Brain diffusion abnormalities in children with fetal alcohol spectrum disorder.

BACKGROUND Children with fetal alcohol spectrum disorder (FASD) have a variety of cognitive, behavioral, and neurological impairments, including structural brain damage. Despite the importance of white matter connections for proper brain function, little is known about how these connections, and the deep gray matter structures that act as relay stations, are affected in children with FASD. The purpose of this study was to use diffusion tensor imaging, an advanced magnetic resonance imaging technique, to examine microstructural differences of white and deep gray matter in children with FASD. METHODS Subjects were 24 children aged 5-13 years previously diagnosed with FASD and 95 healthy children over the same age range. Diffusion tractography was used to delineate 10 major white matter tracts in each individual, and region-of-interest analysis was used to assess 4 deep gray matter structures. Fractional anisotropy, an indicator of white matter integrity, and mean diffusivity, a measure of the average water diffusion, were assessed in all 14 brain structures. RESULTS Diffusion tensor imaging revealed significant differences of diffusion parameters in several areas of the brain, including the genu and splenium of the corpus callosum, cingulum, corticospinal tracts, inferior fronto-occipital fasciculus, inferior and superior longitudinal fasciculi, globus pallidus, putamen, and thalamus. Reduced white and gray matter volumes, as well as total brain volume, were observed in the FASD group. CONCLUSIONS These results demonstrate diffusion abnormalities in FASD beyond the corpus callosum and suggest that several specific white matter regions, particularly commissural and temporal connections, and deep gray matter areas of the brain are sensitive to prenatal alcohol exposure.

[1]  Alexander Leemans,et al.  Microstructural maturation of the human brain from childhood to adulthood , 2008, NeuroImage.

[2]  L. Wickstrom,et al.  SALMONELLAS IN MEAT. , 1964, Lancet.

[3]  R J Sokol,et al.  A revised conservative estimate of the incidence of FAS and its economic impact. , 1991, Alcoholism, clinical and experimental research.

[4]  Arthur W Toga,et al.  Abnormal cortical thickness and brain-behavior correlation patterns in individuals with heavy prenatal alcohol exposure. , 2008, Cerebral cortex.

[5]  A. Slonim,et al.  Ethanol elevates fetal serum glutamate levels in the rat. , 1995, Alcoholism, clinical and experimental research.

[6]  Talma Hendler,et al.  Normal white matter development from infancy to adulthood: Comparing diffusion tensor and high b value diffusion weighted MR images , 2005, Journal of magnetic resonance imaging : JMRI.

[7]  Jun Yoshino,et al.  Demyelination increases radial diffusivity in corpus callosum of mouse brain , 2005, NeuroImage.

[8]  P. May,et al.  Estimating the prevalence of fetal alcohol syndrome. A summary. , 2001 .

[9]  E. Ozer,et al.  Effects of prenatal ethanol exposure on neuronal migration, neuronogenesis and brain myelination in the mice brain. , 2000, Clinical neuropathology.

[10]  Denis Le Bihan,et al.  Looking into the functional architecture of the brain with diffusion MRI , 2003, Nature Reviews Neuroscience.

[11]  E P Riley,et al.  A review of the neuroanatomical findings in children with fetal alcohol syndrome or prenatal exposure to alcohol. , 1998, Alcoholism, clinical and experimental research.

[12]  P. Randall,et al.  Effect of prenatal ethanol exposure on the developmental profile of the NMDA receptor subunits in rat forebrain and hippocampus. , 1998, Alcoholism, clinical and experimental research.

[13]  Edward P. Riley,et al.  Neuroimaging and fetal alcohol spectrum disorders , 2007, Neuroscience & Biobehavioral Reviews.

[14]  Marit Korkman,et al.  Fetal alcohol spectrum disorders in Finland: Clinical delineation of 77 older children and adolescents , 2006, American journal of medical genetics. Part A.

[15]  O. Salonen,et al.  MRI findings in children with school problems who had been exposed prenatally to alcohol , 2002, Developmental medicine and child neurology.

[16]  Martin P Paulus,et al.  Prenatal alcohol exposure affects frontal-striatal BOLD response during inhibitory control. , 2007, Alcoholism, clinical and experimental research.

[17]  Bryon A Mueller,et al.  Diffusion tensor imaging in children with fetal alcohol spectrum disorders. , 2006, Alcoholism, clinical and experimental research.

[18]  S. M. Sumi,et al.  Brain malformations related to prenatal exposure to ethanol. , 1978, The Journal of pediatrics.

[19]  D. Tuch Q‐ball imaging , 2004, Magnetic resonance in medicine.

[20]  E P Riley,et al.  A review of the neurobehavioral deficits in children with fetal alcohol syndrome or prenatal exposure to alcohol. , 1998, Alcoholism, clinical and experimental research.

[21]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

[22]  Joseph L. Jacobson,et al.  Effects of Prenatal Alcohol Exposure on Child Development , 2002, Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism.

[23]  G. Moore,et al.  Magnetic resonance and spectroscopic imaging in prenatal alcohol-exposed children: preliminary findings in the caudate nucleus. , 2006, Neurotoxicology and teratology.

[24]  C. Zorumski,et al.  Neural activity and survival in the developing nervous system , 2000, Molecular Neurobiology.

[25]  Fred L Bookstein,et al.  Many infants prenatally exposed to high levels of alcohol show one particular anomaly of the corpus callosum. , 2007, Alcoholism, clinical and experimental research.

[26]  D. Li,et al.  Structural and functional brain integrity of fetal alcohol syndrome in nonretarded cases. , 2000, Pediatrics.

[27]  V. Menon,et al.  White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. , 2005, Cerebral cortex.

[28]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[29]  E P Riley,et al.  A decrease in the size of the basal ganglia in children with fetal alcohol syndrome. , 1996, Alcoholism, clinical and experimental research.

[30]  Rohit Bakshi,et al.  Interhemispheric asymmetry of brain diffusivity in normal individuals: a diffusion-weighted MR imaging study. , 2005, AJNR. American journal of neuroradiology.

[31]  Christian Beaulieu,et al.  Diffusion tensor imaging of neurodevelopment in children and young adults , 2005, NeuroImage.

[32]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[33]  P. Lemoine,et al.  Les enfants des parents alcooliques. Anomalies observées à propos de 127 cas , 1968 .

[34]  F L Bookstein,et al.  Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. , 1997, Teratology.

[35]  Wei Zhao,et al.  Ethanol blocks both basic fibroblast growth factor- and carbachol-mediated neuroepithelial cell expansion with differential effects on carbachol-activated signaling pathways , 2003, Neuroscience.

[36]  J. Olney Fetal alcohol syndrome at the cellular level , 2004, Addiction biology.

[37]  A. Chudley,et al.  Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis , 2005, Canadian Medical Association Journal.

[38]  M. Raichle,et al.  Tracking neuronal fiber pathways in the living human brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[39]  S. LaConte,et al.  Evaluation of corpus callosum anisotropy in young adults with fetal alcohol syndrome according to diffusion tensor imaging. , 2005, Alcoholism, clinical and experimental research.

[40]  Tianzi Jiang,et al.  Side and handedness effects on the cingulum from diffusion tensor imaging , 2005, Neuroreport.

[41]  A. Anderson Measurement of fiber orientation distributions using high angular resolution diffusion imaging , 2005, Magnetic resonance in medicine.

[42]  E P Riley,et al.  Brain dysmorphology in individuals with severe prenatal alcohol exposure , 2001, Developmental medicine and child neurology.

[43]  David W. Smith,et al.  Recognition of the fetal alcohol syndrome in early infancy. , 1973, Lancet.

[44]  J. Renau‐Piqueras,et al.  Glia and fetal alcohol syndrome. , 2001, Neurotoxicology.

[45]  B. Volk,et al.  Alcohol embryo- and fetopathy Neuropathology of 3 children and 3 fetuses , 1979, Journal of the Neurological Sciences.

[46]  S. Hollins,et al.  Fetal Alcohol Spectrum Disorder: An Overview , 2006, Journal of the Royal Society of Medicine.

[47]  E. Riley,et al.  MK-801 administration during ethanol withdrawal in neonatal rat pups attenuates ethanol-induced behavioral deficits. , 1997, Alcoholism, clinical and experimental research.

[48]  Arthur W Toga,et al.  Mapping White Matter Integrity and Neurobehavioral Correlates in Children with Fetal Alcohol Spectrum Disorders , 2008, The Journal of Neuroscience.

[49]  H. Barr,et al.  Identifying maternal self-reported alcohol use associated with fetal alcohol spectrum disorders. , 2001, Alcoholism, clinical and experimental research.

[50]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.

[51]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[52]  J. Olney,et al.  Neurotransmitters and apoptosis in the developing brain. , 2001, Biochemical pharmacology.

[53]  Susan J. Astley,et al.  Diagnostic Guide for Fetal Alcohol Spectrum Disorders: the 4 - Digit Diagnostic Code , 2004 .

[54]  R J Sokol,et al.  Incidence of fetal alcohol syndrome and economic impact of FAS-related anomalies. , 1987, Drug and alcohol dependence.

[55]  Marjut Timonen,et al.  Brain metabolic alterations in adolescents and young adults with fetal alcohol spectrum disorders. , 2006, Alcoholism, clinical and experimental research.

[56]  Lisa H. Lu,et al.  Functional magnetic resonance imaging of verbal learning in children with heavy prenatal alcohol exposure , 2007, Neuroreport.

[57]  Sean J. Tollison,et al.  Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure. , 2006, Alcoholism, clinical and experimental research.

[58]  S C Williams,et al.  Non‐invasive assessment of axonal fiber connectivity in the human brain via diffusion tensor MRI , 1999, Magnetic resonance in medicine.

[59]  S. Krueger,et al.  Effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on glial cell development in rat optic nerve , 1992, International Journal of Developmental Neuroscience.