2014 Research Findings

The following studies were published in 2014. The grants awarded by ASF to fund these studies may have been distributed in years prior to 2014.

Importance and Practical Application of Early Detection and Intervention:

Feasibility and Effectiveness of Very Early Intervention 
for Infants At-Risk for Autism Spectrum Disorder: A Systematic Review

Early detection methods for autism spectrum disorder (ASD) in infancy are rapidly advancing, yet the development of interventions for infants under two years with or at-risk for ASD remains limited. In order to guide research and practice, Jessica Bradshow systematically reviewed studies investigating interventions for infants under 24 months with or at-risk for ASD. Nine studies were identified and evaluated for: (a) participants, (b) intervention approach (c) experimental design, and (d) outcomes. Studies that collected parent measures reported positive findings for parent acceptability, satisfaction, and improvement in parent implementation of treatment. Infant gains in social-communicative and developmental skills were observed following intervention in most of the reviewed studies, while comparisons with treatment-as- usual control groups elucidate the need for further research. These studies highlight the feasibility of very early inter- vention and provide preliminary evidence that intervention for at-risk infants may be beneficial for infants and parents.

The full study can be found here.

Scaffolded Reaching Experiences Encourage Grasping Activity in Infants at High Risk for Autism

Recent findings suggest impaired motor skill development during infancy in children later diagnosed with autism spectrum disorders (ASD). However, it remains unclear whether infants at high familial risk for ASD would benefit from early interventions targeting the motor domain. The current study led by Drs. Klaus Libertus and Rebecca Landa at the Kennedy Krieger Institute, investigated this issue by providing 3-month-old infants at high familial risk for ASD with training experiences aimed at facilitating independent reaching. A group of 17 high-risk (HR) infants received 2 weeks of scaffolded reaching experiences using “sticky mittens,” and was compared to 72 low-risk (LR) infants experiencing the same or alternative training procedures. Results indicate that HR infants – just like LR infants – show an increase in grasping activity following “sticky mittens” training. In contrast to LR infants, evidence that motor training encouraged a preference for faces in HR infants was inconclusive.

Read a blog by Dr. Libertus about the “sticky mitten” study here and the full study here.

Brain Connectivity in Autism and How it can be Improved by Intervention

Atypical Cross Talk Between Mentalizing and Mirror Neuron Networks in Autism Spectrum Disorder

Dr. Inna Fishman and her colleagues at UCSD investigate whether adolescence with autism show differences in connectivity across two brain regions which have been shown to be affected in ASD.  They are involved in social processing, the ability to recognize and understand the thoughts of others.  They found that people with ASD showed both over and under connectivity in these networks.  There was greater cross talk between areas involving mentalizing and mirror neurons.  This also may explain why these symptoms are so variable in individuals with ASD – it may not be size of the brain, but the connections across regions.

Heterogeneity of Neural Mechanisms of Response to Pivotal Response Treatment

Dr. Pamela Ventola and colleagues at Yale University investigated the mechanisms by which Pivotal Response Treatment (PRT) improves social communication in a case series of 10 preschool-aged children with Autism Spectrum Disorder (ASD). Functional magnetic resonance imaging (fMRI) identified brain responses during a biological motion perception task conducted prior to and following 16 weeks of PRT treatment. Overall, the neural systems supporting social perception in these 10 children were mal-leable through implementation of PRT; following treatment, neural responses were more similar to those of typically developing children (TD). However, at baseline, half of the children exhibited hypoactivation, relative to a group of TD children, in the right posterior superior temporal sulcus (pSTS), and half exhibited hyperactivation in this region. Strikingly, the groups exhibited differential neural responses to treatment: The five children who exhibited hypoactivation at baseline evidenced increased activation in components of the reward system including the ventral striatum and putamen. The five children who exhibited hyperactivation at baseline evidenced decreased activation in subcortical regions critical for regulating the flow of stimulation and conveying signals of salience to the cortex—the thalamus, amygdala, and hippo- campus. Our results support further investigation into the differential effects of particular treatment strategies relative to specific neural targets. Identification of treatment strategies that address the patterns of neural vulnerability unique to each patient is consistent with the priority of creating individually tailored interventions customized to the behavioral and neural characteristics of a given person.

Read a blog on this publication by Dr. Ventola here.

Risk Factors for ASD and Brain Pathways

Convergence of Circuit Dysfunction in ASD: A Common Bridge Between Diverse Genetic and Environmental Risk Factors and Common Clinical Electrophysiology

Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

Etiologies underlying sex differences in Autism Spectrum Disorders.

The male predominance of Autism Spectrum Disorders (ASD) is one of the best-known, and at the same time, one of the least understood characteristics of these disorders. In this paper, Dr. Sara Schaffsma and her mentor Dr. Donald Pfaff, explore epigenetic, hormonal, and environmental mechanisms underlying this male preponderance. Sex-specific effects of Y-linked genes (including SRY expression leading to testicular development), balanced and skewed X-inactivation, genes that escape X-inactivation, parent-of-origin allelic imprinting, and the hypothetical heterochromatin sink are reviewed. These mechanisms likely contribute to etiology, instead of being simply causative to ASD. Environments, both internal and external, also play important roles in ASD’s etiology. Early exposure to androgenic hormones and early maternal immune activation comprise environmental factors affecting sex-specific susceptibility to ASD. The gene-environment interactions underlying ASD, suggested here, implicate early prenatal stress as being especially detrimental to boys with a vulnerable genotype.