Brain Mechanisms for Language Processing in Adolescents With Autism Spectrum Disorder
Condition: Autism Spectrum Disorders
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      The main goal of our study is to find out why some people with Autism Spectrum Disorder (ASD)
      do not develop verbal abilities or remain minimally-verbal throughout adolescence and
      adulthood. Current research focuses on investigating brain differences related to processing
      sounds and initiating speech in adolescents and young adults with ASD varying in language
      skills, compared to adolescents who do not have ASD, in order to clarify whether atypical
      processes of auditory perception, perceptual organization and/or neural oscillation patterns
      may explain why some individuals with ASD fail to acquire functional speech.
    

Detailed description: 
      About 30% of children with Autism Spectrum Disorder (ASD) fail to acquire spoken language.
      This group of children has been seriously neglected in research conducted over the past 2
      decades. Little is known about them, in part because the field lacks the tools to assess
      them, and they often pose significant behavioral challenges that preclude their participation
      in research studies. Among the ~70% individuals with ASD who have spoken language skills,
      about 50% are language impaired; the remaining group have normal language scores on
      standardized tests. Thus, there is enormous heterogeneity in verbal abilities in ASD. To
      date, studies of the brain and cognitive mechanisms that underlie this heterogeneity remain
      quite limited.

      At the cognitive level, current research suggests that language impairment in verbal children
      with ASD involves deficits in phonological working memory, as evident on tests of nonsense
      word repetition. The areas of language that are most affected in this group include complex
      syntax and morphology related to marking tense (Tager-Flusberg et al., 2005). There is also
      considerable evidence from MRI (magnetic resonance imaging) studies of both children and
      adults that there are differences in volume and asymmetry in language regions of the cortex,
      specifically Broca's and Wernicke's areas. Recent studies suggest that these differences do
      not necessarily track with degree of language impairment, though there are conflicting
      findings in the literature. Importantly, most of the participants in cognitive and
      neuroimaging studies of ASD have been adults and individuals who have relatively intact
      language. Far less is known about the processes (either cognitive or neural) that might be
      implicated in the minimally verbal group. This project is designed to address this issue
      using two different brain imaging methods and approaches.

        1. fMRI and DTI: Converging lines of evidence support the view that ASDs are disorders of
           connectivity, in which abnormalities in white matter integrity and reduced coordination
           of activity across brain regions give rise to core features. Recent results from our
           group (Guenther; Manoach) have identified white matter anomalies in the speech network
           of high-functioning verbal adults with ASD, specifically in the pathway between the left
           supplementary motor area (SMA) and left ventral premotor cortex (vPMC), a pathway
           involved in the initiation of speech output according to the Directions into Velocities
           of Articulators (DIVA) model of speech production, a leading model of the neural
           computations underlying speech. These connectivity abnormalities are revealed in both
           DTI and functional connectivity analyses collected using fMRI. NOTE: IRB approval for
           the collection of fMRI/DTI data will be obtained from MGH, where this portion of the
           study will be carried out. Data analyses will be carried out at MGH and BU.

        2. Electrophysiology: EEG/ERP It has long been known that some children with ASD fail to
           respond when spoken to, cover their ears in the presence of certain sounds, yet show
           highly acute hearing in other contexts. Little is known about the mechanisms that might
           underlie these unusual auditory processing profiles. Abnormal neural oscillations have
           been found to be an endophenotype for ASD in infants and adults. However, the picture of
           how oscillations differ from those of non-clinical subjects is unclear and depends on
           the age at testing. Characterizing the oscillations present in the brains of a range of
           adolescents will allow us to quantify the relationship between neural activity and
           severity of language impairment. The main hypothesis that will be tested in this project
           is that abnormal neural connectivity in minimally verbal children with ASD profoundly
           impedes the ability to perceptually organize auditory scenes into meaningful units or
           objects, which has a direct effect on language development in these individuals.
           Event-related brain potentials (ERPs) and frequency-based analysis of the
           electroencephalogram (EEG) will be collected during passive listening tasks, to evaluate
           auditory perception and the perceptual organization of tones and speech using the
           mismatch negativity (MMN) paradigm (the MMN reflects passive deviance detection
           processes indexing low-level acoustic processes in automatic sensory memory mechanisms,
           and it has been widely investigated in studies of auditory perceptual discrimination of
           tones and speech).

      The investigators plan to collect these data from 3 groups of adolescents with ASD varying in
      language skills (minimally verbal, verbal-language impaired, verbal-language normal) and age
      and gender matched non-ASD typical adolescents. The participants will be diagnosed and tested
      using a range of standardized and non-standardized assessments including IQ/cognitive level;
      social abilities; ASD severity; communication skills (nonverbal). These assessments will be
      carried out by trained examiners in the clinical core housed at BU.

      Because many of the participants present with highly challenging behaviors and are difficult
      to test, a number of innovative approaches will be taken to maximize participants' success in
      completing the behavioral assessments, and then to tolerate and provide artifact-free data in
      the electrophysiological and MRI portions of the study.

      Overall, the investigators hypothesize that the groups tested will differ in their neural
      indices of auditory perception, neural indices of perceptual organization, and induced neural
      oscillations. Further, the investigators hypothesize that differences in the degree of
      language impairment across these groups will be correlated with differences in the degree of
      abnormality of the measured neural indices, but not in the form of the abnormality,
      suggesting that the root causes of the differences across the tested subject groups are
      quantitative rather than qualitative.
    

Intervention name(s): No Intervention
Intervention type(s): Other
Intervention description(s): Intervention is not a part of this study.
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Community sample