Autism: A Neurodevelopmental Disorder and a Stratum for Comorbidities

Autism is a neurodevelopmental disorder which is more common in males than females. It is characterized by social communication disorders and restricted repetitive behaviors. There is wide heterogeneity in its etiology, clinical presentations, management and consequently prognosis. Although the etiology of autism remains unclear, the most currently proven theory is that it is a complex neurodevelopmental disorder that displays “brain network abnormalities”. fMRI studies have shown decreased brain connectivity or functional synchronization between frontal and more posterior cortical regions. Dynamic brain activity through high resolution electroencephalograghy (EEG) has revealed local overconnectivity and long-range underconnectivity. This disrupted connectivity pattern would involve connectivity between hemispheres (corpus callosum), together with axonal and synaptic connectivity within each hemisphere. Inconsistent morphometric changes involving both gray and white matter structure also exist. Clinically, autism is associated with multiple comorbidities (somatic, neurologic and psychiatric); some of which are attention deficit hyperactivity disorder, dyspraxia, and sensory processing disorders

Cerebellar gray matter and lobular volumes correlate with core autism symptoms

AbstractNeuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8–13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on right cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile

Mirror neuron activation in children with developmental coordination disorder: A functional MRI study.

The aim of this study was to reveal cortical areas that may contribute to the movement difficulties seen in children with Developmental Coordination Disorder (DCD). Specifically, we hypothesized that there may be a deficit in the mirror neuron system (MNS), a neural system that responds to both performed and observed actions. Using functional MRI, 14 boys with DCD (x¯=10.02 years±1.28, range=8.33-11.17 years) and 12 typically developing controls (x¯=10.10 years±1.16, range=8.02-12 years) were scanned observing, executing and imitating a finger sequencing task using their right hand. Cortical activations of mirror neuron regions, including posterior inferior frontal gyrus, ventral premotor cortex, anterior inferior parietal lobule and superior temporal sulcus were examined. Children with DCD had decreased cortical activation mirror neuron related regions, including the precentral gyrus and inferior frontal gyrus, as well as in the posterior cingulate and precuneus complex when observing the sequencing task. Region of interest analysis revealed lower activation in the pars opercularis, a primary MNS region, during imitation in the DCD group compared to controls. These findings provide some preliminary evidence to support a possible MNS dysfunction in children with DCD

Emerging signs of autism spectrum disorder in infancy:Putative neural substrate

Autism spectrum disorder (ASD) is characterized by altered development of the social brain with prominent atypical features in the fronto-temporo-parietal cortex and cerebellum. Early signs of ASD emerge between 6 and 12 months: reduced social communication, slightly less advanced motor development, and repetitive behaviour. The fronto-temporo-parietal cortex and cerebellum play a prominent role in the development of social communication, whereas fronto-parietal-cerebellar networks are involved in the planning of movements, that is, movement selection. Atypical sensory responsivity, a core feature of ASD, may result in impaired development of social communication and motor skills and/or selection of atypical repetitive behaviour. In the first postnatal year, the brain areas involved are characterized by gradual dissolution of temporary structures: the fronto-temporo-parietal cortical subplate and cerebellar external granular layer. It is hypothesized that altered dissolution of the transient structures opens the window for the expression of early signs of ASD arising in the impaired developing permanent networks

Brain Imaging Correlates of Developmental Coordination Disorder and Associated Impairments

Developmental Coordination Disorder (DCD) is a common developmental disorder characterised by an inability to learn age appropriate complex motor skills. The first aim of this thesis was to characterise additional cognitive impairments and their relationship with motor difficulties in school aged children with DCD. The second aim was to investigate grey and white matter neuroimaging correlates of motor and cognitive deficits identified. Thirty six children aged 8-10 years who met DSM-5 criteria for DCD and an age-matched typically developing group (N=17) underwent standardised assessments of motor, intellectual, attention, speech and language skills as well as structural and diffusion-weighted MRI scans. Grey matter correlates of impairments were identified using subcortical volumetrics and surface-based analyses of cortical morphology. White matter correlates were examined using tractography and fixel-based fibre morphology of the pyramidal tracts, corpus callosum and cerebellar peduncles. Alongside impaired motor skills, children with DCD performed poorer than controls on several domains of executive function (attention and processing speed) and speech motor control. Motor skills did not correlate with impairments in other domains. Cortical thickness was significantly reduced in the left central sulcus in children with DCD compared to controls. Poor motor skills correlated with measures in left sensorimotor circuitry, posterior cingulate cortex and anterior insula. Poor speech motor control was associated with measures in the thalamus and corticobulbar tract. Poor sustained attention was linked to measures in the right superior cerebellar peduncle. Lower processing speed was associated with reduced mean cortical surface area. Children with DCD show co-occurring impairments in attention and speech motor control. DCD is associated with sensorimotor circuits as well as regions that form part of the default mode and salience networks. Disruption of subcortical circuits may underlie additional impairments. This study provides novel evidence of the neural correlates of DCD

What can autism teach us about the role of sensorimotor systems in higher cognition? New clues from studies on language, action semantics, and abstract emotional concept processing.

Within the neurocognitive literature there is much debate about the role of the motor system in language, social communication and conceptual processing. We suggest, here, that autism spectrum conditions (ASC) may afford an excellent test case for investigating and evaluating contemporary neurocognitive models, most notably a neurobiological theory of action perception integration where widely-distributed cell assemblies linking neurons in action and perceptual brain regions act as the building blocks of many higher cognitive functions. We review a literature of functional motor abnormalities in ASC, following this with discussion of their neural correlates and aberrancies in language development, explaining how these might arise with reference to the typical formation of cell assemblies linking action and perceptual brain regions. This model gives rise to clear hypotheses regarding language comprehension, and we highlight a recent set of studies reporting differences in brain activation and behaviour in the processing of action-related and abstract-emotional concepts in individuals with ASC. At the neuroanatomical level, we discuss structural differences in long-distance frontotemporal and frontoparietal connections in ASC, such as would compromise information transfer between sensory and motor regions. This neurobiological model of action perception integration may shed light on the cognitive and social-interactive symptoms of ASC itself, building on and extending earlier proposals linking autistic symptomatology to motor disorder and dysfunction in action perception integration. Further investigating the contribution of motor dysfunction to higher cognitive and social impairment, we suggest, is timely and promising as it may advance both neurocognitive theory and the development of new clinical interventions for this population and others characterised by early and pervasive motor disruption

Fine Motor, Social, and Adaptive Function in Autism Spectrum Disorder

This study researched kernel-based methods and max-margin learning for largescale datasets. It advanced several theoretical and practical aspects of kernel-based and max-margin methods at the intersection with Bayesian modelling. New learning methods were proposed to avoid the curse of kernelisation while simultaneously yielding superior accuracy compared with state-of-the-art baselines

Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay.

In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC.Funding: - UK Medical Research Council. Grant Number: GO 400061 - EU‐AIMS (Innovative Medicines Initiative Joint). Grant Number: 115300 - European Union's Seventh Framework Programme. Grant Number: FP7/2007‐2013 - Sidney Sussex College, Cambridge - William Binks Autism Neuroscience Fellowship - EU‐AIMS - Wolfson College, Cambridge - Shirley Foundation - Wellcome Trust - British Academy - Jesus College, Cambridge - NIHR Cambridge Biomedical Research Centre - Cambridgeshire & Peterborough NHS Foundation Trust, Cambridg