Autism Research and Treatment
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AMBRA1, Autophagy, and the Extreme Male Brain Theory of Autism

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Autism Research and Treatment publishes original research articles, review articles, and clinical studies related to all aspects of autism.

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Autism Research and Treatment maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.

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Research Article

Neural Mechanisms of Reward Prediction Error in Autism Spectrum Disorder

Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).

Research Article

Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial

Background. In contrast to multiple rare monogenetic abnormalities, a common biomarker among children with infantile autism and their parents is the discovery of serum autoantibodies directed to the folate receptor alpha (FRα) localized at blood-brain and placental barriers, impairing physiologic folate transfer to the brain and fetus. Since outcome after behavioral intervention remains poor, a trial was designed to treat folate receptor alpha (FRα) autoimmunity combined with correction of deficient nutrients due to abnormal feeding habits. Methods. All participants with nonsyndromic infantile autism underwent a routine protocol measuring CBC, iron, vitamins, coenzyme Q10, metals, and trace elements. Serum FRα autoantibodies were assessed in patients, their parents, and healthy controls. A self-controlled therapeutic trial treated nutritional derangements with addition of high-dose folinic acid if FRα autoantibodies tested positive. The Childhood Autism Rating Scale (CARS) monitored at baseline and following 2 years of treatment was compared to the CARS of untreated autistic children serving as a reference. Results. In this self-controlled trial (82 children; mean age ± SD: 4.4 ± 2.3 years; male:female ratio: 4.8:1), FRα autoantibodies were found in 75.6 % of the children, 34.1 % of mothers, and 29.4 % of fathers versus 3.3 % in healthy controls. Compared to untreated patients with autism (n=84) whose CARS score remained unchanged, a 2-year treatment decreased the initial CARS score from severe (mean ± SD: 41.34 ± 6.47) to moderate or mild autism (mean ± SD: 34.35 ± 6.25; paired t-test p<0.0001), achieving complete recovery in 17/82 children (20.7 %). Prognosis became less favorable with the finding of higher FRα autoantibody titers, positive maternal FRα autoantibodies, or FRα antibodies in both parents. Conclusions. Correction of nutritional deficiencies combined with high-dose folinic acid improved outcome for autism, although the trend of a poor prognosis due to maternal FRα antibodies or FRα antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy.

Research Article

Risk for ASD in Preterm Infants: A Three-Year Follow-Up Study

Background. The aim of this study was to examine the long-term risk for autism spectrum disorders (ASD) in individuals who are born preterm and full-term using both observational instruments and parental reports. Neonatal risk factors and developmental characteristics associated with ASD risk were also examined. Method. Participants included 110 preterm children (born at a gestational age of ≤ 34 weeks) and 39 full-term children assessed at ages 18, 24, and 36 months. The Autism Diagnostic Observation Schedule, the Modified Checklist for Autism in Toddlers, the Autism Diagnostic Interview-Revised, the Social Communication Questionnaire, and the Mullen Scales of Early Learning were administered. Results and Conclusions. The long-term risk for ASD was higher when parental reports were employed compared to observational instruments. At 18 and 24 months, a higher long-term risk for ASD was found for preterm children compared to full-term children. At 36 months, only one preterm child and one full-term child met the cutoff for ASD based on the ADOS, yet clinical judgment and parental reports supported an ASD diagnosis for the preterm child only. Earlier gestational age and lower general developmental abilities were associated with elevated ASD risk among preterm children.

Research Article

Neuromagnetic Beta-Band Oscillations during Motor Imitation in Youth with Autism

Children with ASD often exhibit early difficulties with action imitation, possibly due to low-level sensory or motor impairments. Impaired cortical rhythms have been demonstrated in adults with ASD during motor imitation. While those oscillations reflect an age-dependent process, they have not been fully investigated in youth with ASD. We collected magnetoencephalography data to examine patterns of oscillatory activity in the mu (8-13 Hz) and beta frequency (15-30 Hz) range in 14 adolescents with and 14 adolescents without ASD during a fine motor imitation task. Typically developing adolescents exhibited adult-like patterns of motor signals, e.g., event-related beta and mu desynchronization (ERD) before and during the movement and a postmovement beta rebound (PMBR) after the movement. In contrast, those with ASD exhibited stronger beta and mu-ERD and reduced PMBR. Behavioral performance was similar between groups despite differences in motor cortical oscillations. Finally, we observed age-related increases in PBMR and beta-ERD in the typically developing children, but this correlation was not present in the autism group. These results suggest reduced inhibitory drive in cortical rhythms in youth with autism during intact motor imitation. Furthermore, impairments in motor brain signals in autism may not be due to delayed brain development. In the context of the excitation-inhibition imbalance perspectives of autism, we offer new insights into altered organization of neurophysiological networks.

Research Article

Role of Inner Speech on Serial Recall in Children with ASD: A Pilot Study Using the Luria Hand Test

This study was conducted to investigate the relation between the effect of articulatory suppression on the serial recall and severity of social impairments among children with autism spectrum disorders (ASD). The Luria hand test (LHT) was administered to evaluate the capacity for serial recall in 13 children with ASD. The LHT was administered under three conditions: control, under articulatory suppression, and under spatial suppression. Performance on the LHT of children with ASD was significantly lower in terms of both articulatory suppression and the spatial suppression condition. Moreover, the severity of social impairment in children with ASD was related to individual differences of effects of articulatory suppression on the LHT, but not with effects of spatial suppression. These results support the notion that dialogic inner speech which mediates complex cognitive abilities has inherently social origins.

Research Article

A Study of the Correlation between VEP and Clinical Severity in Children with Autism Spectrum Disorder

Visual evoked potential (VEP) is a technique used to assess the brain’s electrical response to visual stimuli. The aims of this study were to examine neural transmission within the visual pathway through VEP testing in preschool children with autism spectrum disorder (ASD) and compare it to age-matched controls, as well as search for a correlation between the VEP parameters and the symptoms of ASD. Participants were composed of ASD children (9 males) and typically developing children (8 males and 4 females), aged between 3 and 5 years. Checkerboards were chosen as the pattern-reversal VEP. The clinical severity of ASD was assessed using the Autism Treatment Evaluation Checklist (ATEC) and the Vineland Adaptive Behavior Scales 2nd edition (VABS-II). Our findings demonstrated that children with ASD had significantly longer N145 latency compared to the controls. A longer N145 latency correlated with a higher score of ATEC within the sensory/cognitive awareness subdomain. In addition, a slower N145 response was also associated with a lower VABS-II score within the socialization domain. The correlation between longer VEP latency and abnormal behaviors in children with ASD suggests a delayed neural communication within other neural circuits, apart from the visual pathway. These lines of evidence support the possibility of using VEP, along with clinical parameters, for the assessment of ASD severity.

Autism Research and Treatment
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