Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Abstract

HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and risk-taking behaviors (N = 93). All three clinical groups showed a left-lateralized pattern of GM reduction in the BG relative to controls. However, in the HIV + /POLY + group, stimulant use was associated with increased GM volume within the globus pallidus and putamen. This surpassed the effects from opioid use, as indicated by decreased GM volume throughout the BG in the HIV-/POLY + group. Motor learning was impaired in all three clinical groups, and in the HIV + /POLY + group, motor learning was associated with increased caudate and putamen GM volume. We also observed associations between BG GM volume and risk-taking behaviors in the HIV + /POLY- and HIV-/POLY + groups. The effects of substance use on the BG differed as a function of substance type used, HIV seropositivity, and BG subregion. Although BG volume decreased in association with HIV and opioid use, stimulants can, inversely, lead to BG volume increases within the context of HIV.

Figure 1

Working memory and loop drawing performance during single and dual task conditions. (A) The percent accuracy of letter spans recalled in sequence are reported across trials of increasing letter spans of 3–8 letters. Recall accuracy for letters decreased as the size of letter spans increased, especially in the dual task condition when working memory was performed in conjunction with a motor task. In the single task condition, the HIV + /POLY + group (purple) performed with less accuracy than did the HIV + /POLY- group (blue). (B) The number of loops is reported across each 5-s trial. Loop drawing frequency increased across trials, with most gains occurring in the single task condition. In the dual task condition, loop drawing was done in conjunction with a working memory task that increased cognitive load across trials. The HIV-/POLY- group (red) improved motor learning more than any other group did, suggesting that HIV and substance use history impacted performance. However, when HIV and POLY groups were examined collectively, the HIV + groups (blue plus purple) showed impaired motor learning, whereas the POLY + groups (green plus purple) did not. (Trials 9–12 of the dual task were not included in omnibus analysis). Bars denote one standard error.

Figure 2

Summary of gray matter volume changes within the basal ganglia for each study group. Top: A coronal view schematic of the regions of interest examined within the basal ganglia and midbrain. L = left; R = right. Bottom: Colored regions indicate the locations within the basal ganglia that were associated with duration of substance use, motor learning, and risky behaviors. Patterns indicate the positive or negative direction of the association. Depictions may be compared with Fig. 3 and Table 4.

Figure 3

POLY + group regressions of basal ganglia gray matter volume and substance use duration. (A) Statistical map of z-scores indicating reduced gray matter (GM) as a function of opioid use duration in the HIV-/POLY + group; z-planes = -16, -10, -4, 2, 8, 14 in MNI space; p < 0.05 FWE. R = right hemisphere, L = left hemisphere; (B) Statistical map of z-scores indicating increased GM as a function of stimulant use duration in the HIV + /POLY + group; z-planes = -10, -6, -4, 0, 4, 8 in MNI space; p < 0.05 FWE. R = right hemisphere, L = left hemisphere. (C) Depiction of basal ganglia ROI masks that were used for regression analyses with substance use duration, shown here overlaid on the SPM152 template for visualization.