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Disruptions in Structural and Functional Connectivity Relate to Poststroke Fatigue - PubMed

Disruptions in Structural and Functional Connectivity Relate to Poststroke Fatigue

Judith D Schaechter et al. Brain Connect. 2023 Feb.

Abstract

Introduction: Poststroke fatigue (PSF) is a disabling condition with unclear etiology. The brain lesion is thought to be an important causal factor in PSF, although 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 in 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. Materials and 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 (IL) and contralesional hemispheres. Fatigue-related structural disconnection was most severe in the IL rostral middle frontal cortex. Greater structural disconnection of a subset of fatigue-related frontal cortex regions, including the IL rostral middle frontal cortex, trended toward correlating significantly with greater loss in functional connectivity. Among identified fatigue-related frontal cortex regions, only the IL 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 plays a role in PSF after MCA stroke, with connectivity disruptions of the IL rostral middle frontal cortex having a central role. Impact statement Poststroke fatigue (PSF) is a common disabling condition with unclear etiology. We hypothesized that PSF relates to disruptions in structural and functional connectivity secondary to the focal lesion. Using structural and resting-state functional connectivity magnetic resonance imaging (MRI) in patients with chronic middle cerebral artery (MCA) stroke, we found frontal cortex regions in the ipsilesional (IL) and contralesional hemispheres with greater structural disconnection correlating with greater fatigue. Among these fatigue-related cortices, the IL rostral middle frontal cortex showed loss in functional connectivity correlating with fatigue. These findings suggest that disruptions in structural and functional connectivity play a role in PSF after MCA stroke.

Keywords: MRI; connectome; outcomes; resting-state functional connectivity; rostral middle frontal cortex; stroke.

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Conflict of interest statement

No competing financial interests exist.

Figures

FIG. 1.
FIG. 1.

Location of stroke in MCA territory in patients. All lesions were lateralized to the same hemisphere in MNI space. (A) Slice showing largest lesion extent in each of the 12 patients. Patient numbers correspond to numbering in Table 1. (B) Lesion overlap across the 12 patients. The color scale represents the number of patients with a lesion at the voxel location. IL, IL hemisphere. IL, ipsilesional; MCA, middle cerebral artery; MNI, Montreal Neurological Institute.

FIG. 2.
FIG. 2.

Structural disconnection in patients. Voxel-wise structural disconnection of gray matter is shown for each of the 12 patients. Each patient's lesion is also shown. For ease of visualization, ChaCo scores are displayed in the range of 1–50%. Patient numbers correspond to numbering in Table 1. ChaCo, Change in Connectivity.

FIG. 3.
FIG. 3.

Fatigue-related structural disconnection. (A) Gray matter regions with structural disconnection correlating significantly (PFWE < 0.01) with fatigue severity, including in the IL and CL rostral middle frontal cortices. Color scale represents voxel-wise severity of structural disconnection (mean ChaCo score) across patients. (B) Scatterplots show the relationship between fatigue severity (MFI-GF scores) and structural disconnection (mean ChaCo scores) of voxels in IL and CL rostral middle frontal cortices exhibiting fatigue-related structural disconnection. CL, contralesional; FWE, family-wise error; MFI-GF, general fatigue subscale of the Multidimensional Fatigue Inventory.

FIG. 4.
FIG. 4.

Functional connectivity of fatigue-related frontal cortex regions. (A) For each identified fatigue-related frontal cortex region (see Table 2), a single axial slice of its functional connectivity network is shown, with an asterisk marking the vicinity of seed used in functional connectivity analysis. Color scale represents voxel-wise functional connectivity (mean z-score) across patients. (B) For the IL rostral middle frontal cortex seed, the broad functional connectivity network is shown in several axial slices.

FIG. 5.
FIG. 5.

Relationships among disrupted structural disconnection, functional connectivity, and fatigue. (A) Scatterplots of relationship between structural disconnection and functional connectivity of three fatigue-related frontal cortex regions. (B) Scatterplot of relationship between functional connectivity of the IL rostral middle frontal cortex and fatigue severity.

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