Treatment of a life-threatening dapsone intoxication

The case report describes a case of a severe dapsone (more than 200 tablets dapsone 100 mg) and mild methotrexate intoxication (10 tablets methotrexate 10 mg) as an attempt to commit suicide, resulting in severe cyanosis with elevation in methemoglobin concentration, treated with methylene blue, ascorbic acid, folinic acid, multidose activated charcoal and hemodialysis. Measurements of blood gases, dapsone and methotrexate levels were performed. Furthermore a hepatitis, pulmonary artery thrombus and a strange taste sensation were diagnosed, probably related to dapsone. The patient recovered and was discharged from hospital after five days. Acute intoxication from excessive dapsone intake is uncommon and clear treatment guidelines are lacking. We here report the treatment modalities as a result of a dapsone intoxication, including the effects on the overall condition of the patient.</p

Heritability and cross-species comparisons of human cortical functional organization asymmetry

The human cerebral cortex is symmetrically organized along large-scale axes but also presents inter-hemispheric differences in structure and function. The quantified contralateral homologous difference, that is asymmetry, is a key feature of the human brain left-right axis supporting functional processes, such as language. Here, we assessed whether the asymmetry of cortical functional organization is heritable and phylogenetically conserved between humans and macaques. Our findings indicate asymmetric organization along an axis describing a functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization in humans. These asymmetries were heritable in humans and showed a similar spatial distribution with macaques, in the case of intra-hemispheric asymmetry of functional hierarchy. This suggests (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques. Overall, our findings suggest a genetic basis for asymmetry in intrinsic functional organization, linked to higher order cognitive functions uniquely developed in humans

Examining the relationship between altered brain functional connectome and disinhibition across 33 impulsive and compulsive behaviours

Impulsive and compulsive problem behaviours are associated with a variety of mental disorders. Latent phenotyping indicates the expression of impulsive and compulsive problem behaviours is predominantly governed by a transdiagnostic 'disinhibition' phenotype. In a cohort of 117 individuals, recruited as part of the Neuroscience in Psychiatry Network (NSPN), we examined how brain functional connectome and network properties relate to disinhibition. Reduced functional connectivity within a subnetwork of frontal (especially right inferior frontal gyrus), occipital and parietal regions was linked to disinhibition. Findings provide insights into neurobiological pathways underlying the emergence of impulsive and compulsive disorders

Brain charts for the human lifespan

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes

The SPOTLIGHT virtual audit tool: a valid and reliable tool to assess obesogenic characteristics of the built environment.

BACKGROUND: A lack of physical activity and overconsumption of energy dense food is associated with overweight and obesity. The neighbourhood environment may stimulate or hinder the development and/or maintenance of a healthy lifestyle. To improve research on the obesogenicity of neighbourhood environments, reliable, valid and convenient assessment methods of potential obesogenic characteristics of neighbourhood environments are needed. This study examines the reliability and validity of the SPOTLIGHT-Virtual Audit Tool (S-VAT), which uses remote sensing techniques (Street View feature in Google Earth) for desk-based assessment of environmental obesogenicity. METHODS: A total of 128 street segments in four Dutch urban neighbourhoods - heterogeneous in socio-economic status and residential density - were assessed using the S-VAT. Environmental characteristics were categorised as walking related items, cycling related items, public transport, aesthetics, land use-mix, grocery stores, food outlets and physical activity facilities. To assess concordance of inter- and intra-observer reliability of the Street View feature in Google Earth, and validity scores with real life audits, percentage agreement and Cohen's Kappa (k) were calculated. RESULTS: Intra-observer reliability was high and ranged from 91.7% agreement (k = 0.654) to 100% agreement (k = 1.000) with an overall agreement of 96.4% (k = 0.848). Inter-observer reliability results ranged from substantial agreement 78.6% (k = 0.440) to high agreement, 99.2% (k = 0.579), with an overall agreement of 91.5% (k = 0.595). Criterion validity was substantial to high for most of the categories ranging from 87.3% agreement (k = 0.539) to 99.9% agreement (k = 0.887) with an overall score of 95.6% agreement (k = 0.747). CONCLUSION: These study results suggest that the S-VAT is a highly reliable and valid remote sensing tool to assess potential obesogenic environmental characteristics

Brain charts for the human lifespan

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual diferences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1 . Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantifed by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identifed previously unreported neurodevelo pmental milestones3 , showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological diferences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantifcation of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes

Structural covariance networks in children with autism or ADHD

Abstract While autism and attention-deficit/hyperactivity disorder (ADHD) are considered distinct conditions from a diagnostic perspective, they share some phenotypic features and have high comorbidity. Taking a dual-condition approach might help elucidate shared and distinct neural characteristics. Graph theory was used to analyse properties of cortical thickness structural covariance networks across both conditions and relative to a neurotypical (NT; n=87) group using data from the ABIDE (autism; n=62) and ADHD-200 datasets (ADHD; n=69). This was analysed in a theoretical framework examining potential differences in long and short range connectivity. We found convergence between autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance compared to a neurotypical population. The two conditions also show divergence: less modular overlap between the two conditions than there is between each condition and the neurotypical group. Lastly, the ADHD group also showed reduced wiring costs compared to the autism groups. Our results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD. Both groups show a distance-covariance relation that more strongly favours short-range over long-range. Thus, on some network features the groups seem to converge, yet on others there is divergence

Oxytocin enhances basolateral amygdala activation and functional connectivity while processing emotional faces: preliminary findings in autistic versus non-autistic women

Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala – the brain’s “salience detector” – while processing emotional faces vs. shapes was tested in 16 autistic and 21 non-autistic women by fMRI in a placebo-controlled, within-subjects, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35 voxel cluster, MNI coordinates of peak voxel= -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not non-autistic women (mean change =+0.003%, t=0.153, ptukey=0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin’s effects on the amygdala to specifically include autistic women and specify the subregion of the effect.TLP was supported by the Autism Research Trust, Cambridge Trust, and Natural Sciences and Engineering Research Council of Canada. MVL was supported by an ERC Starting Grant (ERC-2017-STG; 755816). MCL was supported by a Canadian Institutes of Health Research (CIHR) Sex and Gender Science Chair (GSB 171373), the O’Brien Scholars Program within the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children, Toronto, the Academic Scholars Award from the Department of Psychiatry, University of Toronto, the CAMH Foundation, and the Ontario Brain Institute. SBC received funding from the Wellcome Trust 214322\Z\18\Z. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. SBC also received funding from the Autism Centre of Excellence, SFARI, the Templeton World Charitable Fund, the MRC, and the National Institute for Health Research (NIHR). Any views expressed are those of the author(s) and not necessarily those of the funder. RB was supported by the MRC UK, Pinsent Darwin Trust and British Academy post-doctoral fellowship

Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex

Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social-cognition and autobiographical memory. Our findings suggest that genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition