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Brain responses to biological motion predict treatment outcome in young children with autism.

ABSTRACT: Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results-however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment-pivotal response treatment. Neural predictors were identified in the pretreatment levels of activity in response to biological vs scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum and ventral striatum). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Predicting who will respond to a particular treatment for ASD, we believe the current findings mark the very first evidence of prediction/stratification biomarkers in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD.

SUBMITTER: Yang D

PROVIDER: S-EPMC5314125 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Brain responses to biological motion predict treatment outcome in young children with autism.

Yang D D Pelphrey K A KA Sukhodolsky D G DG Crowley M J MJ Dayan E E Dvornek N C NC Venkataraman A A Duncan J J Staib L L Ventola P P

Translational psychiatry 20161115 11

Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results-however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensit ...[more]

PMID: 27845779

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Project description:BackgroundThe development of left and right superior temporal gyrus (STG) 50?ms (M50) and 100?ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder (ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD?+?LI) (and perhaps concomitantly lower general cognitive abilities).MethodsThirty-five TD controls, 63 ASD without language impairment (ASD?-?LI), and 38 ASD?+?LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10?years old) and older groups (11-15?years old).ResultsAlthough M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD?-?LI and ASD?+?LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD?+?LI (90 versus 66%, p?=?0.04), with no differences between TD and ASD?-?LI (90 versus 76%, p?=?0.14) or between ASD?-?LI and ASD?+?LI (76 versus 66%, p?=?0.53). In older subjects, whereas no differences were observed between TD and ASD?+?LI, responses were observed more often in ASD?-?LI than ASD?+?LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups.ConclusionAlthough present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11?years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11?years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.

Project description:BackgroundBiological motion imparts rich information related to the movement, actions, intentions and affective state of others, which can provide foundational support for various aspects of social cognition and behavior. Given that atypical social communication and cognition are hallmark symptoms of autism spectrum disorder (ASD), many have theorized that a potential source of this deficit may lie in dysfunctional neural mechanisms of biological motion processing. Synthesis of existing literature provides some support for biological motion processing deficits in autism spectrum disorder, although high study heterogeneity and inconsistent findings complicate interpretation. Here, we attempted to reconcile some of this residual controversy by investigating a possible modulating role for attention in biological motion processing in ASD.MethodsWe employed high-density electroencephalographic recordings while participants observed point-light displays of upright, inverted and scrambled biological motion under two task conditions to explore spatiotemporal dynamics of intentional and unintentional biological motion processing in children and adolescents with ASD (n = 27), comparing them to a control cohort of neurotypical (NT) participants (n = 35).ResultsBehaviorally, ASD participants were able to discriminate biological motion with similar accuracy to NT controls. However, electrophysiologic investigation revealed reduced automatic selective processing of upright biologic versus scrambled motion stimuli in ASD relative to NT individuals, which was ameliorated when task demands required explicit attention to biological motion. Additionally, we observed distinctive patterns of covariance between visual potentials evoked by biological motion and functional social ability, such that Vineland Adaptive Behavior Scale-Socialization domain scores were differentially associated with biological motion processing in the N1 period in the ASD but not the NT group.LimitationsThe cross-sectional design of this study does not allow us to definitively answer the question of whether developmental differences in attention to biological motion cause disruption in social communication, and the sample was limited to children with average or above cognitive ability.ConclusionsTogether, these data suggest that individuals with ASD are able to discriminate, with explicit attention, biological from non-biological motion but demonstrate diminished automatic neural specificity for biological motion processing, which may have cascading implications for the development of higher-order social cognition.

Dataset Information

Brain responses to biological motion predict treatment outcome in young children with autism.

Publications

Brain responses to biological motion predict treatment outcome in young children with autism.

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