Fetal alcohol syndrome (FAS) is a permanent birth defect syndrome caused by maternal drinking during pregnancy. FAS is characterized by growth deficiency, a unique facial phenotype and central nervous system (CNS) dysfunction. The cognitive/behavioral problems in this condition stem from prenatal organic brain damage. Not all individuals with prenatal alcohol exposure suffer brain damage and not all who do suffer brain damage have FAS. The degree of brain damage among individuals with prenatal alcohol exposure may vary from microcellular and neurochemical aberrations to gross structural anomalies. Similarly, cognitive/behavioral dysfunction varies considerably. Teratogenic physical findings in individuals with FAS lend credence to the clinical judgment that their cognitive and behavioral dysfunction is due, in part, to organic brain damage. But without the physical features of FAS or at least a severe expression of brain damage, the injury often goes undiagnosed and unserved. This project proposes to use (magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MM), and functional MM (fMRI)) to determine if prenatally alcohol-exposed children, with and without FAS, who present along the full continuum of mild to severe CNS dysfunction, have irrefutable evidence of organic brain damage in the form of chemical and structural alterations. An MRS pilot study of prenatally alcohol-exposed monkeys with moderate CNS dysfunction found that levels of choline/creatine in the brain, a marker of cell membrane breakdown, rose with increasing alcohol exposure and increasing neuropsychological dysfunction. An MRS pilot study in children with FAS also showed that choline/creatine increased with increasing neuropsychological dysfunction. These findings are consistent with MRS outcomes in individuals with organic brain damage associated with other disease states. MRI studies in small numbers of people with FAS and in alcohol-exposed monkeys with moderate CNS dysfunction demonstrate significant size alterations of selected brain regions. Together, these studies demonstrate the utility and sensitivity of MM/S in better understanding alcohol teratogenesis. Neuropsychological dysfunction will be measured using a global index of impairment generated from psychometric measures-and with experimental measures of discrete, clinically meaningful cognitive skills subserved by brain regions that prior literature suggests may be affected by alcohol teratogenesis. A pilot feasibility study will also be conducted to determine if fMRI can be effectively administered to this population.
