title: Multimodal Diffusion-MRI and MEG Assessment of Auditory and Language System Development in Autism Spectrum Disorder.
abstract: BACKGROUND
  Auditory processing and language impairments are prominent in children with autism spectrum disorder (ASD). The present study integrated diffusion MR measures of white-matter microstructure and magnetoencephalography (MEG) measures of cortical dynamics to investigate associations between brain structure and function within auditory and language systems in ASD. Based on previous findings, abnormal structure-function relationships in auditory and language systems in ASD were hypothesized.
  
  
  METHODS
  Evaluable neuroimaging data was obtained from 44 typically developing (TD) children (mean age 10.4 ± 2.4 years) and 95 children with ASD (mean age 10.2 ± 2.6 years). Diffusion MR tractography was used to delineate and quantitatively assess the auditory radiation and arcuate fasciculus segments of the auditory and language systems. MEG was used to measure (1) superior temporal gyrus auditory evoked M100 latency in response to pure-tone stimuli as an indicator of auditory system conduction velocity, and (2) auditory vowel-contrast mismatch field (MMF) latency as a passive probe of early linguistic processes.
  
  
  RESULTS
  Atypical development of white matter and cortical function, along with atypical lateralization, were present in ASD. In both auditory and language systems, white matter integrity and cortical electrophysiology were found to be coupled in typically developing children, with white matter microstructural features contributing significantly to electrophysiological response latencies. However, in ASD, we observed uncoupled structure-function relationships in both auditory and language systems. Regression analyses in ASD indicated that factors other than white-matter microstructure additionally contribute to the latency of neural evoked responses and ultimately behavior. RESULTS also indicated that whereas delayed M100 is a marker for ASD severity, MMF delay is more associated with language impairment.
  
  
  CONCLUSIONS
  Present findings suggest atypical development of primary auditory as well as auditory language systems in ASD. Findings demonstrate the need for additional multimodal studies to better characterize the different structural features (white matter, gray matter, neurochemical concentration) that contribute to brain activity, both in typical development and in ASD. Finally, the neural latency measures were found to be of clinical significance, with M100 associated with overall ASD severity, and with MMF latency associated with language performance.
authors.affiliation: Department of Radiology, Children's Hospital of PhiladelphiaPhiladelphia, PA, USA; Department of Radiology, Perelman School of Medicine, University of PennsylvaniaPhiladelphia, PA, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Berman
authors.affiliation: Department of Radiology, Children's Hospital of PhiladelphiaPhiladelphia, PA, USA; Department of Radiology, Perelman School of Medicine, University of PennsylvaniaPhiladelphia, PA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Edgar
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia Philadelphia, PA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Blaskey
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia Philadelphia, PA, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Kuschner
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia Philadelphia, PA, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Levy
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia Philadelphia, PA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ku
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia Philadelphia, PA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Dell
authors.affiliation: Department of Radiology, Children's Hospital of PhiladelphiaPhiladelphia, PA, USA; Department of Radiology, Perelman School of Medicine, University of PennsylvaniaPhiladelphia, PA, USA.
authors.forename: Timothy P L
authors.initials: TP
authors.lastname: Roberts
keywords: auditory pathways; autism spectrum disorders (ASD); diffusion MRI; language; magnetoencephalography (MEG); multimodal imaging