Age-related Changes in Myeloarchitectonics Across Adulthood in Autism Spectrum Disorder
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      There is increasing awareness in the Autism Spectrum Disorder (ASD) research field about the
      deficit of knowledge with regard to the neurobiological, cognitive, and behavioral changes
      that occur in adults with ASD across the later portion of the lifespan. Decline in motor
      skills and cognitive function in typical aging can have devastating impacts on an
      individual's ability to organize and maintain activities of daily living. While there is an
      overall lack of research on how these processes unfold across aging specifically in ASD,
      previous research findings of motor and cognitive deficits in young adults with ASD,
      localization of these functions to the anterior cerebral cortices, and trajectories of
      decline in typical aging indicate that motor skills and executive function are particularly
      at risk in the disorder in later life.

      In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a
      unique view of gray matter structure and has the potential to elucidate abnormalities of
      local cortical connectivity. It has shown promise for the identification of biomarkers of
      disease pathogenesis in clinical studies, and it provides unique information beyond the
      cortical thickness measurements that have been employed in previous studies of ASD and
      typical aging. Myelin mapping may also be a more reliable index of neurobiological aging,
      given some questions about the accuracy of cortical thickness measurements. Given these
      properties, it may be a particularly informative measure in the context of potential
      accelerated decline in ASD. Intracortical myelin development and remodeling are protracted
      across the typical lifespan, with evidence of abnormal cortical myelination in other
      neuropsychiatric disorders, as well as in age-related mild cognitive impairment and dementia.
      In young adults with Autism Spectrum Disorder (ASD) myelin content is reduced in white matter
      and presumably in cortical gray matter as well. However, patterns of intracortical
      myelination have not yet been examined in ASD at any age leaving an important gap in the
      current knowledge base. With the added risk of demyelination associated with aging, older
      adults with ASD may be the most important population to examine as they may be doubly at risk
      of deficits in cortical myelination. Importantly, this could have knock-on effects on
      cognitive and motor functions in light of myelin's role in synaptic plasticity and
      maintenance of intracortical circuits.

      The proposed fellowship project aims to bridge this gap in knowledge by investigating the
      age-related trajectory of intracortical myelin in middle aged to older adults with ASD and
      clarifying the spatial distribution of any abnormalities. Known heterogeneity in the clinical
      presentation and neurobiological phenotype across the autism spectrum poses a significant
      challenge in this research field. The proposed project includes innovative statistical
      approaches to help parse this heterogeneity. Intracortical myelin will be analyzed
      cross-sectionally using both group-wise and subject-specific approaches and with any findings
      confirmed with follow-up longitudinal data. This multifaceted approach will allow for a
      comprehensive characterization of myeloarchitectonics in adults with ASD, and also holds the
      potential to elucidate important links between brain structure and behavior in the disorder.

      Specific Aims Aim 1: Determine if intracortical myelin content and rates of age-related
      change differ between individuals with ASD and age-matched control participants aged 40-65
      years.

      Hypothesis 1: Group-wise analysis will reveal decreased intracortical myelin content in ASD
      in association cortices of the frontal and parietal lobes.

      Hypothesis 2: Subject-specific analyses may reveal spatial variability across individuals in
      the precise brain regions demonstrating abnormalities of intracortical myelination, but with
      frontal and parietal regions more frequently or more heavily affected.

      Hypothesis 3: Both cross-sectional approaches will reveal a pattern of accelerated cortical
      demyelination with greater age in ASD.

      Aim 2: Relate local myelin content measures to cognitive and behavioral abilities that are
      at-risk of decline during aging, including motor skills and executive functions.

      Hypothesis 4: Age-related decline in domain-specific behavioral abilities will correlate with
      atypical patterns of intracortical myelination from Aim 1.
    


Intervention name(s): Anatomical MRI Scan
Intervention type(s): Diagnostic Test
Intervention description(s): T1-weighted (T1w) magnetization prepared rapid gradient echo (MPRAGE) sequence (TR=8.776 milliseconds, TE=3.656 milliseconds, flip angle=8°, matrix=320x320, 0.8mm3 resolution) and T2-weighted (T2w) CUBE sequence (TR=61.803 milliseconds, TE=3200 milliseconds, flip angle=8°, matrix=320x320, 0.8mm3 resolution)
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        San Diego County Community