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THE NEUROBIOLOGICAL BASES OF AUTISM SPECTRUM DISORDERS
Editorial
Explorations and perspectives on the neurobiological bases of autism spectrum disorder
- Pages: 488-496
- First Published: 25 March 2018
A review of joint attention and social-cognitive brain systems in typical development and autism spectrum disorder
- Pages: 497-514
- First Published: 18 September 2017

A new view of social-cognitive neurodevelopment is emerging from imaging studies of joint attention. Theory and these studies suggest that the cortical systems that develop to support joint attention in infancy play a major role in the subsequent development of social-cognitive mentalizing. These studies also support the hypothesis that an impairment of joint attention in the first two years of life is fundamental to atypical social-cognitive neurodevelopment in autism spectrum disorders.
Autism: a transdiagnostic, dimensional, construct of reasoning?
- Pages: 515-533
- First Published: 27 April 2017

This theoretical review discusses the concept of autism in light of new ideas, prior theory, clinical vignettes and recent empirical evidence. Autism may represent a transdiagnostic, dimensional construct of reasoning. Future autism research needs to develop theoretical models that include the social level and mechanisms that relate (1) basic susceptibility, (2) adaptive processes and (3) decompensating factors in a developmental framework.
Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance
- Pages: 534-548
- First Published: 27 April 2017

Genetic, metabolic, immune and environmental factors during late embryonic or early postnatal brain development are thought to contribute to ASD and related comorbidities. These factors may result in reduced inhibition, enhanced excitation and subsequent E/I imbalance, thus altering circuit plasticity and ultimately leading to ASD, epilepsy and intellectual disability.
Eye movements, sensorimotor adaptation and cerebellar-dependent learning in autism: toward potential biomarkers and subphenotypes
- Pages: 549-555
- First Published: 14 June 2017

Examples of saccadic adaptation in a neuro-typical (A) participant and a participant with an autism Spectrum Disorder (B). Saccade amplitudes are plotted as functions of adaptation trial number, and lines of best fit are superimposed. Saccades made by the TD participant clearly change amplitudes over the course of adaptation, whereas those made by the participant with an ASD do not.
Stimulus processing and error monitoring in more-able kindergarteners with autism spectrum disorder: a short review and a preliminary Event-Related Potentials study
- Pages: 556-567
- First Published: 10 April 2017

We provide a focused review of executive function (EF)-related Event-Related Potentials (ERP) studies in children with Autism Spectrum Disorders (ASD), accompanied by preliminary data showing significantly enhanced error/correct-related negativity (ERN, CRN) and less distinct inhibitory P3 in kindergartners with ASD compared to typically developing children. These atypical ERP patterns were also associated with performance on an EF-related task and autism symptom severity.
The effect of age, sex and clinical features on the volume of Corpus Callosum in pre-schoolers with Autism Spectrum Disorder: a case–control study
- Pages: 568-578
- First Published: 23 January 2017

To investigate the volume alterations of the corpus callosum (CC) in pre-school children with ASD: we analysed the structural MRI of 20 male and 20 female children with ASD and 40 matched controls (CTRL); we obtained volume measurements of CC and its sub-regions with Freesurfer; we compared the volumes among groups of subjects; we examined the correlations of volumes with demographic and clinical variables (NVIQ, expressive non-echolalic language, emotional and behavioural problems, autism severity).
Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation
- Pages: 579-591
- First Published: 28 February 2017

Children and adolescents with autism spectrum disorders, along with a matched group of typically developing controls, completed 20–30 h of an electroencephalography neurofeedback training protocol designed to target the human mirror neuron system. In the ASD group but not in the control group, post-training activation increases during a functional magnetic resonance imaging imitation task were observed in that system, along with improvements in social behaviors.
Heightened brain response to pain anticipation in high-functioning adults with autism spectrum disorder
- Pages: 592-601
- First Published: 27 April 2017

We examined pain perception and anticipation in high-functioning adults with autism spectrum disorder (ASD) and matched healthy controls using an anticipatory pain paradigm in combination with fMRI and skin conductance response recording. Compared to controls, ASD participants chose lower levels of stimulation, yet showed increased activations in the anterior cingulate cortex during pain anticipation. These results indicate abnormal attentional orientation to nociceptive signals in ASD.
Variable sensory perception in autism
- Pages: 602-609
- First Published: 05 May 2017

Individuals with autism experience sensory abnormalities that could contribute to the characteristic social deficits: problems processing pitch could impact the interpretation of speech, leading to unusual social behaviour. It will be argued that sensory abnormalities increase the amount of noise in the system, which can be characterised by greater trial-to-trial variability in neural and behavioural responses. Methods to improve sensory processing could help improve social deficits.
Reduced reward-related neural response to mimicry in individuals with autism
- Pages: 610-618
- First Published: 14 June 2017

Adults with and without autism spectrum disorder (ASD) underwent a conditioning task where they were mimicked by one face and ‘anti-mimicked’ by another. They were then presented with the conditioned faces in a MRI scanner. Reward-related ventral striatal response to mimicking vs anti-mimicking faces was lower in the ASD group compared to controls and negatively correlated with autistic traits across the whole sample. The results suggest a lower reward value for being mimicked in ASD.
Deficits in temporal processing in mice prenatally exposed to Valproic Acid
- Pages: 619-630
- First Published: 14 June 2017

Mice prenatally exposed to valproic acid (VPA) and weaned with other VPA-exposed littermates (VPA-VPA mice) exhibit deficits in interval timing accuracy and precision compared to control groups, as well as deviations from the scalar property. We found that striatal dopamine levels are altered in VPA-VPA mice. Understanding temporal information in the VPA model may have clinical impact in autism spectrum disorders.
Identification of lateralized compensatory neural activities within the social brain due to autism spectrum disorder in adolescent males
- Pages: 631-642
- First Published: 29 June 2017

A new whole-brain voxel-wise analysis is developed to identify differences in brain activities due to ASD in adolescent males. The differences specific to ASD symptoms are selected via correlation with respect to clinical severity scores. The most discriminative brain activities due to ASD are found within a subcircuit in the social brain. Results support the social brain hypothesis and its fractionation in ASD. Potential compensatory mechanisms within the affected regions are also identified.
Peak alpha frequency is a neural marker of cognitive function across the autism spectrum
- Pages: 643-651
- First Published: 12 July 2017

Peak alpha frequency is a developmentally sensitive neural marker of network-level brain activity. This study demonstrates that peak alpha frequency is significantly lower in children with ASD than typically developing children. In addition, peak alpha frequency is associated with non-verbal cognitive function in children with ASD. This suggests that disruptions in network-level brain development may contribute to the variation in cognitive function seen across the autism spectrum.
Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders
- Pages: 652-661
- First Published: 25 July 2017

The major fronto-parietal structural pathways, the superior longitudinal fasciculus (SLF) branches (I, II and III), have not been explored in autism spectrum disorder (ASD). Significant group differences were observed in diffusion measures in the left SLF I and the right SLF II (n = 45 ASD, n = 45 CTRL) using CSD tractography. These findings suggest a role for aberrant fronto-parietal white matter organisation in ASD pathology and lend further support to the altered cortical connectivity theory of the disorder.
Distinct patterns of discrimination and orienting for temporal processing of speech and nonspeech in Chinese children with autism: an event-related potential study
- Pages: 662-668
- First Published: 22 August 2017

The present ERP study investigated whether the previously reported duration perception impairment for both speech and nonspeech sounds in children with autism is observable across languages. Chinese-speaking children with autism were found to show duration perception impairment in the pure tone condition but not in the vowel condition, which is consistent with the ‘allophonic speech perception’ theory for autism. The results indicate a deviant language-dependent pattern of phonological processing in autism.
Autism-relevant traits interact with temporoparietal junction stimulation effects on social cognition: a high-definition transcranial direct current stimulation and electroencephalography study
- Pages: 669-681
- First Published: 27 September 2017

This study examines links between Autism-Spectrum Quotient (AQ) scores and social cognition, and interactions between AQ and rTPJ high-definition-tDCS. Cathodal tDCS reduced emotion attribution performance in participants with higher AQ Switching and AQ Social scores. Anodal tDCS interacted with AQ Social scores, in particular regarding reduced delta power in the lTPJ compared to rTPJ, and trend-level positive interactions with P100 and P300 latencies during emotion attribution. Such trait-level variations interact with tDCS effects on both behaviour and neurophysiology.
Atypical brain responses to auditory spatial cues in adults with autism spectrum disorder
- Pages: 682-689
- First Published: 09 September 2017

Using electroencephalography, we measured the brain responses of autistic and control adults as they listened to dichotic pitch stimuli created by interaural timing (ITD) or amplitude (IAD) differences. Autistic adults failed to show a significant object-related negativity (ORN) for ITDs, although their ORN was not significantly smaller than that of the control group. Autistic participants did show an ORN to IADs; however, their subsequent P400 response was missing.
Three shades of grey: detecting brain abnormalities in children with autism using source-, voxel- and surface-based morphometry
- Pages: 690-700
- First Published: 16 September 2017

For the first time, three morphometric approaches were applied on MRI images of children with autistic spectrum disorder (ASD) and controls. Source-based morphometry, an innovative method that extracts grey matter networks from the structural images, showed a temporal–frontal–parietal network specific for ASD children, seeming more powerful than other methods to detect the widespread abnormalities in the brain of ASD children. This circuit is similar to the ASN, a network found previously in adults with ASD.
The neurobiological bases of autism spectrum disorders: the R451C-neuroligin 3 mutation hampers the expression of long-term synaptic depression in the dorsal striatum
- Pages: 701-708
- First Published: 16 September 2017

We report the loss of long-term synaptic depression (LTD) in the dorsal striatum (DS) of the R451C-NL3 mouse model of ASD, suggesting a substantial involvement of the DS in ASD pathophysiology. LTD expression could be partially rescued by CB1 receptor activation or by endocannabinoid tone enhancement. The incomplete rescue obtained by sustaining cannabinoid signaling suggests that the R451C-NL3 mutation may result in DS dysfunction by causing alterations upstream to the endocannabinoid system.
Neural responses to linguistic stimuli in children with and without autism spectrum disorder
- Pages: 709-719
- First Published: 18 September 2017

We recorded ERPs in response to words from four groups of 36-month-olds: low-risk controls, high familial risk (HRA) for ASD without broader autism phenotype (BAP), HRA children with BAP (HRA-Atyp) and children with ASD. When controlling for language abilities, the HRA-Atyp group showed an atypical response in the temporo-parietal sites. Our results suggest that language abilities are important to consider when interpreting neural differences in lexical processing within these populations.
Diminished socially selective neural processing in 5-month-old infants at high familial risk of autism
- Pages: 720-728
- First Published: 23 October 2017

Functional near-infrared spectroscopy was used to investigate the processing of social and non-social dynamic stimuli in 5-month-old infants at low and high familial risk of autism spectrum disorder. While social stimuli elicited enhanced posterior temporal cortex activity in the low-risk infants, socially selective activation was diminished in the high-risk group. These findings provide evidence for social processing atypicalities in infants at high familial risk of autism by 5 months of age.
Lobular patterns of cerebellar resting-state connectivity in adults with Autism Spectrum Disorder
- Pages: 729-735
- First Published: 23 October 2017

Compared to controls, adults with autism spectrum disorder showed a significant cerebellar GM loss in the right Crus II. When looking at functional connectivity, the right Crus II showed decreased functional connectivity with cerebral areas clearly related to social functions, such as frontal, temporal and precuneus regions. Interestingly, the cerebellar GM loss in the right Crus II was related to the degree of autistic traits as expressed by the autism-spectrum quotient.
Cortical responses before 6 months of life associate with later autism
- Pages: 736-749
- First Published: 23 October 2017

This fNIRS study demonstrates that at 4–6 months, infants who went on to ASD at 3 years had altered activation to visual and auditory social stimuli, compared to low risk infants, across inferior frontal (IFG) and temporal (aMTG-STG and pSTS-TPJ) cortical regions. Cortical responses in infancy correlated with parent-reported ASD symptomology in toddlerhood. Results demonstrate an early departure from typical development of brain function in individuals who later receive a diagnosis of ASD.
Microarray analysis of gene expression in the cyclooxygenase knockout mice – a connection to autism spectrum disorder
- Pages: 750-766
- First Published: 21 November 2017

This study investigated the effects of COX-1−/− and COX-2−/− gene knockout on the development of the prenatal male mouse brain at embryonic days 16 and 19 as a model of ASD. Gene and protein network analysis in both models identified many differentially expressed known ASD-risk genes, and networks involved in development of dendritic spines and synaptic transmission. These results provide further insight into the contribution of the COX-PGE2 pathway to brain pathologies that can result in ASD.