Abstract

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. 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. 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. 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.

Highlights

  • The medial forebrain bundle (MFB) is the central pathway of the reward system, which mediates feelings and expectations of pleasure (Schultz et al 1997; Coenen et al 2011)

  • None of the participants met criteria for major depressive disorder (MDD) according to the Mini International Neuropsychiatric Inventory (MINI)

  • Our participants had a mean score of 65 ± 10 on the Bipolar Affective Disorder Dimension Scale (BADDS), indicating a moderate to severe history of depression

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Summary

Introduction

The medial forebrain bundle (MFB) is the central pathway of the reward system, which mediates feelings and expectations of pleasure (Schultz et al 1997; Coenen et al 2011). Coenen et al (2009) were the first to reconstruct the MFB using diffusion magnetic resonance imaging (MRI)-based fibre tracking. In addition to this inferomedial MFB (imMFB) branch, the researchers described a supero-lateral branch (slMFB) proceeding from the ventral tegmental area (VTA) to the forebrain and the frontal lobe (Coenen et al 2009, 2012). 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. We explore associations between diffusion MRI-based metrics of white-matter microstructure of imMFB, slMFB and hedonic tone, the ability to derive pleasure

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