Hedonic tone is associated with left supero-lateral medial forebrain bundle microstructure

Background. The medial forebrain bundle (MFB) is an important pathway of the reward system. Two branches have been described using diffusion magnetic resonance imaging (MRI)-based tractography: the infero-medial MFB (imMFB) and the supero-lateral MFB (slMFB). Previous studies point to white-matter microstructural alterations of the slMFB in major depressive disorder (MDD) during acute episodes. To extend this finding, this study investigates whether white-matter microstructure is also altered in MDD patients that are in remission. Further, we explore associations between diffusion MRI-based metrics of white-matter microstructure of imMFB, slMFB and hedonic tone, the ability to derive pleasure. Method. Eighteen remitted depressed (RD) and 22 never depressed (ND) participants underwent high angular resolution diffusion-weighted imaging (HARDI) scans. To reconstruct the two pathways of the MFB (imMFB and slMFB) we used the damped Richardson-Lucy (dRL) algorithm. Mean fractional anisotropy (FA) was sampled along the tracts. Results. Mean FA of imMFB, slMFB and a comparison tract (the middle cerebellar peduncle) did not differ between ND and RD participants. Hedonic capacity correlated negatively with mean FA of the left slMFB, explaining 21% of the variance. Conclusions. Diffusion MRI-based metrics of white-matter microstructure of the MFB in RD do not differ from ND. Hedonic capacity is associated with altered white-matter microstructure of the slMFB.