Brain Microstructure and Impulsivity Differ between Current and Past Methamphetamine Users

Abstract

Methamphetamine (Meth) use disorder continues to be highly prevalent worldwide. Meth users have higher impulsivity and brain abnormalities that may be different between current and past Meth users. The current study assessed impulsivity and depressive symptoms in 94 participants (27 current Meth users, 32 past Meth users and 35 non-drug user controls). Additionally, brain microstructure was assessed using diffusion tensor imaging (DTI); fractional anisotropy (FA) and mean diffusivity (MD) were assessed in the striatum, and FA, MD, radial and axial diffusivity were quantified in five white matter structures using DtiStudio.Across the three subject groups, current users had the highest self-reported impulsivity scores, while both Meth user groups had larger striatal structures than the controls. Past Meth users had the highest FA and lowest MD in the striatum, which is likely due to greater magnetic susceptibility from higher iron content and greater dendritic spine density. In white matter tracts, current Meth users had higher AD than past users, indicating greater water diffusion along the axons, and suggesting inflammation with axonal swelling. In contrast, past users had the lowest AD, indicating more restricted diffusion, which might have resulted from reactive gliosis. Although current Meth users had greater impulsivity than past users, the brain microstructural abnormalities showed differences that may reflect different stages of neuroinflammation or iron-induced neurodegeneration. Combining current and past Meth users may lead to greater variability in studies of Meth users. Longitudinal studies are needed to further evaluate the relationship between recency of Meth use and brain microstructure.

Keywords: DTI; Impulsivity; Methamphetamine; Striatum; White matter.

Fig. 1

Barratt Impulsiveness Scale in Methamphetamine Users and Non-User Controls. a and b BIS-11 scores are consistently highest in current Meth users, while the scores in the controls are lowest and the past users’ scores are intermediate across all 11 parcels. c and d Consequently, current users have significantly higher scores than past users and controls (who have the lowest scores) on both the cognitive and the behavioral dimension of impulsivity, and the BIS-11 total score. e In current, but not past, Meth users, the BIS-11 total score correlated with the log-transformed average amount of daily Meth used. Data presented are means ± standard errors. P-values from 1-way ANCOVA and 2-way ANCOVA are co-varied for age, gender, and years of education

Fig. 2

Fractional Anisotropy, Mean Diffusivity and Volumes in Striatal Structures a Regions of Interest are shown on an FA map of a single subject. b The Regions of Interest are shown in parcellated regions from the automated JHU-MNI atlas. c Fractional anisotropy is higher in putamen and globus pallidus of the past users compared to both current users and the controls. d Mean diffusivity is lower in putamen and pallidus in past Meth users compared to current users and controls. e Meth users as a group, combining current and past users, had larger putamen compared to controls. f) Furthermore, larger putamen was associated with lower putamen MD. g & h In the globus pallidus, larger volume was associated with higher FA and lower MD across all groups. Data presented are means ± standard errors; p-values in the bar graphs from 1-way ANCOVA and post-hoc analyses are co-varied for age and gender

Fig. 3

Axial Diffusivity in White Matter Structures of Interest a Color map of the fractional anisotropy from a single subject showing the location of the genu of the corpus callosum. b In the genu of the corpus callosum, axial diffusivity (AD) is lower in past Meth users than in current users and controls. c In a single subject, fiber-tracts of the five white matter structures of interest are illustrated to demonstrate the anatomical relationships of these structures. d Regions of Interest (ROIs) from various white matter structures were parcellated using the JHU-MNI atlas, and the ROIs from the five tracts of interest that were evaluated are labeled. e In addition to the abnormal AD in the genu of the corpus callosum (GCC), the AD is also higher in current users but normalized or lower in past Meth users compared to controls, in the anterior corona radiata (ACR), the sagittal stratum (SS) and the superior longitudinal fasciculus (SLF). However, in the inferior fronto-occipital fasciculus (IFO), past Meth users had lower AD than both current Meth users and controls. Data presented are means ± standard errors; p-values from 1-way ANCOVA and post-hoc analyses are co-varied for age and gender

Fig. 4

Relationships between DTI measures and impulsivity. a Only current Meth users with higher FA in the putamen had higher cognitive impulsivity scores. b and c Both current and past Meth users with lower MD had higher cognitive impulsivity and BIS-11 scores. d Only current Meth users with lower AD in the sagittal stratum (SS) had greater BIS-11 scores. e Meth users, regardless of recency of use, with lower AD in the genu of the corpus callosum (GCC) tended to have higher cognitive impulsivity scores. P-values are from two-way-ANCOVAs, co-varied for education and CES-D, for the DTI metrics that had significant effects or interactions in the exploratory multivariate general linear models on the impulsivity measures and were still significant on the post-hoc two-way-ANCOVA