Brain Routes for Reading in Adults with and without Autism: EMEG Evidence

Reading utilises at least two neural pathways. The temporal lexical route visually maps whole words to their lexical entries, whilst the nonlexical route decodes words phonologically via parietal cortex. Readers typically employ the lexical route for familiar words, but poor comprehension plus precocity at mechanically ‘sounding out’ words suggests that differences might exist in autism. Combined MEG/EEG recordings of adults with autistic spectrum conditions (ASC) and controls while reading revealed preferential recruitment of temporal areas in controls and additional parietal recruitment in ASC. Furthermore, a lack of differences between semantic word categories was consistent with previous suggestion that people with ASC may lack a ‘default’ lexical-semantic processing mode. These results are discussed with reference to dual-route models of reading

Brain and behavioral correlates of action semantic deficits in autism.

Action-perception circuits containing neurons in the motor system have been proposed as the building blocks of higher cognition; accordingly, motor dysfunction should entail cognitive deficits. Autism spectrum conditions (ASC) are marked by motor impairments but the implications of such motor dysfunction for higher cognition remain unclear. We here used word reading and semantic judgment tasks to investigate action-related motor cognition and its corresponding fMRI brain activation in high-functioning adults with ASC. These participants exhibited hypoactivity of motor cortex in language processing relative to typically developing controls. Crucially, we also found a deficit in semantic processing of action-related words, which, intriguingly, significantly correlated with this underactivation of motor cortex to these items. Furthermore, the word-induced hypoactivity in the motor system also predicted the severity of ASC as expressed by the number of autistic symptoms measured by the Autism-Spectrum Quotient (Baron-Cohen etal., 2001). These significant correlations between word-induced activation of the motor system and a newly discovered semantic deficit in a condition known to be characterized by motor impairments, along with the correlation of such activation with general autistic traits, confirm critical predictions of causal theories linking cognitive and semantic deficits in ASC, in part, to dysfunctional action-perception circuits and resultant reduction of motor system activation

Lost for emotion words: what motor and limbic brain activity reveals about autism and semantic theory.

Autism spectrum conditions (ASC) are characterised by deficits in understanding and expressing emotions and are frequently accompanied by alexithymia, a difficulty in understanding and expressing emotion words. Words are differentially represented in the brain according to their semantic category and these difficulties in ASC predict reduced activation to emotion-related words in limbic structures crucial for affective processing. Semantic theories view 'emotion actions' as critical for learning the semantic relationship between a word and the emotion it describes, such that emotion words typically activate the cortical motor systems involved in expressing emotion actions such as facial expressions. As ASC are also characterised by motor deficits and atypical brain structure and function in these regions, motor structures would also be expected to show reduced activation during emotion-semantic processing. Here we used event-related fMRI to compare passive processing of emotion words in comparison to abstract verbs and animal names in typically-developing controls and individuals with ASC. Relatively reduced brain activation in ASC for emotion words, but not matched control words, was found in motor areas and cingulate cortex specifically. The degree of activation evoked by emotion words in the motor system was also associated with the extent of autistic traits as revealed by the Autism Spectrum Quotient. We suggest that hypoactivation of motor and limbic regions for emotion word processing may underlie difficulties in processing emotional language in ASC. The role that sensorimotor systems and their connections might play in the affective and social-communication difficulties in ASC is discussed.This work was supported by the Medical Research Council (MRC) (MC_US_A060_0034, U1055.04.003.00001.01 to F.P., MC_US_A060_0043, MC-A060-5PQ90 to Y. S., MRC studentship to R.M.).The is the final published paper originally published in NeuroImage under a CC-BY licence (RL Moseley, Y Shtyrov, B Mohr, MV Lombardo, S Baron-Cohen, F Pulvermüller, NeuroImage 2015, 104, 413-422

Methylmalonic Acidemia: Can Treatment be Improved?

Methylmalonic acidemia (MMA) is a severe metabolic disorder, particularly with complete deficiency of methylmalonyl-CoA mutase. Dietary restriction has led to overt signs of deficiencies including skin rashes, hair loss, and poor growth. More liberal intake of the restricted amino acids has resulted in better growth and less frequent episodes of illness

#4 - Endosomal Proteins in Neurodevelopmental Disorders

Rett Syndrome is a neurodevelopmental disorder that primarily affects females and is detected at 6-18 months of age. Rett Syndrome results from a mutations in the methyl-CpG binding protein 2 gene (MECP2) which is found on the X chromosome. Its mutation results in impairment in cognitive, sensory, emotional, motor and autonomic functions. Schizophrenia is also a neurodevelopmental disorder with onset in adulthood, however there is no single genetic cause. Endosomal proteins have been implicated in both disorders through GWAS studies and animal models, suggesting a common molecular mechanism shared between these neurodevelopmental disorders. Previous research in our lab has demonstrated a disruption in endosomal trafficking in animal models of both disorders. This study explores the levels and localization of endosomal proteins in coronal brain sections for mice models for these neurodevelopmental disorders. Using immunohistochemistry, we will examine protein levels in the hippocampus and cortex for endosomal trafficking markers. We will also use whole-brain derived synaptosomes and western blots to examine the subcellular levels of these endosomal markers. Our data demonstrate a reduction of endosomal proteins in the hippocampus of mouse models of neurodevelopmental disorders. Future studies will include investigations into the affected cargo being mis-trafficked in these disorders

Mental health among healthcare workers and other vulnerable groups during the COVID-19 pandemic and other coronavirus outbreaks: A rapid systematic review.

INTRODUCTION: Although most countries and healthcare systems worldwide have been affected by the COVID-19 pandemic, some groups of the population may be more vulnerable to detrimental effects of the pandemic on mental health than others. The aim of this systematic review was to synthesise evidence currently available from systematic reviews on the impact of COVID-19 and other coronavirus outbreaks on mental health for groups of the population thought to be at increased risk of detrimental mental health impacts. MATERIALS AND METHODS: We conducted a systematic review of reviews on adults and children residing in a country affected by a coronavirus outbreak and belonging to a group considered to be at risk of experiencing mental health inequalities. Data were collected on symptoms or diagnoses of any mental health condition, quality of life, suicide or attempted suicide. The protocol for this systematic review was registered in the online PROSPERO database prior to commencing the review (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=194264). RESULTS: We included 25 systematic reviews. Most reviews included primary studies of hospital workers from multiple countries. Reviews reported variable estimates for the burden of symptoms of mental health problems among acute healthcare workers, COVID-19 patients with physical comorbidities, and children and adolescents. No evaluations of interventions were identified. Risk- and protective factors, mostly for healthcare workers, showed the importance of personal factors, the work environment, and social networks for mental health. CONCLUSIONS: This review of reviews based on primary studies conducted in the early months of the COVID-19 pandemic shows a lack of evidence on mental health interventions and mental health impacts on vulnerable groups in the population

Hadrons at high temperature: an update from the FASTSUM collaboration

We present the most recent results from the FASTSUM collaboration for hadron properties at high temperature. This includes the temperature dependence of the light and charmed meson and baryon spectrum, as well as properties of heavy quarkonia. The results are obtained using anisotropic lattices with a fixed scale approach. We also present the status of our next generation gauge ensembles.Comment: 8 pages, 8 figures. Contribution to the XVth Quark Confinement and the Hadron Spectrum, 1-6 August 2022, Stavanger, Norwa

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Are integrated impact assessments the way forward for mainstreaming in the European Union?

This article assesses the utility of impact assessments (IA) as an effective tool for mainstreaming. Specifically, it analyses whether the European Union’s (EU) system of integrated impact assessments (IIA) contributes to the realisation of six mainstreaming objectives defined in the EU Treaties. The article first studies whether the legal framework for the EU’s system of IIAs makes it a viable tool for mainstreaming. It then proceeds with an empirical analysis of 35 impact assessments to assess the extent to which mainstreaming objectives are taken into account in practice. The analysis shows that all the six mainstreaming objectives have a place within the IIA system, but the system does not ensure systematic consideration of them. There is considerable variation across the mainstreaming agendas as well as across Directorates-General. The article concludes the IIA system is no panacea for mainstreaming, while proposing changes to the institutional framework to improve its mainstreaming potential

The divergence of mental health experiences during the Coronavirus pandemic in the UK

The Coronavirus: Mental Health in the Pandemic study provides unique insights into the mental health effects of the pandemic since mid-March, with five waves of data collected so far across the UK specifically focused on mental health and well-being. We want to use good quality evidence to influence the actions that we need to take as a country to prevent a mental health crisis in the years to come. While we have all been affected by the COVID-19 crisis, the evidence from the Foundation’s Coronavirus: Mental Health in the Pandemic (‘our’) study shows a divergence in people’s experience depending on their social and/or economic context in society. As has been said: we are all in the same storm, but we are not all in the same boat. Even as the measures taken to curb the spread of COVID-19 change, with reduced restrictions for most and sustained isolation for a minority, with some having been affected directly by the virus and many less so, some returning to normal work life and many others experiencing changed employment status, differences in the mental health impact will persist and likely increase