Focal White Matter Integrity Loss in Methamphetamine Use Disorder and Preservation with Regular Exercise in Adolescents: What’s more in Quantitative Anisotropy-based Connectometry than Conventional Diffusion Tensor Imaging?

Methamphetamine (MA) use in adolescence may alter brain development, whereas physical activity has been associated with differences in developing white matter. We evaluated white matter microstructural measures across adolescent MA users, athletes, and controls using quantitative anisotropy (QA)-based connectometry and conventional diffusion tensor imaging (DTI). We retrospectively analyzed DTI data from 30 adolescents: 10 with methamphetamine use disorder (MUD), 10 licensed athletes, and 10 healthy controls. Analyses were performed in DSI Studio using correlational tractography, deterministic tractography, and region-based analysis. Group differences were assessed for fractional anisotropy (FA) using conventional DTI (tractography and region-based analysis) and for quantitative anisotropy (QA) using whole-brain correlational tractography. Conventional FA detected selective differences confined to the bilateral corticospinal tracts (CST), where athletes > MUD ( p < 0.016). QA‑based connectometry revealed broader effects: Athletes > Controls : higher QA localized primarily across interhemispheric callosal tracts, alongside a small contribution from the left corticospinal tract. Athletes > MUD : higher QA across forceps major, tapetum, CST, nondecussating dentatorubrothalamic tracts and the medial lemniscus. Controls > MUD : higher QA in bilateral CST, corticopontine tracts, nondecussating dentatorubrothalamic tracts, left corticostriatal tract and the medial lemniscus. QA-based connectometry identified a broader distribution of tract-level group differences than conventional FA analyses in this cohort. In adolescents, active MA use was associated with lower quantitative anisotropy metrics in motor and brainstem pathways, whereas regular sports participation was associated with higher anisotropy across interhemispheric callosal tracts. QA-based connectometry provided complementary tract-level information beyond conventional FA, revealing distinct microstructural profiles in athletic versus substance-exposed adolescents, although prospective longitudinal studies are required to establish causality.