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Lower reward responsiveness has been associated with fatigue in multiple sclerosis (MS). However, association of MS-related fatigue with damage to the mesocorticolimbic reward pathway (superolateral medial forebrain bundle [slMFB]) has not been assessed. We investigated the association of fatigue and depression with slMFB damage in MS patients stratified based on longitudinal fatigue patterns. Patient stratification 1. Sustained Fatigue (SF) latest two Modified Fatigue Impact Scale (MFIS) ≥ 38 (n = 26); 2. Reversible Fatigue (RF) lates