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Along-Tract Microstructural Alterations Associated with Stimulant Misuse Localized using Diffusion MRI Tractometry
Leila Nabulsi1, Yixue Feng1, Bramsh Q Chandio1,2
1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA.
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
Diffusion MRI reveals localized white matter (WM) changes in stimulant misuse, particularly in hippocampal pathways for pooled stimulant users and broader pathways for amphetamine users. These findings improve anatomical specificity in addiction neuroimaging.
Area of Science:
- Neuroimaging
- Addiction Science
- White Matter Anatomy
Background:
- Substance use disorders are linked to widespread white matter (WM) microstructural alterations.
- Previous diffusion MRI (dMRI) studies lack fine-scale anatomical specificity in identifying these changes.
Purpose of the Study:
- To precisely localize white matter microstructural alterations associated with stimulant misuse using advanced tractometry.
- To compare findings between amphetamine and cocaine misuse and identify pooled stimulant effects.
Main Methods:
- Applied segment-wise along-tract 3D tractometry (Bundle Analytics and Medial Tractography Analysis) to dMRI scans.
- Analyzed diffusion metrics across 33 major WM bundles in independent cohorts of cocaine and amphetamine users.
- Tested associations for pooled stimulant effects, substance-specific effects, and inter-class comparisons.
Main Results:
- Focal, segment-specific WM differences were identified, not uniform changes along entire bundles.
- Pooled stimulant misuse showed alterations in hippocampal pathways, consistent with altered microstructural organization.
- Amphetamine misuse revealed broader segment-wise differences in commissural, projection, and association pathways, indicating altered axonal organization.
Conclusions:
- White matter alterations in stimulant use disorder are spatially localized and reproducible across different tractometry frameworks.
- Along-tract 3D mapping enhances anatomical specificity in addiction neuroimaging research.
- Findings highlight specific white matter vulnerabilities in stimulant misuse, particularly amphetamine use.
