Jennifer H. Foss-Feig

A Systematic Review of Early Intensive Intervention for Autism Spectrum Disorders

CONTEXT: Early intensive behavioral and developmental interventions for young children with autism spectrum disorders (ASDs) may enhance developmental outcomes. OBJECTIVE: To systematically review evidence regarding such interventions for children aged 12 and younger with ASDs. METHODS: We searched Medline, PsycINFO, and ERIC (Education Resources Information Center) from 2000 to May 2010. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength-of-evidence ratings using predetermined criteria. RESULTS: Thirty-four unique studies met inclusion criteria. Seventeen studies were case series; 2 were randomized controlled trials. We rated 1 study as good quality, 10 as fair quality, and 23 as poor quality. The strength of the evidence overall ranged from insufficient to low. Studies of University of California Los Angeles/Lovaas–based interventions and variants reported clinically significant gains in language and cognitive skills in some children, as did 1 randomized controlled trial of an early intensive developmental intervention approach (the Early Start Denver Model). Specific parent-training approaches yielded gains in short-term language function and some challenging behaviors. Data suggest that subgroups of children displayed more prominent gains across studies, but participant characteristics associated with greater gains are not well understood. CONCLUSIONS: Studies of Lovaas-based approaches and early intensive behavioral intervention variants and the Early Start Denver Model resulted in some improvements in cognitive performance, language skills, and adaptive behavior skills in some young children with ASDs, although the literature is limited by methodologic concerns.

An extended multisensory temporal binding window in autism spectrum disorders

Autism spectrum disorders (ASD) form a continuum of neurodevelopmental disorders, characterized by deficits in communication and reciprocal social interaction, as well as by repetitive behaviors and restricted interests. Sensory disturbances are also frequently reported in clinical and autobiographical accounts. However, surprisingly few empirical studies have characterized the fundamental features of sensory and multisensory processing in ASD. The current study is structured to test for potential differences in multisensory temporal function in ASD by making use of a temporally dependent, low-level multisensory illusion. In this illusion, the presentation of a single flash of light accompanied by multiple sounds often results in the illusory perception of multiple flashes. By systematically varying the temporal structure of the audiovisual stimuli, a “temporal window” within which these stimuli are likely to be bound into a single perceptual entity can be defined. The results of this study revealed that children with ASD report the flash-beep illusion over an extended range of stimulus onset asynchronies relative to children with typical development, suggesting that children with ASD have altered multisensory temporal function. These findings provide valuable new insights into our understanding of sensory processing in ASD and may hold promise for the development of more sensitive diagnostic measures and improved remediation strategies.

Altered Auditory and Multisensory Temporal Processing in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are characterized by deficits in social reciprocity and communication, as well as by repetitive behaviors and restricted interests. Unusual responses to sensory input and disruptions in the processing of both unisensory and multisensory stimuli also have been reported frequently. However, the specific aspects of sensory processing that are disrupted in ASD have yet to be fully elucidated. Recent published work has shown that children with ASD can integrate low-level audiovisual stimuli, but do so over an extended range of time when compared with typically developing (TD) children. However, the possible contributions of altered unisensory temporal processes to the demonstrated changes in multisensory function are yet unknown. In the current study, unisensory temporal acuity was measured by determining individual thresholds on visual and auditory temporal order judgment (TOJ) tasks, and multisensory temporal function was assessed through a cross-modal version of the TOJ task. Whereas no differences in thresholds for the visual TOJ task were seen between children with ASD and TD, thresholds were higher in ASD on the auditory TOJ task, providing preliminary evidence for impairment in auditory temporal processing. On the multisensory TOJ task, children with ASD showed performance improvements over a wider range of temporal intervals than TD children, reinforcing prior work showing an extended temporal window of multisensory integration in ASD. These findings contribute to a better understanding of basic sensory processing differences, which may be critical for understanding more complex social and cognitive deficits in ASD, and ultimately may contribute to more effective diagnostic and interventional strategies.

Functional Connectivity of the Inferior Frontal Cortex Changes with Age in Children with Autism Spectrum Disorders: A fcMRI Study of Response Inhibition

Unmasking the neural basis of neurodevelopmental disorders, such as autism spectrum disorders (ASD), requires studying functional connectivity during childhood when cognitive skills develop. A functional connectivity magnetic resonance imaging (fcMRI) analysis was performed on data collected during Go/NoGo task performance from 24 children ages 8-12 years (12 with ASD; 12 controls matched on age and intellectual functioning). We investigated the connectivity of the left and right inferior frontal cortex (IFC; BA 47), key regions for response inhibition, with other active regions in frontal, striatal, and parietal cortex. Groups did not differ on behavioral measures or functional connectivity of either IFC region. A trend for reduced connectivity in the right IFC for the ASD group was revealed when controlling for age. In the ASD group, there was a significant negative correlation between age and 2 right IFC correlation pairs: right IFC-bilateral presupplementary motor area (BA 6) and right IFC-right caudate. Compared with typical controls, children with ASD may not have gross differences in IFC functional connectivity during response inhibition, which contrasts with an adult study of ASD that reported reduced functional connectivity. This discrepancy suggests an atypical developmental trajectory in ASD for right IFC connectivity with other neural regions supporting response inhibition.

The rubber hand illusion in children with autism spectrum disorders: delayed influence of combined tactile and visual input on proprioception

In the rubber hand illusion, perceived hand ownership can be transferred to a rubber hand after synchronous visual and tactile stimulation. Perceived body ownership and self–other relation are foundational for development of self-awareness, imitation, and empathy, which are all affected in autism spectrum disorders (ASD). We examined the rubber hand illusion in children with and without ASD. Children with ASD were initially less susceptible to the illusion than the comparison group, yet showed the effects of the illusion after 6 minutes. Delayed susceptibility to the illusion may result from atypical multisensory temporal integration and/or an unusually strong reliance on proprioception. Children with ASD who displayed less empathy were significantly less likely to experience the illusion than those with more intact ability to express empathy. A better understanding of body representation in ASD may elucidate neural underpinnings of social deficits, thus informing future intervention approaches.

A Substantial and Unexpected Enhancement of Motion Perception in Autism

Atypical perceptual processing in autism spectrum disorder (ASD) is well documented. In addition, growing evidence supports the hypothesis that an excitatory/inhibitory neurochemical imbalance might underlie ASD. Here we investigated putative behavioral consequences of the excitatory/inhibitory imbalance in the context of visual motion perception. As stimulus size increases, typical observers exhibit marked impairments in perceiving motion of high-contrast stimuli. This result, termed “spatial suppression,” is believed to reflect inhibitory motion-processing mechanisms. Motion processing is also affected by gain control, an inhibitory mechanism that underlies saturation of neural responses at high contrast. Motivated by these behavioral correlates of inhibitory function, we investigated motion perception in human children with ASD (n = 20) and typical development (n = 26). At high contrast, both groups exhibited similar impairments in motion perception with increasing stimulus size, revealing no apparent differences in spatial suppression. However, there was a substantial enhancement of motion perception in ASD: children with ASD exhibited a consistent twofold improvement in perceiving motion. Hypothesizing that this enhancement might indicate abnormal weakening of response gain control, we repeated our measurements at low contrast, where the effects of gain control should be negligible. At low contrast, we indeed found no group differences in motion discrimination thresholds. These low-contrast results, however, revealed weaker spatial suppression in ASD, suggesting the possibility that gain control abnormalities in ASD might have masked spatial suppression differences at high contrast. Overall, we report a pattern of motion perception abnormalities in ASD that includes substantial enhancements at high contrast and is consistent with an underlying excitatory/inhibitory imbalance.

Atypical neural substrates of Embedded Figures Task performance in children with Autism Spectrum Disorder

Superior performance on the Embedded Figures Task (EFT) has been attributed to weak central coherence in perceptual processing in Autism Spectrum Disorder (ASD). The present study used functional magnetic resonance imaging to examine the neural basis of EFT performance in 7- to 12-year-old ASD children and age- and IQ-matched controls. ASD children activated only a subset of the distributed network of regions activated in controls. In frontal cortex, control children activated left dorsolateral, medial and dorsal premotor regions whereas ASD children only activated the dorsal premotor region. In parietal and occipital cortices, activation was bilateral in control children but unilateral (left superior parietal and right occipital) in ASD children. Further, extensive bilateral ventral temporal activation was observed in control, but not ASD children. ASD children performed the EFT at the same level as controls but with reduced cortical involvement, suggesting that disembedded visual processing is accomplished parsimoniously by ASD relative to typically developing brains.

Strength of default mode resting‐state connectivity relates to white matter integrity in children

A default mode network of brain regions is known to demonstrate coordinated activity during the resting state. While the default mode network is well characterized in adults, few investigations have focused upon its development. We scanned 9-13-year-old children with diffusion tensor imaging and resting-state functional magnetic resonance imaging. We identified resting-state networks using Independent Component Analysis and tested whether the functional connectivity between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) depends upon the maturation of the underlying cingulum white matter tract. To determine the generalizability of this relationship, we also tested whether functional connectivity depends on white matter maturity between bilateral lateral prefrontal cortex (lateral PFC) within the executive control network. We found a positive relationship between mPFC-PCC connectivity and fractional anisotropy of the cingulum bundle; this positive relationship was moderated by the age of the subjects such that it was stronger in older children. By contrast, no such structure-function relationship emerged between right and left lateral PFC. However, functional and structural connectivity of this tract related positively with cognitive speed, fluency, and set-switching neuropsychological measures.

Response of neural reward regions to food cues in autism spectrum disorders

BackgroundOne hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards.MethodWe asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD) signal in response to the food imagesResultsWe found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD.ConclusionThese results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

Neural response to working memory load varies by dopamine transporter genotype in children.

Inheriting two (10/10) relative to one (9/10) copy of the 10-repeat allele of the dopamine transporter genotype (DAT1) is associated with Attention Deficit Hyperactivity Disorder, a childhood disorder marked by poor executive function. We examined whether functional anatomy underlying working memory, a component process of executive function, differed by DAT1 in 7-12 year-old typically developing children. 10/10 and 9/10 carriers performed a verbal n-back task in two functional magnetic resonance imaging (fMRI) runs varying in working memory load, high (2-back vs. 1-back) and low (1-back vs. 0-back). Performance accuracy was superior in 9/10 than 10/10 carriers in the high but not low load runs. Examination of each run separately revealed that frontal-striatal-parietal regions were more activated in 9/10 than 10/10 carriers in the high load run; the groups did not differ in the low load run. Examination of load effects revealed a DAT1xLoad interaction in the right hemisphere in the caudate, our a priori region of interest. Exploratory analysis at a more liberal threshold revealed this interaction in other basal ganglia regions (putamen, and substantial nigra/subthalamic nuclei - SN/STN) and in medial parietal cortex (left precuneus). The striatal and parietal regions were more activated in 9/10 carriers under high than low load, and DAT1 differences (9/10>10/10) were evident only under high load. In contrast, SN/STN tended to be more activated in 10/10 carriers under low than high load and DAT1 differences (10/10>9/10) were evident only under low load. Thus, 10-repeat homozygosity of DAT1 was associated with reduced performance and a lack of increased basal ganglia involvement under higher working memory demands.