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Disruptions in Structural and Functional Connectivity Relate to Poststroke Fatigue.

INTRODUCTION
Poststroke fatigue (PSF) is a disabling condition with unclear etiology. The brain lesion is thought to be an important causal factor in PSF, though focal lesion characteristics such as size and location have not proven to be predictive. Given that the stroke lesion results not only in focal tissue death, but also widespread changes in brain networks that are structurally and functionally connected to damaged tissue, we hypothesized that PSF relates to disruptions in structural and functional connectivity.


METHODS
Twelve patients who incurred an ischemic stroke in the middle cerebral artery (MCA) territory 1-3 years prior, and currently experiencing a range of fatigue severity, were enrolled. The patients underwent structural and resting-state functional magnetic resonance imaging (MRI). The structural MRI data were used to measure structural disconnection of gray matter resulting from lesion to white matter pathways. The functional MRI data were used to measure network functional connectivity.


RESULTS
The patients showed structural disconnection in varying cortical and subcortical regions. Fatigue severity correlated significantly with structural disconnection of several frontal cortex regions in the ipsilesional and contralesional hemispheres. Fatigue-related structural disconnection was most severe in the ipsilesional rostral middle frontal cortex. Greater structural disconnection of a subset of fatigue-related frontal cortex regions, including the ipsilesional rostral middle frontal cortex, trended toward correlating significantly with greater loss in functional connectivity. Among identified fatigue-related frontal cortex regions, only the ipsilesional rostral middle frontal cortex showed loss in functional connectivity correlating significantly with fatigue severity.


CONCLUSION
Our results provide evidence that loss in structural and functional connectivity of bihemispheric frontal cortex regions play a role in PSF after MCA stroke, with connectivity disruptions of the ipsilesional rostral middle frontal cortex having a central role.