Background: Acquired brain injury (ABI) often produces heterogeneous cognitive and emotional outcomes that are not fully explained by conventional neuropsychological testing. Diffusion tensor imaging (DTI) tractography may capture patient-specific patterns of white matter connectivity and thereby complement clinical assessment. Methods: We conducted an exploratory case series of nine patients in the subacute phase of ABI (traumatic brain injury or subarachnoid hemorrhage). Each underwent a brief cognitive-emotional battery and 1.5 T DTI with deterministic tractography of major association tracts and the corpus callosum. Tract lateralization was quantified using the Structural Asymmetry Index (SAI), and individual profiles were compared with neuropsychological and emotional data. Results: Six patients met criteria for clinically significant anxiety, and four for depression, often dissociated from global cognitive screening. Tractography revealed heterogeneous asymmetry patterns, most often in the superior longitudinal fasciculus, uncinate fasciculus, and cingulum. In several cases, structural asymmetries diverged from neuropsychological findings, suggesting dissociations between behavioral testing and connectivity-based measures. Conclusions: Within-subject tract asymmetry analysis provided preliminary, potentially clinically relevant information not captured by tests alone. These findings indicate that individualized tractography could enrich the interpretation of cognitive and emotional profiles and help guide hypothesis generation for connectivity-informed neurorehabilitation.

Background: 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.Methods: 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. Results: 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. Conclusions: 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.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Psychotherapeutic interventions following acquired brain injury often underestimate the influence of neural connectivity on emotional and cognitive recovery, contributing to treatment response variability. We present a single-case report of an adult with mild acquired brain injury, in whom diffusion tensor imaging (tractography) and neuropsychological assessment were integrated to guide individualized clinical planning. Baseline tractography revealed globally preserved white-matter organization with rightward asymmetries in the uncinate and superior longitudinal fasciculi–pathways involved in cognitive–emotional integration. This specific neuroanatomical profile informed a psychotherapeutic plan that prioritized attentional and experiential strategies, being functionally compatible with the preserved networks, over those requiring complex verbal-analytic processing. After 1 year of intervention (approximately 40 sessions), reassessment documented significant functional improvements, quantified by a reduction in anxiety to a non-clinical range (HADS-A: 11 → 6) and a normalization in cognitive flexibility (TMT-B: 190 → 128 s), without observable structural change. These findings validate the hypothesis that therapeutic change may arise from functional optimization within preserved networks rather than anatomical reorganization. This report proposes the functional compatibility framework as a transferable and theoretically grounded model for precision psychotherapy, bridging the gap between neuroscience and clinical practice.