Tractography-Based Insights into Neuroplasticity and Clinical Heterogeneity in Parkinson’s Disease Subtypes

Parkinson’s disease shows substantial heterogeneity across motor, cognitive, and non-motor domains, reflecting variable patterns of neurodegeneration and compensation across distributed brain circuits. Diffusion magnetic resonance imaging (dMRI) tractography enables pathway-specific characterization of white-matter alterations and provides a framework for linking clinical subtypes to tract-level patterns that may be obscured by skeleton-based or connectomic averaging. Here, we synthesize white-matter evidence across motor, cognitive, genetic, and prodromal dimensions of PD heterogeneity, using tractography as an organizing framework within a broader dMRI and multimodal context. We review diffusion approaches ranging from diffusion tensor imaging to free-water, neurite, and fixel-based models. We distinguish pathway reconstructions from other diffusion and imaging analyses and consider how complementary approaches inform, but do not uniquely determine, interpretations of degeneration and subtype-specific neuroplasticity. Emerging methods, including harmonization pipelines, radiomic tractometry, and machine learning classifiers, may further improve tract-level sensitivity and reproducibility. Cognitive subtypes illustrate how posterior association and limbic tract degeneration, together with cholinergic and noradrenergic dysfunction, shape clinical progression. Integrating tractography with molecular, genetic, functional, and clinical markers may support subtype-specific biomarkers for risk stratification, prognosis, and targeted neuromodulation or rehabilitation strategies, although longitudinal and external validation is required before routine use.