This research proposes to extend the successful work already completed in quantifying the neuroanatomic abnormalities underlying neuropsychological deficits among people with brain damage caused by prenatal alcohol exposure. Although Fetal Alcohol Syndrome (FAS) is a distinct diagnostic entity, it conceals substantial variability of deficits. Many individuals with substantial prenatal alcohol exposure exhibit dysfunctional behaviors that appear to be CNS-based, but do not have facial manifestations of FAS. These features are sometimes referred to as possible fetal alcohol effects (FAE). In prior work, we developed and demonstrated a new method of shape analysis targeting the corpus callosum (CC) that was above 80% accurate in separating FAS/FAE from controls, using a symmetrical four-quadrant data set of male and female adolescents and adults across three diagnostic groups: FAS, FAE, and age/sex matched non-exposed controls. Using newly developed methods, we now propose to reanalyze these magnetic resonance images for additional brain structures, targeting the cerebellum, and to compare these images with the full battery of neuropsychological tests obtained on our 180 subjects. We hypothesize that these new image analyses will reveal significant differences in mean or variance of brain form between FAS/FAE and controls, that FAS and FAE will not differ from each other, and that distinct profiles of association will be observed between neuroanatomy and neuropsychology. Over three years, we will pursue four aims: (1.) To quantify new morphological data from existing magnetic resonance images, to examine additional curves and shapes on and near the cerebellum that will be combined with CC and gray/white matter volumes in detecting FAS/FAE; (2.) To examine the behavioral phenotype of FAS/FAE, using already collected data augmented with new scores from existing data, to study the other three quadrants of subjects for profiles of Executive Function and Motor Function deficits that were related to different CC shape anomalies in adult males; (3.) To conclude the full four-quadrant neuroanatomic/neuropsychologic analysis, using the new data on cerebellar shape and size combined with the augmented behavioral phenotype data; (4.) To develop a data-driven diagnostic protocol based on the principles already demonstrated and utilizing entire data sets from both imaging and behavior. This will be the first systematic study to move directly from state-of-the-art image analysis techniques and neuropsychological testing, to a diagnostic protocol with practical utility, filling a compelling need for diagnosing fetal alcohol brain damage in adolescents and adults and in the absence of the typical facial characteristics.
| Bookstein, Fred L (2016) Reconsidering ""The inappropriateness of conventional cephalometrics"". Am J Orthod Dentofacial Orthop 149:784-97 |
| Bookstein, Fred L; Streissguth, Ann P; Connor, Paul D et al. (2006) Damage to the human cerebellum from prenatal alcohol exposure: the anatomy of a simple biometrical explanation. Anat Rec B New Anat 289:195-209 |
| Connor, Paul D; Sampson, Paul D; Streissguth, Ann P et al. (2006) Effects of prenatal alcohol exposure on fine motor coordination and balance: A study of two adult samples. Neuropsychologia 44:744-51 |
| Streissguth, A P; O'Malley, K (2000) Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Semin Clin Neuropsychiatry 5:177-90 |
| Bookstein, F L (2000) Creases as local features of deformation grids. Med Image Anal 4:93-110 |
| Sampson, P D; Streissguth, A P; Bookstein, F L et al. (2000) On categorizations in analyses of alcohol teratogenesis. Environ Health Perspect 108 Suppl 3:421-8 |
| Connor, P D; Sampson, P D; Bookstein, F L et al. (2000) Direct and indirect effects of prenatal alcohol damage on executive function. Dev Neuropsychol 18:331-54 |
