White Matter Microstructural Alterations in Huntington’S Disease: A Systematic Review of Diffusion Imaging Findings Publisher Pubmed



Salabat D ; Kamalizonouzi S ; Kiani I ; Seyedmirzaei H ; Rezaei S ; Aarabi MH
Source: Brain Imaging and Behavior Published:2026

Abstract

Huntington’s Disease (HD) is characterized by neurodegeneration initially targeting the striatum, before progressively affecting the white matter and cortex. Diffusion Tensor Imaging (DTI) could provide critical insights into microstructural changes in HD patients, unraveling pathophysiological mechanisms linked with this disease and the clinical symptoms. This study systematically reviews the literature on HD-associated microstructural changes identified by means of DTI, and further investigates correlations of DTI metrics with disease progression, motor deficits, cognitive performance, and genetic features. We searched PubMed, Embase, and Scopus, with appropriate keywords for studies that met our inclusion criteria. We identified 33 studies eligible for being included. The reported microstructural alterations spanned across numerous brain regions, and mostly included reduced fractional anisotropy (FA) and increased mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Reduced FA was observed across several brain regions, including the corpus callosum, external and internal capsule, caudate, putamen, dorsal striatum, thalamus, and corticospinal tracts. We reported an association between specific diffusivity measures with both cognitive performance and clinical symptoms. Motor deficits were linked with diffusivity alterations of the corpus callosum and the corticospinal tract. DTI facilitates identification of HD-associated brain abnormalities, potentially elucidating disease etiology and correlations with clinical presentation. Additionally, targeting specific affected brain regions could lead to innovative treatment strategies. Future research is warranted to further elucidate DTI role in HD clinical practice, with the aim of paving the way to new effective treatments and rehabilitation interventions. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.