Brain disconnectivity mapping of post-stroke fatigue

Abstract

Stroke patients commonly suffer from post stroke fatigue (PSF). Despite a general consensus that brain perturbations constitute a precipitating event in the multifactorial etiology of PSF, the specific predictive value of conventional lesion characteristics such as size and localization remain unclear. The current study represents a novel approach to assess the neural correlates of PSF in chronic stroke patients. While previous research has focused primarily on lesion location or size, with mixed or inconclusive results, we targeted the extended structural network implicated by the lesion, and evaluated the added explanatory value of a disconnectivity approach with regards to the brain correlates of PSF. To this end, we estimated individual brain disconnectome maps in 84 stroke survivors in the chronic phase (≥ 3 months post stroke) using information about lesion location and normative white matter pathways obtained from 170 healthy individuals. PSF was measured by the Fatigue Severity Scale (FSS). Voxel wise analyses using non-parametric permutation-based inference were conducted on disconnectome maps to estimate regional effects of disconnectivity. Associations between PSF and global disconnectivity and clinical lesion characteristics were tested by linear models, and we estimated Bayes factor to quantify the evidence for the null and alternative hypotheses, respectively. The results revealed no significant associations between PSF and disconnectome measures or lesion characteristics, with moderate evidence in favor of the null hypothesis. These results suggest that symptoms of post-stroke fatigue are not simply explained by lesion characteristics or brain disconnectome measures in stroke patients in a chronic phase, and are discussed in light of methodological considerations.

Structural disconnectome mapping of cognitive function in post-stroke patients

“…The present cross-sectional study included participants previously described in detail (Dørum et al, 2020; Kolskår et al, 2020; Richard et al, 2020; Ulrichsen et al, 2020). Briefly, the sample comprised 102 stroke survivors from sub-acute (>24h post stroke and in clinical stable condition) to chronic stage.…”

“…The copyright holder for this preprint this version posted June 30, 2021. ; https://doi.org/10.1101/2021.06.25.21259526 doi: medRxiv preprint Ulrichsen et al, 2020). Recent findings using the lesion-network mapping approach suggest that patients with overlapping symptoms have lesions in regions that are functionally connected and that lesions to brain network hubs or their connecting white matter pathways are associated with more symptoms (Fox, 2018).…”

“…Promisingly, preservation and compensatory altered neural activity and connectivity are associated with improved behavioral outcome (A. K. Rehme, Eickhoff, Wang, Fink, & Grefkes, 2011;Saur et al, 2006), and investigation of brain connectomics may increase the predictive utility of functional imaging for outcome following brain perturbations and pathology (Fornito, Zalesky, & Breakspear, 2015). Recent studies have therefore moved beyond traditional lesion-symptom mapping, to include measures of network dysfunction to explain and predict stroke sequelae (Lim & Kang, 2015;Ulrichsen et al, 2020). Recent findings using the lesion-network mapping approach suggest that patients with overlapping symptoms have lesions in regions that are functionally connected and that lesions to brain network hubs or their connecting white matter pathways are associated with more symptoms (Fox, 2018).…”

“…Indeed, even small lesions in a densely connected hub may cause connectome-wide perturbations (Aben et al, 2019). Recent studies have therefore moved beyond traditional lesion-symptom mapping, to include measures of network dysfunction to explain and predict stroke sequelae (Lim & Kang, 2015; Ulrichsen et al, 2020). Recent findings using the lesion-network mapping approach suggest that patients with overlapping symptoms have lesions in regions that are functionally connected and that lesions to brain network hubs or their connecting white matter pathways are associated with more symptoms (Fox, 2018).…”

Structural disconnectome mapping of cognitive function in poststroke patients

“…Indeed, even small lesions in a densely connected hub may cause connectome‐wide perturbations (Aben et al., 2019 ). Recent studies have therefore moved beyond traditional lesion‐symptom mapping, to include measures of network dysfunction to explain and predict stroke sequelae (Lim & Kang, 2015 ; Ulrichsen et al., 2020 ). Recent findings using the lesion‐network mapping approach suggest that patients with overlapping symptoms have lesions in regions that are functionally connected and that lesions to brain network hubs or their connecting white matter pathways are associated with more symptoms (Fox, 2018 ).…”