title: Longitudinal MRI reveals altered trajectory of brain development during childhood and adolescence in fetal alcohol spectrum disorders.
abstract: Diffusion tensor imaging (DTI) of brain development in fetal alcohol spectrum disorders (FASD) has revealed structural abnormalities, but studies have been limited by the use of cross-sectional designs. Longitudinal scans can provide key insights into trajectories of neurodevelopment within individuals with this common developmental disorder. Here we evaluate serial DTI and T1-weighted volumetric MRI in a human sample of 17 participants with FASD and 27 controls aged 5-15 years who underwent 2-3 scans each, ∼2-4 years apart (92 scans total). Increases of fractional anisotropy and decreases of mean diffusivity (MD) were observed between scans for both groups, in keeping with changes expected of typical development, but mixed-models analysis revealed significant age-by-group interactions for three major white matter tracts: superior longitudinal fasciculus and superior and inferior fronto-occipital fasciculus. These findings indicate altered developmental progression in these frontal-association tracts, with the FASD group notably showing greater reduction of MD between scans. ΔMD is shown to correlate with reading and receptive vocabulary in the FASD group, with steeper decreases of MD in the superior fronto-occipital fasciculus and superior longitudinal fasciculus between scans correlating with greater improvement in language scores. Volumetric analysis revealed reduced total brain, white, cortical gray, and deep gray matter volumes and fewer significant age-related volume increases in the FASD group, although age-by-group interactions were not significant. Longitudinal DTI indicates delayed white matter development during childhood and adolescence in FASD, which may underlie persistent or worsening behavioral and cognitive deficits during this critical period.
authors.affiliation: Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada, T6G 2V2.
authors.forename: Sarah
authors.initials: S
authors.lastname: Treit
authors.forename: Catherine
authors.initials: C
authors.lastname: Lebel
authors.forename: Lauren
authors.initials: L
authors.lastname: Baugh
authors.forename: Carmen
authors.initials: C
authors.lastname: Rasmussen
authors.forename: Gail
authors.initials: G
authors.lastname: Andrew
authors.forename: Christian
authors.initials: C
authors.lastname: Beaulieu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D001931:Brain Mapping; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests; D011247:Pregnancy; D013223:Statistics as Topic