As outlined in the request for applications (RFA-DA-04-002) to which we respond here, research that uses rapidly advancing neuro imaging technology to address the effects of drug exposure during development is much needed. We have chosen to investigate this important topic by focusing our efforts on three populations of children, those with prenatal exposure to methamphetamine (MA), those with prenatal exposure to alcohol, and normally developing children without prenatal exposure to drugs of abuse. We will study these populations using structural and functional magnetic resonance imaging, neurocognitive testing, longitudinal data collection, and novel image analyses techniques to assess the following specific aims. 1) To examine brain structural abnormality as a function of prenatal exposure to MA or alcohol, both cross-sectional and longitudinally. 2) To examine differences in brain functional activation between children and adolescents who were exposed to large amounts of MA or alcohol prenatally and those who were not exposed. 3) To examine differences between groups in cognitive functioning using a broad battery of neuropsychological testing instruments. These studies are of critical importance given that very little is known about the effects of prenatal exposure to MA on the developing brain, and MA abuse is rapidly escalating in the United States. Pregnant women are likely among the increased population using this illicit drug, placing an increased sense of importance on our understanding of the consequences of its abuse during pregnancy. To date, there are no published studies describing detailed structural brain abnormalities, functional activation disturbances, or neurocognitive deficits in children with prenatal MA exposure. By comparison, relatively more is known about the teratogenic effects of alcohol on the developing brain, but its abuse during pregnancy is still a significant health problem. The proposal to study two populations with prenatal exposure is critical to our better understanding of the specific neural impact of each drug. This is because the alcohol-exposed individuals will be a better comparison group to assess the effects of prenatal MA exposure, given likely similarities between the groups in pre- and post-natal environments (i.e., nutrition, socioeconomic status, maternal smoking during pregnancy) relative to children without prenatal exposure who are typically studied as a comparison group.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA017830-04
Application #
7283523
Study Section
Special Emphasis Panel (ZDA1-EXL-T (04))
Program Officer
Borek, Nicolette T
Project Start
2004-09-30
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$523,215
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Gautam, P; Nuñez, S C; Narr, K L et al. (2015) Developmental Trajectories for Visuo-Spatial Attention are Altered by Prenatal Alcohol Exposure: A Longitudinal FMRI Study. Cereb Cortex 25:4761-71
Gautam, P; Nuñez, S C; Narr, K L et al. (2014) Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function. Neuroimage Clin 5:19-27
Roussotte, Florence F; Rudie, Jeffrey D; Smith, Lynne et al. (2012) Frontostriatal connectivity in children during working memory and the effects of prenatal methamphetamine, alcohol, and polydrug exposure. Dev Neurosci 34:43-57
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Lebel, Catherine; Mattson, Sarah N; Riley, Edward P et al. (2012) A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development. J Neurosci 32:15243-51
Colby, John B; Smith, Lynne; O'Connor, Mary J et al. (2012) White matter microstructural alterations in children with prenatal methamphetamine/polydrug exposure. Psychiatry Res 204:140-8
Roussotte, Florence F; Sulik, Kathleen K; Mattson, Sarah N et al. (2012) Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders. Hum Brain Mapp 33:920-37
Colby, John B; Soderberg, Lindsay; Lebel, Catherine et al. (2012) Along-tract statistics allow for enhanced tractography analysis. Neuroimage 59:3227-42
Colby, John B; Van Horn, John D; Sowell, Elizabeth R (2011) Quantitative in vivo evidence for broad regional gradients in the timing of white matter maturation during adolescence. Neuroimage 54:25-31
Nuñez, S Christopher; Dapretto, Mirella; Katzir, Tami et al. (2011) fMRI of syntactic processing in typically developing children: structural correlates in the inferior frontal gyrus. Dev Cogn Neurosci 1:313-23

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