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Contains fulltext : 70951.pdf (Publisher’s version ) (Closed access) PURPOSE: Functional magnetic resonance imaging (fMRI) is being used increasingly for language dominance assessment in the presurgical work-up of patients with pharmacoresistant epilepsy. However, the interpretation of bilateral fMRI-activation patterns is difficult. Various studies propose fMRI-lateralization index (LI) thresholds between +/-0.1 and +/-0.5 for discrimination of atypical from typical dominant patients. This study examines if these thresholds allow identifying atypical dominant patients with sufficient safety for presurgical settings. METHODS: 65 patients had a tight comparison, fully controlled semantic decision fMRI-task and a Wada-test for language lateralization. According to Wada-test, 22 were atypical language dominant. In the remaining, Wada-test results were compatible with unilateral left dominance. We determined fMRI-LI for two frontal and one temporo-parietal functionally defined, protocol-specific volume of interest (VOI), and for the least lateralized of these VOIs ("low-VOI") in each patient. RESULTS: We find large intra-individual LI differences between functionally defined VOIs irrespective of underlying type of language dominance (mean LI difference 0.33+/-0.35, range 0-1.6; 15% of patients have inter-VOI-LI differences >1.0). Across atypical dominant patients fMRI-LI in the Broca's and temporo-parietal VOI range from -1 to +1, in the "remaining frontal" VOI from -0.93 to 1. The highest low-VOI-LI detected in atypical dominant patients is 0.84. CONCLUSIONS: Large intra-individual inter-VOI-LI differences and strongly lateralized fMRI-activation in patients with Wada-test proven atypical dominance question the value of the proposed fMRI-thresholds for presurgical language lateralization. Future studies have to develop strategies allowing the reliable identification of atypical dominance with fMRI. The low-VOI approach may be useful.