Different Functional Neural Substrates for Good and Poor Language Outcome in Autism

Abstract

Summary Autism (ASD) is vastly heterogeneous, particularly in early language development. While ASD language trajectories in the first years of life are highly unstable, by early childhood these trajectories stabilize and are predictive of longer-term outcome. Early neural substrates that predict/precede such outcomes are largely unknown but could have considerable translational and clinical impact. Pre-diagnosis fMRI response to speech in ASD toddlers with relatively good language outcome was highly similar to non-ASD comparison groups and robustly recruited language-sensitive superior temporal cortices. In contrast, language-sensitive superior temporal cortices were hypoactive in ASD toddlers with poor language outcome. Brain-behavioral relationships were atypically reversed in ASD and a multimodal combination of pre-diagnostic clinical behavioral measures and speech-related fMRI response showed the most promise as an ASD prognosis classifier. Thus, before ASD diagnoses and outcome become clinically clear, distinct functional neuroimaging phenotypes are already present that can shed insight on an ASD toddler’s later outcome.

Resting-state functional connectivity predicts longitudinal change in autistic traits and adaptive functioning in autism

“…A recent study of ASD outcomes by Lombardo et al (25) corroborates this claim. The authors showed that fMRI data collected during an auditory language task on infants and toddlers, who later developed ASD, predicted a categorical language outcome 1 y postscan [68% accuracy, area under the curve (AUC), 69%].…”

“…Hearteningly, however, there is evidence that some of these regions may be predictive of other outcomes in ASD populations. The study by Lombardo et al (25) of prospective language outcomes in ASD also showed that activity in the anterior insula and anterior cingulate of the SN, as well as medial prefrontal cortex and portions of the superior temporal cortex included in the DMN, correlated with future language ability using partial least squares correlation.…”

“…As such, brain measures may explain additional variance in behavioral outcomes. One previous study has shown that combining functional MRI (fMRI) data with behavioral data increased predictive power for categorical language outcomes in early developing ASD (25). Brain-derived data has also added explanatory power to predictive models of depression (26), dyslexia (27), alcoholism (28), and reading and math ability (29,30).…”

Neurobiological Bases of Autism Spectrum Disorders and Implications for Early Intervention: A Brief Overview

“…In turn, neuroanatomical, neurochemical, and neurophysiological events occurring in cortical and subcortical brain areas trigger and determine the person’s ability to understand the meaning behind pragmatic aspects of communication. Such skills include the decoding of facial expressions, the appropriate use of eye contact, and joint attention [12, 13]. Data suggest that the infant’s attention to a person’s face is mediated by the subcortical area of the visual neural pathway (e.g., from the retina to the occipital lobe) [11, 14].…”

Identification and validation of biomarkers for autism spectrum disorders

“…*The views expressed in this article are the personal views of the author and may not be understood nor quoted as being made on behalf of or reflecting the position of the European Medicines Agency (EMA) or one of its committees or working parties or any of the national agencies. of brain structure 8 and function 9 and relate them to clinical outcome. Neuroimaging techniques also help us to identify the mecha nisms through which interventions improve functioning.…”