E008 Delineating striatal patterns associated to cortico-striatal connections in Huntington’s disease: implications for cognitive profiles

<h3>Background</h3> Despite a common genetic etiology, Huntington’s Disease (HD) presents individual differences in onset, severity, and progression of motor, cognitive, and psychiatric symptoms. The neurobiological basis for this variability remains poorly understood. The striatum, a hallmark of early degeneration in HD, regulates unique motor, associative and limbic functions through topographically organized cortical connections. <h3>Aims</h3> This study investigates whether symptomatic differences in HD are related to specific patterns of cortico-striatal neurodegeneration. Thirty-eight individuals (19 manifest and 19 premanifest) were evaluated for clinical symptoms. Diffusion tensor imaging was used to analyze cortico-striatal white matter connectivity and perform connectivity-based segmentation of the striatum using probabilistic tractography. Fractional anisotropy values in each striatal subregion were measured, and Principal Component Analyses (PCA) were conducted to identify and relate patterns in striatal subregions and clinical symptoms. <h3>Results</h3> The PCA on the striatum’s microstructural variability identified three main factors: (1) regions connected to prefrontal, motor and parietal targets, (2) regions targeting occipital, temporal, and limbic regions, and (3) exclusively limbic regions. The latter was the only factor preserved in premanifest compared to manifest. PCA of clinical profiles found a cognitive-motor and a psychiatric component. The earlier related to the fronto-parietal factor (i.e. 1) while the latter related to the limbic factor (i.e. 3). <h3>Conclusion</h3> This study suggests different patterns of striatal neurodegeneration relate to unique HD clinical profiles, potentially advocating for personalized medicine and tailored clinical trials in HD.