A significant outcome of prospective studies using noninvasive neuroimaging with Magnetic Resoance Imaging (MRI) is the recognition that brain structural anomalies occur even in individuals apparently free of neurological disorders. Recently, we found that 0.6% of 833 adolescent and young adult participants in a large, NIAAA- funded project (NCANDA) had anomalies identified as gray matter heterotopias. These isolated clumps of gray matter neurons located in the wrong part of the brain are thought to be associated with seizures. This incidence of heterotopias was high given that participants with a history of a seizure disorder were excluded from study. We pursued this finding by investigating heterotopia incidence in another larger NIAAA-funded project (ABCD). In a computerized search of 7,863 neuroradiological readings, 84 (1.07%) participants were identified with gray matter heterotopias. Given that heterotopias have been reported in animal models of fetal alcohol exposure, we sought to examine the relation between hetertopias and prenatal alcohol exposure in the ABCD data. Retrospective questioning of mothers of ABCD participants indicated a high incidence of heterotopias in offspring of mothers who answered in the affirmative that they had drunk alcohol while but before finding out they were pregnant. These findings raise the possibility that the incidence of heterotopias in a population enriched with fetal alcohol exposure (FAE) and fetal alcohol syndrome (FAS) should be higher than in unaffected controls and would support the inference that prenatal alcohol exposure causes heterotopias in the cortex of exposed individuals. Accordingly, in collaboration with a clinical neuroradiologist, we will oversee blind clinical readings of the MRIs of 60 FAE, 60 FAS, and 60 control subjects to seek gray matter heterotopias, in addition to other structural anomalies, in these subjects with known outcomes of prenatal alcohol exposure. Such a finding would be novel and clinically significant, serving as a warning to health-care providers of the potential of seizures and as further reason to refrain from drinking alcohol when intending to become pregnant.

Public Health Relevance

In an unselected population based sample, the brain structural abnormality, called gray matter heterotopias, was associated with self-reported potential prenatal alcohol exposure. If this association is causal, the incidence of heterotopias in a population enriched with fetal alcohol exposure should be higher and would support the inference that alcohol consumed prenatally can cause the brain structural anomaly of heterotopia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
3U24AA021697-07S1
Application #
9688085
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Matochik, John A
Project Start
2012-09-15
Project End
2022-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
7
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Sri International
Department
Type
DUNS #
009232752
City
Menlo Park
State
CA
Country
United States
Zip Code
94025
Goldstone, Aimée; Willoughby, Adrian R; de Zambotti, Massimiliano et al. (2018) The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence. Brain Struct Funct 223:669-685
Park, Sang Hyun; Zhang, Yong; Kwon, Dongjin et al. (2018) Alcohol use effects on adolescent brain development revealed by simultaneously removing confounding factors, identifying morphometric patterns, and classifying individuals. Sci Rep 8:8297
Hasler, Brant P; Franzen, Peter L; de Zambotti, Massimiliano et al. (2017) Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol and Marijuana Use in Adolescence: Initial Findings from the National Consortium on Alcohol and Neurodevelopment in Adolescence Study. Alcohol Clin Exp Res 41:1154-1165
Clark, Duncan B; Chung, Tammy; Martin, Christopher S et al. (2017) Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use. Front Behav Neurosci 11:223
Sullivan, Edith V; Lane, Barton; Kwon, Dongjin et al. (2017) Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity. Brain Imaging Behav 11:1302-1315
Sullivan, Edith V; Brumback, Ty; Tapert, Susan F et al. (2017) Effects of prior testing lasting a full year in NCANDA adolescents: Contributions from age, sex, socioeconomic status, ethnicity, site, family history of alcohol or drug abuse, and baseline performance. Dev Cogn Neurosci 24:72-83
Pfefferbaum, Adolf; Rohlfing, Torsten; Pohl, Kilian M et al. (2016) Adolescent Development of Cortical and White Matter Structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking. Cereb Cortex 26:4101-21
Sullivan, Edith V; Brumback, Ty; Tapert, Susan F et al. (2016) Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction. Neuropsychology 30:449-73
Pohl, Kilian M; Sullivan, Edith V; Rohlfing, Torsten et al. (2016) Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study. Neuroimage 130:194-213
Nichols, B Nolan; Pohl, Kilian M (2015) Neuroinformatics Software Applications Supporting Electronic Data Capture, Management, and Sharing for the Neuroimaging Community. Neuropsychol Rev 25:356-68

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