Does empathy predict altruism in the wild?

Why do people act altruistically? One theory is that empathy is a driver of morality. Experimental studies of this are often confined to laboratory settings, which often lack ecological validity. In the present study we investigated whether empathy traits predict if people will act altruistically in a real-world setting, "in the wild". We staged a situation in public that was designed to elicit helping, and subsequently measured empathic traits in those who either stopped to help or walked past and did not help. Results show that a higher number of empathic traits are a significant and positive predictor for altruistic behavior in a real-life situation. This supports the theory that the act of doing good is correlated with empathy.This work was supported by the Autism Research Trust and the Medical Research Council; Pinsent Darwin Trust, Medical Research Council and Cambridge Trust; National Institute for Health Research

Atypical Integration of Sensory-to-Transmodal Functional Systems Mediates Symptom Severity in Autism.

A notable characteristic of autism spectrum disorder (ASD) is co-occurring deficits in low-level sensory processing and high-order social interaction. While there is evidence indicating detrimental cascading effects of sensory anomalies on the high-order cognitive functions in ASD, the exact pathological mechanism underlying their atypical functional interaction across the cortical hierarchy has not been systematically investigated. To address this gap, here we assessed the functional organisation of sensory and motor areas in ASD, and their relationship with subcortical and high-order trandmodal systems. In a resting-state fMRI data of 107 ASD and 113 neurotypical individuals, we applied advanced connectopic mapping to probe functional organization of primary sensory/motor areas, together with targeted seed-based intrinsic functional connectivity (iFC) analyses. In ASD, the connectopic mapping revealed topological anomalies (i.e., excessively more segregated iFC) in the motor and visual areas, the former of which patterns showed association with the symptom severity of restricted and repetitive behaviors. Moreover, the seed-based analysis found diverging patterns of ASD-related connectopathies: decreased iFCs within the sensory/motor areas but increased iFCs between sensory and subcortical structures. While decreased iFCs were also found within the higher-order functional systems, the overall proportion of this anomaly tends to increase along the level of cortical hierarchy, suggesting more dysconnectivity in the higher-order functional networks. Finally, we demonstrated that the association between low-level sensory/motor iFCs and clinical symptoms in ASD was mediated by the high-order transmodal systems, suggesting pathogenic functional interactions along the cortical hierarchy. Findings were largely replicated in the independent dataset. These results highlight that atypical integration of sensory-to-high-order systems contributes to the complex ASD symptomatology

Grey and white matter microstructure is associated with polygenic risk for schizophrenia.

Funder: E.-M.S is supported by a PhD studentship awarded by the Friends of Peterhouse.Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Recent discovery of approximately 270 common genetic variants associated with schizophrenia has enabled polygenic risk scores (PRS) to be measured in the population. We hypothesized that normal variation in PRS would be associated with magnetic resonance imaging (MRI) phenotypes of brain morphometry and tissue composition. We used the largest extant genome-wide association dataset (N = 69,369 cases and N = 236,642 healthy controls) to measure PRS for schizophrenia in a large sample of adults from the UK Biobank (Nmax = 29,878) who had multiple micro- and macrostructural MRI metrics measured at each of 180 cortical areas, seven subcortical structures, and 15 major white matter tracts. Linear mixed-effect models were used to investigate associations between PRS and brain structure at global and regional scales, controlled for multiple comparisons. Polygenic risk was significantly associated with reduced neurite density index (NDI) at global brain scale, at 149 cortical regions, five subcortical structures, and 14 white matter tracts. Other microstructural parameters, e.g., fractional anisotropy, that were correlated with NDI were also significantly associated with PRS. Genetic effects on multiple MRI phenotypes were co-located in temporal, cingulate, and prefrontal cortical areas, insula, and hippocampus. Post-hoc bidirectional Mendelian randomization analyses provided preliminary evidence in support of a causal relationship between (reduced) thalamic NDI and (increased) risk of schizophrenia. Risk-related reduction in NDI is plausibly indicative of reduced density of myelinated axons and dendritic arborization in large-scale cortico-subcortical networks. Cortical, subcortical, and white matter microstructure may be linked to the genetic mechanisms of schizophrenia.E.-M.S is supported by a PhD studentship awarded by the Friends of Peterhouse. This research was co-funded by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and a Marmaduke Sheild grant to R.A.I.B. and V.W.. E.T.B is an NIHR Senior Investigator. R.R.G was funded by a Guarantors of Brain Fellowship. R.A.I.B. is supported by a British Academy Post-Doctoral fellowship and the Autism Research Trust. We wish to thank Dr Petra Vertes and Dr Lisa Ronan for their advice on research design and Dr Simon R White for his statistical advice and support. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was possible due to an application to the UK Biobank (project 20904)

A multi-scale cortical wiring space links cellular architecture and functional dynamics in the human brain.

The vast net of fibres within and underneath the cortex is optimised to support the convergence of different levels of brain organisation. Here, we propose a novel coordinate system of the human cortex based on an advanced model of its connectivity. Our approach is inspired by seminal, but so far largely neglected models of cortico-cortical wiring established by postmortem anatomical studies and capitalises on cutting-edge in vivo neuroimaging and machine learning. The new model expands the currently prevailing diffusion magnetic resonance imaging (MRI) tractography approach by incorporation of additional features of cortical microstructure and cortico-cortical proximity. Studying several datasets and different parcellation schemes, we could show that our coordinate system robustly recapitulates established sensory-limbic and anterior-posterior dimensions of brain organisation. A series of validation experiments showed that the new wiring space reflects cortical microcircuit features (including pyramidal neuron depth and glial expression) and allowed for competitive simulations of functional connectivity and dynamics based on resting-state functional magnetic resonance imaging (rs-fMRI) and human intracranial electroencephalography (EEG) coherence. Our results advance our understanding of how cell-specific neurobiological gradients produce a hierarchical cortical wiring scheme that is concordant with increasing functional sophistication of human brain organisation. Our evaluations demonstrate the cortical wiring space bridges across scales of neural organisation and can be easily translated to single individuals

Atypical genomic cortical patterning in autism with poor early language outcome.

Cortical regionalization develops via genomic patterning along anterior-posterior (A-P) and dorsal-ventral (D-V) gradients. Here, we find that normative A-P and D-V genomic patterning of cortical surface area (SA) and thickness (CT), present in typically developing and autistic toddlers with good early language outcome, is absent in autistic toddlers with poor early language outcome. Autistic toddlers with poor early language outcome are instead specifically characterized by a secondary and independent genomic patterning effect on CT. Genes involved in these effects can be traced back to midgestational A-P and D-V gene expression gradients and different prenatal cell types (e.g., progenitor cells and excitatory neurons), are functionally important for vocal learning and human-specific evolution, and are prominent in prenatal coexpression networks enriched for high-penetrance autism risk genes. Autism with poor early language outcome may be explained by atypical genomic cortical patterning starting in prenatal development, which may detrimentally affect later regional functional specialization and circuit formation

Atypical functional connectome hierarchy in autism.

One paradox of autism is the co-occurrence of deficits in sensory and higher-order socio-cognitive processing. Here, we examined whether these phenotypical patterns may relate to an overarching system-level imbalance-specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Combining connectome gradient and stepwise connectivity analysis based on task-free functional magnetic resonance imaging (fMRI), we demonstrated atypical connectivity transitions between sensory and higher-order default mode regions in a large cohort of individuals with autism relative to typically-developing controls. Further analyses indicated that reduced differentiation related to perturbed stepwise connectivity from sensory towards transmodal areas, as well as atypical long-range rich-club connectivity. Supervised pattern learning revealed that hierarchical features predicted deficits in social cognition and low-level behavioral symptoms, but not communication-related symptoms. Our findings provide new evidence for imbalances in network hierarchy in autism, which offers a parsimonious reference frame to consolidate its diverse features

Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism.

The pathophysiology of autism has been suggested to involve a combination of both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. We studied neuroimaging and phenotypic data in 47 individuals with autism and 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences in structural connectome organization in individuals with autism relative to controls, with strong between-group effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models reveal that the degree of macroscale anomalies is related to atypical increases of recurrent excitation/inhibition, as well as subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic association analysis based on postmortem datasets identifies genes expressed in cortical and thalamic areas from childhood to young adulthood. Finally, supervised machine learning finds that the macroscale perturbations are associated with symptom severity scores on the Autism Diagnostic Observation Schedule. Together, our analyses suggest that atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism

Author Correction: Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Shifts in myeloarchitecture characterise adolescent development of cortical gradients.

Funder: MQ: Transforming Mental Health; Grant(s): MQF17/24We studied an accelerated longitudinal cohort of adolescents and young adults (n = 234, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelin-sensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortical profiles demonstrated two separate processes i) overall increases in MT, and ii) flattening of the MT profile related to enhanced signal in mid-to-deeper layers, especially in heteromodal and unimodal association cortices. This development was independent of morphological changes. Enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Interregional covariance analysis revealed that these intracortical changes contributed to a gradual differentiation of higher-order from lower-order systems. Depth-dependent trajectories of intracortical myeloarchitectural development contribute to the maturation of structural hierarchies in the human neocortex, providing a model for adolescent development that bridges microstructural and macroscopic scales of brain organisation

Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study.

Funder: National Institute for Health Research (NIHR)INTRODUCTION: Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV-2 infection on the brain by diverse potentially pathogenic mechanisms, and with high reliability across multiple sites and scanner manufacturers. Here we describe the development of such a protocol, based upon the UK Biobank, and its validation with a travelling heads study. A multi-modal brain MRI protocol comprising sequences for T1-weighted MRI, T2-FLAIR, diffusion MRI (dMRI), resting-state functional MRI (fMRI), susceptibility-weighted imaging (swMRI), and arterial spin labelling (ASL), was defined in close approximation to prior UK Biobank (UKB) and C-MORE protocols for Siemens 3T systems. We iteratively defined a comparable set of sequences for General Electric (GE) 3T systems. To assess multi-site feasibility and between-site variability of this protocol, N = 8 healthy participants were each scanned at 4 UK sites: 3 using Siemens PRISMA scanners (Cambridge, Liverpool, Oxford) and 1 using a GE scanner (King's College London). Over 2,000 Imaging Derived Phenotypes (IDPs), measuring both data quality and regional image properties of interest, were automatically estimated by customised UKB image processing pipelines (S2 File). Components of variance and intra-class correlations (ICCs) were estimated for each IDP by linear mixed effects models and benchmarked by comparison to repeated measurements of the same IDPs from UKB participants. Intra-class correlations for many IDPs indicated good-to-excellent between-site reliability. Considering only data from the Siemens sites, between-site reliability generally matched the high levels of test-retest reliability of the same IDPs estimated in repeated, within-site, within-subject scans from UK Biobank. Inclusion of the GE site resulted in good-to-excellent reliability for many IDPs, although there were significant between-site differences in mean and scaling, and reduced ICCs, for some classes of IDP, especially T1 contrast and some dMRI-derived measures. We also identified high reliability of quantitative susceptibility mapping (QSM) IDPs derived from swMRI images, multi-network ICA-based IDPs from resting-state fMRI, and olfactory bulb structure IDPs from T1, T2-FLAIR and dMRI data. CONCLUSION: These results give confidence that large, multi-site MRI datasets can be collected reliably at different sites across the diverse range of MRI modalities and IDPs that could be mechanistically informative in COVID brain research. We discuss limitations of the study and strategies for further harmonisation of data collected from sites using scanners supplied by different manufacturers. These acquisition and analysis protocols are now in use for MRI assessments of post-COVID patients (N = 700) as part of the ongoing COVID-CNS study