Regional brain shape abnormalities persist into adolescence after heavy prenatal alcohol exposure.

We assessed regional brain shape abnormalities and spatial relationships between brain shape and abnormalities observed in the underlying tissue in children and adolescents prenatally exposed to large quantities of alcohol. We used high resolution, 3-D, structural magnetic resonance imaging data and novel, whole-brain, surface-based image analysis procedures to study 21 subjects with heavy prenatal alcohol exposure (8-22 years, mean age 12.6 years) and 21 normally developing control subjects (8-25 years, mean age 13.5 years). Significant brain size and shape abnormalities were observed in the alcohol-exposed subjects in inferior parietal/ perisylvian regions bilaterally, where their brains appeared to be narrower than those of the controls in the same general location where they also had increased gray matter density. Highly significant decreased brain surface extent or reduced brain growth was also observed in the ventral aspects of the frontal lobes most prominent in the left hemisphere. For the first time in this report we have mapped brain morphologic abnormalities to the cortical surface in subjects with prenatal alcohol exposure and have shown that the size and shape of the brain is altered in these individuals. The results imply that brain growth continues to be adversely affected long after the prenatal insult of alcohol exposure to the developing brain and the brain regions most implicated, frontal and inferior parietal/ perisylvian, may be consistent with behavioral deficits characteristic of individuals prenatally exposed to alcohol.

[1]  A. Toga,et al.  Mapping sulcal pattern asymmetry and local cortical surface gray matter distribution in vivo: maturation in perisylvian cortices. , 2002, Cerebral cortex.

[2]  E P Riley,et al.  Verbal learning and memory in children with fetal alcohol syndrome. , 1996, Alcoholism, clinical and experimental research.

[3]  Arthur W. Toga,et al.  A Probabilistic Atlas of the Human Brain: Theory and Rationale for Its Development The International Consortium for Brain Mapping (ICBM) , 1995, NeuroImage.

[4]  J. Mazziotta,et al.  MRI‐PET Registration with Automated Algorithm , 1993, Journal of computer assisted tomography.

[5]  F. Bookstein,et al.  Neuropsychological deficits in adolescents with fetal alcohol syndrome: clinical findings. , 1998, Alcoholism, clinical and experimental research.

[6]  A. Toga,et al.  Localizing Age-Related Changes in Brain Structure between Childhood and Adolescence Using Statistical Parametric Mapping , 1999, NeuroImage.

[7]  Joseph J. Volpe,et al.  Maturation-Dependent Vulnerability of Oligodendrocytes to Oxidative Stress-Induced Death Caused by Glutathione Depletion , 1998, The Journal of Neuroscience.

[8]  P. Yakovlev,et al.  The myelogenetic cycles of regional maturation of the brain , 1967 .

[9]  R. Woods,et al.  Cortical change in Alzheimer's disease detected with a disease-specific population-based brain atlas. , 2001, Cerebral cortex.

[10]  C. Fennema-Notestine,et al.  Mesial temporal, diencephalic, and striatal contributions to deficits in single word reading, word priming, and recognition memory , 2001, Journal of the International Neuropsychological Society.

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

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

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

[14]  C. Guerri.  Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. , 1998, Alcoholism, clinical and experimental research.

[15]  R. Zoeller,et al.  Limited postnatal ethanol exposure permanently alters the expression of mRNAS encoding myelin basic protein and myelin-associated glycoprotein in cerebellum. , 1994, Alcoholism, clinical and experimental research.

[16]  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.

[17]  R. Friede.  Gross and Microscopic Development of the Central Nervous System , 1989 .

[18]  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.

[19]  P. Huttenlocher.  Synaptic density in human frontal cortex - developmental changes and effects of aging. , 1979, Brain research.

[20]  E. Cabanis,et al.  The Human Brain: Surface, Three-Dimensional Sectional Anatomy and Mri , 1991 .

[21]  Paul M. Thompson,et al.  Voxel-based morphometric analyses of the brain in children and adolescents prenatally exposed to alcohol , 2001, Neuroreport.

[22]  J. West,et al.  Regional differences in cell loss associated with binge-like alcohol exposure during the first two trimesters equivalent in the rat. , 2001, Alcohol.

[23]  K. Jones,et al.  The fetal alcohol syndrome. , 1979, Hospital Practice.

[24]  Alan C. Evans,et al.  An MRI-Based Probabilistic Atlas of Neuroanatomy , 1994 .

[25]  Elizabeth R. Sowell,et al.  Mapping sulcal pattern asymmetry in vivo: Maturation in posterior Perisylvian cortices , 2000, NeuroImage.

[26]  Alan C. Evans,et al.  Automatic 3D Regional MRI Segmentation and Statistical Probability Anatomy Maps , 1996 .

[27]  H. Kinney,et al.  Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury , 2001, The Journal of Neuroscience.

[28]  F. Bookstein,et al.  Geometric morphometrics of corpus callosum and subcortical structures in the fetal-alcohol-affected brain. , 2001, Teratology.

[29]  N C Andreasen,et al.  Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome. , 1997, Pediatrics.

[30]  Alan C. Evans,et al.  Automated 3-D Extraction of Inner and Outer Surfaces of Cerebral Cortex from MRI , 2000, NeuroImage.

[31]  A. Toga,et al.  Mapping Continued Brain Growth and Gray Matter Density Reduction in Dorsal Frontal Cortex: Inverse Relationships during Postadolescent Brain Maturation , 2001, The Journal of Neuroscience.

[32]  E P Riley,et al.  Implicit and explicit memory functioning in children with heavy prenatal alcohol exposure , 1999, Journal of the International Neuropsychological Society.

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

[34]  R. Spinks.  The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe, 3rd ed. , 2000 .

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

[36]  A. Toga,et al.  Mapping callosal morphology and cognitive correlates , 2001, Neurology.

[37]  小野 道夫,et al.  Atlas of the Cerebral Sulci , 1990 .

[38]  Michael I. Miller,et al.  Bayesian Construction of Geometrically Based Cortical Thickness Metrics , 2000, NeuroImage.

[39]  K Genz,et al.  Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. , 2000, Science.

[40]  R. Woods,et al.  Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain , 2000, Human brain mapping.

[41]  J. Fuster.  The Prefrontal Cortex , 1997 .

[42]  E P Riley,et al.  Behavioral and psychosocial profiles of alcohol-exposed children. , 1999, Alcoholism, clinical and experimental research.

[43]  E P Riley,et al.  Executive functioning in children with heavy prenatal alcohol exposure. , 1999, Alcoholism, clinical and experimental research.

[44]  T. Jernigan,et al.  Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study , 2002, Developmental medicine and child neurology.

[45]  Alan C. Evans,et al.  Multiple surface identification and matching in magnetic resonance images , 1994, Other Conferences.