Prenatal methamphetamine exposure is associated with corticostriatal white matter changes in neonates
Diffusion tensor imaging (DTI) studies have shown that prenatal exposure to methamphetamine is associated with alterations in white matter microstructure, but to date no tractography studies have been performed in neonates. The striato-thalamo-orbitofrontal circuit and its associated limbic-striatal areas, the primary circuit responsible for reinforcement, has been postulated to be dysfunctional in drug addiction. This study investigated potential white matter changes in the striatal-orbitofrontal circuit in neonates with prenatal methamphetamine exposure. Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy, and DTI sequences were acquired in the first postnatal month. Target regions of interest were manually delineated, white matter bundles connecting pairs of targets were determined using probabilistic tractography in AFNI-FATCAT, and fractional anisotropy (FA) and diffusion measures were determined in white matter connections. Regression analysis showed that increasing methamphetamine exposure was associated with reduced FA in several connections between the striatum and midbrain, orbitofrontal cortex, and associated limbic structures, following adjustment for potential confounding variables. Our results are consistent with previous findings in older children and extend them to show that these changes are already evident in neonates. The observed alterations are likely to play a role in the deficits in attention and inhibitory control frequently seen in children with prenatal methamphetamine exposure.
KeywordsMagnetic resonance imaging Diffusion tensor imaging Prenatal methamphetamine exposure Neonate Corticostriatal white matter
We thank A. Hess and A. Mareyam for their work in constructing the bird cage RF coil used in this study under the supervision of L. Wald, Director MRI Core, Martinos Center for Biomedical Imaging, Radiology, Massachusetts General Hospital; the Cape Universities Brain Imaging Centre radiographers N. Maroof and A. Siljeur; N. Dodge, our Wayne-State University-based data manager; and our University of Cape Town research staff M. September, B. Arendse, M. Raatz, and P. Solomon. We greatly appreciate the participation of the Cape Town mothers and infants in the study.
National Institutes of Health (NIH) grants R01-AA016781 (SJ), R21-AA020037 (SJ, EM, AvdK) and R00HD061485–03 (LZ), supplemental funding from the Lycaki/Young Fund, from the State of Michigan (SWJ and JLJ), and the South African Research Chairs Initiative (EM). This research was supported, in part, by the NIMH and NINDS Intramural Research Programs of the NIH (PT). FW is supported by a South African National Research Foundation (NRF) Innovative Scholarship and the Duncan Baxter Scholarship from the University of Cape Town.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflict of interest.
Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Human Ethics committees at Wayne State University and the Faculty of Health Sciences of the University of Cape Town, and with the 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from the mothers of the infants in the study.
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