural changes, is based on molecular interactions associated with the magnetic relaxation of protons. In a longitudinal study of 34 infant non-human primates (NHP) (Macaca mulatta) across the first year of life, we implement a novel, high-resolution, T1-weighted MPnRAGE sequence to examine WM trajectories of the longitudinal relaxation rate (qR1) in relation to DTI metrics and gestational age at scan. To the best of our knowledge, this is the first study to assess developmental WM trajectories in NHPs using quantitative relaxometry and the first to directly compare DTI and relaxometry metrics during infancy. We demonstrate that qR1 exhibits robust logarithmic growth, unfolding in a posterior-anterior and medial-lateral fashion, similar to DTI metrics. On a within-subject level, DTI metrics and qR1 are highly correlated, but are largely unrelated on a between-subject level. Unlike DTI metrics, gestational age at birth (time in utero) is a strong predictor of early postnatal qR1 levels. Whereas individual differences in DTI metrics are maintained across the first year of life, this is not the case for qR1. These results point to the similarities and differences in using quantitative relaxometry and DTI in developmental studies, providing a basis for future studies to characterize the unique processes that these measures reflect at the cellular and molecular level.

Mahalanobis distance tractometry (MaD-Tract) - a framework for personalized white matter anomaly detection applied to TBI.

Imaging-based quantitative measures from diffusion-weighted MRI (dMRI) offer the ability to non-invasively extract microscopic information from human brain tissues. Group-level comparisons of such measures represent an important approach to investigate abnormal brain conditions. These types of analyses are especially useful when the regions of abnormality spatially coincide across subjects. When this is not true, approaches for individualized analyses are necessary. Here we present a framework for single-subject multidimensional analysis based on the Mahalanobis distance. This is conducted along specific white matter pathways represented by tractography-derived streamline bundles. A definition for abnormality was constructed from Wilk's criterion, which accounts for normative sample size, number of features used in the Mahalanobis distance, and multiple comparisons. One example of a condition exhibiting high heterogeneity across subjects is traumatic brain injury (TBI). Using the Mahalanobis distance computed from the three eigenvalues of the diffusion tensor along the cingulum, uncinate, and parcellated corpus callosum tractograms, 8 severe TBI patients were individually compared to a normative sample of 49 healthy controls. For all TBI patients, the analyses showed statistically significant deviations from the normative data at one or multiple locations along the analyzed bundles. The detected anomalies were widespread across the analyzed tracts, consistent with the expected heterogeneity that is hallmark of TBI. Each of the controls subjects was also compared to the remaining 48 subjects in the control group in a leave-one-out fashion. Only two segments were identified as abnormal out of the entire analysis in the control group, thus the method also demonstrated good specificity.

Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

The acute effects of passive heating on endothelial function, muscle microvascular oxygen delivery, and expression of serum HSP90α.

Passive heating has been a therapeutic tool used to elevate core temperature and induce increases in cardiac output, blood flow, and shear stress. We aimed to determine the effects of a single bout of passive heating on endothelial function and serum heat shock protein 90α (HSP90α) levels in young, healthy subjects. 8 healthy subjects were recruited to participate in one bout of whole-body passive heating via immersion in a 40 °C hot tub to maintain a 1 °C increase in rectal temperature for 60 min. Twenty-four hours after heating, shear-rate corrected endothelium-dependent dilation increased (pre: 0.004 ± 0.002%SRAUC; post: 0.006 ± 0.003%SRAUC; p = 0.034) but serum [HSP90α] was not changed (pre: 36.7 ± 10.3 ng/mL; post: 40.6 ± 15.9 ng/mL; p = 0.39). Neither resting muscle O2 utilization (pre: 0.17 ± 0.11 mL O2 min-1 (100 g)-1; post: 0.14 ± 0.09 mL O2 min-1 (100 g)-1); p = 0.28) nor mean arterial pressure (pre: 74 ± 11 mmHg; post: 73 ± 11 mmHg; p = 0.79) were influenced by the heating intervention. Finally, time to peak after cuff release was significantly delayed for % O2 sat (TTPpre = 39 ± 8.9 s and TTPpost = 43.5 ± 8.2 s; p = 0.007) and deoxy-[heme] (TTPpre = 41.3 ± 18.1 s and TTPpost = 51.4 ± 16.3 s; p = 0.018), with no effect on oxy-[heme] (p = 0.19) and total-[heme] (p = 0.41). One bout of passive heating improved endothelium-dependent dilation 24 h later in young, healthy subjects. This data suggests that passive heat treatments may provide a simple intervention for improving vascular health.

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults.

INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aß)42 /Aß40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aß42 /Aß40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.

Sport-Related Concussion Preceding Adrenal Insufficiency and Hypopituitarism.

ABSTRACT: A 49-year-old woman with a history of daily inhaled corticosteroid use for asthma presented to a concussion clinic 7 wk after sport-related head injury with headache, visual blurring, dizziness, nausea, fatigue, polydipsia, and polyuria. Examination revealed difficulty with vestibulo-occulomotor testing due to nausea and visual straining. Cranial CT/MR imaging was unremarkable. Laboratory testing revealed critically low serum cortisol, hypernatremia, and urine studies suggesting diabetes insipidus. The patient was referred to the emergency department. Intravenous fluid resuscitation, corticosteroids, and desmopressin led to significant symptomatic relief. She was maintained on oral hydrocortisone after cosyntropin test revealed adrenal insufficiency. Her clinical picture suggested chronic subclinical adrenal suppression from inhaled corticosteroids, which was exacerbated by hypopituitarism possibly from concussion combined with diabetes insipidus. Adrenal insufficiency should be considered in athletes with history of corticosteroid use and endocrine-related symptoms after concussion, because this can create significant morbidity and can mimic traditional symptoms of concussion.

FreeSurfer based cortical mapping and T1-relaxometry with MPnRAGE: Test-retest reliability with and without retrospective motion correction.

A test-retest study of FreeSurfer derived cortical thickness, cortical surface area, and cortical volume, as well as quantitative R1 relaxometry assessed on the midpoint of the cortex, was performed on a cohort of pediatric subjects (6-12 years old) scanned without sedation using SNARE-MPnRAGE (self navigated retrospective motion corrected magnetization prepared with n rapid gradient echoes) imaging. Reliability was assessed with coefficients of variation (CoVs) and intraclass correlation coefficients (ICCs) and statistical tests were used to determine differences with and without SNARE motion correction. Comparison of the test-retest measures of SNARE-MPnRAGE with prospectively motion corrected PROMO MPRAGE were also performed. When SNARE motion correction was used all parameters had statistically significant improvements and demonstrated high reliability. Reliability varied depending on parameter, region, and measurement type (vertex or region of interest). For mean thickness/surface area/volume/mean R1 across the regions of FreeSurfer's DK Atlas, the mean CoVs (% x100) were (1.2/1.6/1.9/0.9) and the mean ICCs were (0.88/0.96/0.94/0.83). When assessed on a per-vertex basis, the CoVs and ICCs for thickness/R1 had mean values of (2.9/1.9) and (0.82/0.68) across the regions of the DK Atlas. Retrospectively motion corrected MPnRAGE had significantly lower CoVs and higher ICCs for the morphological measures than PROMO MPRAGE. Motion correction effectively removed motion related biases in nearly all regions for R1 and morphometric measures.

Evidence for normal extra-axial cerebrospinal fluid volume in autistic males from middle childhood to adulthood.

Autism spectrum disorder has long been associated with a variety of organizational and developmental abnormalities in the brain. An increase in extra-axial cerebrospinal fluid volume in autistic individuals between the ages of 6 months and 4 years has been reported in recent studies. Increased extra-axial cerebrospinal fluid volume was predictive of the diagnosis and severity of the autistic symptoms in all of them, irrespective of genetic risk for developing the disorder. In the present study, we explored the trajectory of extra-axial cerebrospinal fluid volume from childhood to adulthood in both autism and typical development. We hypothesized that an elevated extra-axial cerebrospinal fluid volume would be found in autism persisting throughout the age range studied. We tested the hypothesis by employing an accelerated, multi-cohort longitudinal data set of 189 individuals (97 autistic, 92 typically developing). Each individual had been scanned between 1 and 5 times, with scanning sessions separated by 2-3 years, for a total of 439 T1-weighted MRI scans. A linear mixed-effects model was used to compare developmental, age-related changes in extra-axial cerebrospinal fluid volume between groups. Inconsistent with our hypothesis, we found no group differences in extra-axial cerebrospinal fluid volume in this cohort of individuals 3 to 42 years of age. Our results suggest that extra-axial cerebrospinal fluid volume in autistic individuals is not increased compared with controls beyond four years of age.

A 16-year study of longitudinal volumetric brain development in males with autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown brain etiology. Our knowledge to date about structural brain development across the lifespan in ASD comes mainly from cross-sectional studies, thereby limiting our understanding of true age effects within individuals with the disorder that can only be gained through longitudinal research. The present study describes FreeSurfer-derived volumetric findings from a longitudinal dataset consisting of 607 T1-weighted magnetic resonance imaging (MRI) scans collected from 105 male individuals with ASD (349 MRIs) and 125 typically developing male controls (258 MRIs). Participants were six to forty-five years of age at their first scan, and were scanned up to 5 times over a period of 16 years (average inter-scan interval of 3.7 years). Atypical age-related volumetric trajectories in ASD included enlarged gray matter volume in early childhood that approached levels of the control group by late childhood, an age-related increase in ventricle volume resulting in enlarged ventricles by early adulthood and reduced corpus callosum age-related volumetric increase resulting in smaller corpus callosum volume in adulthood. Larger corpus callosum volume was related to a lower (better) ADOS score at the most recent study visit for the participants with ASD. These longitudinal findings expand our knowledge of volumetric brain-based abnormalities in males with ASD, and highlight the need to continue to examine brain structure across the lifespan and well into adulthood.

Genomic evidence of introgression and adaptation in a model subtropical tree species, Eucalyptus grandis.

The genetic consequences of adaptation to changing environments can be deciphered using population genomics, which may help predict species' responses to global climate change. Towards this, we used genome-wide SNP marker analysis to determine population structure and patterns of genetic differentiation in terms of neutral and adaptive genetic variation in the natural range of Eucalyptus grandis, a widely cultivated subtropical and temperate species, serving as genomic reference for the genus. We analysed introgression patterns at subchromosomal resolution using a modified ancestry mapping approach and identified provenances with extensive interspecific introgression in response to increased aridity. Furthermore, we describe potentially adaptive genetic variation as explained by environment-associated SNP markers, which also led to the discovery of what is likely a large structural variant. Finally, we show that genes linked to these markers are enriched for biotic and abiotic stress responses.

General anaesthesia during infancy reduces white matter micro-organisation in developing rhesus monkeys.

BACKGROUND: Non-human primates are commonly used in neuroimaging research for which general anaesthesia or sedation is typically required for data acquisition. In this analysis, the cumulative effects of exposure to ketamine, Telazol® (tiletamine and zolazepam), and the inhaled anaesthetic isoflurane on early brain development were evaluated in two independent cohorts of typically developing rhesus macaques. METHODS: Diffusion MRI scans were analysed from 43 rhesus macaques (20 females and 23 males) at either 12 or 18 months of age from two separate primate colonies. RESULTS: Significant, widespread reductions in fractional anisotropy with corresponding increased axial, mean, and radial diffusivity were observed across the brain as a result of repeated anaesthesia exposures. These effects were dose dependent and remained after accounting for age and sex at time of exposure in a generalised linear model. Decreases of up to 40% in fractional anisotropy were detected in some brain regions. CONCLUSIONS: Multiple exposures to commonly used anaesthetics were associated with marked changes in white matter microstructure. This study is amongst the first to examine clinically relevant anaesthesia exposures on the developing primate brain. It will be important to examine if, or to what degree, the maturing brain can recover from these white matter changes.