Altered nociceptive behavior and emotional contagion of pain in mouse models of autism.

Individuals with autism spectrum disorder (ASD) have altered sensory processing but may ineffectively communicate their experiences. Here, we used a battery of nociceptive behavioral tests to assess sensory alterations in two commonly used mouse models of ASD, BTBR T+ Itpr3tf /J (BTBR), and fragile-X mental retardation-1 knockout (Fmr1-KO) mice. We also asked whether emotional contagion, a primitive form of empathy, was altered in BTBR and Fmr1 KO mice when experiencing pain with a social partner. BTBR mice demonstrated mixed nociceptive responses with hyporesponsivity to mechanical/thermal stimuli and intraplantar injections of formalin and capsaicin while displaying hypersensitivity on the acetic acid test. Fmr1-KO mice were hyposensitive to mechanical stimuli and intraplantar injections of capsaicin and formalin. BTBR and Fmr1-KO mice developed significantly less mechanical allodynia following intraplantar injections of complete Freund's adjuvant, while BTBR mice developed slightly more thermal hyperalgesia. Finally, as measured by the formalin and acetic acid writhing tests, BTBR and Fmr1-KO mice did not show emotional contagion of pain. In sum, our findings indicate that depending on the sensation, pain responses may be mixed, which reflects findings in ASD individuals.

Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism.

The pathophysiology of autism has been suggested to involve a combination of both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. We studied neuroimaging and phenotypic data in 47 individuals with autism and 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences in structural connectome organization in individuals with autism relative to controls, with strong between-group effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models reveal that the degree of macroscale anomalies is related to atypical increases of recurrent excitation/inhibition, as well as subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic association analysis based on postmortem datasets identifies genes expressed in cortical and thalamic areas from childhood to young adulthood. Finally, supervised machine learning finds that the macroscale perturbations are associated with symptom severity scores on the Autism Diagnostic Observation Schedule. Together, our analyses suggest that atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism.

Sexually dimorphic patterns in electroencephalography power spectrum and autism-related behaviors in a rat model of fragile X syndrome.

Fragile X syndrome (FXS), a neurodevelopmental disorder with autistic features, is caused by the loss of the fragile X mental retardation protein. Sex-specific differences in the clinical profile have been observed in FXS patients, but few studies have directly compared males and females in rodent models of FXS. To address this, we performed electroencephalography (EEG) recordings and a battery of autism-related behavioral tasks on juvenile and young adult Fmr1 knockout (KO) rats. EEG analysis demonstrated that compared to wild-type, male Fmr1 KO rats showed an increase in gamma frequency band power in the frontal cortex during the sleep-like immobile state, and both male and female KO rats failed to show an increase in delta frequency power in the sleep-like state, as observed in wild-type rats. Previous studies of EEG profiles in FXS subjects also reported abnormally increased gamma frequency band power, highlighting this parameter as a potential translatable biomarker. Both male and female Fmr1 KO rats displayed reduced exploratory behaviors in the center zone of the open field test, and increased distance travelled in an analysis of 24-h home cage activity, an effect that was more prominent during the nocturnal phase. Reduced wins against wild-type opponents in the tube test of social dominance was seen in both sexes. In contrast, increased repetitive behaviors in the wood chew test was observed in male but not female KO rats, while increased freezing in a fear conditioning test was observed only in the female KO rats. Our findings highlight sex differences between male and female Fmr1 KO rats, and indicate that the rat model of FXS could be a useful tool for the development of new therapeutics for treating this debilitating neurodevelopmental disorder.

Vitamin A deficiency exacerbates autism-like behaviors and abnormalities of the enteric nervous system in a valproic acid-induced rat model of autism.

The manifestations of autism spectrum disorder (ASD) are highly heterogeneous. As many individuals with ASD have gastrointestinal (GI) comorbidities, ASD with GI problems is considered to be a subtype of ASD. Vitamin A (VA) plays an important role in the development of both the central and peripheral nervous system. However, the relationship between VA deficiency (VAD) and ASD with GI comorbidities is still unclear. We established rat models with different VA levels based on the valproic acid-induced autism model. Compared to autism model rats with VA normal (VAN), autism model rats with gestational VAD showed more severe autism-like behavior, increased GI transit time, and impairment of the enteric nervous system (ENS). Besides, the expression levels of retinoic acid receptor α (RARα) and Ret in autism model rats with VAD were decreased compared with those in rats with VAN. Supplementation with VA was found to effectively ameliorate autism-like behaviors and impairments of GI motility and the ENS in autism model rats with VAD. Chromatin immunoprecipitation results suggested that RARa can bind to the promoter region of the Ret gene and regulate the Ret signaling pathway. We speculate that VAD in autism might lead to impairments of both the brain and ENS. VAD might be a factor that causes individuals to be more susceptible to ASD-related risk factors and aggravates a subtype of ASD with GI comorbidities.

Everything has Its Time: Narrow Temporal Windows are Associated with High Levels of Autistic Traits Via Weaknesses in Multisensory Integration.

The present study examined whether fundamental sensory functions such as temporal processing and multisensory integration are related to autistic traits in the general population. Both a narrower temporal window (TW) for simultaneous perception, as measured by a temporal order judgement task, and a reduced ability to engage in multisensory integration during the sound-induced flash illusion task were related to higher levels of autistic traits. Additionally, a narrow TW is associated with high levels of autistic traits due to a deficiency in multisensory integration. Taken together, these findings suggest that alterations in fundamental functions produce a cascading effect on higher-order social and cognitive functions, such as those experienced by people with autism spectrum disorder.

Genetic and environmental influences on corticostriatal circuits in twins with autism

Background: Corticostriatal circuits (CSC) have been implicated in the presentation of some restricted and repetitive behaviours (RRBs) in children with autism-spectrum disorder (ASD), and preliminary evidence suggests that disruptions in these pathways may be associated with differences in genetic and environmental influences on brain development. The objective of this investigation was to examine the impact of genetic and environmental factors on CSC regions in twins with and without ASD and to evaluate their relationship with the severity of RRBs. Methods: We obtained T1-weighted MRIs from same-sex monozygotic and dizygotic twin pairs, aged 6­15 years. Good-quality data were available from 48 ASD pairs (n = 96 twins; 30 pairs concordant for ASD, 15 monozygotic and 15 dizygotic; 18 pairs discordant for ASD, 4 monozygotic and 14 dizygotic) and 34 typically developing control pairs (n = 68 twins; 20 monozygotic and 14 dizygotic pairs). We generated structural measures of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), caudate, putamen, pallidum and thalamus using FreeSurfer. Twin pair comparisons included intraclass correlation analyses and ACE modelling (a2 = additive genetics; c2 = common or shared environment; e2 = unique or nonshared environment). We also assessed correlations with RRB severity. Results: Structural variation in CSC regions was predominantly genetically mediated in typically developing twins (a2 = 0.56 to 0.87), except for ACC white matter volume (a2 = 0.42, 95% confidence interval [CI] 0.08 to 0.77). We also observed similar magnitudes of genetic influence in twins with ASD (a2 = 0.65 to 0.97), but the cortical thickness of the ACC (c2 = 0.44, 95% CI 0.22 to 0.66) and OFC (c2 = 0.60, 95% CI 0.25 to 0.95) was primarily associated with environmental factors in only twins with ASD. Twin pair differences in OFC grey matter volume were also correlated with RRB severity and were predominantly environmentally mediated. Limitations: We obtained MRIs on 2 scanners, and analytical approaches could not identify specific genetic and environmental factors. Conclusion: Genetic factors primarily contribute to structural variation in subcortical CSC regions, regardless of ASD, but environmental factors may exert a greater influence on the development of grey matter thickness in the OFC and ACC in children with ASD. The increased vulnerability of OFC grey matter to environmental influences may also mediate some heterogeneity in RRB severity in children with ASD.

Atypical Relationships Between Spontaneous EEG and fMRI Activity in Autism.

Autism spectrum disorders (ASDs) have been linked to atypical communication among distributed brain networks. However, despite decades of research, the exact nature of these differences between typically developing (TD) individuals and those with ASDs remains unclear. ASDs have been widely studied using resting-state neuroimaging methods, including both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). However, little is known about how fMRI and EEG measures of spontaneous brain activity are related in ASDs. In the present study, two cohorts of children and adolescents underwent resting-state EEG (n = 38 per group) or fMRI (n = 66 ASD, 57 TD), with a subset of individuals in both the EEG and fMRI cohorts (n = 17 per group). In the EEG cohort, parieto-occipital EEG alpha power was found to be reduced in ASDs. In the fMRI cohort, blood oxygen level-dependent (BOLD) power was regionally increased in right temporal regions and there was widespread overconnectivity between the thalamus and cortical regions in the ASD group relative to the TD group. Finally, multimodal analyses indicated that while TD children showed consistently positive relationships between EEG alpha power and regional BOLD power, these associations were weak or negative in ASDs. These findings suggest atypical links between alpha rhythms and regional BOLD activity in ASDs, possibly implicating neural substrates and processes that coordinate thalamocortical regulation of the alpha rhythm.

Developmental social vulnerability as the intrinsic origin of psychopathology: A paradigm shift from disease entities to psychiatric derivatives within human diversity.

How a social episode is perceived by a person and how the experience affects her/his subsequent behaviors will inevitably and sometimes accidentally vary in each case on the developmental trajectory from the birth of consciousness to death. Both the preceding developmental conditions and the social impact of the episode become a starting point for the following states of human complex conditions, creating the extraordinary diversity that characterizes our complex society. In this evolutionarily carved landscape, genetic factors including stochastic epistasis, environmental modification, and gene-environment interactions are all active. In these processes, interactions between developmental social vulnerability and environmental influences can lead to the emergence and persistence of some derivative states with social maladaptation. In our model, every psychiatric condition including aberrant paranoid-hallucinatory states is classified as a derivative state. The probability distribution curve for these derivative states has a non-linear relationship with the liability in the population, and there is none with probability 1.0 or zero. Individuals with trivial social vulnerability or high resilience may develop the derivative states in tremendously stressful circumstances, and individuals with huge social vulnerability may not necessarily develop the derivative states in the presence of adequate social supports. Social skillfulness/unskillfulness and behavioral flexibility/inflexibility form the core of the vulnerability-related dimensions. The clinical picture of a derivative manifestation is profiled depending on the individual trait levels in the derivative-related dimensions. Each derivative state has a requisite lineup of dimensions and each dimension can contribute to multiple psychiatric conditions. For example, aberrant paranoid-hallucinatory states and bipolar condition may share some developmental conditions as the derivative-related dimensions. Therefore, multiple derivative states can co-occur or be sequentially comorbid. Although the 'learned strategies' can ostensibly mask the clinical manifestation of developmental deviations, the change of the true dimensional position to the socially skillful direction is efficiently obtained through social experiences in a supportive environment. The liability-probability model makes it impossible to discriminate individuals with psychiatric diagnosis from individuals without the diagnosis and allows all of us to reside in the same human complex diversity.

Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms.

Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2-11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments.

Prenatal immune activation alters the adult neural epigenome but can be partly stabilised by a n-3 polyunsaturated fatty acid diet.

An unstable epigenome is implicated in the pathophysiology of neurodevelopmental disorders such as schizophrenia and autism. This is important because the epigenome is potentially modifiable. We have previously reported that adult offspring exposed to maternal immune activation (MIA) prenatally have significant global DNA hypomethylation in the hypothalamus. However, what genes had altered methylation state, their functional effects on gene expression and whether these changes can be moderated, have not been addressed. In this study, we used next-generation sequencing (NGS) for methylome profiling in a MIA rodent model of neurodevelopmental disorders. We assessed whether differentially methylated regions (DMRs) affected the chromatin state by mapping known DNase I hypersensitivity sites (DHSs), and selected overlapping genes to confirm a functional effect of MIA on gene expression using qPCR. Finally, we tested whether methylation differences elicited by MIA could be limited by post-natal dietary (omega) n-3 polyunsaturated fatty acid (PUFA) supplementation. These experiments were conducted using hypothalamic brain tissue from 12-week-old offspring of mice injected with viral analogue PolyI:C on gestation day 9 of pregnancy or saline on gestation day 9. Half of the animals from each group were fed a diet enriched with n-3 PUFA from weaning (MIA group, n = 12 units, n = 39 mice; Control group, n = 12 units, n = 38 mice). The results confirmed our previous finding that adult offspring exposed to MIA prenatally had significant global DNA hypomethylation. Furthermore, genes linked to synaptic plasticity were over-represented among differentially methylated genes following MIA. More than 80% of MIA-induced hypomethylated sites, including those affecting chromatin state and MECP2 binding, were stabilised by the n-3 PUFA intervention. MIA resulted in increased expression of two of the 'top five' genes identified from an integrated analysis of DMRs, DHSs and MECP2 binding sites, namely Abat (t = 2.46, p < 0.02) and Gnas9 (t = 2.96, p < 0.01), although these changes were not stabilised by dietary intervention. Thus, prenatal MIA exposure impacts upon the epigenomic regulation of gene pathways linked to neurodevelopmental conditions; and many of the changes can be attenuated by a low-cost dietary intervention.

Therapeutic body wraps (TBW) for treatment of severe injurious behaviour in children with autism spectrum disorder (ASD): A 3-month randomized controlled feasibility study.

INTRODUCTION: The use of therapeutic body wraps (TBW) has been reported in small series or case reports, but has become controversial. OBJECTIVES: This is a feasibility, multicentre, randomized, controlled, open-label trial with blinded outcome assessment (PROBE design). SETTING: Children with autism and severe-injurious behaviours (SIB) were enrolled from 13 specialized clinics. INTERVENTIONS: Dry-sheet TBW (DRY group) vs. wet-sheet TBW (WET group). PRIMARY OUTCOME MEASURES: 3-month change in the Aberrant Behaviour Checklist irritability score (ABC-irritability) within per-protocol (PP) sample. RESULTS: From January 2008 to January 2015, we recruited 48 children (age range: 5.9 to 9.9 years, 78.1% male). Seven patients (4 in the DRY group, 3 in the WET group) were dropped from the study early and were excluded from PP analysis. At endpoint, ABC-irritability significantly improved in both groups (means (standard deviation) = -11.15 (8.05) in the DRY group and -10.57 (9.29) in the WET group), as did the other ABC scores and the Children Autism Rating scale score. However, there was no significant difference between groups. All but 5 patients were rated as much or very much improved. A repeated-measures analysis confirmed the significant improvement in ABC-irritability scores according to time (p < .0001), with no significant difference between the two groups (group effect: p = .55; interaction time x group: p = .27). Pooling both groups together, the mean 3-month change from baseline in ABC-irritability score was -10.90 (effect size = 1.59, p < .0001). CONCLUSIONS: We found that feasibility was overall satisfactory with a slow recruitment rate and a rather good attrition rate. TBW was a safe complementary therapy in this population. There was no difference between wet and dry TBW at 3 months, and ABC-irritability significantly decreased with both wet and dry sheet TBW. To assess whether TBW may constitute an alternative to medication or behavioural intervention for treating SIB in ASD patients, a larger randomized comparative trial (e.g. TBW vs. antipsychotics) is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT03164746.

Role of inter-trial phase coherence in atypical auditory evoked potentials to speech and nonspeech stimuli in children with autism.

OBJECTIVE: This autism study investigated how inter-trial phase coherence (ITPC) drives abnormalities in auditory evoked potential (AEP) responses for speech and nonspeech stimuli. METHODS: Auditory P1-N2 responses and ITPCs in the theta band (4-7 Hz) for pure tones and words were assessed with EEG data from 15 school-age children with autism and 16 age-matched typically developing (TD) controls. RESULTS: The autism group showed enhanced P1 and reduced N2 for both speech and nonspeech stimuli in comparison with the TD group. Group differences were also found with enhanced theta ITPC for P1 followed by ITPC reduction for N2 in the autism group. The ITPC values were significant predictors of P1 and N2 amplitudes in both groups. CONCLUSIONS: Abnormal trial-to-trial phase synchrony plays an important role in AEP atypicalities in children with autism. ITPC-driven enhancement as well as attenuation in different AEP components may coexist, depending on the stage of information processing. SIGNIFICANCE: It is necessary to examine the time course of auditory evoked potentials and the corresponding inter-trial coherence of neural oscillatory activities to better understand hyper- and hypo- sensitive responses in autism, which has important implications for sensory based treatment.

Why is vitamin B6 effective in alleviating the symptoms of autism?

Many factors are reported to be involved in the complex pathophysiological processes of autism, suggesting that there is considerable variability in the manifestations of this disease. Several interventions are used to treat this disorder. Among them, vitamin B6 is widely used to treat the symptoms observed in autism. Vitamin B6 is beneficial for about half of autistic individuals in decreasing behavioral problems. However, until now, it remains unknown why vitamin B6 is effective for this disease. Although the exact pathogenesis is not defined, it is evident that certain neurotransmitter systems are impaired in the brains of autistic patients, causing the symptoms observed in the disease. In fact, impairment of many neurotransmitter systems has been reported, including GABA, serotonin, dopamine, and noradrenalin. Furthermore, vitamin B6 is important for the synthesis of many neurotransmitters, including GABA, serotonin, dopamine, noradrenalin, histamine, glycine, and d-serine, indicating that vitamin B6 supplementation may enhance many neurotransmitter systems. Thus, vitamin B6 supplementation can treat the impaired neurotransmitter systems in a given patient, even if the actual impaired neurotransmitter systems are not defined in that patient.

Distinct ERP profiles for auditory processing in infants at-risk for autism and language impairment.

Early identification of autism spectrum disorder (ASD) is crucial for the formulation of effective intervention programs. Language deficits may be a hallmark feature of ASD and language delay observed in ASD shows striking similarities to that observed in children with language impairment (LI). Auditory processing deficits are seen in both LI and ASD, however, they have not previously been compared directly using Event-Related Potentials (ERPs) in the two at-risk populations. This study aims to characterize infants at-risk for ASD (HR-ASD) at the electrophysiological level and to compare them with infants at-risk for LI (HR-LI) and controls, to find specific markers with predictive value. At 12-month-old, auditory processing in HR-ASD, HR-LI and controls was characterized via ERP oddball paradigm. All infants were then evaluated at 20 months, to investigate the associations between auditory processing and language/ASD-related outcomes. In both HR-ASD and HR-LI, mismatch response latency was delayed compared to controls, whereas only HR-ASD showed overall larger P3 amplitude compared to controls. Interestingly, these ERP measures correlated with later expressive vocabulary and M-CHAT critical items in the whole sample. These results may support the use of objective measurement of auditory processing to delineate pathophysiological mechanisms in ASD, as compared to LI.

NREM sleep EEG activity and procedural memory: A comparison between young neurotypical and autistic adults without sleep complaints.

Delta EEG activity (0.75-3.75 Hz) during non-Rapid eye movement (NREM) sleep reflects the thalamo-cortical system contribution to memory consolidation. The functional integrity of this system is thought to be compromised in the Autism spectrum disorder (ASD). This lead us to investigate the topography of NREM sleep Delta EEG activity in young adults with ASD and typically-developed individuals (TYP). The relationship between Delta EEG activity and sensory-motor procedural information was also examined using a rotary pursuit task. Two dependent variables were computed: a learning index (performance increase across trials) and a performance index (average performance for all trials). The ASD group showed less Delta EEG activity during NREM sleep over the parieto-occipital recording sites compared to the TYP group. Delta EEG activity dropped more abruptly from frontal to posterior regions in the ASD group. Both groups of participants learned the task at a similar rate but the ASD group performed less well in terms of contact time with the target. Delta EEG activity during NREM sleep, especially during stage 2, correlated positively with the learning index for electrodes located all over the cortex in the TYP group, but only in the frontal region in the ASD group. Delta EEG activity, especially during stage 2, correlated positively with the performance index, but in the ASD group only. These results reveal an atypical thalamo-cortical functioning over the parieto-occipital region in ASD. They also point toward an atypical relationship between the frontal area and the encoding of sensory-motor procedural memory in ASD. Autism Res 2018, 11: 613-623. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Slow EEG waves recorded from the scalp during sleep are thought to facilitate learning and memory during daytime. We compared these EEG waves in young autistic adults to typically-developing young adults. We found less slow EEG waves in the ASD group and the pattern of relationship with memory differed between groups. This suggests atypicalities in the way sleep mechanisms are associated with learning and performance in a sensory-motor procedural memory task in ASD individuals.

Mismatch Negativity and P3a in Adolescents and Young Adults with Autism Spectrum Disorders: Behavioral Correlates and Clinical Implications.

In a sample of 37 adolescents and young adults with autism spectrum disorder (ASD) and 35 typically-developing controls (TDC), we investigated sensory symptoms by clinical measures, and Mismatch Negativity and P3a component at Fz with the frequency and duration oddball paradigms of event-related potentials. Results showed that compared to TDC, ASD participants reported more sensory symptoms, and presented a shorter P3a peak latency in the duration paradigm, which was correlated with more social awareness deficits. In the frequency paradigm, P3a parameters were correlated with sensation avoiding and attention characteristics of ASD. Our findings suggest that sensory abnormality in ASD may extend into adolescence and young adulthood. P3a latency might be a potential neurophysiological marker for ASD.

Changes in intrinsic local connectivity after reading intervention in children with autism.

Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs.

"Decoding versus comprehension": Brain responses underlying reading comprehension in children with autism.

Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain's reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading-related neural resources in ASD children and suggest specific weaknesses in top-down modulation of semantic processing.

Speech-specific categorical perception deficit in autism: An Event-Related Potential study of lexical tone processing in Mandarin-speaking children.

Recent studies reveal that tonal language speakers with autism have enhanced neural sensitivity to pitch changes in nonspeech stimuli but not to lexical tone contrasts in their native language. The present ERP study investigated whether the distinct pitch processing pattern for speech and nonspeech stimuli in autism was due to a speech-specific deficit in categorical perception of lexical tones. A passive oddball paradigm was adopted to examine two groups (16 in the autism group and 15 in the control group) of Chinese children's Mismatch Responses (MMRs) to equivalent pitch deviations representing within-category and between-category differences in speech and nonspeech contexts. To further examine group-level differences in the MMRs to categorical perception of speech/nonspeech stimuli or lack thereof, neural oscillatory activities at the single trial level were further calculated with the inter-trial phase coherence (ITPC) measure for the theta and beta frequency bands. The MMR and ITPC data from the children with autism showed evidence for lack of categorical perception in the lexical tone condition. In view of the important role of lexical tones in acquiring a tonal language, the results point to the necessity of early intervention for the individuals with autism who show such a speech-specific categorical perception deficit.

Design of a Physiology-Sensitive VR-Based Social Communication Platform for Children With Autism.

Individuals with autism are often characterized by impairments in communication, reciprocal social interaction and explicit expression of their affective states. In conventional techniques, a therapist adjusts the intervention paradigm by monitoring the affective state e.g., anxiety of these individuals for effective floor-time-therapy. Conventional techniques, though powerful, are observation-based and face resource limitations. Technology-assisted systems can provide a quantitative, individualized rehabilitation platform. Presently-available systems are designed primarily to chain learning via aspects of one's performance alone restricting individualization. Specifically, these systems are not sensitive to one's anxiety. Our presented work seeks to bridge this gap by developing a novel VR-based interactive system with Anxiety-Sensitive adaptive technology. Specifically, such a system is capable of objectively identifying and quantifying one's anxiety level from real-time biomarkers, along with performance metrics. In turn it can adaptively respond in an individualized manner to foster improved social communication skills. In our present research, we have used Virtual Reality (VR) to design a proof-of-concept application that exposes participants to social tasks of varying challenges. Results of a preliminary usability study indicate the potential of our VR-based Anxiety-Sensitive system to foster improved task performance, thereby serving as a potent complementary tool in the hands of therapist.