Altered White Matter Integrity in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: A Tract-Based Spatial Statistics Study

Abstract

Objective: Human immunodeficiency virus (HIV) infection has been known to damage the microstructural integrity of white matter (WM). However, only a few studies have assessed the brain regions in HIV-associated neurocognitive disorders (HAND) with diffusion tensor imaging (DTI). Therefore, we sought to compare the DTI data between HIV patients with and without HAND using tract-based spatial statistics (TBSS).

Materials and methods: Twenty-two HIV-infected patients (10 with HAND and 12 without HAND) and 11 healthy controls (HC) were enrolled in this study. A whole-brain analysis of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was performed with TBSS and a subsequent 20 tract-specific region-of-interest (ROI)-based analysis to localize and compare altered WM integrity in all group contrasts.

Results: Compared with HC, patients with HAND showed decreased FA in the right frontoparietal WM including the upper corticospinal tract (CST) and increased MD and RD in the bilateral frontoparietal WM, corpus callosum, bilateral CSTs and bilateral cerebellar peduncles. The DTI values did not significantly differ between HIV patients with and without HAND or between HIV patients without HAND and HC. In the ROI-based analysis, decreased FA was observed in the right superior longitudinal fasciculus and was significantly correlated with decreased information processing speed, memory, executive function, and fine motor function in HIV patients.

Conclusion: These results suggest that altered integrity of the frontoparietal WM contributes to cognitive dysfunction in HIV patients.

Keywords: Diffusion tensor imaging; HIV; HIV-associated neurocognitive disorders (HAND); Human immunodeficiency virus; TBSS.

Fig. 1. TBSS analysis of FA maps.

Areas in sky blue-blue represent brain regions with significant decrease in FA (FWE-corrected p < 0.05) in HAND group relative to HC. Results are shown overlaid on Montreal Neurological Institute 152-T1 template and mean FA skeleton (green). Left side of image corresponds to right hemisphere of brain. FA = fractional anisotropy, FWE = family-wise error, HAND = HIV-associated neurocognitive disorders, HC = healthy controls, HIV = human immunodeficiency virus, TBSS = tract-based spatial statistics

Fig. 2. TBSS analysis of MD maps.

Areas in orange-red represent brain regions with significant increase in MD (FWE-corrected p < 0.05) in HAND group relative to HC. Green represents mean white matter skeleton of all subjects. MD = mean diffusivity

Fig. 3. TBSS analysis of RD maps.

Areas in orange-red represent brain regions with significant increase in RD (FWE-corrected p < 0.05) in HAND group relative to HC. Green represents mean white matter skeleton of all subjects. RD = radial diffusivity

Fig. 4. Bar graph representing mean DTI values in JHU WM tractography-based ROIs that were extracted from TBSS results (MD and RD values were multiplied by 1000 for good visibility).

^*p < 0.05 in trend analyses. ATR = anterior thalamic radiation, CCG = cingulum (cingulate gyrus), Ch = cingulum (hippocampus), CON = healthy controls, CST = corticospinal tract, DTI = diffusion tensor imaging, FCPM = forceps major, FCPm = forceps minor, HIV-IC = HIV-infected patients with intact cognition, IFOF = inferior fronto-occipital fasciculus, ILF = inferior longitudinal fasciculus, JHU = Johns Hopkins University, L = left, R = right, ROI = region-of-interest, SLF = superior longitudinal fasciculus, SLFTP = SLF temporal part, UF = uncinate fasciculus, WM = white matter

Fig. 5. Correlation analysis with FA value in right SLF masks and NP test results.

Region in pink represents right SLF mask in JHU WM tractography atlas. Inside this mask, regions that showed significantly decreased FA between HAND and HIV-IC groups on TBSS analysis are marked in red and was used as mask for ROI (A). Mean FA value in this ROI was correlated with NP test results. Correlation results are shown graphically in (B). K-AVLT = Korean version of Auditory Verbal Learning Test, NP = neuropsychological, TMT A = trail making test part A, TMT B = trail making test part B