Microstructural changes in the reward system are associated with post-stroke depression

Lena K.L Oestreich,Paul Wright,Michael J O'Sullivan

doi:10.1016/j.nicl.2020.102360

Lena K.L Oestreich, Paul Wright + Show 1 more

Open Access

https://doi.org/10.1016/j.nicl.2020.102360

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Abstract

BackgroundStudies of lesion location have been unsuccessful in identifying mappings between single brain regions and post-stroke depression (PSD). Based on studies implicating the reward system in major depressive disorder without stroke, we investigated structural correlates within this system and their associations with PSD. MethodsThe study enrolled 16 healthy controls, 12 stroke patients with PSD and 34 stroke patients free of PSD. Participants underwent 3T structural and diffusion MRI. Graph theoretical measures were used to examine global topology and whole-brain connectome analyses were employed to assess differences in the interregional connectivity matrix between groups. Structural correlates specific to the reward system were examined from grey matter volumes and by reconstructing its main white matter pathways, namely the medial forebrain bundle and cingulum connections, using deterministic tractography. Fractional anisotropy (FA) was derived as a measure of microstructural organization, and extracellular free-water (FW) as a possible proxy of neuroinflammation. ResultsSubnetworks of decreased FA-weighted and increased FW-weighted connectivity were observed in patients with PSD relative to healthy controls. These networks subsumed the majority of regions constituting the reward system. Within the reward system, FA and FW of major connection pathways and grey matter volume were collectively predictive of PSD, explaining 37.8% of the variance in depression severity. ConclusionsPSD is associated with grey matter volume loss, reduced FA and increased extracellular FW in the reward system, similar to features observed in major depression without stroke. Structural characterization of the reward system is a promising biomarker of vulnerability to depression after stroke.

Highlights

Post-stroke depression (PSD) is a common complication after stroke, with approximately 31% of stroke survivors meeting the criteria for major depression 3–6 months after stroke (Hackett and Pickles, 2014)
We found post-stroke depression (PSD) to be associated with global network topology and subnetworks identified from structural connectome analysis that mapped predominantly onto fronto-subcortical regions and connections defined as constituting the reward system
Our focused analysis of grey and white matter correlates within the reward system showed that grey matter volumes of this circuit, together with Fractional anisotropy (FA) and extracellular FW content of major connection pathways in this system were collectively predictive of PSD severity

Summary

Introduction

Post-stroke depression (PSD) is a common complication after stroke, with approximately 31% of stroke survivors meeting the criteria for major depression 3–6 months after stroke (Hackett and Pickles, 2014). More recent studies using voxel-based lesion symptom mapping, which normalizes and coregisters brain imaging data into a standard template and represents a more quantitative approach to study lesion locations, have reported conflicting findings (Gozzi et al, 2014; Kim et al, 2017; Terroni et al, 2011) This inconsistency among single studies is reflected in systematic reviews (Carson et al, 2000; Nickel and Thomalla, 2017; Wei et al, 2015) and meta-analyses (Narushima et al, 2003; Yu et al, 2004), which have been unable to reveal any straightforward. Results: Subnetworks of decreased FA-weighted and increased FW-weighted connectivity were observed in patients with PSD relative to healthy controls These networks subsumed the majority of regions constituting the reward system. Structural characterization of the reward system is a promising biomarker of vulnerability to depression after stroke

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