This study investigates the efficacy of deep-learning models in expediting the generation of disconnectomes for individualized prediction of neuropsychological outcomes one year after stroke. Utilising a 3D U-Net network, we trained a model on a dataset of N = 1333 synthetic lesions and corresponding disconnectomes, subsequently applying it to N = 1333 real stroke lesions. The model-generated disconnection patterns were then projected into a two-dimensional 'morphospace' via uniform manifold approximation and projection for dimension reduction dimensionality reduction. We correlated the positioning within this morphospace with one-year neuropsychological scores across 86 metrics in a novel cohort of 119 stroke patients, employing multiple regression models and validating the findings in an out-of-sample group of 20 patients. Our results demonstrate that the 3D U-Net model captures the critical information of conventional disconnectomes with a notable increase in efficiency, generating deep-disconnectomes 720 times faster than current state-of-The-Art software. The predictive accuracy of neuropsychological outcomes by deep-disconnectomes averaged 85.2% (R2 = 0.208), which significantly surpassed the conventional disconnectome approach (P = 0.009). These findings mark a substantial advancement in the production of disconnectome maps via deep learning, suggesting that this method could greatly enhance the prognostic assessment and clinical management of stroke survivors by incorporating disconnection patterns as a predictive tool. © 2024 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.< Leer menos