title: A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure.
abstract: Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.
authors: Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa ; MRC/UCT Medical Imaging Research Unit, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
authors: E M
authors: EM
authors: Meintjes
authors: Department of Neurology, Geffen School of Medicine, University of California Los Angeles (UCLA), 710 Westwood Plaza, Los Angeles, CA 90095, USA.
authors: K L
authors: KL
authors: Narr
authors: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Room 2301, Building 149, 13th Street, Charlestown, MA 02129, USA ; Department of Radiology, Harvard Medical School, 23 Shattuck Street, Boston, MA 02115, USA.
authors: A J W
authors: AJ
authors: van der Kouwe
authors: Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa.
authors: C D
authors: CD
authors: Molteno
authors: Department of Neurology, Geffen School of Medicine, University of California Los Angeles (UCLA), 710 Westwood Plaza, Los Angeles, CA 90095, USA.
authors: T
authors: T
authors: Pirnia
authors: Imaging Genetics Center, University of Southern California, 4676 Admiralty Way, Marina del Rey, CA 90292, USA.
authors: B
authors: B
authors: Gutman
authors: Department of Neurology, Geffen School of Medicine, University of California Los Angeles (UCLA), 710 Westwood Plaza, Los Angeles, CA 90095, USA.
authors: R P
authors: RP
authors: Woods
authors: Imaging Genetics Center, University of Southern California, 4676 Admiralty Way, Marina del Rey, CA 90292, USA.
authors: P M
authors: PM
authors: Thompson
authors: Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa ; Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa ; Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 3901 Chrysler Drive, Suite 2-C, Detroit, MI 48201, USA.
authors: J L
authors: JL
authors: Jacobson
authors: Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa ; Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa ; Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 3901 Chrysler Drive, Suite 2-C, Detroit, MI 48201, USA.
authors: S W
authors: SW
authors: Jacobson
mesh_terms: D001921:Brain / Q000473:pathology*; D002648:Child; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size / Q000502:physiology
keywords: AA, absolute alcohol; Brain structure; CSF, cerebrospinal fluid; FAS, fetal alcohol syndrome; FASD, fetal alcohol spectrum disorders; Fetal alcohol spectrum disorders; ICA, independent component analyses; MDT, minimal deformation target; MEMPRAGE, multiecho magnetization prepared rapid gradient echo; Morphology; Neurodevelopment; Prenatal alcohol exposure; Structural MRI; TBM, tensor-based morphometry; Tensor-based morphometry; WISC-IV, Wechsler Intelligence Scale for Children