White matter microstructural alterations in children with prenatal methamphetamine/polydrug exposure

Abstract

Little is known about the effects of prenatal methamphetamine exposure on white matter microstructure, and the impact of concomitant alcohol exposure. Diffusion tensor imaging and neurocognitive testing were performed on 21 children with prenatal methamphetamine exposure (age 9.8±1.8 years; 17 also exposed to alcohol), 19 children with prenatal alcohol but not methamphetamine exposure (age 10.8±2.3 years) and 27 typically developing children (age 10.3±3.3 years). Whole-brain maps of fractional anisotropy (FA) were evaluated using tract-based spatial statistics. Relative to unexposed controls, children with prenatal methamphetamine exposure demonstrated higher FA mainly in left-sided regions, including the left anterior corona radiata (LCR) and corticospinal tract Post-hoc analyses of these FA differences showed they likely result more from lower radial diffusivity (RD) than higher axial diffusivity (AD). Relative to the methamphetamine-exposed group, children with prenatal alcohol exposure showed lower FA in frontotemporal regions-particularly, the right external capsule. We failed to find any group-performance interaction (on tests of executive functioning and visuomotor integration) in predicting FA; however, FA in the right external capsule was significantly associated with performance on a test of visuomotor integration across groups. This report demonstrates unique diffusion abnormalities in children with prenatal methamphetamine/polydrug exposure that are distinct from those associated with alcohol exposure alone, and illustrates that these abnormalities in brain microstructure are persistent into childhood and adolescence--long after the polydrug exposure in utero.

Figure 1. Alcohol exposure clinical severity by group

Exp = Exposed (least severe), ARND = Alcohol-related neurodevelopmental disorder, Sent = Sentinel (shows mild facial dysmorphology), PFAS = partial FAS, FAS = Fetal alcohol syndrome (most severe). MA = Methamphetamine-exposed group, ALC = alcohol-exposed group.

Figure 2. Group differences in fractional anisotropy (FA)

A) MA>CON group contrast. B) MA>ALC contrast. C) MA>CON contrast with alcohol exposure clinical severity covariate. Note: Results dilated back into white matter for visualization (red). Areas of greatest significance are displayed as bright centers along the skeleton (yellow and aqua). Background image is ICBM152 1mm standard brain. Slice numbers referenced from y = 0 mm coronal slice in MNI coordinates. MA = methamphetamine-exposed group, ALC = alcohol-exposed group, CON = typically-developing control group.

Figure 3. Regional scatterplots of DTI metrics

Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), are plotted versus age. These plots are facetted into a matrix by brain region, and color is used to encode group membership (Control, ALC, MA). Linear trendlines are added to all plots for visual reference. Each region of interest was obtained by centering a 5mm sphere on the respective cluster center from Table 2, and intersecting this with the associated P<0.05 statistical map from Figure 2. Note: These plots are intended only to give a general regional view of the raw data, and to allow inspection for gross outliers. All statistical testing was performed on the original voxelwise maps.

Figure 4. Brain-behavior analysis

A) Right external capsule (REC) region of interest (ROI) extracted from thresholded whole-skeleton statistical map (dilated back into white matter for visualization). B) Box and scatter plot displaying the median and quartile distribution of the fractional anisotropy (FA) values for each group within the ROI. C) Partial regression plot between FA in the REC and visuomotor integration (VMI) raw score. Both axes are residualized for age and group.