Change detection in children with autism: an auditory event-related fMRI study

Autism involves impairments in communication and social interaction, as well as high levels of repetitive, stereotypic and ritualistic behaviours, and extreme resistance to change. This latter dimension, whilst required for a diagnosis, has received less research attention. We hypothesise that this extreme resistance to change in autism is rooted in atypical processing of unexpected stimuli. We tested this using auditory event-related fMRI to determine regional brain activity associated with passive detection of infrequently occurring frequency-deviant and complex novel sounds in a no-task condition. Participants were twelve 10 to 15-year-old children with autism, and a group of 12 age- and sex-matched healthy controls

From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition.

Growing evidence points toward a critical role for early (prenatal) atypical neurodevelopmental processes in the aetiology of autism spectrum condition (ASC). One such process that could impact early neural development is inflammation. We review the evidence for atypical expression of molecular markers in the amniotic fluid, serum, cerebrospinal fluid (CSF), and the brain parenchyma that suggest a role for inflammation in the emergence of ASC. This is complemented with a number of neuroimaging and neuropathological studies describing microglial activation. Implications for treatment are discussed.Medical Research Council, Autism Research Trust, William Binks Autism Neuroscience FellowshipThis is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13229-016-0068-

Pupil dilation as an index of preferred mutual gaze duration

Most animals look at each other to signal threat or interest. In humans, this social interaction is usually punctuated with brief periods of mutual eye contact. Deviations from this pattern of gazing behaviour generally make us feel uncomfortable and are a defining characteristic of clinical conditions such as autism or schizophrenia, yet it is unclear what constitutes normal eye contact. Here, we measured, across a wide range of ages, cultures and personality types, the period of direct gaze that feels comfortable and examined whether autonomic factors linked to arousal were indicative of people’s preferred amount of eye contact. Surprisingly, we find that preferred period of gaze duration is not dependent on fundamental characteristics such as gender, personality traits or attractiveness. However, we do find that subtle pupillary changes, indicative of physiological arousal, correlate with the amount of eye contact people find comfortable. Specifically, people preferring longer durations of eye contact display faster increases in pupil size when viewing another person than those preferring shorter durations. These results reveal that a person’s preferred duration of eye contact is signalled by physiological indices (pupil dilation) beyond volitional control that may play a modulatory role in gaze behaviour

On the brain structure heterogeneity of autism: Parsing out acquisition site effects with significance-weighted principal component analysis.

Neuroimaging studies have reported structural and physiological differences that could help understand the causes and development of Autism Spectrum Disorder (ASD). Many of them rely on multisite designs, with the recruitment of larger samples increasing statistical power. However, recent large-scale studies have put some findings into question, considering the results to be strongly dependent on the database used, and demonstrating the substantial heterogeneity within this clinically defined category. One major source of variance may be the acquisition of the data in multiple centres. In this work we analysed the differences found in the multisite, multi-modal neuroimaging database from the UK Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) in terms of both diagnosis and acquisition sites. Since the dissimilarities between sites were higher than between diagnostic groups, we developed a technique called Significance Weighted Principal Component Analysis (SWPCA) to reduce the undesired intensity variance due to acquisition site and to increase the statistical power in detecting group differences. After eliminating site-related variance, statistically significant group differences were found, including Broca's area and the temporo-parietal junction. However, discriminative power was not sufficient to classify diagnostic groups, yielding accuracies results close to random. Our work supports recent claims that ASD is a highly heterogeneous condition that is difficult to globally characterize by neuroimaging, and therefore different (and more homogenous) subgroups should be defined to obtain a deeper understanding of ASD. Hum Brain Mapp 38:1208-1223, 2017. © 2016 Wiley Periodicals, Inc.Contract grant sponsor: UK Medical Research Council AIMS network; Contract grant number: G0400061; Contract grant sponsors: “Vicerrectorado de Relaciones Internacionales de la Universidad de Granada” and CEI BioTic Granada; Contract grant: “Convocatoria de Movilidad Internacional de Estudiantes de Doctorado Curso 2013/2014”; Contract grant sponsor: MINECO/ FEDER; Contract grant numbers: TEC2012-34306 and TEC2015- 64718-R; Contract grant sponsor: Consejeria de Economia, Innovacion, Ciencia y Empleo (Junta de Andalucia, Spain); Contract grant numbers: P09-TIC-4530 and P11-TIC-710

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder, anxiety and autism spectrum disorder

Background Children with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms. Methods Infants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24 and 38 months, and 7 years of age. Symptoms of ASD, ADHD and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations. Results Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became nonsignificant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal. Conclusions The specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Family coordination in families who have a child with autism spectrum disorder

Little is known about the interactions of families where there is a child with autism spectrum disorder (ASD). The present study applies the Lausanne Trilogue Play (LTP) to explore both its applicability to this population as well as to assess resources and areas of deficit in these families. The sample consisted of 68 families with a child with ASD, and 43 families with a typically developing (TD) child. With respect to the global score for family coordination there were several negative correlations: the more severe the symptoms (based on the child’s ADOS score), the more family coordination was dysfunctional. This correlation was particularly high when parents had to play together with the child. In the parts in which only one of the parents played actively with the child, while the other was simply present, some families did achieve scores in the functional range, despite the child’s symptom severity. The outcomes are discussed in terms of their clinical implications both for assessment and for interventio

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception