title: Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity.
abstract: BACKGROUND
  While asymmetry in the fusiform gyrus (FFG) has been reported in functional and structural studies in typically developing controls (TDC), few studies have examined FFG asymmetry in autism spectrum disorder (ASD) subjects and those studies are limited by small sample sizes, and confounded by cognitive ability or handedness. No previous work has examined FFG surface area or cortical thickness asymmetry in ASD; nor do we understand the trajectory of FFG asymmetry over time. Finally, it is not known how FFG structural asymmetry relates to ASD symptom severity.
  
  
  METHODS
  In this study, we examined FFG volume, surface area, and cortical thickness asymmetry, as well as their cross-sectional trajectories in a large sample of right-handed males aged 7 to 25 years with 128 ASD and 127 TDC subjects using general linear models. In addition, we examined the relationship between FFG asymmetry and ASD severity using the Autism Diagnostic Observation Schedule (ADOS) and Gotham autism severity scores.
  
  
  RESULTS
  Findings revealed that while group differences were evident with mean leftward asymmetry in ASD and mean near symmetry in TDC volume and surface area, asymmetry for both groups existed on a spectrum encompassing leftward and rightward asymmetry. In ASD subjects, volume asymmetry was negatively associated with ADOS and autism severity score symptom measures, with a subset of rightward asymmetric patients being most severely affected. We also observed differential trajectory of surface area asymmetry: ASD subjects exhibited a change from leftward asymmetry toward symmetry from age 7 to 25, whereas TDCs exhibited the reverse trend with a change from near symmetry toward leftward symmetry over the observed age range.
  
  
  CONCLUSIONS
  Abnormalities in FFG structural asymmetry are related to symptom severity in ASD and show differential developmental trajectory compared to TDC. This study is the first to note these findings. These results may have important implications for understanding the role of FFG asymmetry in ASD.
authors.affiliation: Autism and Developmental Medicine Institute, Geisinger Health System, 120 Hamm Drive, Lewisburg, PA 17837 USA.
authors.forename: Chase C
authors.initials: CC
authors.lastname: Dougherty
authors.affiliation: Department of Psychology, Program in Neuroscience, Bucknell University, 701 Moore Avenue, Lewisburg, PA 17837 USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Evans
authors.affiliation: Autism and Developmental Medicine Institute, Geisinger Health System, 120 Hamm Drive, Lewisburg, PA 17837 USA ; Chester F. Carlson Center for Imaging Science, Rochester Institute of Technology, Rochester, NY 14623 USA.
authors.forename: Gajendra J
authors.initials: GJ
authors.lastname: Katuwal
authors.affiliation: Autism and Developmental Medicine Institute, Geisinger Health System, 120 Hamm Drive, Lewisburg, PA 17837 USA ; Chester F. Carlson Center for Imaging Science, Rochester Institute of Technology, Rochester, NY 14623 USA ; Institute for Advanced Application, Geisinger Health System, 100 N Academy Ave, Danville, PA 17822 USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Michael
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D003430:Cross-Sectional Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000033:anatomy & histology*; D055815:Young Adult
keywords: Asymmetry; Autism spectrum disorder; Development; Fusiform gyrus; Structural imaging