White Matter Tract Integrity and Cognitive, Emotional, and Social Outcomes After Acquired Brain Injury: Exploratory Tractography Findings for Personalized Neurorehabilitation

<b>Background:</b> Acquired brain injury (ABI) leads to cognitive, emotional, and social impairments that substantially affect quality of life. Although cortical lesions have traditionally received more attention, increasing evidence highlights the importance of the integrity of major white matter association tracts. However, few studies have simultaneously examined cognitive, affective, and social domains within a tractography framework. <b>Methods:</b> In this exploratory pilot study, ten ABI patients underwent diffusion-based tractography of the principal association tracts-the superior and inferior longitudinal fasciculi, the uncinate fasciculus, the inferior fronto-occipital fasciculus, and the cingulum-together with a comprehensive neuropsychological battery covering global cognition, executive functions, memory, emotional symptoms, and empathy. <b>Results:</b> Marked interindividual variability was observed in both tract profiles and neuropsychological outcomes. Findings revealed paradoxical associations, such as larger volumes of the left superior longitudinal fasciculus being linked to poorer cognitive performance, suggesting maladaptive reorganization. Hemispheric lateralization patterns were also identified, with the uncinate fasciculus showing differential contributions to immediate memory and working memory across hemispheres. Notably, empathy scores consistently correlated with volumes of the inferior longitudinal fasciculus, the uncinate fasciculus, and the cingulum, in line with recent evidence on the structural basis of socio-emotional outcomes after ABI. <b>Conclusions:</b> Although limited by sample size, this study provides novel evidence regarding the structure-function paradox, hemispheric specialization, and the clinical relevance of empathy in ABI. Overall, the results support the integration of tractography of the main association tracts with neuropsychological assessment as complementary tools to advance personalized neurorehabilitation.